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					                       Standard Operating Procedures:
               Research Integrity and Human Subject Protection

                             Version: September 10, 2011



Facility Signature:


Approved:_______________________________         Date:______________________




Chief Research Officer Signature:



Approved:_______________________________         Date:______________________




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Standard Operating Procedures: Research Integrity and Human Subject Protection
Version: September 10, 2011
Table of Contents


Definitions and Acronyms .....................................................................................................................7
Administrative Policies ........................................................................................................................14
Informed Consent.................................................................................................................................20
Institutional Review Boards .................................................................................................................31
Adverse Events ....................................................................................................................................37
Special Circumstances for Medical Products ......................................................................................43
Confidentiality of Research Information .............................................................................................55
Recruitment and Retention of Subjects................................................................................................61
Privacy of Protected Health Information in Research .........................................................................78
Accountability of Investigational Products ..........................................................................................93
Laboratory Process.............................................................................................................................102
Research Documentation Maintenance..............................................................................................109
General Administrative Policies ........................................................................................................116
Forms .................................................................................................................................................121




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Expanded Table of Contents

Definitions and Acronyms .....................................................................................................................7
Administrative Policies ........................................................................................................................14
         Overview, Regulatory Support and References: ......................................................................14
    Policies on Standard Operating Procedures (―SOPs‖) for Research .............................................15
         Procedure for Periodic Review of SOPs ..................................................................................15
         Procedure For Additions/Modifications/Deletions To SOPs ...................................................15
         Procedure For Planned and Temporary SOP Deviation ..........................................................16
    Training on, Availability of, and Interpretation of SOPs...............................................................18
         Procedure for Initial SOP Training and Routine Review ........................................................18
         Procedure for Training on Changes to SOP .............................................................................18
         Procedure for Manual Availability ..........................................................................................19
         Procedure for Interpretations of SOPs .....................................................................................19
Informed Consent.................................................................................................................................20
         Overview, Regulatory Support and References: ......................................................................20
    Policies on Informed Consent Content ..........................................................................................21
         Procedure for a Waiver of Documentation of Informed Consent ............................................24
         Procedure for Obtaining a Waiver/Alteration of Informed Consent .......................................24
    Policies on Obtaining Informed Consent .......................................................................................26
         Procedure for Delegating Informed Consent ...........................................................................27
         Procedure for Consenting Non-English Speaking Subjects.....................................................27
         Procedure for Consenting Illiterate Subjects ...........................................................................27
         Procedure for Assent of Children ............................................................................................27
         Procedure for Obtaining Revised Informed Consent ...............................................................28
         Procedure for Documenting Informed Consent .......................................................................29
         Procedure for Using the ―Short Form‖ to Document Informed Consent.................................30
Institutional Review Boards .................................................................................................................31
         Overview, Regulatory Support and References: ......................................................................31
    Need For and Selection of an IRB .................................................................................................32
         Procedure for Assignment of Central IRB ...............................................................................32
    Communications with the IRB.......................................................................................................34
    IRB Audits .....................................................................................................................................36
Adverse Events ....................................................................................................................................37
         Overview, Regulatory Support and References: ......................................................................37
    Identifying, Handling and Reporting AEs .....................................................................................38
         Procedure for Identifying Adverse Events ...............................................................................38
         Procedure for Handling Adverse Events with the Subject.......................................................39
         Procedure for Unblinding Investigational Products .................................................................40
         Procedure for Reporting Internal AEs and SAEs ....................................................................40
    Handling Information on Adverse Events From External Sources ...............................................41
         Procedure for Processing External AEs and SAEs ..................................................................41
Special Circumstances for Medical Products ......................................................................................43
         Overview, Regulatory Support and References: ......................................................................43
    Differentiation between ―Off-Label‖ Use and Need for IND/IDE ................................................44
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        Procedure to Document IND Filing .........................................................................................44
    Additional Review of Phase 4/Postmarketing Studies...................................................................45
        Procedure for Approval of Phase 4/Postmarketing Studies .....................................................45
    Use of Investigational Products When Subjects Enter the Facility as a Second Institution ..........46
        Procedures To Follow When Facility/Staff are NOT Engaged in Research ...........................46
        Procedures to Follow for Engaged Facility/Staff is an Extension of the Research
        Environment .............................................................................................................................47
    Emergency Treatment Use of an Unapproved (Test) Article ........................................................48
        Procedures Prior to and After Emergency Use ........................................................................49
    Humanitarian Use Devices (HUD) and Humanitarian Device Exemptions (HDE) ......................51
        Procedure for Obtaining IRB Approval of an HUD or HDE...................................................51
    Radiopharmaceuticals ....................................................................................................................52
        Procedure for Starting a Protocol Involving Radiopharmaceuticals: ......................................53
    Recombinant DNA and Gene Transfer Therapy Research ............................................................54
        Procedure for Creation of an Institutional Biosafety Committee (IBC): .................................54
Confidentiality of Research Information .............................................................................................55
    Research Material Confidentiality .................................................................................................56
        Procedure for Obtaining Confidentiality Agreements .............................................................57
        Procedure for Release of Information to Third Parties ............................................................57
        Procedure for Redacting Study Documents for Release ..........................................................57
    Publication/Presentation of Study Results .....................................................................................59
        Procedure to Accept Authorship Credit ...................................................................................59
        Procedure to Publish/Present Study Data Independently.........................................................60
Recruitment and Retention of Subjects................................................................................................61
        Overview, Regulatory Support and References .......................................................................61
    Equitable Selection of Subjects .....................................................................................................63
        Procedure to Assure Equitable Selection .................................................................................64
        Procedure to Systematically Exclude a Certain Class of Individuals ......................................64
    Referencing Investigational Products in Public .............................................................................65
    Direct Advertising for Study Subjects ...........................................................................................65
        Procedures For Pre-Approval Of Media ..................................................................................67
        Procedure for Internet Study Database Listings ......................................................................67
    Respecting Subject Privacy and Therapeutic Relationships in Recruitment ................................68
        Procedure for Contacting Subjects...........................................................................................68
        Procedure for Approaching another Physician’s Hospitalized Patient ....................................69
    Compensation Surrounding Recruitment .......................................................................................70
        Procedure to offer Remuneration to Subjects ..........................................................................71
        Procedure to offer Remuneration to Referral Sources .............................................................71
    Prescreening of Subjects ................................................................................................................73
        Procedure for Pre-Screening in the Assessment & Referral (A&R) Department:...................73
    Pre-Screening and Screening/Enrollment Logs .............................................................................74
        Procedure for Disclosing Pre-Screening Logs to Sponsor, IRB or Regulators .......................74
    Retention of Subjects in Research Protocols .................................................................................75
        Procedure To Handle Requests To Withdraw .........................................................................75
    Referring Patients to Studies the Institution is Not Engaged In ....................................................77
Privacy of Protected Health Information in Research .........................................................................78
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       Overview, Regulatory Support and References: ......................................................................78
   Disclosure of De-Identified Data ...................................................................................................79
       Procedures to De-Identify PHI: ...............................................................................................79
   Disclosure of a Limited Data Set ...................................................................................................81
       Procedures for Creating a Data Use Agreement ......................................................................81
       Procedures for Creating a Limited Data Set ............................................................................82
   Disclosure of PHI With Individual Authorization .........................................................................83
       Procedures for Obtaining HIPAA Authorizations to Release PHI: .........................................84
   Disclosure of PHI Without Individual Authorization- IRB Waiver ..............................................85
   Use and Disclosure of PHI Without Individual Authorization- Prepatory to Research ................87
       Procedures for Use Supporting Internal Research Activities ..................................................87
       Procedures for Disclosure Supporting External Research Activities ......................................87
   Use or Disclosure of PHI Without Individual Authorization- Research on Decedents .................89
       Procedure for Use or Disclosure of PHI for Research on Decedents: .....................................89
   Identification of Subjects in Communications ...............................................................................90
       Procedure for Redacting Identifiers for Release of Documents ..............................................90
   Certificates of Confidentiality........................................................................................................91
       Procedure for Obtaining a Certificate of Confidentiality ........................................................92
Accountability of Investigational Products ..........................................................................................93
       Overview, Regulatory Support and References: ......................................................................93
   Accountability Logs .......................................................................................................................94
       Procedures upon Receipt of Investigational Product from Sponsor ........................................94
       Procedures for Logging Administration/Dispensing of Investigational Product to Subjects ..94
       Procedures for Logging Return of Investigational Product to Facility ....................................95
       Procedures for Logging The Return-To-Sponsor/Destruction of Investigational Product ......95
       Procedures for Inventory Discrepancies ..................................................................................95
   Storage of Investigational Product .................................................................................................96
       Procedure for Temperature Logs .............................................................................................96
       Procedure for Relocating Investigational Product to Alternate Storage ..................................97
   Dispensing for Inpatient Use .........................................................................................................98
       Procedure for Administration to Inpatient Research Subjects .................................................98
   Dispensing for Outpatient Use .......................................................................................................99
       Procedures for Dispensing to Research Subjects for Outpatient Use ......................................99
   Return-To-Sponsor or Destruction of Investigational Product ....................................................100
       Procedure for the Return of Unused Investigational Product ................................................100
       Procedure for the Disposal of Unused Investigational Product .............................................100
Laboratory Process.............................................................................................................................102
       Overview, Regulatory Support and References: ....................................................................102
   Receipt and Storage of Laboratory Supplies ...............................................................................103
   Phlebotomy ..................................................................................................................................104
       Procedure for Review of Phlebotomy Policies ......................................................................104
       Procedure for Storage of Specimens Prior to Transport ........................................................104
   Training Requirements for Packaging and Shipping of Specimens ............................................106
       Procedure for Diagnostic Specimens Training ......................................................................106
       Procedures for Infectious Substances (a.k.a. ―HazMat Training‖ or ―DOT/IATA
       Certification‖) ........................................................................................................................106
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       Procedures for Dry Ice Training/Packing ..............................................................................108
Research Documentation Maintenance..............................................................................................109
       Overview, Regulatory Support and References: ....................................................................109
   Required Information in Inpatient Medical Records ...................................................................110
   Retention of Inpatient Medical Records and Research Records ..................................................111
   Access of Records by Auditors ....................................................................................................112
       Procedure for Outside Parties Accessing Research Records .................................................112
   Storage and Destruction of Paper-Based Research Documentation ............................................113
       Procedures for Storing Paper-Based Research Documentation .............................................113
       Procedure for Destruction of Paper-Based Research Documentation ...................................114
   Electronic Communication ..........................................................................................................115
General Administrative Policies ........................................................................................................116
   Credentialing of Physicians or other Staff to Do Research .........................................................117
       Procedures For FDA Background Check ..............................................................................117
   Handling Complaints and Serious/Continuing Noncompliance ..................................................118
       Procedures for Receipt of Compliant .....................................................................................118
       Procedures for Routine Investigation.....................................................................................119
       Procedure for Reporting of Serious or Continuing Non-Compliance to Governmental
       Authorities..............................................................................................................................120
Forms .................................................................................................................................................121
   FORM: Research SOP Training Attestation Log: Review of Complete Manual ........................122
   FORM: Research SOP Training Attestation Log: Change of SOP .............................................123
   FDA Form 1572 ...........................................................................................................................123
   FDA Form 1572 ...........................................................................................................................124
   Supplement to Credentialing: Research Activity Form ...............................................................125
   Supplement to Credentialing: Research Activity Form ...............................................................126
   FORM: Research Deviation/Violation or Other Reportable Event Form ...................................126
   FORM: Research Deviation/Violation or Other Reportable Event Form ...................................127
   FORM: Research Deviation/Violation or Other Reportable Event Form ...................................128




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                                Definitions and Acronyms
          510(k)    A particular FDA Class For Medical Devices
               AE   Adverse Event
             CFR    Code of Federal Regulations
            CMS     United States Center for Medicare and Medicaid Services
            CRA     Clinical Research Associate
            CRC     Clinical Research Coordinator
             CRF    Case Report Form
            CRO     Contract Research Organization
         DHHS       United States Department of Health and Human Services
            DOT     United States Department of Transportation
         DSMB       Data Safety Monitoring Board
            FDA     United States Food and Drug Administration
            FWA     Federal-Wide Assurance
            GCP     International Council on Harmonization’s E6: Good Clinical Practices
            HDE     Humanitarian Device Exemption (FDA Class For Medical Devices)
         HIPAA      Health Insurance Portability and Accountability Act of 1996
            HUD     Humanitarian Use Device (FDA Class of Medical Devices)
           IATA     International Air Transport Association
               IB   Investigator’s Brochure
             IBC    Institutional Biosafety Committee
             ICH    International Council on Harmonization
             IDE    Investigational Device Exemption (FDA Class For Medical Devices)
          IDMC      Independent Data Monitoring Committee
             IND    Investigational New Drug (FDA Class For Drugs)
             IRB    Institutional Review Board
           IVRS     Interactive Voice Response System
            NDA     New Drug Application (FDA Class For Drugs)
             NIH    United States National Institutes of Health
            NSR     Non-Significant Risk (FDA Risk Classification of Medical Device)
              PHI   Protected Health Information as defined by the Health Insurance
                    Portability and Accountability Act of 1996
          PMA       Pre-Market Application (FDA Class For Medical Devices)
         RDRC       Radioactive Drug Research Committee
           SAE      Serious Adverse Event
          SMO       Site Management Organization
           SOP      Standard Operating Procedures
        SPOOS       Significant Payments Of Other Sorts
            SR      Significant Risk (FDA Risk Classification of Medical Device)
          UAE       Unexpected Adverse Event

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    Adverse Event (AE) Any untoward medical occurrence in a patient or clinical
                       investigation subject administered a product and that does not
                       necessarily have a causal relationship with this treatment. An AE
                       can therefore be any unfavorable and unintended sign (including an
                       abnormal laboratory finding), symptom, or disease temporally
                       associated with the use of a medicinal (investigational) product,
                       whether or not related to the medicinal (investigational) product.

                Assent A child’s affirmative agreement to participate in a clinical
                       investigation. Mere failure to object may not, absent affirmative
                       agreement, be construed as assent.
           Beneficence Doing no harm. Maximizing benefits while minimizing risks.
      Case Report Form A printed, optical, or electronic document designed to record all of
                (CRF) the protocol-required information to be reported to the sponsor on
                       each trial subject.

  Chief Research Officer The highest ranked individual with direct responsibility for research
                         operations. This is usually a corporate position.
                Children Persons who have not attained the legal age for consent to
                         treatments or procedures involved in clinical investigations, under
                         the applicable law of the jurisdiction in which the clinical
                         investigation will be conducted.
       Clinical Research The person at the site who manages the daily operations of a
     Coordinator (CRC) protocol and who is responsible to the Principal Investigator.
      Contract Research A person or organization that assumes, as an independent contractor
    Organization (CRO) with the sponsor, one or more of the obligations of a sponsor, e.g.,
                         design of a protocol, selection or monitoring of investigations,
                         evaluation of reports, and preparation of materials to be submitted
                         to the Food and Drug Administration
         Data and Safety A committee of scientists, physicians, statisticians and others that
      Monitoring Board collects and analyzes data during the course of a research study to
                (DSMB) monitor for adverse effects (events) and other trends (such as an
                         indication that one treatment is significantly better than another,
                         particularly when one arm of the study involves a placebo control)
                         that would warrant modification or termination of the study or
                         notification of subjects about new information that might affect
                         their willingness to continue in the study. Also called Data
                         Monitoring Committee.
    Delegated Authority The power given to an individual by the Principal Investigator as
                         evidenced only in writing on the Delegation of Authority Log (or
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                           equivalent) and housed in the Regulatory Binder
   Diagnostic Specimen     Any human or animal material, including excreta, secreta, blood
                           and its components, tissue, and tissue fluids being transported for
                           diagnostic or investigational purposes, but excluding live infected
                           humans or animals.
           Double-Blind    The design of a study in which neither the investigator nor the
                           subject knows which treatment the subject is receiving.
       Expedited review    Review of proposed research by the IRB chair or a designated
                           voting member or group of voting members rather than by the
                           convened IRB. Federal rules permit expedited review for certain
                           kinds of research involving no more than minimal risk and for
                           minor changes in approved research.
         Family Member     Any one of the following legally competent persons: Spouse;
                           parents; children (including adopted children); brothers, sisters, and
                           spouses of brothers and sisters; and any individual related by blood
                           or affinity whose close association with the subject is the equivalent
                           of a family relationship.
 Federalwide Assurance     An agreement or contract between the organization and OHRP, on
               (FWA)       behalf of the Secretary, DHHS, affirming that the organization will
                           protect the welfare of research subjects in accordance with the
                           regulations. The FWA replaces all other previous forms of
                           assurance (i.e., MPA, SPA, etc.).
                Guardian   An individual who is authorized under applicable State or local law
                           to consent on behalf of a child to general medical care when general
                           medical care includes participation in research.
         Human Subject     An individual who is or becomes a participant in research, either as
                           a recipient of the test article or as a control. A subject may be either
                           a healthy human or a patient.
    Inclusion/Exclusion    The characteristics that must be present (inclusion) or absent
                Criteria   (exclusion) in order for a subject to qualify for a research protocol.
      Independent Data     See Data Safety and Monitoring Committee
  Monitoring Committee
               (IDMC)

     Infectious Substance A material known to contain or suspected of containing a pathogen.
                           A pathogen is a virus or micro-organism (including its viruses,
                           plasmids, or other genetic elements, if any) or a proteinaceous
                           infectious particle (prion) that has the potential to cause disease in
                           humans or animals.
   Institutional Biosafety A committee based at the site that reviews, approves and oversees
        Committee (IBC) recombinant DNA and/or gene transfer projects. This committee is
                           not a replacement for, but a supplement to the IRB approval of a
                           study.
      Investigational New An investigational drug is a drug or biologic that is used in a
 Drug (or Investigational clinical investigation. The FDA considers the term ―Investigational
              Drug) (IND) New Drug‖ synonymous (21CFR 312.3). However, an
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                           investigational drug may be an approved drug that is being studied
                           for an unapproved or approved use in a controlled, randomized or
                           blinded clinical trial.

     Institutional Review Any board, committee, or other group formally designated by an
              Board (IRB) institution to review biomedical research involving humans as
                           subjects, to approve the initiation of and conduct periodic review of
                           such research.
  Investigational Product An Investigational Drug or Device
  Investigator's Brochure A compilation of the clinical and nonclinical data on the
                      (IB) investigational product(s) that is relevant to the study of the
                           investigational product(s) in human subjects
        Interactive Voice A telephone contact system that allows the user to key in requests
        Response System and receive instructions or information.
                   (IVRS)
      Legally Authorized An individual or judicial or other body authorized under applicable
           Representative law to consent on behalf of a prospective subject to the subject’s
                           participation in the procedure(s) involved in the research.
        Medical Monitor The physician at the Sponsor who is responsible for the clinical
                           investigation of a test product.
               MedWatch The FDA Medical Products Reporting Program is an initiative
                           designed to educate health professionals about the critical
                           importance of monitoring for and reporting adverse events and
                           problems to FDA and/or the manufacturer and to ensure that new
                           safety information is rapidly communicated to the medical
                           community, thereby improving patient care. The purpose of the
                           MedWatch program is to enhance the effectiveness of
                           postmarketing surveillance of medical products as they are used in
                           clinical practice and to rapidly identify significant health hazards
                           associated with these products.
            Minimal Risk The degree of risk in which the probability and magnitude of harm
                           or discomfort anticipated in the research are not greater in and of
                           themselves than those ordinarily encountered in daily life or during
                           the performance of routine physical or psychological examinations
                           or tests.
                  Monitor When used as a noun, means an individual designated by a sponsor
                           or contract research organization to oversee the progress of an
                           investigation. The monitor may be an employee of a sponsor or a
                           consultant to the sponsor, or an employee of or consultant to a
                           contract research organization. Monitor, when used as a verb,
                           means to oversee an investigation.
              Open-Label A study in which the subjects and the investigator are aware of the
                           treatment the subject is receiving (i.e. not single-blinded or double-
                           blinded).
                    Parent A child’s biological or adoptive parent
                   Placebo An inactive substance designed to resemble the article being tested.
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   Principal Investigator An individual who actually conducts a clinical investigation, i.e.,
                          under whose immediate direction the test article is administered or
                          dispensed to, or used involving, a subject, or, in the event of an
                          investigation conducted by a team of individuals, is the responsible
                          leader of that team.
                Protocol A plan that includes, at minimum, the objectives, rationale, design,
                          methods and other conditions for conducting a research study.
         Randomization The process of assigning trial subjects to treatment or control
                          groups using an element of chance to determine the assignments in
                          order to reduce bias.
                Research A systematic investigation, including research development, testing
                          and evaluation, designed to develop or contribute to generalizable
                          knowledge.
   Research Coordinator See Clinical Research Coordinator
          Research Staff Staff directly involved in research related activities. This is meant
                          to include roles such as Principal Investigator, Sub-Investigator and
                          Clinical Research Coordinator. Although other staff may interact
                          with research subjects, for purposes of this manual the term
                          ―Research Staff‖ does not include support staff such as billing,
                          dietary etc.
  Serious Adverse Event Any untoward medical occurrence that:
                  (SAE) 1. Results in death,
                          2. Is life-threatening (places the patient or subject, in the view of
                              the investigator, at immediate risk of death from the reaction as
                              it occurred, i.e., it does not include a reaction that, had it
                              occurred in a more severe form, might have caused death)
                          3. Requires inpatient hospitalization or prolongation of existing
                              hospitalization,
                          4. Results in persistent or significant disability/incapacity, or
                          5. Is a congenital anomaly/birth defect.
                          Important medical events that may not result in death, be life-
                          threatening, or require hospitalization may be considered a serious
                          adverse drug experience when, based upon appropriate medical
                          judgment, they may jeopardize the patient or subject and may
                          require medical or surgical intervention to prevent one of the
                          outcomes listed in this definition. Examples of such medical events
                          include allergic bronchospasm requiring intensive treatment in an
                          emergency room or at home, blood dyscrasias or convulsions that
                          do not result in inpatient hospitalization, or the development of drug
                          dependency or drug abuse. (21CFR312.32(a))
Significant Payments Of Payments made by the sponsor of a covered study to the
   Other Sorts (SPOOS) investigator or the institution to support activities of the investigator
                          that have a monetary value of more than $25,000, exclusive of the
                          costs of conducting the clinical study or other clinical studies, (e.g.,
                          a grant to fund ongoing research, compensation in the form of
                          equipment or retainers for ongoing consultation or honoraria)
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                         during the time the clinical investigator is carrying out the study
                         and for 1 year following the completion of the study
                    Site The local institution which the research activity will actually be
                         conducted.
      Source Documents Original documents, data, and records (e.g., hospital records,
                         clinical and office charts, laboratory notes, memoranda, subjects'
                         diaries or evaluation checklists, pharmacy dispensing records,
                         recorded data from automated instruments, copies or transcriptions
                         certified after verification as being accurate and complete,
                         microfiches, photographic negatives, microfilm or magnetic media,
                         x-rays, subject files, and records kept at the pharmacy, at the
                         laboratories, and at medico-technical departments involved in the
                         clinical trial).
                Sponsor An entity (person or organization) who initiates a clinical
                         investigation, but who does not actually conduct the investigation,
                         i.e., the test article is administered or dispensed to or used
                         involving, a subject under the immediate direction of another
                         individual. A person other than an individual (e.g., corporation or
                         agency) that uses one or more of its own employees to conduct a
                         clinical investigation it has initiated is considered to be a sponsor
                         (not a sponsor-investigator), and the employees are considered to be
                         investigators.
    Sponsor-Investigator An individual who both initiates and actually conducts, alone or
                         with others, a clinical investigation, i.e., under whose immediate
                         direction the test article is administered or dispensed to, or used
                         involving, a subject. The term does not include any person other
                         than an individual, e.g., corporation or agency.
         Subinvestigator Any individual member of the clinical trial team designated and
                         supervised by the investigator at a trial site to perform critical trial
                         related procedures and/or to make important trial-related decisions
                         (e.g., associates, residents, research fellows).
                 Subject See Human Subject
            Test Article Any drug (including a biological product for human use), medical
                         device for human use, human food additive, color additive,
                         electronic product, or any other article subject to regulation under
                         the FDA or other federal regulations.
    Unexpected Adverse Any adverse experience, the specificity or severity of which is not
           Event (UAE) consistent with the current investigator brochure; or, if an
                         investigator brochure is not required or available, the specificity or
                         severity of which is not consistent with the risk information
                         described in the general investigational plan or elsewhere in the
                         current application, as amended. (21CFR312.32(a))
     Vulnerable Subjects Individuals whose willingness to volunteer in a clinical trial may be
                         unduly influenced by the expectation, whether justified or not, of
                         benefits associated with participation, or of a retaliatory response
                         from senior members of a hierarchy in case of refusal to participate.
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                       Examples are members of a group with a hierarchical structure,
                       such as medical, pharmacy, dental, and nursing students,
                       subordinate hospital and laboratory personnel, employees of the
                       pharmaceutical industry, members of the armed forces, and persons
                       kept in detention. Other vulnerable subjects include patients with
                       incurable diseases, persons in nursing homes, unemployed or
                       impoverished persons, patients in emergency situations, ethnic
                       minority groups, homeless persons, nomads, refugees, minors, and
                       those incapable of giving consent.
                 Ward A child who is placed in the legal custody of the State or other
                       agency, institution, or entity, consistent with applicable Federal,
                       State, or local law.
            Well-Being The physical and mental integrity of the subjects participating in a
                       research protocol.




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                                  Administrative Policies

Overview, Regulatory Support and References:

Policy manuals are made to reflect what we do and what we do should be reflected in Policy
manuals. Policies provide the framework for consistent behavior and a uniform methodology for
dealing with situations. Following policy manuals allows people to get on with their jobs and not
have to keep on discussing and re-discussing the same issues every time they arise (i.e. thought out
decision can be applied to many similar cases efficiency).

Regulations and their standards of conduct concerning research change over time therefore policies
should either lead or immediately follow these trends. Not only must policies be revised, but people
must also be familiar with them and able to comply with them as they are revised.

Ideally all this can be accomplished; however the real world demonstrates that policies are deviated
from either intentionally or unintentionally. This may result from a simple misinterpretation of the
policy, lack of knowledge of the policy, disregard of the policy or the simple inability of a manual to
address every potential situation. Unintentional deviations should be avoided by training.
Intentional deviations should be pre-approved and accompanied by a revisiting of the policy to
assure it is meeting the needs of research operations.



   Partnership for Human Research Protections: Accreditation Standards ONR(HRP)1B1 (May
    2003 ed.) www.phrp.org




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Policies on Standard Operating Procedures (“SOPs”) for Research
Policy Number: SOPR-ADMIN-100.V01
Effective Date: January 1, 2005


PURPOSE: The best research practices should be in place at all times.


POLICIES:

1. The facility has the following SOP manual in place, which govern the conduct of research
   (including clinical trials) in the facility.
2. Periodic, but no less than annual, review of this manual shall be performed.
3. Whenever a new policy, a revision to an existing policy or the deletion of a policy is needed,
   appropriate review of said policy is completed. A historic record is kept so that any given date, it
   can be easily determined what policy was in place.
4. From time to time, deviations from this policy will either occur or be necessary in ―single case‖
   scenarios. If prior written approval for such deviation from the Chief Research Officer is not
   possible (i.e. emergent need or discovered negligence that occurred in the past), the Chief
   Research Officer is to be informed as soon as possible after the deviation occurs.


Procedure for Periodic Review of SOPs

1. The governing body of the facility shall review these policies at least once annually and
   document such review in their official minutes.
2. The relevant governing body(ies) of the facility shall review the most current version of this
   manual in it’s entirety at the periodicity of it’s general policy reviews and, provided no changes
   are necessary, adopt the Manual and it’s subsequent revisions until the next review.


Procedure For Additions/Modifications/Deletions To SOPs

1. Unless initiated by the Chief Research Officer, in the event a particular policy is requested to be
   generated or modified or deleted, a written request to the Chief Research Officer containing the
   following information will be sent prior to implementing the change:
   1.1. The reason for requesting the addition/modification/deletion
       1.1.1. Statements such as ―required by law/accrediting body/etc‖ cannot be considered
            unless accompanied by the relevant citation of such external requirement; AND
   1.2. The relevant policy number (for modification or deletion requests); AND
   1.3. The proposed change (preferably in a redline format) or new policy that molds to the same
        format as this manual; AND
   1.4. Any other relevant information.
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2. Once received, the Chief Research Officer will research the policy request and decide the
   following:
   2.1. Compliance with relevant federal, state and local laws as well as GCPs
   2.2. Approval ―As-Is‖; Approval with modifications (and provide modifications); OR
        Disapproval (with justifications)
   2.3. Appropriateness of the request, regardless of decision at the requesting Site, as it may
        pertain to other Sites within the scope of their service. If appropriate, the Chief Research
        Officer shall initiate the modification.
3. To maintain historic integrity on NEW policies…
   3.1. A Version tag of ―.V01‖ shall be placed in the policy number.
   3.2. An Effective Date shall be provided in the policy header
4. To maintain historic integrity on MODIFIED policies…
   4.1. The Version tag shall be increased to reflect the next version (e.g. .V01 to .V02)
   4.2. An Effective Date shall be provided in the policy header
   4.3. The old policy shall be kept in an Archive section of the manual for a period pertaining to
        the record retention section in this manual.
5. To maintain historic integrity on DELETED policies…
   5.1. A Version tag of ―.V-DELETED‖ shall be placed as the policy number.
   5.2. The Title of the Policy shall be changed to include the words ―DELETED POLICY‖ prior to
        the rest of the title.
   5.3. The archived policy shall note the date no longer effective.
   5.4. As necessary, a description of the reason for deletion.
   5.5. The deleted policy shall be kept in an Archive section of the manual for a period pertaining
        to the record retention section in this manual.


Procedure For Planned and Temporary SOP Deviation

1. Criteria for a planned SOP deviation are as follows:
   1.1. The change is necessary to protect the safety of staff/subjects AND/OR the protocol calls for
        procedures contrary to our SOPs; AND
   1.2. The change is temporary, individual to a certain situation and not sufficient to request a
        permanent change to the policies.
2. The request for temporary policy deviation is to be sent to the Chief Research Officer in writing
   with the following information:
   2.1. Policy Number/Section necessary to deviate from
   2.2. Justification for deviation
3. Once received, the Chief Research Officer will research said policy deviation request and decide
   the following:
   3.1. Compliance with relevant federal, state and local laws as well as GCP
   3.2. Approval ―As-Is‖; Approval with modifications (and provide modifications); OR
        Disapproval (with justifications)
   3.3. Appropriateness of the request, regardless of decision at the requesting Site, as it may
        pertain to other Sites that may have a similar situation (e.g. conducting the same protocol).
        If appropriate, the Chief Research Officer shall initiate the approval of the deviation on his
        own.
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   3.4. If approved, documentation of the Chief Research Officers approval shall be kept in the
        Approved Deviations section of this Manual.




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Training on, Availability of, and Interpretation of SOPs
Policy Number: SOPR-ADMIN-110.V01
Effective Date: January 1, 2005

PURPOSE: Without the relevant staff being knowledgeable of the policies, the best-written policies
are useless.

POLICIES:

1. All staff are to be trained on the most recent version of this manual prior to undertaking their
   duties.
2. Changes to SOPs are to be communicated to relevant staff with sufficient time prior to their
   effective date to accomplish the transition to the new procedures.
3. The manual shall be readily available to those that will need it for reminders.
4. The Chief Research Officer shall be the ultimate authority on the interpretation of and resolution
   of any ambiguity in this manual.


Procedure for Initial SOP Training and Routine Review
1. At a minimum, the following staff shall receive a copy of this manual prior to undertaking
   duties:
   1.1. Principal Investigators that are either
       1.1.1. Employed OR
       1.1.2. Otherwise engaged on behalf of the Site
   1.2. Sub-Investigators that are either
       1.2.1. Employed OR
       1.2.2. Otherwise engaged on behalf of the Site
   1.3. Clinical Research Coordinators that are either
       1.3.1. Employed OR
       1.3.2. Otherwise engaged on behalf of the Site
2. As research involves ancillary staff at the Site (e.g. billing, business development etc), these staff
   should be aware of at least the relevant portions pertaining to their duties.
3. At initial employment/engagement and no less than annually thereafter, the entire manual must
   be reviewed and attested to in writing by said staff on the FORM: Research SOP Training
   Attestation Log: Review of Complete Manual, which will be kept in the Training section of the
   manual.


Procedure for Training on Changes to SOP

1. New policies, modification of policies and deletions of policies, once approved by the Chief
   Research Officer, shall be distributed to the highest-ranking research administration official at
   the Site.
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2. The FORM: Research SOP Training Attestation Log: Change of SOP will be used as a cover
   sheet and the new policy shall be stapled to it. The new policy will be circulated so that all
   relevant individuals have a change to review it prior to the effective date. It is preferred that
   each individual not have any longer than 48 hours to review to allow enough time to circulate.
   Once completed, the form along with the stapled policy will be kept in the Training section of
   the manual and the new/revised/deleted policy(ies) will be filed accordingly.


Procedure for Manual Availability

1. At all times, one copy of this manual must be available at the Site for staff to review. This can
   be accomplished in one of many ways such as:
   1.1. Print Version
   1.2. Company Intranet
2. Research Staff should be readily able to state where this manual is located
3. Unless absolutely necessary, copies of policies should be discouraged to prevent version control
   issues and loss of confidentiality of business practices.


Procedure for Interpretations of SOPs

1. Questions concerning any ambiguities or uncertainties in this manual are to be routed to the
   Chief Research Officer.
2. The policies shall be interpreted by the Chief Research Officer in accordance to the spirit of the
   law, GCPs and the company’s mission statement.
3. Any disagreements with the Chief Research Officer’s interpretations are encouraged to be
   voiced, particularly if there is an ethical or legal concern. This may lead to the written
   clarification of the policy or bring into light additional information that may influence a change
   in the interpretation.
4. The Chief Research Officer shall have the final authority on such interpretations.
5. Any employee has a right to follow the compliance policy in the event they believe that an
   interpretation is unethical or illegal.




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                                      Informed Consent

Overview, Regulatory Support and References:

Informed consent is the hallmark ethical requirement regarding research with human subjects.
Informed consent is not simply a form or a one-time event, but an ongoing process that begins before
the subject is enrolled and lasts until after they have completed participation in the research project.
Informed consent is the combination of the state of understanding the nature of the research activity
and the ability to voluntarily choose whether or not to begin or continue participation. Adherence to
ethical principals as well as federal/local laws not only protects both the subject’s autonomy and the
investigator from liability, but also fosters public trust in the research process to which medical
progress is dependent.


   21 CFR50.23, 24, 25(a)(1-8), 25(b)(1–6), 27(b)(2)
   45 CFR46.116(a)(1-8), 116(b)(1–6), 117(a), 117(b)(2), 117(c)
   ICH Harmonized Tripartite Guideline E6: Good Clinical Practice: 1.9, 4.8.1, 4.8.3, 4.8.5, 4.8.7,
    4.8.8, 4.8.9, 4.8.10, 4.8.11, 4.8.15 (http://www.fda.gov/cder/guidance/959fnl.pdf)
   FDA Information Sheets—The Consent Process
    (http://www.fda.gov/oc/ohrt/irbs/informedconsent.html)
   Partnership for Human Research Protections: Accreditation Standards ICS1C, ICS1D, ICS1E,
    ICS1F, ICS2A & ICS3A (May 2003 ed.) www.phrp.org
   OHRP: Tips On Informed Consent (Revised 3/16/93)
    http://www.hhs.gov/ohrp/humansubjects/guidance/ictips.htm
   OHRP: Obtaining And Documenting Informed Consent Of Subjects Who Do Not Speak English
    (November 9, 1995) http://www.hhs.gov/ohrp/humansubjects/guidance/ic-non-e.htm
   OHRP: Informed Consent--Legally Effective and Prospectively Obtained (August 12, 1993)
    http://www.hhs.gov/ohrp/humansubjects/guidance/hsdc93-03.htm
   OHRP: "Exculpatory Language" in Informed Consent (November 15, 1996)
    http://www.hhs.gov/ohrp/humansubjects/guidance/exculp.htm
   IRB Guidebook III A and B (http://www.hhs.gov/ohrp/irb/irb_chapter3.htm#e2)




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Policies on Informed Consent Content
Policy Number: SOPR-IC-100.V1
Effective Date: January 1, 2005

PURPOSE: Information presented to potential and active subjects should be of sufficient detail for
them to adequately make an informed decision about initial or continued participation.


POLICIES:

1. Required Elements of Consent
   1.1. Informed consent must have all the required elements unless:
       1.1.1. The IRB has waived the requirement for documentation of consent
       1.1.2. The IRB has waived one of the required elements
   1.2. The Required Elements of consent are
       1.2.1. A statement that the study involves research;
       1.2.2. An explanation of the purposes of the research;
       1.2.3. The expected duration of the subject’s participation;
       1.2.4. A description of the procedures to be followed;
       1.2.5. Identification of any procedures which are experimental, including a description of
            administration of any study drugs;
       1.2.6. The probability for random assignment to each of the protocol’s arms (i.e. research
            group, placebo group, control group etc);
       1.2.7. A description of any reasonably foreseeable risks or discomforts to the subject;
       1.2.8. A description of any benefits to the subject or to others which may reasonably be
            expected from the research;
           1.2.8.1.   Even if the benefit is solely limited to a sense of helping the public at large, it
                  must still be mentioned.
           1.2.8.2.   Payments or other reimbursements to the subject are not considered to be
                  expected benefits.
           1.2.8.3.   When there is no intended clinical benefit to the subject, the subject should be
                  made aware of this.
       1.2.9. A disclosure of appropriate alternative procedures or courses of treatment, if any, that
            might be advantageous to the subject;
       1.2.10. A description of the extent, if any, which confidentiality of study data identifying the
            subject will be maintained (NOTE: The Health Insurance Portability and Accountability
            Act of 1996 (HIPAA) has certain written language required to disclose information for
            research purposes. This language may be utilized in a separate ―Stand-Alone‖ form. In
            the event a separate form is not used, the elements required by that form are to be
            included in this confidentiality section of the informed consent document- See section
            on Privacy in this manual);
           1.2.10.1. If the investigational product is governed by the FDA, then this section must
                  note the possibility that the Food & Drug Administration may also inspect the
                  records;
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       1.2.11. For research involving more than minimal risk (which includes risk of non-physical
            injury), an explanation as to whether any compensation is available if injury occurs and,
            if so, what it consists of and who will be responsible for paying, and where further
            information may be obtained;
       1.2.12. For research involving more than minimal risk (which includes risk of non-physical
            injury), an explanation as to whether any medical treatment is available if injury occurs
            and, if so, what it consist of , who will be responsible for paying, and where further
            information may be obtained;
       1.2.13. An explanation of i)whom to contact for answers to pertinent questions about the
            research; ii) whom to contact for questions concerning research subjects’ rights; and iii)
            whom to contact in the event of a research-related injury to the subject;
           1.2.13.1. All three areas must be addresses in the document
           1.2.13.2. One person/agency cannot be the contact for all three areas. There must be at
                  least two names (e.g. Primary Investigator for area 1 and IRB contact for areas 2
                  and 3) with local telephone numbers for contacts to answer questions in these
                  areas.
           1.2.13.3. If any of the numbers are long distance numbers, a Toll Free or Collect-Call
                  option should be given
       1.2.14. A statement that participation is voluntary
       1.2.15. A statement that refusal to participate will involve no penalty or loss of benefits to
            which the subject is otherwise entitled (NOTE: use of that exact phrase is preferred as
            opposed to ―not affect your treatment at this facility‖ or other phrase that may imply
            other limitations)
       1.2.16. A statement that the subject may discontinue participation at any time without penalty
            or loss of benefits to which the subject is otherwise entitled (NOTE: use of that exact
            phrase is preferred as opposed to ―not affect your treatment at this facility‖ or other
            phrase that may imply other limitations).
2. Additional Elements of Consent Forms
   2.1. When appropriate, the following elements of information shall also be provided to each
        subject unless:
       2.1.1. The criteria for the element is not met; OR
       2.1.2. IRB considers and documents its conclusion that the additional element is not
            required for a particular protocol—even if the protocol meets the criteria described
            below.
   2.2. Additional elements include:
       2.2.1. ELEMENT: A statement that the particular treatment or procedure may involve risks
            to the subject or to the embryo or fetus, if the subject is or may become pregnant, which
            are currently unforeseeable- CRITERIA: Any study that involves currently unforseeable
            risks to the subject or to an embryo or fetus, if the subject is or may become pregnant
            (this is especially true with studies conducted under an Investigational New Drug
            Application (IND) or Investigational Device Exemption (IDE));
       2.2.2. ELEMENT: Anticipated circumstances under which the subject’s participation may
            be terminated by the investigator without regard to the subject’s consent- CRITERIA:
            Any study in which the protocol outlines circumstances under which the subject’s
            participation may be terminated without regard to the subject’s consent (an unexplained
            statement that the investigator and/or the sponsor may withdraw subjects at any time
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             does not adequately inform the subject of anticipated circumstances for such
             withdrawal);
       2.2.3. ELEMENT: Any additional costs to the subject that may result from participation in
             the research- CRITERIA: Any study in which the subjects may incur additional costs
             because they are participating in research (i.e. copayments, deductibles or denial of
             coverage as some insurance and/or other reimbursement mechanisms may not fund
             some or all care that is delivered in a research context);
       2.2.4. ELEMENT: The consequences of a subject’s decision to withdraw from the research
             and procedures for orderly termination of participation by the subject- CRITERIA: Any
             protocol in which withdrawal may have deleterious effects on the subject’s health or
             welfare or would result in additional procedures (example: continues hospitalization to
             restabalize on a different medication);
       2.2.5. ELEMENT: A statement that significant new findings developed during the course of
             the research which may relate to the subject’s willingness to continue participation will
             be provided to the subject- CRITERIA: Any study in which the subject’s participation
             is expected to continue over a period of time during which new findings may become
             available to investigators or the public;
       2.2.6. ELEMENT: The approximate number of subjects to be involved in the study-
             CRITERIA: The IRB determines that the number of subjects in a study is material to
             the subject’s decision to participate (this is particularly true in studies involving small
             numbers of subjects, as in Phase 1 and 2 studies);
       2.2.7. ELEMENT: BOTH the amount AND schedule of remuneration to subjects for their
             participation- CRITERIA: Studies involving remuneration to subjects.
3. Understandability: The information that is given to the subject or the representative shall be in
   language that is understandable to the subject or the representative.
   3.1. The consent process (particularly any written documents) should be conducted in the
        subject’s native language
   3.2. The consent process (particularly any written documents) should be at an education level
        that is equal or below that of the prospective subjects (NOTE: Readability does not
        necessarily equate to grade level as determined by scales like the Flesch-Kincaid. Although
        these scales may be used as an aid, they should not be a stand-alone determination on
        readability as they do not evaluate the content of the language such as sequencing, cadence,
        validity etc).
4. Non-exculpatory Language Requirement: No informed consent document may include any
   exculpatory language through which the subject or the representative is made to waive or appear
   to waive any of the subject’s legal rights, or releases or appears to release the investigator, the
   sponsor, the institution or its agents from liability for negligence.
   4.1. Although not required, language such as the following is suggested:
       4.1.1. Avoidance of phrases such as ―I understand…‖
       4.1.2. Avoidance of certifying language such as ―This study has been fully explained to me‖
       4.1.3. Avoidance of overly optimistic or reassuring language such as ―This study has been
             approved by an ethics board that has already determined that the potential benefits
             outweigh the risks‖ or ―This drug is in the final stages of approval‖.
       4.1.4. Use of Second-Person Writing style is recommended so the form reads as if ―I/we‖
             are the investigators and ―you‖ is the subject.

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5. The IRB has the ultimate authority on interpretation on what is allowable or not allowable in the
   informed consent documents. Any decision on the IRB’s part that is contrary to the spirit of
   human subject protection should be brought to the attention of the Chief Research Officer.
6. Ideally all required information should be presented at one time (e.g. in a single document) to
   prevent confusion or accidental omission of a required element. If a staging technique is a
   necessary part of the study, the initial presentation should explain that subjects will be asked to
   participate in the additional phases. It should be clear whether the phases are steps in one study
   or separate but interrelated studies.
7. Any Informed Consent Document, Waiver of Documentation of Informed Consent, Waiver of
   Informed Consent or Waiver/Alteration of Required Elements of Informed Consent etc. must
   have prior approval by the IRB.



Procedure for a Waiver of Documentation of Informed Consent

1. First, the facility must understand that a Waiver of Documentation of Informed Consent differs
   from a Waiver of Informed Consent to assure they are requesting the correct review from the
   IRB. Also Waiver of Documentation of Informed Consent differs from Waiver of Written
   Authorization to Release Protected Health Information, which has separate criteria as detailed in
   the Privacy Section of this manual and must be evaluated as such.
2. CRITERIA: The requirement to waive a signed consent form for some or all subjects may be
   approved by the IRB if either:
   2.1. The only record linking the subject and the research would be the consent document, AND
        the principal risk would be potential harm resulting from a breach of confidentiality. Each
        subject will be asked whether they want documentation linking them with the research, and
        the subject's wishes will govern; or
   2.2. The research presents no more than minimal risk of harm to the subject and involves no
        procedures for which written consent is normally required outside of the research context.
3. The Principal Investigator shall apply to the IRB to waive the documentation requirements of
   informed consent.
4. The IRB is the only authority authorized to waive documentation of informed consent.
5. In cases in which the documentation requirement is waived, the IRB may require the Principal
   Investigator to provide subjects with a written statement regarding the research.
6. A detailed written copy of the IRB approval waiving documentation of informed consent shall be
   filed in the Regulatory Binder prior to enacting the waived/modified informed consent process.
   Note that Written Authorization to Release Protected Health Information may still be required
   unless additionally waived by the IRB or a Privacy Board in conjunction with the IRB.



Procedure for Obtaining a Waiver/Alteration of Informed Consent

1. First, the facility must understand that a Waiver of Informed Consent differs from a Waiver of
   Documentation of Informed Consent to assure they are requesting the correct review from the
   IRB. Also Waiver of Informed Consent differs from Waiver of Written Authorization to Release
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   Protected Health Information, which has separate criteria as detailed in the Privacy Section of
   this manual and must be evaluated as such.
2. CRITERIA:
   2.1. The research could not practicably be carried out without the waiver or alteration, AND
   2.2. The research or demonstration project is to be conducted by or subject to the approval of
        state or local government officials and is designed to study, evaluate, or otherwise examine:
       2.2.1. Programs under the Social Security Act or other public benefit or service programs,
             OR
       2.2.2. Procedures for obtaining benefits or services under those programs, OR
       2.2.3. Possible changes in or alternatives to those programs or procedures, OR
       2.2.4. Possible changes in methods or levels or payment for benefits or services under those
             programs.
       OR

      2.2.5. The research involves no more than minimal risk to the subjects; AND
      2.2.6. The waiver or alteration will not adversely affect the rights and welfare of the
            subjects, AND
      2.2.7. The research could not practicably be carried out without the waiver or alteration;
            AND
      2.2.8. Whenever appropriate, the subjects will be provided with additional pertinent
            information after participation.
3. The Principal Investigator shall apply to the IRB to waive informed consent in it’s entirety or the
   required element(s).
4. The IRB is the only authority authorized to waive any or all required elements of informed
   consent.
5. A detailed written copy of the IRB approval as to which elements have been waived (or informed
   consent in it’s entirety) shall be filed in the Regulatory Binder prior to enacting the
   waived/modified informed consent process. Note that Written Authorization to Release Protected
   Health Information may still be required unless additionally waived by the IRB or a Privacy
   Board in conjunction with the IRB.




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Policies on Obtaining Informed Consent
Policy Number: SOPR-IC-110.V1
Effective Date: January 1, 2005

PURPOSE: Information presented to potential and active subjects should be understandable and
non-coercive for them to adequately make an informed decision about initial and/or continued
participation. Documentation of the process should be of sufficient detail so that the state of
informed consent can be easily ascertained.

POLICIES:

1. Only the Principal Investigator or his/her delegate for this purpose may conduct the informed
   consent process.
2. The initial informed consent process takes place before any investigational product is
   administered, or the administration of any control articles or research-related examinations that
   otherwise would not be performed absent a protocol. For example, if an individual is admitted to
   the hospital and would receive a History and Physical Examination but not an ECG as part of
   that admission- if the protocol requires both for screening, the informed consent may be
   completed before or after the History & Physical Exam but the ECG may only be done after the
   subject has agreed to be in the study. This policy item may be amended if the federal criteria and
   necessary approvals for Emergency Research are met and obtained respectively.
3. The initial informed consent process shall ideally take place at one of the locations where the
   research will take place. This will give the subject a chance to be better informed about the
   research environment. Exceptions may be made at the subject’s request.
4. Potential subjects or their legal representative should be offered the opportunity to participate in
   a study only under circumstances that provide sufficient opportunity to consider whether or not
   to participate and that minimize the possibility of coercion or undue influence.
   4.1. The information that is given to the subject or the representative shall be in language that is
        understandable to the subject or the representative.
   4.2. No informed consent, whether oral or written, may include any exculpatory language
        through which the subject or the representative is made to waive or appear to waive any of
        the subject’s legal rights, or releases or appears to release the investigator, the sponsor, the
        institution or its agents from liability for negligence.
   4.3. The subject or their representative shall have adequate space, time and privacy to read any
        and all documents pertaining to initial informed consent before anything is signed. NOTE:
        Because of the confidential nature of the information provided, subjects and/or their
        representatives are not to be able to leave the premise with an unsigned copy of an Informed
        Consent Form or any other material (this includes sending copies to an outside party via
        paper or electronic means) without advance written permission from the sponsor of the
        research project.
5. The governing IRB or their representative may observe the informed consent process at any time
   pursuant to their review.



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Procedure for Delegating Informed Consent

1. Any delegate authorized by the Principal Investigator to conduct the informed consent process
   should be:
   1.1. Adequately trained as defined in the training policy.
   1.2. Documented (e.g. listed on a Delegation of Authority form) in the Regulatory Binder.
   1.3. Listed as a sub-investigator on the FDA Form 1572, if applicable.
2. Additions of delegates should have begin dates.
3. Deletions of delegates should have end dates.


Procedure for Consenting Non-English Speaking Subjects

1. Whenever it is planned to enroll non-English speaking individuals, a translated consent form
   should be approved by the IRB in advance.
   1.1. The translation should be a performed by a company with core competencies in this area and
        not an ad-hoc/informal translation.
2. In the event of an unexpected encounter of a non-English speaking subject, an oral translated
   presentation may be done accompanied with following the procedure for a ―short form‖ that is in
   the native language of the subject.
   2.1. Additional documentation on how the subject understood the information presented is
        required. Similar to documenting the understanding of English speaking individuals, a
        simple note of ―the subject understood the information presented‖ does not describe in
        sufficient detail on how this understanding was evidenced.


Procedure for Consenting Illiterate Subjects

1. CRITERIA: A person who can understand and comprehend spoken English, but is physically
   unable to talk or write, can be entered into a study if:
   1.1. the person retains the ability to understand the concepts of the study and evaluate the risk
         and benefit of being in the study when it is explained verbally (still competent) AND;
   1.2. is able to indicate approval or disapproval to study entry, they may be entered into the study.
2. A note to file should document the method used for communication with the prospective subject
   (i.e. oral presentation).
3. An impartial third party should witness the entire consent process and sign the consent document
   as a witness.
4. For those who cannot write, a signature can be accomplished by "making their mark" on the
   consent document, when consistent with applicable state law.


Procedure for Assent of Children

1. The facility must determine that the subject does not have capacity to sign for themselves under
   local law. This may include review of information such as:
   1.1. Age
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     1.2. Emancipation/Marital Status
     1.3. Other legal documents
2.   The parent/guardian is the entity who gives consent and the child is the entity that provides
     assent.
3.   Based on the degree of risk of the study, the IRB determines if it is only necessary for one
     parent/guardian to sign the consent form when there are two or more parents/guardians. In
     general, even if only one signature is required, it is preferred that all parental parties concur with
     the child’s participation.
     3.1. When the IRB requires two signatures, the second signature may only be waived when one
           parent is deceased, unknown, incompetent or when the child is in the sole legal custody of
           one parent. The one parent must provide justifying evidence and copies of such should be
           placed in the research records in order to proceed.
     3.2. When the child is a ward of the state or other custodial institution, the proper state signatory
           for medical purposes is considered the signatory official however the child must be
           appointed an advocate independent of both the custodial institution and the institution. The
           advocate need not co-sign nor be present for the consent process but needs to be aware of
           the consent. An individual can be an advocate for more than one ward. Note that any
           remuneration awarded by the study goes to the custodial agency and not the signing official.
4.   Based on the nature of the study, the IRB shall determine if assent may be waived. This is not
     possible for studies of products governed by the FDA.
5.   Proper clinical judgment should be used as to if the child and parents should be informed
     separately to prevent coercion.
6.   Although not required by this policy, a sponsor or IRB may request the child sign an Assent
     Form.
     6.1. This form does not have to duplicate all the required elements of an informed consent
           document but must give sufficient explanation of the study in an age-appropriate manner.
     6.2. This form should be at an education level equivalent to or below that of the child’s. Several
           Assent Forms may be used for the same study enrolling varying age groups, any/all of which
           must have prior approval by the IRB in a manner similar to an informed consent document.
     6.3. The same methodology on items such as distribution of copies, version controls etc as used
           for consent forms should be used for Assent Forms.
7.   Regardless if an assent form us used or not, a substantial note to file should be documented
     indicating how the child understood what was explained verbally and/or in the consent
     document. A statement that ―the subject understood the information presented‖ is not adequate,
     as it does not explain how this was determined.


Procedure for Obtaining Revised Informed Consent

1. The Principal Investigator, IRB or Sponsor may initiate a proposed change of an Informed
   Consent Document however the IRB has the final authority of the document.
   1.1. All consent forms should meet requirements as a ―stand alone‖ document. It cannot be a
        simple paragraph describing the changes.
2. No subjects should be presented with a revised consent document until it has been approved by
   the IRB.

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3. The site shall ensure that there is a system that identifies the most currently approved consent
   document that eliminates the potential use of older versions (i.e. a date stamp or version
   number).
4. Copy of IRB approval shall be kept in the Regulatory Binder. Whenever practical, a ―track-
   changes‖ or ―red-lined‖ version should be filed to easily compare the old version with the new
   version.
5. The following classes of subjects shall be asked to sign the revised form.
   5.1. New subjects to the study
   5.2. Current subjects to which the changes apply
       5.2.1. Example: If the study adds an ECG on visit 2, all subjects past that visit need not sign
            the revised consent form unless the ECG was added because a previously disclosed
            cardiovascular risk was identified.
   5.3. Any other class as instructed by the IRB
6. The timing of re-consent shall be appropriate to the degree of risk of the change. For example,
   re-consenting people in a drug study due a new discovery of increased chance of kidney failure
   should be done promptly as opposed to re-consenting subjects due to the protocol adding a
   Quality of Life questionnaire.



Procedure for Documenting Informed Consent

1. Unless otherwise waived by the IRB or the Short Form is used, there should be an informed
   consent form signed AND dated by:
   1.1. The subject (or their legal representative)
   1.2. The person conducting the consent interview
2. An original signed consent document shall be kept in the research files. IN ADDITION, it is
   also required to have:
   2.1. One copy given to the subject
   2.2. One copy on the subjects official medical record
3. For initial informed consent, a substantial note to file should be documented indicating how the
   subject understood what was explained verbally and/or in the consent document. A statement
   that ―the subject understood the information presented‖ is not adequate as it does not explain
   how this was determined. In general, the more detailed the note, the better. Examples on how
   this is determined may include but are not limited to:
   3.1. A written Post-Test
   3.2. Verbal recollection of key study points such as:
       3.2.1. Identification of experimental elements
       3.2.2. Potential risks
       3.2.3. Expected length of participation
       3.2.4. Ability to withdraw at any time without penalty or loss of benefits
   3.3. For subjects which may have compromised decision-making abilities due to their illness
        (e.g. psychiatry studies), documentation of their mental status as it pertains to decision-
        making at the time of consent.
4. For ongoing consent, at each visit a note to file should detail the subject’s desire to continue in
   the study. Similar to above, a note simply stating ―subject wishes to continue in study‖ does not
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   adequate as it does not demonstrate how it was determined that they are still in a state of
   continued informed consent. Examples on how this is determined may include but are not
   limited to:
   4.1. Verbal recollection of key study points such as
   4.2. Verbal recollection of key study points such as:
       4.2.1. Identification of experimental elements
       4.2.2. Potential risks
       4.2.3. Expected length of participation
       4.2.4. Ability to withdraw at any time without penalty or loss of benefits
   4.3. Verbal acknowledgement of understanding a newly developed risk(s)
   4.4. For subjects which may have compromised decision-making abilities due to their illness
        (e.g. psychiatry studies), documentation of their mental status as it pertains to decision-
        making at the time of consent.


Procedure for Using the “Short Form” to Document Informed Consent

1. In lieu of a signed Informed Consent Form, a ―short form‖ written consent document stating that
   the elements of informed consent approved by the IRB have been presented orally to the subject
   or the subject's legally authorized representative may be used.
2. When this method is used, there shall be a witness to the oral presentation during the entire
   consent interview, not just for signing the documents.
3. The IRB must approve a written summary of what is to be said to the subject or the
   representative (which may be the informed consent document).
4. Only the short form itself is to be signed by the subject or the representative, however, the
   witness shall sign both the short form and a copy of the summary, and the person actually
   obtaining the consent shall sign a copy of the summary.
5. A copy of the summary shall be given to the subject or the representative in addition to a copy of
   the short form.
6. In addition to the original copies in the research records, copies of both the short form and the
   summary shall be placed in the regular medical chart, if applicable.




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                             Institutional Review Boards

Overview, Regulatory Support and References:

The Principal Investigator is ultimately responsible for all study activity, including data integrity,
operations, recruitment, scheduling and many other things including ultimately the protection of the
rights and well-being of the research subjects. The IRB is an independent administrative body,
however, that focuses exclusively in the area of protection of the rights and well-being of human
subjects. The membership represents the community and statutorily includes, among other things,
both scientific and non-scientific members. Although no committee can ever be a substitute for a
concerned Principal Investigator exercising integrity in his/her decisions, a properly run IRB offers
an objective, multidisciplined, publically oriented and (most importantly) binding concern to all
aspects of the research that pertain to the protection of human subjects.

As the facility does not maintain it’s own IRB, selection of the governing IRB is crucial and should
not be taken lightly due to economics or commercial pressures from sponsors to take the IRB that
―comes with the study‖. The IRB should be selected based solely on it’s capabilities on maximizing
efficiencies without sacrificing any aspect of human subject protections, especially when the IRB is
not familiar with the regulations and culture of the location nor has intimate understanding of the
policies, staff and operational constraints of the facility.


      21CFR56.107; 56.114; 312.64; 312.66
      45CFR46.107(a); 46.114
      FDA Information Sheet (1998): Non-Local IRB Review
       (http://www.fda.gov/oc/ohrt/irbs/nonlocalreview.html)
      FDA Information Sheet (1998): Cooperative Research
       (http://www.fda.gov/oc/ohrt/irbs/research.html)
      FDA Information Sheet (1998): Sponsor-Investigator-IRB Relationship
       (http://www.fda.gov/oc/ohrt/irbs/toc4.html)
      PHRP Accreditation Standard ONR(HRP)1B7; ONR(HRP)2; IRB6
      OHRP Guidance (7/9/1991) ―General Guidance On The Use Of Another Institution's IRB‖
       (http://www.hhs.gov/ohrp/humansubjects/guidance/irb-rely.htm)
      OHRP Memorandum (2/4/97) ―Update - Suitability of a Designated Institutional Review Board
       (IRB)‖ (http://www.hhs.gov/ohrp/humansubjects/guidance/ind-irb.htm)
      OHRP Memorandum (1/26/99) ―Engagement of Institutions in Research‖
       (http://hhs.gov/ohrp/humansubjects/assurance/engage.htm)




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Need For and Selection of an IRB
Policy Number: SOPR-IRB-100.V01
Effective Date: January 1, 2005

PURPOSE: Prior to their undertaking, all research activity (protocol, advertisements etc.) must receive
a favorable opinion from an IRB, whose sole interest is the protection of human subjects. The IRB must
be qualified to conduct the review.

POLICIES:

1. Although the facility may choose, for any reason, not to engage in research approved by an IRB, the
   facility may not under any circumstance engage in a research activity until it has been approved or
   waived by an IRB. This is not limited to drugs and devices, but also includes studies of data,
   registry studies, genetic banking, psychology studies etc.
2. The facility shall assign an IRB to review the following:
   2.1. Any research activity it is engaged in. An institution becomes "engaged" in human subjects
        research as evidenced by either:
       2.1.1. Its employees, agents (including all individuals performing institutionally designated
             activities or exercising institutionally delegated authority or responsibility) space, systems,
             technology or equipment does either of the following:
            2.1.1.1.    intervenes or interacts with living individuals for research purposes; or
            2.1.1.2.    obtains individually identifiable private information for research purposes
       2.1.2. Funds are paid by or to the institution for research purposes; OR
   2.2. Requests for a waiver of the written authorization requirement imposed by the federal Health
        Insurance Portability and Accountability Act (―HIPAA‖) for a specific study, if the study is
        eligible for review by the IRB under any one of the Site-related circumstances listed directly
        above.
   2.3. If there is any doubt as to if an activity is required to be reviewed by an IRB, the Chief Research
        Officer shall be consulted.
3. The Facility shall not run it’s own IRB but shall outsource this function to other qualified IRBs.
4. Although the IRB may have it’s own reporting policy, the Institution is still in charge of the
   research, therefore the Chief Research Officer should be apprised of all reportable events on the
   FORM: Research Deviation/Violation or Other Reportable Event Form, regardless of which IRB is
   used.



Procedure for Assignment of Central IRB

1. Before submitting a protocol to an IRB, the facility should forward the protocol and consent form to
   the Chief Research Officer and indicate which IRB is preferred for the study.
2. If the IRB is not on the approved list compiled by the Chief Research Officer, he/she shall begin
   undertaking the process of evaluating that IRB for use.

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3. The Chief Research Officer shall be the authority to review any IRB Authorization form or contract
   with an IRB.




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Communications with the IRB
Policy Number: SOPR-IRB-120.V01
Effective Date: January 1, 2005

PURPOSE: The IRB must be fully informed of the research activity to best fulfill their role in
human subject protection. The Facility/Principal Investigator must be fully informed of the IRB’s
decisions to aid in his/her protection in human subjects as well.

POLICIES:

1. No study may begin without having the written approval (or documented waiver) from the IRB
   in hand. Verbal approval is not acceptable.
2. All information included below, if applicable, and any additional information deemed necessary
   by the IRB should be submitted timely.
3. The Facility shall maintain all correspondence to and from the IRB in the Regulatory Binder for
   the study (or other location if the facility is not the primary research site).

Procedures for Submitting for Initial Review

1. The Facility will submit the following to the IRB
   1.1. Proposed research (or request exemption from IRB review) including all the below as relevant:
       1.1.1. Protocol
       1.1.2. Informed Consent Form
       1.1.3. Information on the Informed Consent Process including
           1.1.3.1.   Who will conduct the informed-consent process
           1.1.3.2.   when the process will take place
           1.1.3.3.   where the process will take place
           1.1.3.4.   how the investigator will determine that the subject or representative understands
                  what has been explained
           1.1.3.5.   what opportunity will be afforded to the prospective subject, or the legally
                  authorized representative, to consider whether or not to participate
           1.1.3.6.   for studies that will continue over a period of time, how the investigator will
                  determine the ongoing consent of the subject
       1.1.4. Proposed Advertisements
       1.1.5. Identification of Risks that may result from the research
       1.1.6. Sources of those risks
       1.1.7. How risks have been minimized
       1.1.8. Impact of various components on study design as it pertains to it’s increasing and
            decreasing risks
       1.1.9. How safety will be monitored (DSMB or otherwise)
       1.1.10. Sponsor’s classification of any medical devices (NSR or SR status), if applicable
       1.1.11. If Vulnerable Subjects are included,
           1.1.11.1. Justification for their inclusion in research
           1.1.11.2. Additional safeguards to protect the rights and welfare of the vulnerable subjects
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       1.1.12. The probable benefits to the research subjects or a statement indicating that there are no
            probable benefits to the subject.
       1.1.13. The importance of knowledge reasonable expected from the research
       1.1.14. Methods to obtain information about participants
       1.1.15. Provisions for protecting the confidentiality of research data
       1.1.16. List of qualified clinician(s) (investigator or sub-investigator) responsible for all study-
            related healthcare decisions
       1.1.17. Attestation that the investigator will refer for needed health care during research or for
            follow-up after the research
   1.2. For circumstances where Facility staff is not the primary researching staff, a Hospital IRB
        Waiver/Authorization document may be the only thing necessary to complete.
2. If the Sponsor submits any of this on the Investigator’s behalf, documentation of such should be
   maintained and the facility should be kept apprised of any discussions.
3. All correspondence to and from the IRB should be filed in the study’s Regulatory Binder (or other
   location if the facility is not the primary research site).

Procedures for Submitting New Information, Continuing Reviews and Termination Reports

1. As the study progresses, the Principal Investigator shall submit the following to the IRB
   1.1. Proposed changes in research, including but not limited to
       1.1.1. Proposed changes in the protocol
       1.1.2. Proposed changes in consent forms
       1.1.3. Other proposed changes made to improve the protection of subjects
   1.2. Reports on deviations from the approved protocol or other regulations and policies
   1.3. Reports on adverse events
   1.4. Reports on unanticipated problems involving risks to subjects
   1.5. Continuing review data, including
       1.5.1. number of subjects entered in the study
       1.5.2. gender of subjects entered into the study
       1.5.3. minority status of subjects entered into the study
       1.5.4. any other information specified by the IRB
   1.6. Study termination/completion reports
2. This information must be submitted in the shorter of the timeframes dictated by the IRB, protocol, or
   this policy.
3. All correspondence to and from the IRB in the Regulatory Binder (or other location if the facility is
   not the primary research site).
4. Continuing Review shall be submitted within the sooner of the IRB’s deadline or one year from the
   previous approval date. Even if the IRB makes an error and extends approval beyond one year, the
   investigator is still obligated to submit continuing review of FDA regulated products within that one
   year of the previously review date.
5. If the Sponsor submits any of this on the Investigator’s behalf, documentation of such should be
   maintained and kept apprised of any discussions.
6. Continuing review should be submitted with sufficient lead time (preferred at least one month) to
   allow for any mishaps in processing and to avoid any unnecessary suspension in research activity
   due to lapsed approval.

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IRB Audits
Policy Number: SOPR-IRB-130.V01
Effective Date: January 1, 2005

PURPOSE: To aid the IRB’s process in their dedicated function of protecting human subjects.

POLICY:

1. The facility shall make reasonable accommodations for the IRB to audit the operations or
   consent process.




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                                         Adverse Events

Overview, Regulatory Support and References:

Pursuit for Adverse Events should be an active process and not a passive one. Caution should be
utilized that the pursuit is not active to the extent that the subject experiences placebo effect related
adverse events or falsely reports adverse events in an effort to ―please the investigator‖. Improved
identification and reporting of adverse events at the site level leads to more accurate safety profiles
for sponsors to make development decisions on, regulatory agencies to make approval and labeling
decisions on and healthcare professionals to use in their prescribing decisions. Without reliable and
valid adverse event profile, the development of new treatments suffers.

Most importantly, information on adverse events should be communicated in appropriate timeframes
so that subjects (or their representatives) that are currently on the causing (or potentially causing)
agent are informed of the newly discovered risk either they or others have experienced. This shows
respect for persons and beneficence.

Finally, scientific integrity should be maintained but not to the point that subjects may be harmed.
Actions such as ―breaking a blind‖ or withdraw from the protocol should be considered but not
automatic.


      21CFR312.64(a); 312.64(b); 312.66
      FDA Form 1572: Section 9 (http://www.fda.gov/opacom/morechoices/fdaforms/FDA-
       1572.pdf)
      FDA: ―The Clinical Impact of Adverse Event Reporting‖
       (http://www.fda.gov/medwatch/articles/medcont/postrep.htm)
      ICH Harmonized Tripartite Guideline E6: Good Clinical Practice: 4.3.2, 4.7 & 4.11
       (http://www.fda.gov/cder/guidance/959fnl.pdf)




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Identifying, Handling and Reporting AEs
Policy Number: SOPR-AE-100.V01
Effective Date: January 1, 2005


PURPOSE: Information on any adverse experiences of subjects should be identified, included as a
study finding and evaluated as part of the risk/benefit ratio for the continuance of the study.
Throughout this process, the subject’s well-being should be maintained.

POLICIES:

1. Investigators and CRCs should gather information from subjects about adverse subject
   experiences during and between visits.
        a. Subjects should be encouraged, not discouraged, in reporting adverse events.
        b. Questions should not be too vague or open-ended to help prompt their memory (i.e.
            ―Have you seen a doctor since our last visit?‖ instead of ―Have you been feeling ok?‖).
2. Investigators and CRCs should actively gather information from other reliable and available
   sources about any potential adverse subject experiences during and between visits.
3. No adverse event should be ignored, no matter how seemingly insignificant. It may be the onset
   of a more clinically significant pathology.
4. Any Adverse Events found should be documented consistently in both source documents and
   research CRFs.
5. Reporting of Adverse Events should favor ―Over-Reporting‖ as opposed to ―Under-Reporting‖.
   If there is ever a question as to if an event should be reported to a Sponsor or IRB, the answer
   will always be that it should.
6. Events classified as Serious Adverse Events are reported to the Sponsor and IRB according to
   their accelerated timeframe.
7. Unless a sooner reporting timeframe is requested by the IRB or Sponsor, the timeframes to report
   are as follows:
   7.1. Serious Adverse Events
        7.1.1. To the Sponsor: Within 24 Hours of Being Notified
        7.1.2. To the IRB: Within 5 Business Days of Being Notified
   7.2. Adverse Events:
        7.2.1. To the Sponsor: Documented to CRFs within 3 business days
        7.2.2. To the IRB: At time of continuing review but not to exceed annually
   7.3. Unexpected Adverse Events
        7.3.1. To the Sponsor: 10 working days (if not SAE)
        7.3.2. To the IRB: 10 working days (if not SAE)



Procedure for Identifying Adverse Events


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1. At each study visit, the subject should be sufficiently asked if they have or have had any adverse
   events. Documentation of this discussion should be in the source documents, even if not required
   by the sponsor.
2. Additional sources of adverse events should be sought when available. Examples include:
   2.1. Inpatient studies should have the medical record carefully checked every day for new
        information
   2.2. Significant others should be consulted when available.
   2.3. Clinical Observations
   2.4. Subject Diaries that may conflict with oral statements
3. Detail of documentation of an adverse event should include the following:
   3.1. Date/Time of onset
   3.2. Circumstances preceding onset (e.g. meal, activity etc)
   3.3. Severity
       3.3.1. Mild: Experiencing mild discomfort with insignificant changes in daily activity or
             clinical status.
       3.3.2. Moderate: Makes accommodating changes in normal daily activity but can still
             function relatively well. Noticeable changes in clinical status.
       3.3.3. Severe: Makes major changes in (or is prevented from accomplishing) normal daily
             activity. Major changes in clinical status.
   3.4. Narrative of Progression
   3.5. Date/Time of resolution (if applicable)
   3.6. Association with Investigational Drug/Device/Procedure as determined by the Principal
        Investigator
4. This documentation should be in both the research and medical records.



Procedure for Handling Adverse Events with the Subject

1. Upon identification of an adverse event:
   1.1. The medically necessary treatment should be determined with the subjects best interest in
        mind.
   1.2. The determination as to suspend or halt use if investigational product should be determined.
2. The subject should informed when medical care is needed for intercurrent illness(es).
3. Whenever appropriate, treatment within the limitations of the protocol should be exhausted first,
   unless the subject wishes to withdraw from the protocol.
4. Where necessary to eliminate apparent immediate hazards, the protocol may be deviated from for
   the benefit of the subject.
   4.1. The Sponsor AND IRB must be notified of the protocol deviation.
   4.2. The Principal Investigator should determine if the subject should be removed from the
        protocol.
5. The Medical Monitor of the Sponsor, if available, may be enlisted to aid in the treatment,
   particularly in an actively treated SAE.
6. All AEs should be followed until resolved, referred or determined permanent.


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Procedure for Unblinding Investigational Products

1. CRITERIA: Every effort should be maintained to protect the blind unless there is a medical
   emergency and:
   1.1. The treating physician needs immediate knowledge to optimize the clinical management
   1.2. The clinical management would be a different course of action depending on the results of
        the unblinding (example, in an overdose situation, if the course of action would be the same
        if the subject were on Drug A versus Drug B, unblinding is not necessary).
2. Whenever possible, the sponsor should be notified before the blind is broken.
3. The protocol should dictate the manner in which the blind is able to be broken. In the absence of
   such explanation, the sponsor’s policies should dictate. Examples are as follows:
   3.1. Peal Off Labels
   3.2. Scratch-Off Lables
   3.3. IVRS
4. The blind should only be broken for the subject at hand.
5. In the absence of a medical emergency, the code should only be broken in accordance with the
   protocol.
6. The investigator should promptly document and explain to the sponsor any premature unblinding
   of the investigational product(s) with consideration for the criteria above.


Procedure for Reporting Internal AEs and SAEs

1. DEFINITION: An Internal Adverse Event is one occurring to a subject enrolled in our study.
2. The PI must determine if the event is classified as a Serious Adverse Event (defined in this
   policy).
3. The event must be reported within the relevant timeframe.
   3.1. If a Serious Adverse Event,
       3.1.1. the immediate report (Note: a more detailed report will promptly follow) to the
             Sponsor and the IRB within the sooner of their timeframes or those stated by this policy
       3.1.2. The more detailed report shall follow upon resolution of the event or as requested by
             the sponsor/IRB
       3.1.3. A copy of these reportings must be sent to the Chief Research Officer
   3.2. If not a Serious Adverse Event, then the information must be reported according to IRB
        policy (usually at Continuing Review time) and Sponsor policy (usually just documentation
        on the CRFs).
4. The mechanism for reporting shall vary according to Sponsor and IRB policy.
5. Subjects should only be identified by their code or other de-identified manner.
6. In the event the Principal Investigator believes the Informed Consent Document should be
   modified but the Sponsor or IRB denies this request, the Chief Research Officer should be
   contacted for guidance.




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Handling Information on Adverse Events From External Sources
Policy Number: SOPR-AE-110.V01
Effective Date: January 1, 2005


PURPOSE: Adverse experiences often occur with the use of the Investigational Product at other
research sites or in the worldwide market. This information should be considered in the risk/benefit
ratio of any study activity.

POLICIES:

1. The site accepts information from all sources that may have bearing on the safety of the subjects.
   Most commonly, these come in the form of:
   1.1. IND Safety Reports from the Sponsor (a.k.a. Medwatch Reports)
   1.2. News and Journals
2. Whenever there is a question on if an adverse event should be reported, error should be made in
   ―over-reporting‖ as opposed to ―under-reporting‖.
3. Unless a sooner reporting timeframe is requested by the IRB or Sponsor, the timeframes to report
   are as follows:
   3.1. Serious Adverse Events
       3.1.1. To the Sponsor: Within 24 Hours of Being Notified
       3.1.2. To the IRB: Within 24 Hours of Being Notified
   3.2. Adverse Events:
       3.2.1. To the Sponsor: Documented to CRFs within 3 business days
       3.2.2. To the IRB: At time of continuing review but not to exceed annually
   3.3. Unexpected Adverse Events
       3.3.1. To the Sponsor: 10 working days (if not SAE)
       3.3.2. To the IRB: 10 working days (if not SAE)
4. In the event a Sponsor has submitted to the IRB on our behalf, a copy of such submittal should
   be kept in the study’s Regulatory Binder.


Procedure for Processing External AEs and SAEs

1. The Principal Investigator should review the information and consider if a change in the
   protocol, consent form or other study activity is desired. If so, this request should be submitted
   to the Sponsor/IRB for approval.
2. A copy of the information should be sent within 5 working days of it’s receipt to the Sponsor and
   IRB unless it comes from one of these organizations.
3. Any additional procedures to follow or forms to be completed will generally follow the policies
   of the IRB and Sponsor/CRO however any filing deadlines to follow shall be deemed as the
   sooner between theirs and this policy.
4. The information source (i.e. copy of the IND Safety Report) along with confirmation of receipt
   by the Sponsor and/or IRB shall be stored in the study’s Regulatory Binder. A letter stating that
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   the information was submitted to the IRB by the Sponsor on the site’s behalf is evidence of
   submittal to the IRB.
5. In the event the Principal Investigator believes the Informed Consent Document should be
   modified but the Sponsor or IRB denies this request, the Chief Research Officer should be
   contacted for guidance.




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                   Special Circumstances for Medical Products




Overview, Regulatory Support and References:

Many situations can occur surrounding the use if medical products that intersect or interact with the
research of these products. The nature of products may result in the requirement for extra or
different procedures to enhance protection of subjects. The intended use may also result in extra or
different procedures as well.




      FDA Information Sheet (1998): "Off-Label" and Investigational Use
       Of Marketed Drugs, Biologics, and Medical Devices
       (http://www.fda.gov/oc/ohrt/irbs/offlabel.html)
      FDA Information Sheet (1998): Use of Investigational Products
       When Subjects Enter a Second Institution
       (http://www.fda.gov/oc/ohrt/irbs/investigational.html)
      FDA Information Sheet (1998): Emergency Use of an Investigation Drug or Biologic
       (http://www.fda.gov/oc/ohrt/irbs/drugsbiologics.html#emergency)
      FDA Information Sheet (1998): Emergency Use of Unapproved Medical Devices
       (http://www.fda.gov/oc/ohrt/irbs/devices.html#emergency)
      NIH Guidelines for Research Involving Recombinant DNA Molecules
       (http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html)
      Humanitarian Device Exemptions (HDE) Regulation: Questions and Answers; Final
       Guidance for Industry (July 12, 2001) (http://www.fda.gov/cdrh/ode/guidance/1381.html)
      21CFR 814.124 Subpart H: Humanitarian Use Devices/Institutional Review Board
       requirements
      21 CFR 361.1 Radioactive drugs for certain research uses




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Differentiation between “Off-Label” Use and Need for IND/IDE
Policy Number: SOPR-SPEC-110.V01
Effective Date: January 1, 2005

PURPOSE: Good medical practice and the best interests of the patient require that physicians use
legally available drugs, biologics and devices according to their best knowledge and judgment. If
physicians use a product for an indication not in the approved labeling, they have the responsibility
to be well informed about the product, to base its use on firm scientific rationale as well as sound
medical evidence, and to maintain records of the product's use and effects. Use of a marketed
product in this manner when the intent is the "practice of medicine" does not require the submission
of an Investigational New Drug Application (IND), Investigational Device Exemption (IDE) or
review by an Institutional Review Board (IRB). However, the institution at which the product will be
used may, under its own authority, require IRB review or other institutional oversight.

POLICY:
1. In order for research to be done with a drug or biologic that does not have NDA approval by the
   FDA, the test article must have an Investigational New Drug application on file with the FDA.
   IN order for research to be done one medical devices that does not have 510(k), PMA, HUD or
   HDE approval, an IDE is required.
2. Even for products with NDA/510(k)/PMA/HUD/HDE approval, an IND or IDE is usually
   required if the research pertains to one of the following:
   2.1. New indication not on the label
   2.2. Manufacturer’s intention to change product label
   2.3. Intended to support a significant change in advertising
   2.4. Uses a new route of administration
   2.5. Uses a new dosage level
   2.6. The product is used in new patient population that either significantly increases the risks or
        decreases the acceptability of the risks associated with the use of the product.
3. If the facility has any doubt as to whether a product requires an IND or IDE, the facility will
   require an IND/IDE for the study to proceed.


Procedure to Document IND Filing

1. When an IND is determined to be needed, the facility should obtain documentation of either:
   1.1. The IND approval from the FDA (the IND number will suffice)
   1.2. Dated copy of IND filing and a written attestation from the investigator that the FDA has not
        responded within 30 days.
2. Any question to the validity of the claim shall be verified with the FDA.
3. Documentation shall be given to the pharmacy.




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Additional Review of Phase 4/Postmarketing Studies
Policy Number: SOPR-SPEC-120.V01
Effective Date: January 1, 2005

PURPOSE: It is been the case that some Phase 4 ―studies‖ have been nothing more disguised
methodologies to offer incentives to a physician to switch patients to a particular drug. The facility
should avoid conducting any protocol that has the appearance of impropriety.


POLICIES:
1. For studies classified as Phase 4 (or equivalent names to identify the postmarketing nature),
   particular attention is paid to the scientific merit of the activity.
2. For this reason, the Chief Research Officer should document the presence, or lack of, scientific
   validity of the study (i.e. is there a comparison arm such as a placebo or competing drug or does the
   protocol only call for switching patients to the drug to ―gather more data‖ or ―see how it works‖?).
3. The special approval needed for Phase 4 protocols is in addition, and not a substitute for, any other
   necessary approvals needed to conduct the study (e.g. IRB).


Procedure for Approval of Phase 4/Postmarketing Studies

1. The Protocol and Contract are to be reviewed by the Chief Research Officer prior to signing the
   contract. Ideally, this review should be done prior to undertaking any more than minimum
   resources surrounding study start-up.
2. The Chief Research Officer shall indicate the approval or disapproval of the activity and the
   reasons in writing.




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Use of Investigational Products When Subjects Enter the Facility as a Second
Institution
Policy Number: SOPR-SPEC-130.V01
Effective Date: January 1, 2005

PURPOSE: From time to time, an individual on an investigational drug/device will be admitted to
the hospital where continuing use of the investigational product is in the best interest of the subject.

POLICIES:


1. When a subject who is participating in a research study at an independent institution is admitted
   to the facility, procedures to follow will differ depending on whether or not the facility is
   considered to be participating as a research site.
2. For some cases, the facility is only providing incidental medical care and is not participating as a
   research site.
   2.1. This occurs when:
       2.1.1. The facility is not listed as a research site for the protocol; AND
       2.1.2. A subject's treatment/hospitalization is not part of the research, typically unexpected
             and based on medical necessity; AND
       2.1.3. The attending physician has determined that it is appropriate to continue the subject
             (now patient) on the test article; AND
       2.1.4. Even though the test article is being given in the facility, only routine medical
             monitoring is conducted with little or no reporting to the investigator, who remains
             responsible for the test drug administration.
       2.1.5. The Chief Research Officer is to be notified as soon as possible.
3. When the facility is designated as an extension to the research milieu (i.e. responsible for a
   portion of the research protocol) or a facility employee has been identified in the protocol as a
   sub-investigator who will be involved in conducting examinations of subjects to monitor status
   and measure effects of the test article (data collection), the facility is considered to be engaged in
   research.
4. The facility will also have to follow all policies and procedures pertaining to research and human
   subject protections.


Procedures To Follow When Facility/Staff are NOT Engaged in Research

1. Unless they are one in the same, the attending physician should obtain from the clinical
   investigator the information necessary to safely continue the investigational product. The
   information conveyed might include a description of treatment procedures, warnings of possible
   adverse reactions, emergency procedures, an emergency contact number and unblinding
   procedures as necessary.
2. The usual procedures for dealing with drugs/devices prescribed out-of-facility would be followed
   (often, this is a Pharmacy Department policy).

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3. Whenever possible, the subject (now patient) or their legally authorized representative should
   sign a release of information to allow the facility to send information to the Principal Investigator
   to aid in the safety evaluation of the research.
4. A copy of the signed informed consent document shall be placed in the medical record.
5. All relevant staff shall be informed of the activity, such as:
   5.1. Nursing
   5.2. Admissions
   5.3. Billing


Procedures to Follow for Engaged Facility/Staff is an Extension of the Research Environment


1. The Chief Research Officer shall be notified as early as possible. Since this requires applications
   on behalf of the Principal Investigator giving ample time for the below procedures to be
   completed if reported from the very beginning. Delays in this process will likely result in delays
   in study start-up.
2. The Chief Research Officer shall be the reviewing official on an IRB Waiver review.
3. The Chief Research Officer should review the Protocol as well as the Informed Consent Form
   and/or HIPAA Authorization language and may request changes to the external IRB’s informed
   consent document prior to it’s use. If changes are not honored, then arrangements to have a
   second informed consent document should be generated.
4. The Chief Research Officer shall review of the contract between the Primary Institution and the
   Sponsor to assure that the facility is properly indemnified for their participation. A Letter of
   Indemnification from the sponsor may be acceptable as well. A study MAY NOT BEGIN until
   the Chief Research Officer has approved this.
5. All relevant staff shall be informed of the activity, such as:
   5.1. Nursing
   5.2. Admissions
   5.3. Billing




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Emergency Treatment Use of an Unapproved (Test) Article
Policy Number: SOPR-SPEC-140.V01
Effective Date: January 1, 2005

PURPOSE: Emergencies arise in life-threatening situations for which there is no standard therapy, but
an investigational or unapproved article may offer a life-saving alternative. This policy pertains to the
very limited use of test articles outside the approved protocols. This policy is not intended to define or
limit the authority of a physician or other health care provider to use previously approved
products in an “off-label” manner for treatment purposes or to provide other emergency medical
care, to the extent they are licensed or permitted to do so under applicable Federal, State, and
local law.

NOTE: As the facility does not have an Emergency or Operating Room, it is extremely unlikely that
this policy will be needed.


POLICIES:

1. For the purpose of this policy, an ―unapproved‖ drug or biologic is defined as a drug or biologic that
   is used for a purpose or condition for which the drug of biologic has IND approval but does not have
   NDA approval. Unless otherwise determined by the FDA, an IND is required, even for emergency
   use.
2. An ―unapproved‖ medical device is defined as a device that is used for a purpose or condition for
   which the device requires, but does not have, an approved Pre-Marketing Application (PMA),
   510(k), Humanitarian Use Device (HUD) or Humanitarian Device Exemption (HDE). An
   unapproved device may be used in human subjects only if it is approved for clinical testing under an
   approved application for an Investigational Device Exemption (IDE). Devices that have had IDEs
   denied by the FDA are not allowed, even for emergency treatment use.
3. If a test article is obtained from a sponsor and used for emergency medical care in accordance with
   the criteria described below, but without prior IRB review and approval, the patient may not be
   considered to be a research subject. Such emergency care may not be claimed as research, nor may
   the outcome of such care be included in any research report of a research activity or test article,
   however the data may be used in appropriately approved retrospective research. Simply stated, HHS
   regulations pertaining to the protection of human subjects do not permit research activities to be
   started, even in emergency, without prior IRB review and approval.
4. If the proposed use of the test article does not have all necessary approvals by an IRB or the FDA to
   be administered, it can only be used as an emergency medical treatment. If a physician chooses to
   use an unapproved article in such an emergency, the physician must justify the use to the IRB (and
   possibly the FDA) within 5 days of the use as described below.
5. Physicians should exercise reasonable foresight with respect to potential emergencies and make
   appropriate arrangements for IRB and/or IDE approval far enough in advance to avoid creating a
   situation in which such arrangements are impracticable. The physician may not conclude that an
   "emergency" exists in advance of the time when treatment may be needed based solely on the
   expectation that IDE approval procedures may require more time than is available. This emergency
   use provision is only an exemption from prior review and approval by the IRB in an emergency
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   situation and not intended to be used as a ―loophole‖ for healthcare providers to side-step the
   necessary approvals. The exemption allows for only one (1) emergency use of a test article without
   prospective IRB review. Any subsequent use of the investigational product at the institution must
   have prospective IRB review and approval, however, that it would be inappropriate to deny
   emergency treatment to subsequent individuals if the only obstacle is that the IRB has not had
   sufficient time to convene a meeting to review the issue.
6. Subsequent emergency use may not occur unless the physician or another person obtains approval
   from the IRB (and an IDE approval from the FDA for devices).
7. If an IDE application for subsequent use has been filed with the FDA and the FDA disapproves the
   IDE application, the device may not be used even if the circumstances constituting an emergency
   exist.
8. If after a full committee review, the IRB disapproves of subsequent use of the test article, it may not
   be used even if the circumstances constituting an emergency exist.


Procedures Prior to and After Emergency Use

1. Prior to emergency use, the Physician must do the following:
   1.1. The Physician must justify the emergency use by verifying the situation meets the following
        criteria:
       1.1.1. The patient is in either a potentially life-threatening or severely debilitating situation
             (severely debilitating means diseases or conditions that cause major irreversible morbidity
             such as blindness, loss of arm, leg, hand or foot, loss of hearing, paralysis or stroke; AND
       1.1.2. Immediate intervention is required to prevent death or major irreversible morbidity; AND
       1.1.3. No generally acceptable alternative for treating the patient is available; AND
       1.1.4. There is substantial reason to believe that benefits will exist from the unapproved use;
             AND
       1.1.5. There is not sufficient time to obtain IRB approval (and/or an IDE approval from the
             FDA).
   1.2. The Physician must obtain an independent medical assessment by an uninvolved physician that
        the criteria listed above are met. If immediate use of the test article is, in the investigator's
        opinion, required to preserve the life of the subject, and time is not sufficient to obtain the
        independent determination required in advance of using the test article, the determinations of the
        clinical investigator shall be made and, within 5 working days after the use of the article, be
        reviewed and evaluated in writing by the independent physician; AND
   1.3. Written informed consent from the patient or legally authorized representative is required,
        unless before use of the test article both the treating provider and a physician who is not
        otherwise participating in the clinical investigation certify the below criteria. If immediate use
        of the test article is, in the treating provider’s opinion, required to preserve the life of the
        subject, and time is not sufficient to obtain the independent determination required above in
        advance of using the test article, the determinations of the treating provider shall be made and,
        within 5 working days after the use of the article, be reviewed and evaluated in writing by a
        physician who is not participating in the clinical investigation. These certifications shall also be
        submitted in writing to the IRB within 5 working days after the use of the test article. The
        criteria are:

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       1.3.1. The human subject is confronted by a life-threatening or severely debilitating situation
             necessitating the use of the test article (severely debilitating means diseases or conditions
             that cause major irreversible morbidity such as blindness, loss of arm, leg, hand or foot, loss
             of hearing, paralysis or stroke).
       1.3.2. Informed consent cannot be obtained from the subject because of an inability to
             communicate with, or obtain legally effective consent from, the subject.
       1.3.3. Time is not sufficient to obtain consent from the subject's legal representative.
       1.3.4. There is no available alternative method of approved or generally recognized therapy
             that provides an equal or greater likelihood of saving the life of the subject.
2. Notify institutional officials as specified by institutional policies.
3. After an unapproved device is used in an emergency, the physician must:
   3.1. Report to the IRB within five days and otherwise comply with provisions of the IRB
        regulations. Such report will have the certification of the above 4 criteria from the
        administering physician along with the signed certification of the physician independent of the
        activity; AND
   3.2. Evaluate the likelihood of a similar need occurring again, and if future use is likely, immediately
        initiate efforts to obtain IRB approval (and an approved IDE for devices) for subsequent use;
        AND
   3.3. For devices, if an IDE for the use does exist, notify the sponsor of the emergency use, or if an
        IDE does not exist, notify the FDA of the emergency use and provide the FDA with a written
        summary of the conditions constituting the emergency, subject protection measures, and results.
4. Although the IRB does not ―approve‖ an emergency use (note, the IRB may only review this under a
   full board review) their documentation on confirmation that the IRB has received the submission and
   either has reviewed or will review it at the next convened meeting should be stored for future
   reference.




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Humanitarian Use Devices (HUD) and Humanitarian Device Exemptions (HDE)
Policy Number: SOPR-SPEC-150.V01
Effective Date: January 1, 2005

PURPOSE: To accommodate for the legal use of devices not fully approved by the FDA but approved
for humanitarian use in particular infrequent diagnoses.

POLICIES:

1. All devices classified as a Humanitarian Use Device or approved by the FDA under a Humanitarian
   Device Exemption are to be approved by an IRB prior to it’s first non-emergent use in the facility,
   regardless of its use in a research OR treatment setting. This is a federal regulation.
2. The facility may not conclude that an "emergency" exists in advance of the time when treatment may
   be needed based solely on the expectation that IRB approval procedures may require more time than
   is available. The emergency use provision is only an exemption from prior review and approval by
   the IRB in an emergency situation and not intended to be used as a ―loophole‖ for healthcare
   providers to side-step the necessary approvals. Reference the policy on Emergency Use for more
   information.


Procedure for Obtaining IRB Approval of an HUD or HDE

1. An initial application is submitted to a full board review of an IRB (note IRB’s cannot conduct an
   initial review of an HUD or HDE under expedited review).
2. Any additional information for initial or subsequent reviews should be timely submitted.
3. In the event the IRB denies use, the HUD or HDE should not be purchased and any inventory should
   be removed.
4. In the event the IRB restricts use (i.e. certain populations, approval for each use etc), documentation
   of such should be housed with the inventory.




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Radiopharmaceuticals
Policy Number: SOPR-SPEC-160.V01
Effective Date: January 1, 2005

PURPOSE: To protect the well-being of individuals who volunteer for protocols utilizing a
          radioactive drug(s) for eventual therapeutic or diagnostic implications.

       Note: Being a freestanding psychiatric facility, serious consideration should be taken prior to
       undertaking a radiopharmaceutical protocol.

POLICIES:

1. The radioactive exposure should be justified by the quality of the study and importance of
   information it seeks to obtain.
2. Subjects shall receive the smallest radiation dose with which it is practical to perform the study.
   2.1. The sum of the radiation shall contain all essential and non-essential radionuclides contained
        in the drug in addition to any ancillary radiation procedures (e.g. X-Ray) conducted in the
        protocol.
   2.2. Numerical calculations shall be based on an absorbed fraction method of radiation absorbed
        dose calculation.
       2.2.1. Such a system is set forth by the Medical Internal Radiation Dose Committee of the
             Society of Nuclear Medicine.
       2.2.2. Such a system is also set forth by the International Commission on Radiological
             Protection.
   2.3. The amount of radiation from a single study or cumulative studies conducted within a one
        year priod shall in no way exceed the following:
       2.3.1. For Whole Body, active blood forming organs, lens of the eye and gonads
           2.3.1.1.    Age 18 or over: Single dose is 3 Rems not to exceed 5 Rems total in one year
           2.3.1.2.    Children Under Age 18: Single dose is 3/10 (.3) Rems not to exceed 5/10 (.5)
                  Rems total in one year
       2.3.2. For Other Organs
           2.3.2.1.    Age 18 or over: Single dose is 5 Rems not to exceed 15 Rems total in one year
           2.3.2.2.    Children Under Age 18: Single dose is 5/10 (.5) Rems not to exceed 1.5 Rems
                  total in one year
   2.4. The amount of active ingredient shall not be known to have detectable pharmacological
        effects unless the active ingredient is the Investigational New Drug or there is an attempt to
        treat as well. In this event, the sum of the active ingredient(s) shall not exceed the dose
        limitation of a separate administration of the active ingredient(s) without the radionuclide.
3. Each investigator shall be qualified by training and experience to conduct the proposed research
   studies.
4. In the case of reactor-produced isotopes, the facility shall assure that either it or the investigator
   shall be licensed by the Nuclear Regulatory Commission or Agreement State to possess and use
   the specific radionuclide or have a broad license to possess and use radionuclides.
5. In the case of non-reactor-produced radionuclides, the investigator shall comply with the state
   and local licensing to possess and use the radionuclide.
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6. All portions of the policies and procedures regarding informed consent shall be followed with the
    following additions:
    6.1. Females of childbearing potential shall either state in writing that she is not currently
         pregnant or confirmed as not pregnant by an acceptable pregnancy test in order to
         participate.
    6.2. Females of childbearing potential shall consent to use of an acceptable method of birth
         control while in the study.
    6.3. Children under the age of 18 are not permitted to participate unless the Radioactive Drug
         Research Committee has granted authorization to permit children into the study.
7. The Radioactive Drug Research Committee shall attest that the drug meets the standards of
    strength, purity, identity and quality of the drug and the production process.
8. The Radioactive Drug Research Committee must state that knowledge and benefit is likely to
    result from the study.
9. The facility shall follow the policies and procedures for adverse reactions with the following
    additions:
    9.1. The investigator must also inform the Radioactive Drug Research Committee.
10. The membership of the Radioactive Drug Research Committee shall comprise of:
    10.1.       A physician recognized as a specialist in nuclear medicine
    10.2.       A person qualified by training and experience to formulate radioactive drugs
    10.3.       A person with special competence in radiation safety and radiation dosemetry
    10.4.       At least two other people qualified in various disciplines of Nuclear Medicine (e.g.
         radiology, internal medicine, radiopharmacy, radiation therapy etc.)
    10.5.       In the event children under the age of 18 are being considered as subjects, a pediatric
         specialist shall be on the committee or consulted by the committee.
11. The Radioactive Drug Research Committee is not a substitution for an IRB approval which must
    also be obtained.
12. The Radioactive Drug Research Committee shall be approved by the Food and Drug
    Administration’s Center for Drug Evaluation and Research.


Procedure for Starting a Protocol Involving Radiopharmaceuticals:

1. The facility shall obtain the following from the Radioactive Drug Research Committee:
   1.1. Proof of Certification by the FDA Center for Drug Evaluation and Research
   1.2. List of the Radioactive Drug Research Committee members, credentials and their
        representation capacity.
   1.3. Copy of the Radioactive Drug Research Committee’s approval of the study.
2. All other necessary approvals (i.e. IRB) need to be obtained.




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Recombinant DNA and Gene Transfer Therapy Research
Policy Number: SOPR-SPEC-170.V01
Effective Date: January 1, 2005

PURPOSE: To give the necessary review surrounding the safety of subjects, staff and the general
public surrounding the use of vectors in genetic research.

       Note: Being a freestanding psychiatric facility, serious consideration should be taken prior to
       undertaking a recombinant DNA or gene transfer protocol.


POLICIES:

1. For genetic research, the facility works in conjunction with it’s Institutional Biosafety Committee
   (IBC) to protect the human subjects.
2. BOTH IBC and IRB approval must be obtained prior to the conduct of the research.
3. The facility relies on the IBC to assure that Biosafety Levels are appropriate and maintained
   throughout the study (such as security, insect/rodent protection plan in physical locations where
   vectors are prepared etc).


Procedure for Creation of an Institutional Biosafety Committee (IBC):

1. A copy of the NIH’s Recombinant DNA Advisory Council (RAC) review and approval of the
   protocol is obtained.
2. As an IBC is not a standing committee at the facility AND NIH has no provisions for use of other
   institution’s IBC as they do for IRBs, the facility, under guidance of the Chief Research Officer, will
   form an IBC that complies with the guidelines of the NIH Office of Biotechnology Activities.
3. The RAC approval, protocol, support for Biosafety Level determination and any other necessary
   information will be submitted to the IBC for approval.
4. IBC approval and IRB approval may be applied for simultaneously to prevent delays in the research
   from starting, however the facility recognizes that the IRB cannot approve this type of research until
   it has received final approval from the IBC.




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                    Confidentiality of Research Information

Overview:

Information given to the facility from a sponsor often contains proprietary information that could
cause injury, financial or otherwise, to the sponsor if disclosed to non-study personnel OR if it is
used for purposes other than the feasibility evaluation or conduct of the study (i.e for personal
financial gain). The sponsor should be in control of how and when it’s proprietary information is
disclosed.

The results of research are also proprietary to the sponsor and should be treated as such. Although
there is a great amount of exploratory or non-statistically significant research, it is usually the intent
to communicate clinical research results to the scientific and/or non-scientific community. This may
be accomplished in many formats including that of an article in a journal, a poster or lecture-type
presentation at a trade association meeting or a listing on a website or other registry for viewing.
Caution, however, should be utilized as undue authorship credit could be considered a kick-back in
exchange for past or future prescriptions.

Regulatory Support and References:

      International Committee of Medical Journal Editors: ―Uniform Requirements for
       Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical
       Publication‖ (October 2004) (http://www.icmje.org/)
      Pharmaceutical Research and Manufacturers of America: ―PhRMA Principles of Clinical
       Trials‖ (6-30-04) (http://www.phrma.org/publications/publications//2004-06-30.1035.pdf)




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Research Material Confidentiality
Policy Number: SOPR-CRI-100.V1
Effective Date: January 1, 2005

PURPOSE: The relationship between the sponsor and the facility is based on the trust that
proprietary information disclosed to the facility will only be used as necessary to conduct the study.
Situations arise, however, when the information needs to be disclosed by the facility to a third-party
for reasons that may or may not be related to the conduct of the study.

POLICIES:

1. Prior to the beginning of a study, it is customary that an agreement addressing confidentiality of
   the study supplies be signed between the facility and the Sponsor. This is known as a
   Confidentiality Agreement (CA), Non-Disclosure Agreement (NDA), Confidential Disclosure
   Agreement (CDA) or some variant thereof.
2. Information covered in this policy is any item containing the following:
   2.1. Sponsor’s Name
   2.2. Protocol (including the title and/or number)
   2.3. Informed Consent Form
   2.4. Information of the investigational product (including it’s name and supporting
        documentation such as an Investigator’s Brochure or other non-public documentation)
   2.5. Any other information given under the auspices of confidentiality
3. In the absence of a Confidentiality Agreement or in the presence of a more lenient one, the
   facility shall at a minimum:
   3.1. Only discuss the study with the following:
       3.1.1. Sponsor company
       3.1.2. Fellow Employees on a need-to-know basis
       3.1.3. Representatives of the IRB
       3.1.4. Representatives of the FDA, OHRP or other regulating entity
       3.1.5. Potential subjects (NOTE: Unless the Sponsor approves in writing, copies of
             unsigned consent forms should not be allowed to leave the premises. This is not
             intended to limit the amount of time given to a potential subject to review the consent
             form but an effort to protect study information from further disclosure (accidental or
             otherwise) in the event the subject does not enroll. Every effort must be taken to clarify
             sponsor approval to allow unsigned consent forms to be taken home. The Chief
             Research Officer should be sought for guidance on this.
   3.2. Not use the information for purposes other than the intent to conduct the study (i.e.
        investment/inlicensing recommendations, research & development decisions, interviews
        with reporters/financial analysts etc).
4. Although a sponsor may call for the return or destruction of confidential information, the facility
   must allow contractually for the maintenance of at least one copy of the material for historic
   purposes for the length of time dictated by facility policy, even if the study was not undertaken.


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Procedure for Obtaining Confidentiality Agreements

1. Submit proposed contract to the Chief Research Officer
2. Allow Chief Research Officer to do one the following:
   2.1. Submit to Sponsor a previously agreed contract that would govern the release (i.e. a ―Global
        CDA‖)
   2.2. Submit to sponsor requested changes to the CDA
   2.3. Approve the CDA
3. Maintain in good faith any information submitted to facility in conjunction with the CDA (i.e.
   Protocol Summaries) with the expectation that the CDA will be signed



Procedure for Release of Information to Third Parties

1. Review the Confidentiality Agreement and other written instructions from the sponsor. Usually
   this will allow for disclosure to:
   1.1. CRO
   1.2. IRB
   1.3. FDA, OHRP or other governing authority
   1.4. Other entities directly involved with the conduct or approval of the study (i.e. medical
        executive boards, pharmacy committees etc.).
2. If needed pursuant to the conduct of the study, a request for Confidentiality Agreement between
   the facility and the potential recipient (i.e. a potential investigator) must be made to the Chief
   Research Officer unless one of the following is true:
   2.1. the sponsor has a separate Confidentiality Agreement with the potential recipient
   2.2. the recipient is also party to the facility’s Confidentiality Agreement
3. If disclosure is required pursuant to a court order, the sponsor should be notified as soon as
   possible to allow for them to utilize their own legal resources to prevent the disclosure if they
   deem appropriate.
4. Any other requests for disclosures (reporters, physicians not involved in the study) should be
   directed to the sponsor for disposition. If the sponsor opts for us to disclose the information, this
   will be obtained in writing prior to disclosure.



Procedure for Redacting Study Documents for Release

1. Make a paper copy of the original. If the original is electronic, print the document (do not send
   the document in it’s electronic form as word processing tools such as ―Track Changes‖ make it
   difficult to completely alter an original document. This is referenced as the ―First Copy‖.
2. Read the First Copy and with a thick black pen, render unreadable any information that is
   considered confidential as spelled out in said policy and the Confidentiality Agreement.
3. Note any information that may be a HIPAA identifier and redact per that policy.
4. Note any information that may be proprietary to the facility (i.e. business practices, referral
   sources, financial information etc) and redact per policy or under advisement of the CEO.
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5. Once all information is fully blacked over, make 2 copies (―Second Copies‖) of the document.
   This prevents the blacked-out information from being readable from the backs of pages.
6. Proof the Second Copies so that no redacted information can be deciphered.
7. Shred the First Copy, send one Second Copy and keep one Second Copy for the files.




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Publication/Presentation of Study Results
Policy Number: SOPR-CRI-120.V1
Effective Date: January 1, 2005


PURPOSE: Publications/presentations should be factual in data content as well as adequately
describe the conduct of the study (including who and to what degree one participated). Study
publications/presentations should also be respectful of sponsor/subject confidentiality.

POLICIES:

1. Any intent to publish any results should first be addressed in the Clinical Trial Agreement with
   the sponsor (if a sponsored study).
2. The content should be altogether in conformance with the most recent revision of the
   International Committee of Medical Journal Editors ―Uniform Requirements for Manuscripts
   Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication‖.
3. Data referenced in the content should only be in aggregate form and not reference any individual
   subjects without their prior written consent.
4. The content of the publication should be a consensus between the facility, the Chief Research
   Officer and the Sponsor (if a Sponsor funded study).


Procedure to Accept Authorship Credit

1. CRITERIA:
   1.1. Authorship credit shall be based on ALL of the below criteria.
       1.1.1. substantial contributions to conception and design, or acquisition of data, or analysis
             and interpretation of data;
       1.1.2. drafting the article or revising it critically for important intellectual content; and
       1.1.3. final approval of the version to be published.
   1.2. Authorship permission shall expressly not be granted for the following:
       1.2.1. Solely from the acquisition of funding, collection of data, or general supervision of
             the research group
       1.2.2. As remuneration, implied or otherwise, for the prescription of the sponsor’s products
       1.2.3. As remuneration for a certain number or rate of enrollment
       1.2.4. A document that was substantially written by (or by an agent of) the sponsor without
             input from the researcher (i.e. ―ghost written‖).
2. Submit draft to Chief Research Officer (who will also handle any other corporate approvals)
   along with list of intended journals/trade association.
3. If selected to be published/presented, the Chief Research Officer should be notified of the
   manner of disclosure.



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Procedure to Publish/Present Study Data Independently

1. Review the Confidentiality Agreement, the Clinical Trial Agreement and any other relevant
   documents to obtain the limits of publication rights.
2. Review publication standards of intended journals/trade association prior to drafting content.
3. Submit draft to Chief Research Officer (who will also handle any other corporate approvals)
   along with list of intended journals/trade association.
4. If the research is sponsored by an external agency, once approved by the Chief Research Officer,
   the draft should be sent to the sponsor. The Chief Research Officer must review any proposed
   modifications by sponsor.
5. Submit to prospective journals/trade association. The Chief Research Officer must review any
   proposed modifications by editor.
6. If selected, the Chief Research Officer should be notified of the intent to publish/present.
7. Additional copies of the journals/poster/slides should be requested for potential distribution
   internally and externally.




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                    Recruitment and Retention of Subjects

Overview, Regulatory Support and References

Recruitment marks the first step in the informed consent process and therefore must not be coercive
or misleading. Although some forms of research may be retrospective, data from research such as
clinical trials is completely dependent on prospective recruitment and retention of subjects. The
relationship between potential subject and research staff does not exist in a vacuum. There are often
other therapeutic relationships the subject may have with providers whose treatment plan must be
respected. Even though these relationships exist, Respect for Persons includes recognizing their
right to autonomy and self-determination. Subjects should volunteer in an environment free of
coercion and those persons considered vulnerable should have additional protections in this process
to assure lack of coercion. Finally, there may be commercial pressures to enroll subjects that may
either offer incentives or give the appearance of incentives to researchers to coerce subjects into
studies. To avoid even the appearance of impropriety, certain practices that are seemingly
unprofessional or coercive should not be condoned.

      21CFR56.111(b)
      45CFR46.111(b)
      ICH GCP 4.4.1; 5.8.3; 8.2.3; 8.2.7; 8.3.2; 8.3.3
      FDA Information Sheet (1998) ―Recruiting Study Subjects‖
       (http://www.fda.gov/oc/ohrt/irbs/toc4.html#recruiting)
      FDA Information Sheet (1998) ―Payment to Research Subjects‖
       (http://www.fda.gov/oc/ohrt/irbs/toc4.html#payment)
      FDA Information Sheet (1998) ―Screening Tests Prior to Study Enrollment‖
       (http://www.fda.gov/oc/ohrt/irbs/toc4.html#screening)
      OHRP IRB Guidebook Chapter 3, Section C ―Selection of Subjects‖
       (http://www.hhs.gov/ohrp/irb/irb_chapter3.htm#e3)
      OHRP IRB Guidebook Chapter 6 ―Special Classes of Subjects‖
       (http://www.hhs.gov/ohrp/irb/irb_chapter6.htm)
      OHRP IRB Guidebook Chapter 3 ―Incentives For Participation‖
       (http://www.hhs.gov/ohrp/irb/irb_chapter3.htm#e7)
      OHRP IRB Guidebook Chapter 3 ―Identification And Recruitment Of Subjects‖
       (http://www.hhs.gov/ohrp/irb/irb_chapter4.htm#f12)
      Health and Human Services, Office of Inspector General—Recruiting Human Subjects-
       Sample Guidelines for Practice (http://oig.hhs.gov/oei/reports/oei-01-97-00196.pdf)
      Health and Human Services, Office of Inspector General—Report on Recruiting Human
       Subjects (http://oig.hhs.gov/oei/reports/oei-01-97-00195.pdf)
      PHRP Accreditation Standards CRB3A, CRB3C
      American Medical Association E-4.01, 6.02, 6.021 & 6.3 (http://www.ama-
       assn.org/ama/pub/category/8365.html)
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      American Medical Association E-6.021 ―Fee Splitting‖ June 1994
      American Psychiatric Association ―The Principles of Medical Ethics With Annotations
       Especially Applicable to Psychiatry‖ Section 2 Annotation 7
       (http://www.psych.org/psych_pract/ethics/ppaethics.cfm)




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Equitable Selection of Subjects
Policy Number: SOPR-RCRT-110.V01
Effective Date: January 1, 2005

PURPOSE: The Belmont Report calls for ―Justice‖, or the equal distribution of research burdens
and benefits. Targeting specific populations over others without scientific justification is neither
better nor worse then excluding the same population from participation. Both result in inadequate
representation and thus, the research findings will be skewed as such (for example, if women are
excluded or are not appropriately represented, the data generated by the study may not be
generalizable beyond the male study population).

POLICIES:

1. The demographics of individuals targeted for and participating in research should be
   representative of the population that would benefit from the research. Any skewing of definable
   classes within the population should be due only to randomness and not due to any systematic
   overutilization or underutilization of that class (regardless if it is intentional or unintentional).
   1.1. Classes are not limited to typical demographics such as sex, race, age etc. They may also
        include things such as diabetics, hypertensives, specific neighborhoods, patients of a certain
        clinic, indigent patients only etc).
2. Subjects that may otherwise directly or indirectly benefit from the research should not be
   systematically over-utilized or under-utilized simply because of their ease of availability, their
   compromised position or their manipulability.
3. The facility should not place additional barriers to participation (i.e. additional inconveniences,
   discomforts, embarrassments etc) on any individuals or class of individuals over others (i.e. only
   returning phone calls from certain subjects or class of subjects would not demonstrate equitable
   selection).
4. Exclusion of certain individuals or class of individuals should only be due to medical necessity.
5. When protecting certain individuals or a class of individuals, the facility shall not be unduly
   paternalistic.
   5.1. Unless otherwise determined incompetent, the mentally ill have the right to self-
        determination.
   5.2. Subjects may volunteer for research projects as often as they wish, provided that there is no
        scientific or medical justification for excluding them (i.e. cannot be on more than one
        investigational drug at any given time).
6. Refusal to participate shall not cause any individuals or class of individuals to lose any rights to
   which they would otherwise be entitled.
   6.1. A subject has the right to treatment within the limitations of the facility as if they appeared
        there in the absence of a study.
   6.2. Any hospitalized or residential treatment patients should not feel that their discharge or other
        privileges they would otherwise be entitled to are conditioned on enrollment in a study.
7. Any potential subject that is also a patient of one of the investigators has the right to discuss their
   situation with another physician

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Procedure to Assure Equitable Selection

1. The Facility shall submit information to the IRB that details the following:
   1.1. the purposes of the research
   1.2. the setting in which the research occurs
   1.3. inclusion criteria
   1.4. exclusion criteria (if any)
   1.5. consideration of the scientific and ethical justification for including vulnerable populations
        such as children, prisoners, pregnant women, mentally disabled persons or economically or
        educationally disadvantaged persons
2. The integrity of any randomization procedure in the IRB approved protocol must be maintained.
   2.1. Any randomization procedures should not be tampered with
   2.2. Individual subjects should not be scheduled for randomization based on a perceived
        ―cracking‖ of the code
3. When an unintentional discrimination is discovered, a plan to correct this should be addressed in
   the study team meeting.
4. When an intentional discrimination is discovered, a plan to correct this should be addressed in
   the study team meeting as well as a report to the Chief Research Officer and the IRB.
5. At continuing review time or at the request of the IRB, the facility will comply with the request
   of the IRB for a breakdown of the classes of population enrolled.



Procedure to Systematically Exclude a Certain Class of Individuals

1. The facility shall fully disclose to the sponsor and the IRB the scientific and/or ethical
   justification for systematically excluding the specific population.
2. Reasons may include, but not be limited to:
   2.1. lack of safety information of the drug in that class (i.e. to a fetus)
   2.2. additional medical vulnerability resulting either directly from an element in the protocol or
        during the period of withdrawal of the investigational/control element
   2.3. Scientific target limits recruitment to a certain class (EXAMPLE: A protocol evaluating a
        drug’s effects on the Hispanic population should limit the enrollment to Hispanics).
3. The IRB has the final authority on exclusion. If the facility does not agree or cannot comply in
   good faith with the IRB’s decision to not exclude the requested class, they should not conduct
   the protocol.
4. If the exclusion is allowed, it is preferred to be a written part of the protocol however other
   documentation of this decision from the IRB may suffice. This information should be filed in
   the study’s Regulatory Binder.




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Referencing Investigational Products in Public
Policy Number: SOPR-RCRT-120.V01
Effective Date: January 1, 2005

PURPOSE: Referencing the investigational product to individuals, agencies or the general public is
unavoidable. It should be done in a manner that is factual, non-coercive and respectful of any
proprietary information held by others.

POLICIES:

1. The identity of the drug/device and the sponsoring company are usually restricted from
   disclosure to the general public by a confidentiality agreement. Without written permission, this
   information should not be disclosed except to viable subjects going through the initial informed
   consent process.
2. Neither the Investigators nor any other employee shall imply or endorse an investigational
   product to prospective subjects or referral sources as ―new‖. The only exception is using the
   FDA’s official classifications of ―Investigational New Drug‖ and ―New Drug Application‖.
3. Neither the Investigators nor any other employee shall imply or endorse an investigational
   product as ―effective‖.
4. Neither the Investigators nor any other employee shall imply or endorse an investigational
   product as ―safe‖.
5. Neither the Investigators nor any other employee shall imply or endorse an investigational
   product as an alternative ―treatment‖ for the client’s symptoms unless it is to a drug that the FDA
   has granted ―Treatment IND‖ status.
6. Neither the Investigators nor any other employee shall imply or endorse an investigational
   product as equivalent or superior to any other drug, biologic or device
7. If the drug/device is already marketed but being tested for something it is not labeled for, it may
   be referred to as ―approved‖ only for what it is approved for coupled with the disclaimer of the
   investigational nature.
   7.1. EXAMPLE: For research on a new indication (i.e. an anti-psychotic approved for
        schizophrenia being tested for acute mania), it could be referred to as ―approved for
        schizophrenia but being tested for acute mania‖.
   7.2. EXAMPLE: For research on a new route of administration (i.e. an antipsychotic approved in
        pill form being tested in an injectable formulation), it could be referred to as ―approved in
        oral form for schizophrenia but the injectable form is still investigational‖
   7.3. EXAMPLE: For research on a new demographic (i.e. an oral antipsychotic approved in
        adults but not labeled for children), it could be referred to as ―approved for use in adults
        with schizophrenia but not labeled for use in children with schizophrenia‖.



Direct Advertising for Study Subjects
Policy Number: SOPR-RCRT-130.V01
Effective Date: January 1, 2005
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PURPOSE: Direct advertising for research subjects (i.e. advertising that is intended to be seen or
heard by prospective subjects) may be an effective meand of communicating the availability of the
study to a large population. Direct recruiting advertisements are seen as part of the informed consent
and subject selection processes. The facility shall take the necessary steps to ensure that the
information presented in print, radio, television, internet of other media advertisements are not
misleading to subjects and conform to both the FDA and the NIH Office of Human Research
Protections standards as interpreted by the IRB.


POLICIES:

1. The facility may freely advertise without IRB approval that they are generally involved in
   research or conducting research.
   1.1. These ads must be generalized to ―research‖ or ―clinical trials‖ as a global function of the
        facility.
   1.2. These ads may specify certain diagnostic categories of which the facility conducts or plans
        to conduct trials (i.e. ―Schizophrenia‖, ―Depression‖).
   1.3. Under no circumstance may these ―general ads‖ refer to specific studies regardless if the
        study is completed, in-progress or expected to begin. This includes but is not limited to the
        following:
        1.3.1. medications being tested
        1.3.2. inclusion/exclusion criteria
        1.3.3. naming sponsors
        1.3.4. stating patient stipends are available
2. Advertisements geared towards recruiting subjects for protocols shall be objective and non-
   coercive. The below criteria shall be met:
   2.1. Any advertisement to recruit subjects should be limited to the information the prospective
        subjects need to determine their eligibility and interest.
        2.1.1. The ad should contain the name and address of the clinical investigator and/or
              research facility.
        2.1.2. The ad should state the condition under study and/or the purpose of the research.
        2.1.3. The ad should contain the person or office to contact for further information.
        2.1.4. The ad may contain, in summary form, the criteria that will be used to determine
              eligibility for the study.
        2.1.5. The ad may contain a brief list of participation benefits, if any (e.g., a no-cost health
              examination).
        2.1.6. The ad may contain the time or other commitment required of the subjects.
        2.1.7. The ad shall not state or imply a certainty of favorable outcome or other benefits
              beyond what is outlined in the consent document and the protocol.
        2.1.8. Language used in print ads should conform to the policy on referencing
              investigational products in public.
        2.1.9. Advertisements should not promise "free medical treatment," when the intent is only
              to say subjects will not be charged for taking part in the investigation. If the ad intends
              to promote that study related medical care will be provided at no cost, then this should
              be clearly described.
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        2.1.10. Advertisements may state that subjects will be paid, but should not emphasize the
              payment or the amount to be paid.
   2.2. The relative size of type used and other visual/audio effects shall not be coercive in nature.
        2.2.1. Audio/visual effects shall not be utilized to emphasize the benefits of participation.
        2.2.2. Audio/Visual effects shall not be utilized to de-emphasize the risks of participation.
   2.3. These media ads must follow through the policies and procedures of media ad approval
        through the Vice President of Operations.
3. Media referencing the facility should only have contact information for the facility unless
   explicitly excepted for by the Chief Research Officer (e.g. a sponsor using a national call center
   not affiliated with the facility as the contact number for the facility)


Procedures For Pre-Approval Of Media

1. Prior to the submittal of any printed ads to a publication agency (e.g. newspaper, journal, Web
   Site host) that fit the requirement for IRB approval, the facility shall have written verification
   that the IRB has approved such ad.
   1.1. This verification shall be in writing and on the letterhead of the IRB.
   1.2. The verification shall have an attached copy of the ad.
2. Prior to the submittal of any taped ads (e.g. radio, TV) to a media agency, the facility shall have
   written verification that the IRB has approved such ad.
   2.1. It is encouraged (particularly if the facility is underwriting the cost of developing the ads)
        that the IRB review and approve the wording of the advertisement prior to taping to preclude
        re-taping because of inappropriate content.
   2.2. The IRB should review the final audio/video tape.
   2.3. This verification shall be in writing and on the letterhead of the IRB.
3. The facility shall, early on in the process, invoke it’s usual media approval and/or purchasing
   process in proceeding with the project and for final approval of the advertisement.


Procedure for Internet Study Database Listings

1. Confirm that the internet listing agency’s format molds to the FDA Guidance on this topic: that
   of ―the system format limits the information provided to basic trial information, such as: the title;
   purpose of the study; protocol summary; basic eligibility criteria; study site location(s); and how
   to contact the site for further information.‖
2. If fitting the format, although the FDA does not require IRB review, the IRB and/or Sponsor may
   require review of the listing.
3. Obtain documentation of IRB approval to list as evidenced by either standing permission from
   the IRB (i.e. in the Formal Agreement) or a study specific listing.
4. Periodically review the ad to make sure it molds to the format acceptable.




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Respecting Subject Privacy and Therapeutic Relationships in
Recruitment
Policy Number: SOPR-RCRT-140.V01
Effective Date: January 1, 2005


PURPOSE: People, in general, have the right to know of active research needing volunteers as well
as a right to privacy. Overzealous researchers may infringe on privacy rights and overprotective
privacy practices may infringe upon the right of knowledge on active research, particularly research
that may have a direct or indirect benefit to the person. Maximizing one right without infringing
upon another is part of the challenge researchers and society face today.

POLICIES:

1. All usual privacy policies should be followed when contacting potential subjects such as the
   following.
   1.1. Telephone contact
   1.2. Mail contact
   1.3. Email contact
2. Any patient that has established a ―Do Not Call‖ relationship or other special communications
   procedures with the institution shall also have those procedures honored in the practice of
   recruitment.
3. When querying a database, the Privacy Policy on Prepatory to Research should be followed
   including:
   3.1. The use and/or disclosure is sought solely to review protected health information as
        necessary to prepare a research protocol or for similar purposes prepatory to research.
   3.2. No protected health information is to be removed from our site by the researcher.
   3.3. The protected health information for which use or access is sought is necessary for the
        research purposes.
4. To contact potential subjects, employed researchers may contact individuals following all usual
   policies on contacting patients. External researchers need IRB approval AND business
   permission from the institution to do so.
5. Although people have the right to self-determination, respect for current providers and their
   existing therapeutic relationships should be considered in their decision .
6. For subjects seeing other providers, the subject should return to their original provider upon their
   completion of or withdraw from the protocol.



Procedure for Contacting Subjects

1. When contacting by telephone:
   1.1. know if you can leave a message identifying who you are and where you are calling from
   1.2. know policies pertaining to dealing with Caller-ID
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2. When contacting by mail:
   2.1. Review policy on whether the following can be done
       2.1.1. Identify recipient by name or must put ―Resident‖
       2.1.2. Have a the facility’s name on the return address on the outside of the envelope or if it
            should be blinded
3. When contacting by email:
   3.1. Generally, all email should be sent to subjects with their address in the BCC or ―Blind
        Carbon Copy‖ field instead of in the ―To‖ or ―CC‖ field.
   3.2. Review and follow any other policies on email communications with patients



Procedure for Approaching another Physician’s Hospitalized Patient

1. If the institution plans to initiate contact with the potential subject that is hospitalized:
   1.1. If it is known to the institution that the subject is under the care of another physician, the
        attending physician should be approached first to assure that approaching the subject will
        not be countertherapeutic.
   1.2. Discussions with the subject about the research should not be construed as a
        ―recommendation‖ by their attending physician.
2. If the subject initiated the contact (through word of mouth, advertisement etc), it is preferred that
   a HIPAA Authorization be signed to exchange information with the attending physician.
3. The subject should understand that they will only see the research staff for purposes of the
   research and that they will return to their current attending physician for treatment.




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Compensation Surrounding Recruitment
Policy Number: SOPR-RCRT-150.V01
Effective Date: January 1, 2005

PURPOSE: Although reasonable payments or other remuneration is expected for offsetting the cost
on the part of the facility or the subject in the conduct of the study, the use of special incentives,
bonuses, ―finder’s fees‖ or other similar activities have the potential to create conscious or
unconscious coercion to enroll, refer to enroll, or retain subjects. Any remuneration scheme that
may be construed as an impropriety or has the potential to erode the informed consent process
should be avoided.

POLICIES:

1. The facility will always use commercially reasonable efforts to recruit subjects in a timely
   manner and retain them uncoercively throughout the study. Remuneration from the sponsor (or
   their designee) to facilities tied solely to a particular number or rate of enrollment or retention
   shall not be accepted.
   1.1. EXAMPLE: ―If the facility enrolls 2 subjects prior to June 30, the facility receives $1000”.
        This is clearly tied to the number or rate of enrollment. Instead, the sponsor should
        compensate the cost of screening the records independent of the number/rate of enrollment.
   1.2. EXAMPLE: ―The compensation per subject is $5000 for the first 3 enrolled and $7500 for
        the 4th subject on.” Unless there are procedural cost or inflationary factors that justify this
        raise, it appears to be purely an incentive for further enrollment.
   1.3. EXAMPLE: “Sites that show completion of their IRB approval by June 30th shall receive a
        bonus of $2000”. Although this is a bonus, it is not tied to the number or rate of enrollment
        and therefore acceptable.
2. Remuneration to research subjects for participation in studies is not considered a benefit (i.e.
   should not be considered in the evaluation of risks/benefits, nor listed in the informed consent as
   a benefit), it is a recruitment incentive and will be reviewed as such.
   2.1. Any remuneration to a subject (or potential subject) should be approved by the IRB in
        advance.
3. Remuneration to referral sources shall only be for work performed and under a written contract.
   Extreme caution should be utilized that payments are undeniably for bona-fide services and not a
   ―referral fee‖ or other type of kick-back.
   3.1. EXAMPLE: “We will pay you $50 for each patient from your practice you refer to the
        study. This is to compensate you for your time in filling out the inclusion/exclusion sheet.”
        Although many provisions like this limit the payment to subjects only if they enroll, this
        example is still not acceptable as there is no bona-fide service supporting the research. This
        scenario is different if the referring physician is a sub-investigator for the study and is doing
        a protocol defined screening procedure for which they will be compensated on a fee for
        service basis. Sometimes the above example may be referred to as a ―consultant fee‖ to
        make it seem like there is service performed but it is not logical for a physician to do a
        consult on his/her own patient. A ―consultant fee‖ would be appropriate if the facility
        referred a potential subject (who was not otherwise the physician’s patient) to the physician
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        as a new referral, to perform medically necessary services to confirm a questionable
        diagnosis that would be relevant to the inclusion/exclusion criteria.
4. Any flow of cash should have documentation supporting it such as:
   4.1. Informed consent document documenting the subject stipend.
   4.2. Clinical Trial Agreement documenting the study budget
   4.3. Consultant contract for medically necessary services
5. As a rule of thumb, if you would not tell a patient what you are doing or you would not like to
   see your name affiliated with the activity reported in the news, you should not be doing it.


Procedure to offer Remuneration to Subjects

1. The proposed amount and schedule of remuneration should be set. Certain criteria are to be
   followed:
   1.1. Remuneration should reflect the degree of risk, inconvenience, or discomfort associated with
        participation.
   1.2. Although remuneration is usually monetary, both subjects and normal healthy volunteers
        may be offered other remuneration in lieu of or in addition to money.
   1.3. No monetary or other inducements (e.g., free care) may be offered to induce the decision to
        terminate a pregnancy for research purposes.
   1.4. The proposed method and timing of disbursement is neither coercive nor presents undue
        influence.
   1.5. Any credit for remuneration should accrue as the study progresses and not be contingent
        upon the subject completing the entire study, however a small proportion as an incentive for
        completion of the study is acceptable, providing that such incentive is not, in the opinion of
        the IRB, so large as to unduly induce subjects to stay in the study when they would
        otherwise withdraw.
   1.6. When offering remuneration to children, in general cash equivalents should be given to
        parents. Any remuneration given directly to children should be age appropriate and
        evaluations of uncoerciveness should take the age into consideration.
2. The amount and schedule of all remuneration should be presented to the IRB at the time of initial
   review.
3. If approved by the IRB, the final (and all subsequent) informed consent form should detail out
   the amount and schedule of remuneration.
4. The accounts payable department shall have on file
   4.1. A completed W-9 form from the subject
   4.2. A copy of the informed consent form
5. Monetary payments shall be in check or money order format (never cash) to allow the site to
   verify the receipt of the reimbursement.
6. All tax reporting laws are to be followed.



Procedure to offer Remuneration to Referral Sources



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1. CRITERIA: Remuneration to referral sources should only be done for investigators or sub-
   investigators of the study and in amounts that are fair market value for bona-fide protocol
   procedures.
2. A request for a Principal Investigator or Sub-Investigator contract should be made to the Chief
   Research Officer.
3. The following should be maintained on file
   3.1. Information supporting their Investigator status such as listed on a FDA Form 1572 or other
        study plan.
   3.2. Documentation on the Delegation of Authority form in the Regulatory Binder that they are
        authorized to do what they are doing
   3.3. The written contract.
4. No payments are issued or implied to be issued until the contract is completed.




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Prescreening of Subjects
Policy Number: SOPR-RCRT-160.V01
Effective Date: January 1, 2005

1. When communicating with individuals as potential subjects for a research protocol, the needs of
   an individual as a patient supercede the need for enrollment.
2. When Prescreening a subject, no research procedures shall be performed without the subject’s
   completing the informed consent process. Only procedures that would be done to the subject as
   patient (i.e. absent a study) are allowed. For example, if a protocol calls for patients diagnosed
   with schizophrenia and have a negative HIV test, if the potential subject shows for triage and the
   normal course of action (absent a study) would be a diagnostic interview but not any blood
   draws, the diagnosis confirmation can be done as part of prescreening but the HIV lab draw may
   not be done until after the subject has completed the initial informed consent process.
3. In the event that potential subjects meet the criteria for more than one study being performed at a
   facility, they will be informed of all studies for which they are eligible to participate, without any
   coercion or preference toward a particular study.


Procedure for Pre-Screening in the Assessment & Referral (A&R) Department:

1. A&R Staff should follow their usual policies to determine the medical necessity of treatment and
   risk factors.
2. Give appropriate recommendations for immediate treatment of presenting problems before
   discussing research opportunities.
3. If the patient meets the written profile for suitable research subject candidacy, give brief
   information concerning the clinical study to the client. Referral to research opportunities shall
   not be offered to any individual who clearly is incapable of providing informed consent. This
   includes but is not limited to: acutely suicidal persons, acutely agitated individuals, acutely
   psychotic individuals, the mentally retarded or minors (prior to reviewing with their legal
   guardian).
4. All policies on referencing study drug in public should be followed.
5. If applicable, give the client an IRB approved written handout containing description of the
   clinical study and, if they are not readily available, information the client on how to contact the
   next appropriate person (usually the Principal Investigator or the Study Coordinator but may also
   include Sub-Investigators as well).




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Pre-Screening and Screening/Enrollment Logs
Policy Number: SOPR-RCRT-170.V01
Effective Date: January 1, 2005

PURPOSE: Prescreening and Screening logs should be kept to reflect study activity by
demonstrating that active recruitment efforts are being made as well as provide evidence that we are
screening out individuals that do not fit the criteria of the study. These logs can also provide useful
feedback to the sponsor and/or the institution on common reasons why people are not enrolling in
the study.


POLICIES:

1. Pre-Screening logs are kept reflecting activity on those individuals prescreened but not
   consenting to the protocol. They usually contain information such as:
   1.1. Subject Name or Initials
   1.2. Subject contact information
   1.3. Date of screening
   1.4. Date of Consent or Reason not consented (excluded, refused etc)
2. Screening/Enrollment logs are often kept once individuals consent to reflect those that either
   screen-failed or otherwise progress through the protocol. Information may be similar to
   prescreening logs but the difference is that Pre-Screening occurs prior to informed consent where
   screening occurs after consent to confirm the inclusion/exclusion criteria prior to receipt of
   investigational product.
3. Privacy policies apply to information contained in the Pre-Screening Logs as well as Screening
   logs.
4. The facility may either create their own logs or use a sponsor supplied logs.
5. Prescreen-Logs may be used as a potential resource to recruit subjects to other studies.



Procedure for Disclosing Pre-Screening Logs to Sponsor, IRB or Regulators

1. Print the document if electronic. Word processing tools such as ―Track Changes‖ make it
   difficult to completely alter an original document.
2. Make a copy of the original (you do not want to black-out parts of your original).
3. Read the copy/printout and with a thick black pen, render unreadable any information that is a
   HIPAA identifier (names, dates etc) as spelled out in said policy.
4. Note any information that may be proprietary to the facility (i.e. business practices, referral
   sources, financial information etc) and redact per policy or under advisement of the CEO.
5. Proof the redacted copy so that no information can be deciphered.
6. If being sent by mail (for fax or other scanned method, this step is not necessary) send a second
   copy of the document. This prevents the blacked-out information from being readable from the
   backs of pages. Shred the first copy.

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Retention of Subjects in Research Protocols
Policy Number: SOPR-RCRT-180.V01
Effective Date: January 1, 2005


PURPOSE: Protocols were written to be completed by subjects, therefore every reasonable method
should be undertaken to assure that subjects complete provided it is the subject’s uncoerced desire to
do so.

POLICIES:


   1. All methods of retention shall be uncoercive.
   2. Extra remuneration to a subject based upon their completion is acceptable provided that it is
      valued at an amount that is uncoercive as approved by the IRB.
   3. Acceptable appointment reminder methods should be utilized which may include the
      following:
           a. Telephone reminders, following such policy
           b. Appointment cards
   4. If the facility offers transportation assistance to non-study patients, study subjects should
      receive equitable treatment.



Procedure To Handle Requests To Withdraw

1. If the request comes from a source other than the subject or their legal guardian
   1.1. The person’s concerns should be heard
   1.2. Any misinformation should be clarified (this may be misinformation on the part of the
        requestor OR the researcher)
   1.3. The requestor should be reminded that the subject has the right to informed self-
        determination and that their concerns should be taken up with the subject themselves.
   1.4. The requestor has the right to appeal this decision with the CEO or Chief Research Officer
2. If the request comes from the subject/guardian
   2.1. The core concerns should be heard and addressed if possible (i.e. requesting removal from a
        protocol because they cannot tolerate the regular unit’s smoking schedule could otherwise
        be addressed by allowing extra smoking time for them)
   2.2. If the concerns are otherwise not permissible by the protocol or result from additional
        anxiety or adverse events, some ―cheerleading‖ is appropriate but not to the point where it is
        coercive. Additionally, the subject should be reminded of any procedures/timelines for
        orderly withdraw from the protocol so that they may make an informed decision.
   2.3. If the subject is persistent and the Principal Investigator has not been notified, they should
        be notified at this time.


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   2.4. If the subject is persistent with the Principal Investigator, the PI should engage the sponsor’s
        procedures to withdraw the subject from the study.
   2.5. If the subject is persistent and the PI does not withdraw them from the study, the Chief
        Research Officer should be contacted




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Referring Patients to Studies the Institution is Not Engaged In
Policy Number: SOPR-RCRT-190.V01
Effective Date: January 1, 2005

PURPOSE: The institution is continuously approached asking for referrals to studies being
  undertaken by external providers/agencies. There are legal and ethical issues surrounding this.

POLICY:

1. The institution may not refer patients to studies it is not wholly or partially engaged in unless it
   has permission from either:
   1.1. the patient’s attending physician
   1.2. the Chief Research Officer
2. When approached, the facility should explain the policy and ask the external researcher how the
   facility may become a provider or sub-investigator in the study.




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             Privacy of Protected Health Information in Research

Overview, Regulatory Support and References:

The Belmont Report’s principles of Respect for Persons and Beneficence implies for us to protect
the privacy of personal health information. Research, however, is dependent on the release of
information to individuals that may not have the legal obligation or safeguards customarily found in
a healthcare setting. Given that, an individual should know who will receive their data, what data is
needed, when will it be released (or no longer released) and any other information surrounding the
further use and disclosure of their data. With that knowledge, the subject may give their written
authorization to release the data necessary to do the research.

Many times, the information needed is not anything in and of itself (or coupled with other data) that
can identity the individual thus does not need their authorization. Other times, a written
authorization may be impossible or an unnecessary barrier given the amount of additional
protections for the privacy of the data over the level of risk. In consideration for this, federal laws
pose certain criteria under certain circumstances for the release of Protected Health Information
without the written authorization.

      45C.F.R. 164.502(a)(1)(i), 164.508, 164.512(i), 164.514(a), 164.514(b), 164.514(e)
      NIH’s ―Protecting Personal Health Information in Research: Understanding the HIPAA
       Privacy Rule‖ (April 14, 2003)
       http://privacyruleandresearch.nih.gov/pdf/HIPAA_Booklet_4-14-2003.pdf
      NIH’s ―Clinical Research and the HIPAA Privacy Rule‖ (February 5, 2004)
       http://privacyruleandresearch.nih.gov/pdf/clin_research.pdf
      Guidance for Industry: IRB Review of Stand-Alone HIPAA Authorizations Under FDA
       Regulations (http://www.fda.gov/OHRMS/DOCKETS/98fr/03d-0204-gdl0001.pdf)




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Disclosure of De-Identified Data
Policy Number: SOPR-PRIV-110.V01
Effective Date: January 1, 2005

PURPOSE: Information that is needed for research may be disclosed without an individual’s
written authorization if it is in a format that it cannot be linked back to the individual.

POLICIES:

1. The facility will create de-identified protected health information, when appropriate, for research
   purposes and for other disclosures when necessary.
2. De-identification of information will be performed only under the close supervision of
   appropriate personnel, who shall have knowledge of and experience with generally accepted
   statistical and scientific principles and methods for rendering information not individually
   identifiable.
3. The facility will not use or disclose reference codes or other means of record identification or
   mechanism used to re-identify health information for any other purpose unless approved by the
   owner of the data and other appropriate personnel.
4. Disclosure of De-Identified Data is not subject to the Accounting of Disclosures policy.
5. Knowledge of a violation or potential violation of this policy must be reported directly to the
   Facility Privacy Liaison and Chief Research Officer (or to the employee compliance hotline).


Procedures to De-Identify PHI:

1. The appropriate personnel will make decisions as to whether protected health information should
   be de-identified.
2. The reason for de-identification will be documented and maintained.
3. The following individual identifiable information elements will be removed or otherwise
   concealed to create de-identified information:
   3.1. Names
   3.2. Birth date
   3.3. Admission date
   3.4. Discharge date
   3.5. Date of death
   3.6. All ages over 89
   3.7. All elements of dates (including year) indicative of age 89, except that such ages and
        elements may be aggregated into a single category of age 90 or older
   3.8. Telephone numbers
   3.9. Fax numbers
   3.10.       Electronic mail addresses
   3.11.       Social security numbers
   3.12.       Medical record numbers
   3.13.       Health plan beneficiary numbers
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   3.14.       Account numbers
   3.15.       Certificate/license numbers
   3.16.       Vehicle identifiers and serial numbers, including license plate numbers
   3.17.       Device identifiers and serial numbers
   3.18.       Web Universal Resource Locators (URLs)
   3.19.       Internet Protocol (IP) address numbers
   3.20.       Biometric identifiers, including finger and voice prints
   3.21.       Full face photographic images and any comparable images
   3.22.       All geographic subdivisions smaller than a State, including street address, city,
        county, precinct, zip code and their equivalent geocodes.
   3.23.       Any other unique identifying number, characteristic, or code; other than a code
        assigned to a record to permit re-identification of the information. The initial three digits of
        a zip code may be used if, according to the current publicly available data from the Bureau
        of the Census:
           3.23.1.1. the geographic unit formed by combining all zip codes with the same three
                  initial digits contains more than 20,000 people; and
           3.23.1.2. the initial three digits of a zip code for all such geographic units containing
                  20,000 or fewer people is changed to 000.
4. If any of the listed identifiers are not removed, then the information will only be disclosed when
   appropriate personnel:
   4.1. Determines that the risk is very small that the information could be used, alone or in
        combination with other reasonably available information, by an anticipated recipient to
        identify an individual who is a subject of the information, and
   4.2. Documents the methods and results of the analysis that justify such determination.
5. The Facility may assign a code or other means of record identification to allow information de-
   identified under this policy to be re-identified by the facility, provided that:
   5.1. The code or other means of record identification is not derived from or related to
        information about the individual (i.e. their initials) and is not otherwise capable of being
        translated so as to identify the individual; and
   5.2. The facility does not use or disclose the code or other means of record identification for any
        other purpose, and does not disclose the mechanism for re-identification.




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Disclosure of a Limited Data Set
Policy Number: SOPR-PRIV-120.V01
Effective Date: January 1, 2005

PURPOSE: When more information than allowed in a De-Identified dataset is needed for research,
and only specific non-identifying information is needed, a ―Limited Data Set‖ may be released
without individual authorization in a manner that offers additional protections to prevent re-
identification of the individuals.

POLICIES:

1. A Limited Data Set may be created and disclosed in the event that De-Identified Data is not
   sufficient for research purposes but minimum necessity criteria does not support the disclosure of
   individual identifiers.
2. Before disclosing any information contained in such Limited Data Set to the recipient, the
   facility will enter into a Data Use Agreement that meets the requirements of applicable laws and
   regulations with any proposed recipients of a Limited Data Set.
3. If there is knowledge that a limited data set recipient has breached or violated a data use
   agreement, the facility will take steps to cure the breach or end the violation, and, in the event
   such actions are unsuccessful, the facility will discontinue disclosure of protected health
   information to the recipient; and report the problem to the Secretary of Health and Human
   Services.
4. Disclosure of the Limited Data Set is not subject to the Accounting of Disclosures policy.
5. Knowledge of a violation or potential violation of this policy must be reported directly to the
   Facility Privacy Liaison and Chief Research Officer (or to the employee compliance hotline).


Procedures for Creating a Data Use Agreement

1. A Data Use Agreement, which may be in the form of a formal contract or part of another
   agreement with a larger scope, will be generated with the following items addressed:
   1.1. The Data Use Agreement with the Limited Data Set recipient will establish:
       1.1.1. who is permitted to use or receive the Limited Data Set; and
       1.1.2. the permitted uses and disclosures of such information by the recipient consistent
            with the limited purposes of research, public health or health care operations.
   1.2. The Data Use Agreement will provide adequate assurances that the recipient of the Limited
        Data Set will:
       1.2.1. Not authorize the Limited Data Set recipient to use or further disclose the information
            in a manner that is inconsistent with applicable laws and regulations.
       1.2.2. Not attempt to re identify or contact the individuals whose information is contained in
            the limited data set;
       1.2.3. Use appropriate safeguards to prevent uses or disclosures outside the terms of the data
            use agreement
       1.2.4. Specify how much, if any of the data can be disclosed to a subcontractors or other
            tertiary recipient and if allowed, the recipient will ensure that any subcontractors or
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            other tertiary recipients of the data agree to and abide by the terms of the Data Use
            Agreement.
       1.2.5. Report any breaches of the information or agreement to the covered entity in a timely
            manner.
       1.2.6. Not use or disclose the Limited Data Set for purposes beyond the scope of the
            agreement.
2. The normal legal procedure for the generation and approvals of research contracts should be
   followed.


Procedures for Creating a Limited Data Set

1. The Facility Privacy Liaison, in coordination with the Chief Research Officer will make
   decisions as to whether a Limited Data Set should be created and/or disclosed.
2. The reason for creating and/or disclosing information in a Limited Data Set will be documented
   and maintained.
3. The following individually identifying elements of an individual, relatives, employers and
   household members of the individual will be removed or otherwise excluded from protected
   health information in order to create a Limited Data Set:
   3.1. Names
   3.2. Postal address information, other than town or city, State, and zip code
   3.3. Telephone numbers
   3.4. Fax numbers
   3.5. Electronic mail addresses
   3.6. Social security numbers
   3.7. Medical record numbers
   3.8. Health plan beneficiary numbers
   3.9. Account numbers
   3.10.       Certificate/license numbers
   3.11.       Vehicle identifiers and serial numbers, including license plate numbers
   3.12.       Device identifiers and serial numbers
   3.13.       Web Universal Resource Locators (URLs)
   3.14.       Internet Protocol (IP) address numbers
   3.15.       Biometric identifiers, including finger and voice prints; and
   3.16.       Full face photographic images and any comparable images.
4. A code or other means of unique record identification may be disclosed to allow information de-
   identified under this policy to be re-identified by the facility, provided that:
   4.1. The code or other means of record identification is not derived from or related to
        information about the individual (i.e. initials) and is not otherwise capable of being
        translated so as to identify the individual; AND
   4.2. The facility does not use or disclose the code or other means of record identification for any
        other purpose, and does not disclose the mechanism for re-identification.
5. The disclosure will comply with the HIPAA Minimum Necessary Policy in determining what
   information to include in a Limited Data Set.


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Disclosure of PHI With Individual Authorization
Policy Number: SOPR-PRIV-130.V01
Effective Date: January 1, 2005

PURPOSE: An individual can request to release of his/her PHI provided they have full knowledge
of the issues surrounding the release.

POLICY:

1. An authorization for the use or disclosure of Protected Health Information for a research study
   (a.k.a. ―HIPAA Authorization‖) may be combined with any other type of written permission for
   the same research study, including another authorization for the use or disclosure of Protected
   Health Information for such research or an Informed Consent Document to participate in such
   research.
   1.1. Regardless if the HIPAA Authorization is combined or separate, all policies and
        requirements regarding Informed Consent must be followed in addition to the this one.
   1.2. Facility may condition the provision of research-related treatment on provision of an
        authorization for the use or disclosure of Protected Health Information for such research.
2. The authorization must meet the following criteria:
   2.1. A valid authorization under this section must contain at least the following core elements:
       2.1.1. A description of the information to be used or disclosed that identifies the information
             in a specific and meaningful fashion.
       2.1.2. The name or other specific identification of the person(s), or class of persons,
             authorized to make the requested use or disclosure.
       2.1.3. The name or other specific identification of the person(s), or class of persons, to
             whom the covered entity may make the requested use or disclosure.
       2.1.4. A description of each purpose of the requested use or disclosure. The statement ―at
             the request of the individual‖ is a sufficient description of the purpose when an
             individual initiates the authorization and does not, or elects not to, provide a statement
             of the purpose.
       2.1.5. An expiration date or an expiration event that relates to the individual or the purpose
             of the use or disclosure. The statement ―end of the research study,‖ ―none,‖ or similar
             language is sufficient if the authorization is for a use or disclosure of protected health
             information for research, including for the creation and maintenance of a research
             database or research repository.
       2.1.6. Signature of the individual and date. If the authorization is signed by a personal
             representative of the individual, a description of such representative’s authority to act
             for the individual must also be provided.
   2.2. In addition to the core elements, the authorization must contain statements adequate to place
        the individual on notice of all of the following:
       2.2.1. The individual’s right to revoke the authorization in writing, and either:
            2.2.1.1.   The exceptions to the right to revoke and a description of how the individual
                   may revoke the authorization; or
            2.2.1.2.   A reference to the facility’s Notice of Privacy Practices if the issue is
                   addressed there.

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       2.2.2. The ability or inability to condition treatment, payment, enrollment or eligibility for
             benefits on the authorization, by stating either:
           2.2.2.1.    The Facility may not condition treatment, payment, enrollment or eligibility
                  for benefits on whether the individual signs the authorization; or
           2.2.2.2.    The consequences to the individual of a refusal to sign the authorization when,
                  in accordance with HIPAA, the covered entity can condition treatment, enrollment
                  in the health plan, or eligibility for benefits on failure to obtain such authorization
                  applies (NOTE: Under HIPAA, a covered entity may condition the provision of
                  research related treatment on the signing of an authorization for the use or
                  disclosure of protected health information for such research)
       2.2.3. The potential for information disclosed pursuant to the authorization to be subject to
             redisclosure by the recipient and no longer be protected by HIPAA.
       2.2.4. The authorization must be written in plain language.
       2.2.5. The facility must provide the individual with a copy of the signed authorization.
   2.3. An individual may revoke an authorization provided at any time, provided that the
        revocation is in writing, except to the extent that the facility has taken action in reliance
        thereon.
3. Disclosure of PHI pursuant to Individual Authorization is not subject to the Accounting of
   Disclosures policy.
4. All other Privacy policies should be followed.



Procedures for Obtaining HIPAA Authorizations to Release PHI:

1. Facility will obtain Authorization meeting the above criteria from the individual prior to any
   release of Protected Health Information.
   1.1. If an external IRB or sponsor has submitted authorization language that is different from that
        of the facility’s template, the facility’s Privacy Liaison or the Chief Research Officer shall
        assure that the language is consistent with both:
       1.1.1. any relevant federal, state or local laws (including but not limited to HIPAA); AND
       1.1.2. the facility’s policies and procedures.
2. Copies of any such authorizations and/or revocations, regardless of being combined with an
   Informed Consent Document or any other document, shall be kept in BOTH the medical record
   AND the research record.




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Disclosure of PHI Without Individual Authorization- IRB Waiver
Policy Number: SOPR-PRIV-140.V01
Effective Date: January 1, 2005

PURPOSE: Federal law provides for the disclosure of PHI without the individual’s authorization in
circumstances when obtaining permission is unduly burdensome and there are protections
surrounding privacy of the information.


POLICIES:

1. Facility may use or disclose protected health information for research, regardless of the source of
   funding of the research, provided that the facility obtains documentation that an alteration to or
   waiver, in whole or in part, of an individual authorization for use or disclosure of protected
   health information has been approved by either:
   1.1. An Institutional Review Board (IRB), or
   1.2. A privacy board that:
       1.2.1. Has members with varying backgrounds and appropriate professional competency as
            necessary to review the effect of the research protocol on the individual’s privacy rights
            and related interests;
       1.2.2. Includes at least one member who is not affiliated with the covered entity, not
            affiliated with any entity conducting or sponsoring the research, and not related to any
            person who is affiliated with any of such entities; and
       1.2.3. Does not have any member participating in a review of any project in which the
            member has a conflict of interest.
2. The documentation must include all of the following:
   2.1. A statement identifying the IRB or privacy board and the date on which the alteration or
        waiver of authorization was approved;
   2.2. A statement that the IRB or privacy board has determined that the alteration or waiver, in
        whole or in part, of authorization satisfies the following criteria:
       2.2.1. The use or disclosure of protected health information involves no more than a
            minimal risk to the privacy of individuals, based on, at least, the presence of all the
            following elements;
           2.2.1.1.    An adequate plan to protect the identifiers from improper use and disclosure;
           2.2.1.2.    An adequate plan to destroy the identifiers at the earliest opportunity
                  consistent with conduct of the research, unless there is a health or research
                  justification for retaining the identifiers or such retention is otherwise required by
                  law; and
           2.2.1.3.    Adequate written assurances that the protected health information will not be
                  reused or disclosed to any other person or entity, except as required by law, for
                  authorized oversight of the research study, or for other research for which the use
                  or disclosure of protected health information would be permitted by this subpart;
       2.2.2. The research could not practicably be conducted without the waiver or alteration; and
       2.2.3. The research could not practicably be conducted without access to and use of the
            protected health information.
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   2.3. A brief description of the protected health information for which use or access has been
        determined to be necessary by the IRB or privacy board has determined.
   2.4. A statement that the alteration or waiver of authorization has been reviewed and approved
        under either normal or expedited review procedures, as follows:
       2.4.1. An IRB must follow the requirements of all regulations and internal policies for either
             normal review OR expedited review.
       2.4.2. A privacy board must review the proposed research at convened meetings at which a
             majority of the privacy board members are present, including at least one member who
             satisfies the criterion stated above, and the alteration or waiver of authorization must be
             approved by the majority of the privacy board members present at the meeting. A
             privacy board may use an expedited review procedure if the research involves no more
             than minimal risk to the privacy of the individuals who are the subject of the protected
             health information for which use or disclosure is being sought. If the privacy board
             elects to use an expedited review procedure, the review and approval of the alteration or
             waiver of authorization may be carried out by the chair of the privacy board, or by one
             or more members of the privacy board as designated by the chair.
   2.5. The documentation of the alteration or waiver of authorization must be signed by the chair
        or other member, as designated by the chair, of the IRB or the privacy board, as applicable.
3. Simply because the release had been approved by an IRB or Privacy Board, the facility is not
   obligated to do so as it must also make the business decision to release the data as well. The
   facility may also impose further restrictions on the release.




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Use and Disclosure of PHI Without Individual Authorization- Prepatory to
Research
Policy Number: SOPR-PRIV-150.V01
Effective Date: January 1, 2005


PURPOSE: PHI may be used or disclosed without individual authorization to assist in the
preparation of/for a research project when obtaining such authorization is an undue burden and there
are enough protections in place to protect the confidentiality of the data as well as the subject’s
privacy.

POLICIES:

1. Facility shall allow the use and disclosure of protected health information for purposes
   ―prepatory to research‖ which shall include but not be limited to the preparation of a research
   protocol, determination of protocol feasibility, aid in study recruitment etc.
2. A researcher employed by the facility may use protected health information to prepare for or
   contact prospective research subjects for a protocol being conducted by the facility (hereby
   classified as ―Internal Research Activity‖).
3. A researcher employed by the facility may NOT use protected health information to contact
   prospective research subjects for a protocol not being conducted by the facility (i.e. if they are
   moonlighting) without written permission from the Director of Research Administration (hereby
   classified as ―External Research Activity‖).
4. A researcher NOT employed by the facility but allowed to access protected health information
   prepatory to research may NOT use the information to contact prospective research subjects
   without a partial waiver from an IRB or Privacy Board (hereby classified as ―External Research
   Activity‖).
5. The Accounting of Disclosures policy applies to disclosure outside of the facility’s workforce
   but not to use within the facility.


Procedures for Use Supporting Internal Research Activities

1. A researcher engaged in Internal Research Activity may access protected health information for
   purposes prepatory to research.
2. A researcher may not disclose this information without proper authorization or alteration/waiver
   of authorization per facility policy.
3. As data is not disclosed to external agencies, the accounting of disclosure policy does not apply.


Procedures for Disclosure Supporting External Research Activities




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1. A written request for disclosure of Protected Health Information for purposes prepatory to
   research must be completed by the researcher and submitted to the Chief Research Officer. The
   request must contain the following:
   1.1. The use and/or disclosure is sought solely to review protected health information as
        necessary to prepare a research protocol or for similar purposes prepatory to research.
   1.2. No protected health information is to be removed from our site by the researcher in the
        course of review.
   1.3. The protected health information for which use or access is sought is necessary for the
        research purposes.
   1.4. A statement that information obtained cannot be used to contact individuals for recruitment.
2. At the discretion of the Chief Research Officer, this request may be denied or approved.
3. A contract with the researcher addressing any other business issues along with any other privacy
   issues shall be signed and executed prior to their access to the data.
4. Facility will account for this disclosure per the relevant policy(ies).
5. If the researcher wishes to contact individuals for recruitment or remove protected health
   information from the site without authorization of the individual, then they need to show
   documentation of a partial waiver of individual authorization from an Institutional Review
   Board. Although the decision of external Institutional Review Boards/Privacy Boards is
   required, only the Chief Research Officer may give final approval for such activity.




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Use or Disclosure of PHI Without Individual Authorization- Research on
Decedents
Policy Number: SOPR-PRIV-160.V01
Effective Date: January 1, 2005


PURPOSE: The PHI of recently deceased individuals may be used or disclosed for research
purposes under federal law provided certain criteria is met to protect privacy/confidentiality.

POLICY:

1. Regardless if the researcher is an employee of the organization or an outside researcher, written
   documentation from the researcher acceptable to the Chief Research Officer or his/her designee
   is required for access to protected health information for research on decedents.
2. A researcher (regardless of employment status of the facility) accessing data for a protocol being
   conducted by the facility shall follow any below procedures referencing ―Internal Research
   Activity‖.
3. A researcher (regardless of employment status of the facility) accessing data for a protocol NOT
   being conducted by the facility shall follow any below procedures referencing ―External
   Research Activity‖.


Procedure for Use or Disclosure of PHI for Research on Decedents:

1. Regardless of employment status, any researcher shall provide a written request to the Chief
   Research Officer to access Protected Health Information for purposes of research on decedents.
   The request must contain the following:
   1.1. The use and/or disclosure is sought solely for research on the protected health information of
        decedents.
   1.2. Documentation of the death of such individuals
   1.3. The protected health information is necessary for the research purposes.
2. At the discretion of the Chief Research Officer, this request may be denied or approved.
3. In the event of External Research Activity, a contract with the researcher addressing any other
   issues shall be signed prior to access to the data.




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Identification of Subjects in Communications
Policy Number: SOPR-PRIV-170.V01
Effective Date: January 1, 2005

PURPOSE: Referencing individuals in verbal or written communications should be mindful of
confidentiality.

POLICIES:

1. For communications outside of the facility (or it’s affilites), the randomization number should be
   the only method used to reference a specific subject (NOTE: subject initials are derived from
   personably identified information therefore NOT de-identified and would have to have a written
   HIPAA Authorization in place or other mechanism of disclosure without written authorization
   such as an IRB privacy waiver).
2. For communications within the facility or between it’s affiliated companies, any communications
   being conducted electronically (email, fax etc), shall abide by the same standard due to the risk
   of inadvertent delivery to an unintended recipient.
3. In the event documents must be communicated which contain information that is not de-
   identified, the document should be modified to a redacted version that strips it of all HIPAA
   defined identifiers as well as other proprietary information.


Procedure for Redacting Identifiers for Release of Documents

1. Copy or print the document (word processing tools such as ―Track Changes‖ make it difficult to
   completely alter an original document). This is referenced as the ―First Copy‖.
2. Read the First Copy and with a thick black pen, render unreadable any information that is a
   HIPAA identifier (names, dates etc) as spelled out in said policy.
3. Note any information that may be proprietary to the sponsor and redact per policy
4. Note any information that may be proprietary to the facility (i.e. business practices, referral
   sources, financial information etc) and redact per policy or under advisement of the CEO.
5. Once all information is fully blacked over, make 2 copies (―Second Copies‖) of the document.
   This prevents the blacked-out information from being readable from the backs of pages.
6. Proof the Second Copies so that no information can be deciphered.
7. Shred the First Copy, send one Second Copy and keep one Second Copy for the files.




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Certificates of Confidentiality
Policy Number: SOPR-PRIV-180.V01
Effective Date: January 1, 2005


PURPOSE: Particular attention is given to studies in which data is being collected about sensitive
issues (such as illegal behavior, alcohol or drug use, or sexual practices or preferences) and may require
special protection of the subjects’ confidentiality. There have been instances where the identities of
subjects or research data about particular subjects have been sought by law enforcement agencies,
sometimes under subpoena, and with the threat of incarceration of the uncooperative researcher. Under
federal law (and some state laws), researchers can obtain a ―Certificate of Confidentiality‖ which is an
advance grant of confidentiality that will provide protection from compelled release of research data,
even against a subpoena.

POLICIES:

1. Certificates of Confidentiality issued by the National Institutes of Health, if not part of the
   submitted research plan, can be recommended by the facility or required by the IRB for
   biomedical, behavioral, clinical or other types of research that is ―sensitive.‖
   1.1. ―Sensitive‖ means that disclosure of identifying information could:
       1.1.1. Have adverse consequences for subjects; OR
       1.1.2. Damage their financial standing, employability, insurability, or reputation.
   1.2. Examples of sensitive research activities include but are not limited to the following:
       1.2.1. Collecting genetic information;
       1.2.2. Collecting information on psychological well-being of subjects;
       1.2.3. Collecting information on subjects' sexual attitudes, preferences or practices;
       1.2.4. Collecting data on substance abuse or other illegal risk behaviors;
       1.2.5. Studies where subjects may be involved in litigation related to exposures under study
            (e.g., breast implants, environmental or occupational exposures).
2. In the event a study meets the criteria for a Certificate of Confidentiality but the sponsor has not
   provided one, the facility shall apply to NIH (and/or state or other federal agency as appropriate)
   for the Certificate. NOTE: The application to NIH by the investigator for the Certificate of
   Confidentiality requires a copy of the IRB approval of the study and an informed consent form
   with the language as if a Certificate of Confidentiality had been obtained. The IRB may give
   conditional approval pending the receipt of a Certificate of Confidentiality for projects involving
   Certificates of Confidentiality. The IRB may also give approval of an alternate Informed
   Consent Document in the event the NIH department does not honor the request for Certificate, if
   the IRB has considered the risks and has voted in the alternative, to approve the study if a
   Certificate is denied.




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Procedure for Obtaining a Certificate of Confidentiality

1. If the criteria for a Certificate of Confidentiality are met, the facility shall apply for one.
2. If the request is denied, the IRB should be notified and the IRB and facility should determine:
   2.1. what additional protections, if any, may be needed along with adequate disclosure in the
         consent form that the information may be released by subpoena
   2.2. to not conduct the study.
3. If a Certificate is obtained, the study personnel must inform participants in the informed consent
   document of the following:
   3.1. The existence of the Certificate of Confidentiality;
   3.2. What it is;
   3.3. The effective date; and the expiration date;
   3.4. A statement that data gathered during the time the Certificate of Confidentiality is in effect
         is still protected after the Certificate expires;
   3.5. A description of identifiable information involved in the study; and
   3.6. The circumstances in which voluntary disclosures would be made, disclosures such as:
        3.6.1. Child abuse reports
        3.6.2. Communicable disease reports
        3.6.3. Subject’s threatened violence to self or others
        3.6.4. DHHS audit or program evaluation requests
        3.6.5. Information required to be disclosed by the Federal Food, Drug, and Cosmetic Act.
   3.7. Although a Certificate is in place, the subject may request, in writing, the disclosure of
         identifying information.
4. The facility should submit requests for modifications, amendments, and extensions at least three
   months prior to the date needed and should be accompanied by a reason for requesting it and
   documentation of the most recent IRB approval.
5. If there are significant modifications to the project or the informed consent form, this should be
   submitted to the issuing agency (i.e. NIH) so that they may considering modification to the
   existing Certificate of Confidentiality.
6. If the project is not completed in the time specified in the application for the Certificate, the
   facility should apply for an extension to the expected date of completion of the project.




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                   Accountability of Investigational Products


Overview, Regulatory Support and References:

      ICH Harmonized Tripartite Guideline E6: Good Clinical Practice:
      Poison Prevention Protection Act (15 U.S.C. 1471-1476) (Public Law 91-601, 84 Stat. 1670,
       December 30, 1970, as amended)
      Title 16--Commercial Practices / CHAPTER II--CONSUMER PRODUCT SAFETY
       COMMISSION/PART 1700--POISON PREVENTION PACKAGING
      U.S. Consumer Product Safety Commission June 22,2000 Letter to Canon Communications,
       LLC ―RE: Drugs dispensed for household use in clinical trials‖
       (http://www.cpsc.gov/BUSINFO/trials.pdf)




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Accountability Logs
Policy Number: SOPR-AIP-110.V1
Effective Date: January 1, 2005

PURPOSE: There should at all times be a current accounting of the Investigational Product
inventory.

POLICIES:

1. The facility is to maintain adequate records of the current inventory of Investigational Product
   including dates, quantity, use by subjects and final return/destruction.
2. Such accountability logs shall be maintained in accordance and for the duration of the record
   retention policy.
3. Any discrepancies are to be followed up until resolved or documented as unaccounted for.


Procedures upon Receipt of Investigational Product from Sponsor

1. Receipt of Investigational Product should be documented in the Accountability Log, which may
   be a site or sponsor generated form:
   1.1. Date of Receipt
   1.2. The unique identifiers (including any Lot/Serial/Randomization numbers)
   1.3. Quantity Received (if bottles are closed, ―sealed bottle‖ shall suffice)
2. Physical examination of the packaging should search for the following:
   2.1. The statement ―Caution: New Drug (Or Device)- Limited by U.S. Law to Investigational
        Use‖ or subsequently approved FDA statement
   2.2. An expiration date, if appropriate
       2.2.1. if the date is not labeled on the container but in the form of a letter, it should be
             handwritten on the container unless otherwise directed not to do so by the study sponsor
       2.2.2. a statement from the sponsor that they will maintain the expiration date shall suffice
             in lieu of having a documented date
3. Any discrepancies or errors should immediately be documented and reported to the sponsor.


Procedures for Logging Administration/Dispensing of Investigational Product to Subjects

1. Each time an Investigational Product is administered or dispensed to a subject, the
   Accountability Log should be updated with the following information:
   1.1. Date dispensed/administered
   1.2. Unique identifier(s) of the administered/dispensed product (Lot/Serial/Randomization/Visit
        etc)



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Procedures for Logging Return of Investigational Product to Facility

1. Each time an Investigational Product is returned, the Accountability Log should be updated with
   the following information:
   1.1. Date of return
   1.2. Unique identifier(s) of returned product (Lot/Serial/Randomization/Visit etc)
   1.3. Quantity returned with as much detail as possible
       1.3.1. For example, for pills dispensed in a bottle, ―6 pills returned‖ would suffice
       1.3.2. For example, for pills dispensed in a blister pack, ―3 pills returned pertaining to Day 3
            AM, Day 7 PM and Day 8 AM‖ would suffice


Procedures for Logging The Return-To-Sponsor/Destruction of Investigational Product

1. When Investigational Product is returned to the sponsor or destroyed, the Accountability Log
   should be updated with the following information:
   1.1. Date of return/destruction
   1.2. Unique identifier(s) of returned/destroyed Investigational Product
2. All other procedures in this area are to be followed.


Procedures for Inventory Discrepancies

1. When a discrepancy occurs between the physical count and the logs, documentation of such will
   be completed in the study files.
   1.1. Date discrepancy noticed
   1.2. Narrative of attempts to reconcile
   1.3. Resolution of reconciliation
2. A hospital Incident Report should be filled out.
3. A Protocol Deviation should be reported internally pursuant to that policy as well as notifying
   any external parties as required (sponsor, IRB etc).
4. Sufficient detail of product that is unaccounted for should be logged so that there maintains an
   accurate inventory (example ―Missing 2 bottles (V3 and V4)‖ instead of ―missing bottles)




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Storage of Investigational Product
Policy Number: SOPR-AIP-120.V1
Effective Date: January 1, 2005

PURPOSE: Storage of Investigational Products shall maintain the integrity of the Investigational
Product as well as to prevent accidental release for which it is not intended.


POLICIES:

1. This policy does not apply to radiopharmaceuticals, biologics or genetic therapy vectors, which
   will be governed under separate policy if utilized.
2. Investigational Products do not need to be stored in the inpatient Pharmacy however the
   Pharmacy maintains the right to evaluate the storage conditions and inventory of any drug used
   for inpatients.
3. Physical storage requirements include ―Double-Lock‖ conditions
   3.1. Limited access through the first lock by non-research/non-administrative staff
   3.2. Second lock shall be in form of an affixed or substantially constructed
        container/cabinet/refrigerator etc.
   3.3. Access through the second lock should be limited to the Principal Investigator and study
        staff.
4. Investigational Products should be stored within the temperature requirements of the
   Investigator’s Brochure, packaging insert or other authoritative document.
5. A Sponsor, IRB, IBC or other relevant organization may impose additional storage requirements
   and these are also to be documented as to how they will be followed.
6. In the event Investigational Product is stored on a patient unit (i.e. medication room), the
   container with the Investigational Product will be identified and temperature logs are to be kept.
7. When relocating Investigational Products, the storage specifications regard to temperature shall
   be maintained throughout the move.
8. Other requirements for storage by the sponsor (e.g. humidity logs, rodent/insect protection plans
   etc.) will be documented accordingly.


Procedure for Temperature Logs

1. A Temperature Log shall be kept at all times the specimens are stored, regardless of the
   temperature range (i.e. even if stored at room temperature, documentation that the room did not
   get too hot is necessary). The log shall, at a minimum:
   1.1. Be labeled and proximal to the storage medium (i.e. taped on or above the freezer, by the
        cabinet etc.) so that it is not confused with other logs.
   1.2. Shall specify in each case or at the top of the page whether the temperature scale is
        Centigrade (C) or Fahrenheit (F).
   1.3. Documented on Daily

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2. If Investigational Products are to be stored at other than room temperature (i.e. refrigerated), then
   a backup system should be in place in the event of power failure. Examples of this can be the
   following:
   2.1. The preferred method is connecting the refrigerator to a ―generator‖ outlet
   2.2. Separate cooler that could maintain the temperature range
   2.3. Moving the Investigational Product to another similarly secure location while maintaining
        the storage conditions during transport
3. Copies of the relevant Temperature logs can be placed in study folders upon archiving so that the
   study documents can be complete.
   3.1. In the event one log is kept and is to be used for multiple studies, a copy of the log for each
        day of an active study should be filed with the study so that the packaged study is a
        ―complete set‖ of documents.


Procedure for Relocating Investigational Product to Alternate Storage

1. Storage specifications (i.e. temperature requirements) shall be maintained throughout transport.
   Specific transport containers (use of coolers, dry ice etc) with a thermometer may be used as
   necessary.
2. During transport, the transporting individual will maintain line-of-sight with the product.
3. Transportation may be accomplished in private vehicle as necessary however, transportation
   should be directly from the Transport-From Site directly to the Transport-To Site (i.e. no stops to
   the shopping mall, transporters home etc).
4. All of the following should be part of the permanent study record (narrative format is acceptable)
   4.1. Departing inventory and temperature of original storage medium.
   4.2. Time of removal from storage.
   4.3. Internal temperature of transport medium upon placement of Investigational Product.
   4.4. Internal temperature of transport medium upon removal of Investigational Product.
   4.5. Arriving inventory (any discrepancies should follow respective policy)
   4.6. Time of placement in storage and Temperature of such storage.
   4.7. Any significant events that occurred during transport
5. Return to Double-Lock conditions.




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Dispensing for Inpatient Use
Policy Number: SOPR-AIP-130.V1
Effective Date: January 1, 2005

PURPORSE: Administering Investigational Products for inpatient use shall be done in an
accountable and safe manner.

POLICIES:

1. Investigational Products are only to be administered to those who have provided written
   Informed Consent pursuant to the requirements of the IRB.
2. Investigational Drugs can only be ordered by an appropriately licensed practitioner listed on the
   most current version of the FDA Form 1572 for the protocol and only with proper delegation of
   authority to do so as documented in advance in the Regulatory Binder.
3. Only those personnel permitted to do so by hospital policy shall administer Investigational
   Products to subjects.
4. Documentation of the administration shall follow the facility’s Policies and Procedures for the
   administration of FDA approved drugs/devices.


Procedure for Administration to Inpatient Research Subjects

1. The normal procedures should be followed for the administration of FDA approved
   drugs/devices however special accommodations should be given when protocols call for a
   conflicting administration regime that should be followed such as:
   1.1. Specific time(s) of administration (e.g. at 8:00 AM when the usual morning medication time
        is at 7:00 AM; exactly 30 minutes after beginning a meal when no other meds would be
        passed at that time etc.)
   1.2. Sequencing of administration with other events (e.g. prior to an ECG, after an anxiety exam
        etc.)
2. At a minimum, documentation of administration shall contain the following:
   2.1. Time and Date of administration
   2.2. Quantity of administration
   2.3. Method of administration
   2.4. Confirmation of administration
3. This documentation shall be part of the medical record
4. Accountability logs should be updated.




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Dispensing for Outpatient Use
Policy Number: SOPR-AIP-140.V1
Effective Date: January 1, 2005

PURPOSE: Dispensing investigational products for outpatient use should be done in an accountable
and safe manner.

POLICIES:

   1. Investigational Products are only to be dispensed to those who have provided written
      Informed Consent pursuant to the requirements of the IRB.
   2. Investigational Drugs can only be dispensed under the supervision of an appropriately
      licensed practitioner listed on the most current version of the FDA Form 1572 for the
      protocol and only with proper delegation of authority to do so as documented in advance in
      the Regulatory Binder.
   3. Packaging shall be in conformance with applicable laws (e.g. to prevent accidental poisoning
      etc)



Procedures for Dispensing to Research Subjects for Outpatient Use

1. Oral Investigational Products, when dispensed to outpatients, shall be dispensed in packaging
   that has at least one Child-Resistant feature,
   1.1. This includes but is not limited to the following:
       1.1.1. Blister Packs that only allow the opening of one pill at a time
       1.1.2. Child-Proof caps
   1.2. The only exceptions to Child-Resistant features are the following
       1.2.1. The amount of Investigational Product dispensed will not cause serious injury or
             illness to a young child; AND
       1.2.2. Data demonstrating the lack of expectation of serious injury to children must:
           1.2.2.1.     be kept on site with the research records
           1.2.2.2.     available to Consumer Product Safety Committee
       1.2.3. Notification from the Chief Research Officer acknowledging the intent should be kept
             on file.
2. No further breaking down of the Investigational Product packaging shall be done on site
3. In the event subjects wish to open the packaging on-site (i.e. to place pills in ―Sunday-through-
   Saturday‖ or other ―convenience packs‖, they can do so on their own. If they ask about the use
   of convenience packs for their home use, they are to be encouraged to take appropriate measures
   to assure that the convenience packs will not get into the hands of children.
4. Documentation in the Accountability Log(s) should be completed at the time of dispensing.



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Return-To-Sponsor or Destruction of Investigational Product
Policy Number: SOPR-AIP-150.V1
Effective Date: January 1, 2005

Purpose: Investigational Products should not be maintained in inventory when their use is not
anticipated.

Policies:

1. When it no longer becomes necessary for the facility to keep an inventory of the Investigational
   Product, it shall be returned to the sponsor or destroyed. Examples of such times would include:
   1.1. The Study is completed or discontinued.
   1.2. The Investigational Product has expired.
   1.3. The Investigational Product is damaged, returned by a subject or otherwise unfit for use.
2. Returning the Investigational Product to the sponsor shall be the preferred method of clearing out
   the inventory as opposed to alternative methods of disposal.
3. In the event the Sponsor desires that the Investigational Product be disposed of by the facility as
   opposed to being returned, it shall be done according to the Sponsor’s written request provided it
   comply with all applicable federal, state, local laws and other relevant Site policies.

Procedure for the Return of Unused Investigational Product

1. Documentation shall be maintained concerning the return of the Investigational Product which
   shall contain:
   1.1. The quantity of the Investigational Product returned; AND
   1.2. In the event the Investigational Product is packaged with identifiers on it (e.g. serial number
        or randomization number), the documentation shall reflect such detail; AND
   1.3. The date and manner of shipment (i.e. FedEx, picked up by sponsor etc.).
   1.4. Confirmation that the shipment was received; AND
       1.4.1. Written confirmation shall be in the form of a written acknowledgement of receipt by
             the company or a copy of the signed receipt from the shipping company; AND
       1.4.2. Verbal confirmation, although not preferred, is acceptable when documented as to the
             date, time and person spoken to at the sponsor’s office.
2. In the event the drug is shipped (as opposed to being picked up by the sponsor)
   2.1. The manner of shipment shall have a mechanism of being traced.
   2.2. In the event the sponsor does not receive the shipment within a reasonably expected
        timeframe, the facility shall take the necessary actions with the shipping company to locate
        the package and have it delivered appropriately.


Procedure for the Disposal of Unused Investigational Product

1. The facility shall receive, in writing, documentation specifically stating the sponsor does not
   wish to have the unused Investigational Product returned to them AND the method the sponsor
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   wishes to have the Investigational Product disposed of. This request shall be stored in the
   appropriate location in the study binders
2. Documentation shall be maintained concerning the disposal of the Investigational Product which
   shall contain:
   2.1. The quantity of the Investigational Product disposed of; AND
   2.2. In the event the Investigational Product is packaged with identifiers on it (e.g. serial number
        or randomization numbers), the documentation shall reflect such detail; AND
   2.3. The date and manner of disposal; AND
   2.4. The staff member who conducted the disposal AND
   2.5. At least one (1) witness to the disposal.
3. A copy of this documentation shall be sent to the sponsor and kept with the research records.




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                                    Laboratory Process


Overview, Regulatory Support and References:

Laboratory work is often performed in the clinical research setting. From the beginning, the
equipment provided should be appropriate for the task. The staff obtaining the specimens should be
adequately trained. Specimens should be stored in a manner that maintains the integrity of the
specimen until the laboratory can process it. If shipped to a remote lab, not only must the integrity
of the specimen be maintained throughout the varying shipping time and handling conditions, but it
must be appropriately packaged and labeled as it will be going across public highways and/or
airways. All of this is necessary to protect the subject from unnecessary redraws, the data from loss
of integrity, the research environment/personnel from infections and the general public from
accidental exposure.

   49CFR172.704, 173.196, 173.199
   49CRF175.10(13) Exceptions/Carbon dioxide, solid (dry ice)
   International Air Transport Association: Packing Instructions 650
    (http://www.iata.org/NR/ContentConnector/CS2000/SiteInterface/sites/whatwedo/dangerousgoo
    ds/file/PI650.pdf)
   2004 Emergency Response Guidebook Guide 158 (http://hazmat.dot.gov/pubs/erg/g158.pdf)
   2004 Emergency Response Guidebook Guide 120 (http://hazmat.dot.gov/pubs/erg/g120.pdf)




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Receipt and Storage of Laboratory Supplies
Policy Number: SOPR-LAB-110.V1
Effective Date: January 1, 2005

PURPOSE: The chance of unnecessary redraws or other delays in the research process due to
insufficient, damaged or expired laboratory supplies should be minimized.

POLICIES:

1. Upon receipt of laboratory supplies for a study, the following will be noted:
   1.1. Any storage environment requirements
   1.2. Any expiration dates
2. If not conducted by the sponsor or their designee, a random sampling of materials should be
   done to assure that enough supplies are in the kits.
3. Upon initial receipt and throughout the study, any missing, damaged or soon to be expired
   supplies should have a replenishment request initiated with ample time to have it shipped to the
   site. Sponsors and Central Labs may differ in their request procedures and those procedures
   should be followed.
4. In the event storage conditions are not met, the sponsor should be contacted as to the disposition
   of the supplies.




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Phlebotomy
Policy Number: SOPR-LAB-120.V1
Effective Date: January 1, 2005

PURPOSE: Acceptable phlebotomy practices should be followed with research subjects.

POLICIES:

1. The Site should follow it’s own policies independent of this manual on the drawing of blood and
   the issues that surround it which should include but not be limited to the following:
   1.1. General Phlebotomy
   1.2. Restick Policies
   1.3. Needle-Stick protocols
   1.4. Use of Saline/Heparin Locks and IVs etc.
   1.5. Appropriate Training/Licensure of Staff
   1.6. Demonstration of Competency
2. In addition to the reporting requirements of adverse events occurring during phlebotomy required
   by the Site’s policies, these events may also need to be reported through research-related
   mechanisms as well (i.e. to the IRB, Sponsor etc).
3. Storage of specimens prior to transport shall be adequate and monitored.


Procedure for Review of Phlebotomy Policies

1. Staff performing phlebotomy services should review and follow the Site’s policies on such
   matters.
2. Any issues that arise (including the absence or inadequacy of a policy) should follow the Site’s
   procedures in getting the policy amended/waived etc. prior to committing to undertake the
   protocol.
3. In the event the Site is unable to change their Policies and such inability would adversely affect
   the conduct of the protocol, the Chief Research Officer should be notified for guidance.


Procedure for Storage of Specimens Prior to Transport

1. Specimen storage shall be in accordance with the Sites policies on storage of biohazardous
   materials.
2. In the event sub-ambient temperatures are required for storage,
   2.1. The storage medium should be prepared for loss of power to protect the integrity of the
        specimens in the event of such power loss.
   2.2. A Temperature Log shall be kept at all times the specimens are stored awaiting packaging
        (i.e. frozen for batch shipment). The log shall, at a minimum:

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       2.2.1. Be clearly labeled and proximal to the storage medium (i.e. taped on or above the
            freezer) so that it is not confused with other logs.
       2.2.2. Shall specify the temperature scale as Centigrade (C) or Fahrenheit (F) in either
           2.2.2.1.   at the top of the page stating something such as ―All entries are on the
                  Centigrade (C) temperature scale‖; or
           2.2.2.2.   at each entry.
       2.2.3. Documented on daily




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Training Requirements for Packaging and Shipping of Specimens
Policy Number: SOPR-LAB-130.V1
Effective Date: January 1, 2005

PURPOSE: The safety of our employees, the general public and integrity of research specimens
resulting from accidents or incidents involving the packaging and transport of specimens can be
better assured through proper training.

POLICIES:

1. Employees packaging specimens shall be trained in the appropriate classification, identification,
   packing, marking, labeling, documenting, and arranging for acceptance by a courier for
   transportation.
   1.1. Employees who package substances classified by the Department of Transportation as Class
         6.2 INFECTIOUS SUBSTANCES for shipment receive training consistent with the
         applicable regulations (49 CFR 171-180 a.k.a. ―Hazardous Materials Regulations‖, 42 CFR
         72 a.k.a. ―Interstate Shipment of Etiologic Agents‖ and International Air Transport
         Association (IATA)’s ―Infectious Substances Shipping Guidelines‖), are tested to these
         standards and receive certification (a.k.a. ―DOT/IATA Certification‖) from their employing
         company. Such employees (as the Department of Transportation identified as ―HazMat
         Employees‖) are limited in their scope of hazardous materials to Class 6.2 INFECTIOUS
         SUBSTANCES, AFFECTING HUMANS and Class 9 DRY ICE unless receiving function
         specific training for other classes of hazardous materials.
2. It is the Site’s responsibility to assure that the employees are adequately trained.
3. Employees are not allowed to transport packaged or unpackaged hazardous materials (except
   properly packaged Dry Ice) in their own vehicles, facility-owned vehicles or off of facility
   grounds by any other mode of transportation including but not limited to ground, rail, water or
   air.


Procedure for Diagnostic Specimens Training

1. All research employees or other employees that may assist in this function of the research
   process shall complete the most current module entitled ―Packaging Requirements for Diagnostic
   Specimens‖ prior to undertaking duties.
2. As modules are updated, employees shall complete the updated modules.
3. Copies of any documentation of training shall be kept in the employee’s personnel file.



Procedures for Infectious Substances (a.k.a. “HazMat Training” or “DOT/IATA
Certification”)

1. Initial and recurrent training.
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   1.1. Initial training. A new hazmat employee, or a hazmat employee who changes job functions
        may perform those functions prior to the completion of training provided
       1.1.1. The employee performs those functions under the direct supervision of a properly
             trained and knowledgeable hazmat employee; and
       1.1.2. The training is completed within 90 days after employment or a change in job
             function.
   1.2. Recurrent training. A hazmat employee shall receive the training required by this policy at
        least once every two years.
   1.3. Relevant Training. Relevant training received from a previous employer or other source may
        be used in lieu of supervised activity during the first 90 days of employment provided 1) a
        current record of training and the materials is obtained from the employees' previous
        employer, 2) the materials are consistent with our own training program and 3) the duties are
        performed within two years of the date of certification by the other agency. The employee
        must still complete the facility-endorsed training within 90 days.
2. Hazmat employee training shall include the following:
   2.1. General awareness/familiarization training. Each hazmat employee shall be provided
        general awareness/familiarization training designed to provide familiarity with the
        requirements and to enable the employee to recognize and identify hazardous materials
        consistent with the hazard communication standards. This may be accomplished by viewing
        the most current version of the U.S. Department of Transportation’s ―Hazardous Materials:
        General Awareness and Familiarization‖ video.
   2.2. Function-specific training. Each hazmat employee shall be provided function-specific
        training concerning Class 6.2 INFECTIOUS SUBSTANCES which are specifically
        applicable to the functions the employee performs.
   2.3. Safety training. Each hazmat employee shall receive safety training containing the
        following:
       2.3.1. Emergency response information including but not limited to:
            2.3.1.1.    immediate hazards to health,
            2.3.1.2.    immediate methods for handling spills or leaks,
            2.3.1.3.    preliminary first aid measures, and
            2.3.1.4.    necessity for emergency response telephone numbers;
       2.3.2. Measures to protect the employee from the hazards associated with hazardous
             materials to which they may be exposed in the work place, including specific measures
             the hazmat employer has implemented to protect employees from exposure; and
       2.3.3. Methods and procedures for avoiding accidents, such as the proper procedures for
             handling packages containing hazardous materials.
3. Certification.
   3.1. After the employee reviews the training materials, they will complete the approved Post-
        Test;
   3.2. The Post-Test is submitted to the Corporate Trainer, scored and the results are forwarded to
        the hospital’s Director of Human Resources;
   3.3. Once the employee scores 100% on the post test questions, the facility shall issue a written
        and dated ―Letter of Certification‖ indicating that the employee has been 1) trained and 2)
        tested in the DOT and IATA regulations for the classification, identification, packing,
        marking, labeling, documenting for transportation of substances classified as Class 6.2

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        INFECTIOUS SUBSTANCES and that such certification is honored by the company for
        two years.
4. Recordkeeping.
   4.1. A record of current training, inclusive of any previous training used as a substitute for
        supervised work during the first 90 days of employment, shall be created and retained in the
        employee’s personnel folder for as long as that employee is employed as a hazmat employee
        and for a minimum of 90 days thereafter.
       4.1.1. The record shall include:
       4.1.2. The hazmat employee's name;
       4.1.3. The most recent training completion date of the hazmat employee's training;
           4.1.3.1.    A description, copy, or the location of the training materials used to meet the
                  requirements of section 2 above;
           4.1.3.2.    The name and address of the person providing the training; and
           4.1.3.3.    Written and dated ―Certificate of Training‖ which may include some of the
                  above.
   4.2. The ―Certificate of Training‖ must be presented upon request by a private or government
        courier (e.g. Fed Ex, UPS, U.S. Post Office etc.) accepting the package for transportation or
        a representative of Federal, State or local government conducting an investigation involving
        the hazardous materials (e.g. Department of Transportation, Occupational Safety and Health
        Administration, Office of Public Health etc.).


Procedures for Dry Ice Training/Packing

   1. Establish if Dry Ice Certification is needed (usually it is not):
      1.1. Dry Ice certification is not required when
      1.2. packaged in quantities not exceeding 2.3 kg (5.07 pounds) per package
      1.3. packed in packaging designed and constructed to permit the release of carbon dioxide
           gas to prevent a build-up of pressure that could rupture the packaging
      1.4. used as a refrigerant for the contents of the package.
   2. The package must be marked with the name of the contents being cooled (e.g. Diagnostic
      Specimens) , the net weight of the dry ice or an indication that the net weight is 2.3 kg (5.07
      pounds) or less, and also marked ''Carbon Dioxide, Solid'' or ''Dry Ice''.




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                   Research Documentation Maintenance

Overview, Regulatory Support and References:

Research data must be verifiable not only immediately but also have the ability to be reverified many
years in the future. Documentation of the activity and the basis of the data should be accomplished
in real time. The monitoring process shall help give guidance to the site on better ways to verify and
recreate the study. Monitors and auditors should have access to the necessary information to fulfill
this function. Finally, as the data may be subject to further audits after the study is completed, the
study information should be stored in an organized and easily retrievable manner. This also includes
any support documentation not customarily stored in the research CRFs (i.e. a hospital medical
record). Finally, with the growing amount of information being kept electronically, safeguards
should be in place to protect the confidentiality and integrity of the information used/gathered.



      21CFR312.62 Investigator recordkeeping and record retention
      FDA Guidance for Industry (April 1999): Computerized Systems Used In Clinical Trials
       (http://www.fda.gov/ora/compliance_ref/bimo/ffinalcct.htm)
      FDA Guidance for Industry (August 2003): Part 11, Electronic Records; Electronic
       Signatures - Scope and Application (http://www.fda.gov/cder/guidance/5667fnl.htm)




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Required Information in Inpatient Medical Records
Policy Number: SOPR-RIM-100.V1
Effective Date: January 1, 2005

PURPOSE: The information in the inpatient medical record should support the documentation for
research purposes as well as adhere to relevant laws and accreditation agencies.

POLICIES:

1.    In the event a patient is admitted to a research protocol, the medical records for that admission
      shall be a ―stand alone‖ document. This maximizes the integrity of the research documentation
      and minimizes the potential for confidentiality breach in the event of an audit by the Sponsor,
      IRB, FDA or other regulatory entity.
2.    The inpatient medical record must meet all requirements of the JCAHO, licensing agencies,
      internal policy and all other requirements necessary absent a study. The medical record is not
      immune to these requirements simply because it pertains to a study subject.
3.    For patients hospitalized pursuant to a research protocol, the medical record and Source
      Document binder shall have all necessary documentation in support of the research present
      under that particular admission.
4.    Whenever possible, any oral history from the subject/significant other shall be supported by
      observable medical records.
5.    Unless waived by the IRB, a copy of the following information shall be in the medical record
      AND any research folders
     5.1. informed consent document(s)
     5.2. any additional authorizations to release protected health information (if not combined with
          the Informed Consent Document)
6.    Documentation that the patient met the Inclusion/Exclusion criteria to be admitted to the study
      shall be substantiated in the medical record.
     6.1. In the event the portions of the criteria are based on historical data, the record shall specify
          whether the data was gathered by report from the subject/significant other or from past
          medical data.
     6.2. In the event the facility does not have documented medical data that supports the subject’s
          meeting the Inclusion/Exclusion criteria and such documentation is reasonably believed to
          exist, the facility will pursue the obtainment of said documentation from external agencies
          through obtaining proper release of this information from the subject or subject’s legally
          authorized representative.
          6.2.1. Any and all efforts of retrieval of such documentation shall be documented and/or
                attached on the checklist.
          6.2.2. In the event such documentation is not obtained but is verbally verified by a third
                party, this shall also be documented on the checklist.
     6.3. It is the ultimate judgment of the Principal Investigator to validate any historical reports as
          accurate.


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Retention of Inpatient Medical Records and Research Records
Policy Number: SOPR-RIM-110.V1
Effective Date: January 1, 2005

PURPOSE: The facility recognizes the difference between the inpatient medical record and other
source documents/Case Report Forms used exclusively for research. There are also other essential
documents that pertain to research protocols that are not patient related such as regulatory
documents.

POLICIES:

1. The facility will retain the medical records of the patient according to the longer of the relevant
   Policies and Procedures of the facility OR the timeframes specified for research docuents below.
2. For the Case Report Forms, Regulatory Documents and other research related documents, the
   facility shall retain the documents for the longer of the following timeframes:
   2.1. As specified in 21CFR 312.62(c) or it’s relevant successors which currently states ―2 years
        following the date a marketing application is approved for the drug for the indication for
        which it is being investigated; or, if no application is to be filed or if the application is not
        approved for such indication, until 2 years after the investigation is discontinued and FDA is
        notified.‖ OR
   2.2. As otherwise agreed to with the Sponsor in writing (i.e. in the Clinical Study Agreement).
3. The facility shall take the necessary precautions to prevent accidental or premature destruction of
   the research documents.




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Access of Records by Auditors
Policy Number: SOPR-RIM-120.V1
Effective Date: January 1, 2005

PURPOSE: The integrity of the research data as well as evidence of protection of the human
subjects shall be available for verification by research sponsors and regulators.

POLICIES:

1. The facility shall provide to relevant agencies access to the documentation necessary to assure
   that the research was conducted properly and that the rights of the subjects were protected. In
   doing so, all necessary provisions to protect the confidentiality of the subject shall be undertaken.


Procedure for Outside Parties Accessing Research Records

1. The facility shall provide certain parties access to the Case Report Forms, medical records (or
   other source documents) and any other documents related to the research process at reasonable
   times.
2. Relevant agencies include but are not limited to:
   2.1. Food and Drug Administration representatives
   2.2. Office of Human Research Protections
   2.3. Monitors/Auditors of the sponsor or the sponsor’s designee.
3. The facility shall verify that the individual requesting access to the medical record has the proper
   authority to do so.
4. Whenever appropriate, subject identifying information shall be eliminated from the review
   unless the criteria for disclosure as stated below has been met:
   4.1. Records of particular individuals require a more detailed study of the case.
       4.1.1. This may be for scientific purposes.
       4.1.2. This may be for purposes of protection of rights or investigation in the potential
             breaking of their rights.
   4.2. The reviewing agency provides reasonable doubt that the records do not represent actual
        cases.
   4.3. The reviewing agency provides reasonable doubt that results reported are not reflected in the
        medical record.
   4.4. The criteria for federal/state/local law that mandates breach of confidentiality (e.g. to
        prevent imminent harm to the subject or others) has been met.
   4.5. The individual has given appropriate written authorization for such release.
5. Although scanning and/or copying is permitted, identifying information on the medical record or
   other relevant document(s) must be extracted.
6. The policies protecting patient confidentiality must also be met as well.



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Storage and Destruction of Paper-Based Research Documentation
Policy Number: SOPR-RIM-130.V1
Effective Date: January 1, 2005

PURPOSE: Storage and/or destruction of paper-based research records shall adhere to the
appropriate conditions and timeframes, respecting sponsor and subject confidentiality as well as
consider that the documents may need to be unpacked to recreate the study given relatively short
time periods.

POLICIES:

1. In the event shelf-space becomes an issue, research records for closed protocols may be stored or
   destroyed, but only in accordance with this policy.
2. Storage shall
   2.1. Be secure from accidental loss, damage and/or disclosure
   2.2. Allow for easy retrieval and recreation of the research activity.
3. The facility shall destroy research related documents when they no longer remain useful to the
   facility, the sponsor AND other regulatory agencies. Destruction shall only be done after the
   required retention period had ended. In the event the facility wishes to destroy documents and
   the time is after the regulatory retention requirements has passed but before the obliged
   timeframe contractual to the sponsor, the sponsor may be contacted to amend the contracted
   timeframe or provide for the shipment of documents to the Sponsor or their designee.


Procedures for Storing Paper-Based Research Documentation

1. Storage Boxes shall be durable and labeled on the outside in easily readable markings with:
   1.1. ―Research Documentation Storage‖
   1.2. Sponsor
   1.3. Protocol Number
   1.4. Dates of Study
   1.5. Box ―X‖ of ―Y‖
   1.6. ―Do Not Destroy Before‖ Date (with reference to the destruction policy)
2. If space in the box is an issue, it is acceptable to recycle the binders from CRFs or separate
   source document binders. It is not preferable to break down the regulatory binders due to the
   potential of disrupting the integrity of the documents and the order in which they exist.
3. Storage area shall be secure and not conducive to physical harm to the records or unauthorized
   access. Examples are as follows:
   3.1. Adequate prevention from water damage
   3.2. Controlled access similar to that of access to patient files must me maintained
4. In the event any records are moved off-site, the storage conditions and security shall be at least
   similar to those of the facility.
   4.1. A record of where the boxes are located should be kept.
5. If a single study has multiple boxes, the boxes shall be kept proximal to each other.


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Procedure for Destruction of Paper-Based Research Documentation

1. The timelines for destruction of documents shall be verified and the longest most distant date
   shall be used as the destruction date. This includes a review of at least the following:
       1.1.21CFR312.62 or its relevant successor or equivilant for non-drug studies
       1.2.The timeframe specified by the sponsor contractually, whichever is longer.
2. The facility shall send a certified letter with return receipt requested to the Sponsor or the
   Sponsor’s successor indicating the intent to destroy the documents within 90 days.
       2.1.This letter shall indicate that the timeframes initially set forth by the sponsor have
            expired.
       2.2.This letter shall indicate the one contact person at the facility that has the authority to stop
            the destruction process.
       2.3.The letter should specify a date which is a minimum of 90 days from the date of the letter
            (i.e. ―The records will be destroyed on or after October 3rd, 2005‖).
       2.4.The letter shall indicate that a non-response to the letter shall be construed as approval for
            the process.
       2.5.The letter shall be copied to the Chief Research Officer.
3. In the event the Sponsor or Sponsor’s successor has received the first correspondence and not
   responded, a second letter shall be sent via certified mail with return receipt requested indicating
   the intent to destroy the documents within 30 days.
       3.1.This letter shall also indicate the one contact person at the facility that has the authority to
            stop the destruction process.
       3.2.The letter should specify a date which is a minimum of 30 days from the date of the letter
            (i.e. ―The records will be destroyed on October 3rd, 2005‖).
       3.3.The letter shall indicate that the previous letter was not responded to and a non-response
            to the letter shall be construed as approval for the process.
       3.4.The letter should indicate that this is the ―Final Notice‖.
       3.5.The letter shall be copied to the Chief Research Officer.
4. In the event the Sponsor or Sponsor’s successor has received the second correspondence and not
   responded, and the Chief Research Officer gives permission, the records are to be destroyed in
   accordance with the policies and procedures for destroying confidential documents of the
   facility.
5. In the event the Sponsor or Sponsor’s successor requests the records be not be destroyed, the
   records shall be shipped to the sponsor’s designated address, preferably at their expense.




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Electronic Communication
Policy Number: SOPR-RIM-140.V1
Effective Date: January 1, 2005

PURPOSE: Email, although a very effective means of communication, has it’s risks. Intentional or
unintentional activity can result in loss of patient or sponsor confidentiality as well as not having
access to information in the future due to accidental or systematic deletion.

POLICIES:

1. Emails should not be deleted.
   1.1. In the event an email folder gets close to a designated capacity, arrangements should be
        made to archive the folder.
2. Emails relevant to the study should be printed and filed in the relevant correspondence sections
   in the study binders.
3. Emails that contain internal discussions should not be forwarded, CC’d or BCC’d to individuals
   outside of the company.
4. Emails that contain confidential information should not be forwarded, CC’d or BCC’d to
   individuals not authorized to receive such information.




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                       General Administrative Policies

Overview, Regulatory Support and References:

      FDA Debarment List (http://www.fda.gov/ora/compliance_ref/debar/)
      FDA Disqualified/Restricted/Assurances Lists For Clinical Investigators
       (http://www.fda.gov/ora/compliance_ref/bimo/dis_res_assur.htm)
      21 CFR 56.108(b)
      21 CFR 46.108(b)
      OHRP Guidance on Written IRB Procedures (July 11, 2002):
       (http://www.hhs.gov/ohrp/humansubjects/guidance/irbgd702.htm)




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Credentialing of Physicians or other Staff to Do Research
Policy Number: SOPR-GEN-110.V1
Effective Date: January 1, 2005


PURPOSE: Prescribing investigational treatments or being involved in research calls for a more
restrictive background check than the usual standard of care.

POLICIES:

1. No individual may engage in research activity without being properly credentialed by the
   facility.
2. The scope of general credentialing shall equivalent to the work expected to be performed. For
   example, if the bylaws require a Board Certified Child/Adolescent Psychiatrist to be the
   attending physician for the Child Unit, but the researcher will only be doing rating scales and not
   be the attending physician, only the rating scales portion of general credentialing needs to be
   done.
3. In addition, a Supplement to Credentialing: Research Activity Form should be completed with all
   relevant attachments.
4. The reported FDA history pertaining to debarment, disqualification, assurances or restrictions
   shall be verified.
5. Additional background checking may be completed at the discretion of the facility (i.e. BMIS,
   CIIL, Warning or Determination Letter Scan).
6. This process shall be repeated at each recredentialing period.


Procedures For FDA Background Check

1. The credentialing staff shall assure that the researcher is not DEBARRED from prescribing
   investigational agents as evidenced by not being on the FDA Debarment List located at
   http://www.fda.gov/ora/compliance_ref/debar/default.htm.
2. The credentialing staff shall assure that the researcher is not DISQUALIFIED from prescribing
   investigational agents as evidenced by not being on the FDA Disqualified/Totally Restricted List
   located at http://www.fda.gov/ora/compliance_ref/bimo/disqlist.htm
3. The credentialing staff shall note if the investigator has an active ASSURANCE (located at
   http://www.fda.gov/ora/compliance_ref/bimo/asurlist.htm) or other RESTRICTION (located at
   http://www.fda.gov/ora/compliance_ref/bimo/restlist.htm) on file with the FDA concerning their
   use of investigational agents.
   3.1. In the event there is an Assurance or Restriction, the credentialing approval letter shall
        dictate that they may not practice outside of the scope allowed by such
        Assurance/Restriction.
4. Documentation on the application form or other note to file indicating the above checks have
   been verified and the nature of any Assurance or Restriction.

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Handling Complaints and Serious/Continuing Noncompliance
Policy Number: SOPR-GEN-120.V1
Effective Date: January 1, 2005


PURPOSE: Complaints or reports of noncompliance should be evaluated and corrective actions
taken when appropriate.

POLICIES:

1. Reports of non-compliance with regulations or policies, whether internally or externally
   generated, shall immediately be reported to the Chief Research Officer.
2. At any time, the Chief Research Officer has the discretion to turn all or part of the matter over to
   the corporate compliance program in lieu of following this process.
3. The Chief Research Officer or designated member will review the allegation and any other
   information necessary to determine whether a full investigation is warranted. Possible
   recommendations may include:
   3.1. Dismissal of the allegation or complaint as unjustified
   3.2. Referral of the matter to another more appropriate process or authority within the institution
        for resolution (e.g., Medical Staff Committee)
   3.3. Resolution through corrective or educational measures where the violation of human
        subjects regulations is minor or inadvertent
   3.4. A formal investigation where the allegation or complaint appears founded and is of a serious
        nature.
4. At any time during the inquiry or investigation process, the Chief Research Officer may
   determine that it is necessary to suspend accrual of research subjects or to suspend approval of
   research project(s) to ensure the protection of human subjects. Unless there is the potential of
   imminent harm to research subjects or others, the Chief Research Officer will generally not
   suspend research studies until the researcher has had an opportunity to respond to the initial
   allegation of non-compliance.
5. The Chief Research Officer will determine whether the identity of those persons making
   allegations should be provided to the investigator being reviewed, consistent with applicable
   policies.
6. The Chief Research Officer may also initiate a complaint based on information available to
   him/her (e.g., deficiencies noted in IRB files, media or scholarly reports of research activity).
7. The Chief Research Officer shall report all serious or continuing non-compliance to the relevant
   agency (FDA and/or OHRP) as well as other agencies for reportable issues that do not pertain to
   human subject protection or scientific misconduct.


Procedures for Receipt of Compliant


1. The facility accepts complaints from any source, which may include:
   1.1. Subjects and/or their significant others

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   1.2. Research Staff
   1.3. Non-Research Staff
   1.4. IRB or other Regulatory Authority
   1.5. General Public/Media
2. The complaints involving scientific misconduct or human subject protections violations should
   be forwarded, in writing, immediately to the Chief Research Officer.
3. An acknowledgement of receipt of the complaint should be generated.



Procedures for Routine Investigation

1. The Chief Research Officer and/or other individuals appointed by the Chief Research Officer
   whose areas of expertise are suited to reviewing the complaint and area of study will conduct the
   investigation (known as the ―Investigation Committee‖).
2. The Investigation Committee may use any and all materials and reports gathered during the
   initial inquiry phase.
3. The Investigation Committee may obtain documents and other records relevant to the
   investigation and may interview any persons who may have information relevant to the
   complaint.
4. The researcher under investigation will be given an opportunity to submit written comments and
   to appear before the Investigation Committee on at least one occasion prior to the committee
   issuing its report.
5. Based on its investigation, the Investigation Committee will prepare a report summarizing the
   information it considered and outlining its conclusions and recommended actions.
6. The Investigation Committee will send the report to the Chief Research Officer for final
   disposition.
7. Depending on the case, the investigation phase is generally expected to be completed within 60
   working days.
8. Actions the Chief Research Officer may take with respect to the investigation include, but are not
   limited to:
   8.1. Dismissal of the complaint as unjustified
   8.2. Remediation or educational measures
   8.3. Monitoring of research activities
   8.4. Increased reporting by the researcher of his/her human subjects research activities
   8.5. Restrictions on research practice, such as limiting the privilege to minimal risk or supervised
        projects
   8.6. Suspension of approval for one or more of the researcher's studies
   8.7. Termination of approval for one or more of the researcher's studies
   8.8. Referral to other institution officials or committees for possible further review and action by
        those bodies.
9. In cases that appear to involve misconduct outside of the realm of Human Subject Protections or
   Scientific Misconduct (e.g. financial improprieties) OR actions that cross other professional/legal

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    barriers (e.g. sexual abuse of a subject), the Investigative Committee should report allegations of
    such misconduct to appropriate institutional officials.
10. The Chief Research Officer will send a copy of its decision to the investigator and the site’s
    Chief Executive Officer.


Procedure for Reporting of Serious or Continuing Non-Compliance to Governmental
Authorities

1. Based on the findings, the Chief Research Officer shall determine if the misconduct meets the
   appropriate Federal Department or Agency’s definition of ―serious or continuing
   noncompliance‖ with the regulations governing the protection of human subjects or other
   reportable event involving a different governmental agency (i.e. fraudulent billing).
2. Reports will be prepared and submitted by the Chief Research Officer in accordance with similar
   policies on self-disclosure to regulatory agencies.




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                                           Forms
FORM: Research SOP Training Attestation Log: Review of Complete Manual
FORM: Research SOP Training Attestation Log: Change of SOP
FDA Form 1572
Supplement to Credentialing: Research Activity Form
FORM: Research Deviation/Violation or Other Reportable Event Form




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FORM: Research SOP Training Attestation Log: Review of Complete Manual




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FORM: Research SOP Training Attestation Log: Change of SOP




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                                      FDA Form 1572




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                 Supplement to Credentialing: Research Activity Form




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       FORM: Research Deviation/Violation or Other Reportable Event Form




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