The Federal Regulations and Good Clinical Practices (GCP) require investigators
to maintain numerous documents as their research records. The Federal
Regulations require that an investigator maintain files that provide evidence of
the ethical conduct of human subjects research. This includes records of IRB
review and approval and documentation of informed consent. While GCP only
applies to studies regulated by the FDA, they provide guidance to all
investigators about how to organize and maintain essential study documents.
According to Good Clinical Practices, essential documents are those documents
that permit the evaluation of the conduct of a trial and the quality of the data
produced. The investigator’s essential documents establish the compliance of
the investigator with regulatory requirements as well as the standards of good
research practice. The following guidance is intended to delineate the
documents that investigators should keep and to help investigators organize their

Investigators should have their essential documents organized and easily
accessible for inspection and continuing review. Also, investigator’s documents
should be maintained in such a way that allows the investigator to monitor his/her
own level of compliance as well as protocol adherence. It is recommended that
the documents be maintained in a binder with dividers labeling the types of
documents contained in the different sections. This binder is often called a
regulatory binder. All of the documents should be kept in reverse chronological
order in the appropriate section. Additionally, investigators are encouraged to
note the date of receipt on all documents that did not originate with the
investigator. The following list defines documents that should be maintained by
the investigator.

   1. Applications
            a. Copy of the grant application
            b. Copy of the original human subjects research application
                submitted to the IRB.

   2. All signed agreements
              a. Investigator/institution and sponsor
              b. Investigator/institution and Contract Research Organization (if
          c. Investigator/institution and authorities (where required)

3. Financial papers
         a. Financial disclosures
         b. Financial agreement between the investigator/institution and the
             sponsor for the trial.

4. Insurance statements
         a. Compensation document for trial-related injury

5. Regulatory authorization, approval, and/or notification
         a. All forms submitted to any federal agency (i.e. HHS, FDA, etc.)
            pertaining to human subjects research.
         b. Authorization/approval/notification of protocol.
         c. Authorization/approval/notification of protocol amendment(s)
         d. Authorization/approval/notification of other documents.

6. Documents submitted to the IRB
        a. IRB approvals/acknowledgements for the following documents,
             copies of the approved documents, and any revisions to the
              i. IRB application
             ii. Research Plan
            iii. Study Protocol
           iv. A copy of the final, IRB-approved dated protocol
             v. Amendments to the protocol
           vi. Documents showing dates and reasons for any deviation
                 from the protocol
           vii. Initial IRB approval letter
          viii. Amendments to the protocol
           ix. All related study instruments, including:
                     1. Informed consent forms (all translations and all
                     2. Case Report Forms (if applicable);
                     3. Written information provided to subjects (i.e., diaries,
                         pain scales, questionnaires, educational booklets);
                     4. Advertisement for recruiting purposes.
             x. Certificate of translation (if applicable)
           xi. Subject compensation
           xii. Verification of Confidential Nature (VCN) Forms
        b. Adverse Event Reports
        c. Progress Reports
        d. Continuing Review applications
        e. Protocol Inactivation Report
        f. Other documents requiring IRB approval/acknowledgments
7. Other IRB documents
          a. IRB membership list
          b. IRB meeting schedule

8. Informed Consent Forms
         a. Original signed Informed Consent forms

9. HIPAA Documents
        a. HIPAA Application
        b. Signed Authorizations and related documents
        c. IRB approval of HIPAA waivers of Authorization
        d. Data Use Agreements
        e. Business Associate Agreements

10. Communications
        a. The regulatory binder must include copies of all
            correspondences with:
             i. The IRB,
            ii. The sponsor and CRO,
           iii. Other investigators,
           iv. The monitor,
            v. FDA , and
           vi. All other correspondences involving human research
        b. The retained communications should include all required
            reports, e-mails, faxes, memoranda, and letters. In addition,
            logging phone conversations is encouraged to track when
            conversations take place and the substance of the

11. Study staff information
          a. Curriculum vitae for all investigator(s) and key research office
               i. CVs should be signed, dated, and updated every 2 years.
          b. Licenses
          c. Training records and certifications for investigators and key
              research office personnel
          d. Human Subjects Research Training
          e. HIPAA Training (if applicable)

12. FDA Documentation (if applicable)
         a. Sponsor’s protocol
         b. Investigator brochure
         c. Package insert
         d. Device manual
e. Investigational device exemption information
f. Investigator-initiated IND or IDE application
g. Investigational New Drug Application FDA Form 1571 if the PI is
    a Sponsor-Investigator
h. Current FDA Form 1572 for all involved investigators
i. Sample of product label
j. Instructions for handling investigational product(s) and trial-
    related materials.
k. Source Documents
l. Subject’s case histories and exposures to the investigational
m. Adverse Event reports
n. DSMB reports
o. IND safety reports
p. All data derived from the study.
q. Sample of the Case Report Form
r. Records of changes and corrections to CRFs.
s. Signed, dated, and completed CRFs
t. FDA Financial Disclosure Form
u. Laboratory Documentation
     i. Laboratory certifications
    ii. Updates to normal value(s)/range(s) for medical lab
        technical procedure(s), test(s) included in the protocol
   iii. Updates on medical/laboratory/technical procedures/tests
             1. Certificates
             2. Accreditation
             3. Established quality controls/external quality
             4. Other validations
   iv. Copy of the laboratory director’s CV.
v. Shipping records for investigational products and study related
     i. Documented shipment dates, batch numbers, and methods
        of shipping the investigational product.
    ii. Certificates of analysis of investigational products shipped
   iii. For devices, records of receipt, use or disposition of the
        device relating to the type and quantity of the device, the
        dates of its receipt, the batch number or code mark; the
        names of all persons who received, used, and disposed of
        each device; and why and how many units of the device
        were returned to the sponsor, repaired, or disposed of.
w. Decoding procedures in blinded trials for emergency situations.
x. Master randomization list (instructions on how to randomize)
y. Trial monitoring reports
     i. Pre-trial visit
    ii. Initiation visit
                 iii. Periodic monitoring
                 iv. Closeout visit
              z. Study Logs
                   i. Subject screening log
                  ii. Subject identification code list
                 iii. Subject enrollment log
                 iv. Signature sheet
                  v. Delegation of Responsibility
                 vi. Monitor Visit Log
                vii. Drug/device dispensing/accountability
                viii. Product Accountability Log
                 ix. Record of retained body fluids/tissue samples.

   13. A signed and dated note-to-file should be created:
             a. To note an error in record keeping,
             b. To record missing documentation or incomplete data,
             c. To explain how information was obtained,
             d. To detail who obtained information,
             e. To clarify any discrepancies.

Case Report Form: A printed, optical, or electronic document
designed to record all of the protocol-required information to be
reported to the sponsor on each trial subject.
Investigator’s Brochure: A compilation of the clinical and nonclinical
data on the investigational product(s) that is relevant to the study of the
investigational product(s) in human subjects.
Monitoring Report: A written report from the monitor to the sponsor
after each site visit and/or other trial-related communication according
to the sponsor’s SOP’s.
Signature Sheet: Signatures and initials of all people authorized to
make entries and/or corrections on CRFs.
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).
Subject Identification Code List: A confidential list of the unique
identifiers matched to each trial subject’s name to protect the subject’s
identity and to allow the investigator to reveal the identity of any
subject if necessary.
Subject Screening Log: Identifies of subjects who entered pretrial

International Conference on Harmonisation; Good Clinical Practice:
Consolidated Guideline. 62 Federal Register, 25691-25709 (May 9,
2 CFR 215.53(b)
21 CFR 312.57
21 CFR 312.62(c)
21 CFR 812.140(d)
45 CFR 164.528

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