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Clinical Research at UCLA

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					             Obtaining Pre-study
          Approvals for Clinical Trials


                   Yvonne Chapman, RN, BSN
                UCLA Institute of Urologic Oncology




K 30 Feb 2011
           What type of approvals are
                   needed?
   Administrative-UCLA
        Departmental-i.e. Hem/Onc Internal Scientific Review
         Committee
        Financial-Budget Review Committee


   Regulatory OPRS, Radiation Safety

   Contract/Grant-Office of Contracts & Grants

K 30 Feb 2011
           What will you learn today?

   A little bit of everything……..
        Different types of research defined
        Grants and Contracts
        Clinical Trials at UCLA
        Budgeting
        Regulatory Requirements
        Human Subjects Protection
        Conflicts of Interest (COI)
K 30 Feb 2011
            Basic Research vs Clinical
                    Research
Research is defined as: “a systematic investigation, including research
  development, testing and evaluation, designed to develop or
  contribute to generalizable knowledge” [45 CFR 46.102(d)]

Basic Research “is the investigation of a subject to increase
  knowledge and understanding about it. The main motivation is to
  expand man's knowledge , not to create or invent something.”

Clinical Research is generally understood as research in human
   subjects.




K 30 Feb 2011
                Research at UCLA
                                     Research




                               Clinical Research
                                  Clinical Trials
                                                    For Profit
                                                    Pharma,
                  Non Profit                        Biotech
                  (NIH, Fnd,
                  UCLA)           PI Initiated       Sponsor
                                  Protocol           Initiated
                                                     Protocol




K 30 Feb 2011
           Some Examples of Basic
                 Research
   “For example, scientists might study certain types of cancer cells to
    observe how they multiply and grow in a lab. Other research
    models, such as studies involving animals, often are used to gain
    such knowledge.”

   How cells develop and grow

   Genomics -- the role genes play in the development of disease




K 30 Feb 2011
         Examples of Clinical Research
   Feasibility/pilot studies
   Epidemiologic studies
       Study of the causes, distribution and control of disease
        in populations
   Retrospective/prospective chart review
    (registry studies)
   Specimen banking
   Clinical drug or device trials


K 30 Feb 2011
                What’s next?




K 30 Feb 2011
                   Getting started:
                the idea for the study
                         Whose idea is it?
                             The Principal Investigator
                             PI at a different institution
                             Consortium (a group of
                              institutions)
                             For-profit (pharma, biotech,
                              device company)
                             Non-profit (NIH, NSF, DOD)

K 30 Feb 2011
                   Getting started:
                the funding for the study
                       Who will pay for the costs of the study?
                         The department/division/PI

                         Grant from the National Institutes of
                          Health (NIH) or National Science
                          Foundation (NSF)
                             Unsolicited (R01 or RFA) or Solicited
                              (RFP (request for proposal)
                         Another university

                         A foundation (e.g. American Heart
                          Association)
                         A consortium

                         Pharmaceutical, biotech, or device
                          company

K 30 Feb 2011
Grants vs Clinical Trial Contracts
   Grants (F&A 54% MTDC)
      Submission deadlines
      Funding available upon grant/regulatory approval
      Strict guidelines for expenditures
      F&A rate 54%
      Hard end date

   Clinical Trial Contracts (F&A 26% TDC)
      IRB fees apply
      Minimal start-up costs
      Payment after completion of work/milestones
      Frequent delays in payment


K 30 Feb 2011
       What is F&A or Indirect Costs?

   Basic expenses of running research institute
    (overhead)

   “Indirect Costs”, in 1966 Fed Govt replaced
    Indirect Cost term with F&A (Facilities &
    Administrative)




K 30 Feb 2011
                What is a grant?

   Financial assistance mechanism providing
    money, property, or both to an eligible
    entity to carry out an approved project or
    activity. A grant is used whenever the NIH
    Institute or Center anticipates no
    substantial programmatic involvement
    with the recipient during performance of
    the financially assisted activities.
K 30 Feb 2011
                          Grants
          http://www.research.ucla.edu/ora/

   Find funding opportunity
   Write/submit application through OCGA
        Agencies typically provide very straight-forward
         guidelines on submission format & deadlines
        Prepare & submit budget proposal following agency
         guidelines
   If funded, seek IRB/ARC approval
   Upon IRB/ARC approval, approved funding
    made available with start date of grant
K 30 Feb 2011
   Submission pathways will differ for grants
    and contracts

        Non-Profit Grants Submission
             Office of Contracts & Grants Administration
              (OCGA)
        Industry Contracts Submission
           Clinical Trials Contracting Unit (CTCU)
           Office of Intellectual Property Administration

            (OIPA )



K 30 Feb 2011
          The Process – Submitting
                   Grants
   Step 1 - Identify agencies
        Federal agencies
           NIH
           DOD

        Other non-profit organizations
           Susan Komen
           American Heart Association

           American Lung Association



K 30 Feb 2011
          The Process – Submitting
                   Grants
   Step 2 – Notify Fund Manager

        Fund manager will work on budget and
         administrative items.
        Online submission – grants.gov, Cayuse
        Be sure to inform fund manager as soon as
         possible to avoid delays.

K 30 Feb 2011          K-30 February 2010
          The Process – Submitting
                   Grants
   Step 3 - Final submission

        Grant will be submitted to agency with all
         required documents and all UCLA internal
         documents completed and sent to OCGA.
        Once you have been notified that you have
         received a fundable score, proceed with
         institutional regulatory submissions.

K 30 Feb 2011           K-30 February 2010
    The Process – When an award is
                 made
   Once the award is made, it will be
    assigned an account number which will be
    used for all spending.
   Important note: The award will not be
    released by OCGA until all required
    documents are on file, i.e. internal
    documents, IACUC/ARC approval, IRB
    approval
K 30 Feb 2011
The Process – Managing the award
       and Final Close out
   Monthly meeting- Investigators/Fund
    Managers.
          To help ensure accurate spending of funds,
          the fund manager will meet with the PI on a
          regular basis to review expenditures.

   Close out and final reporting to agency


K 30 Feb 2011
            What about Contracts?




K 30 Feb 2011
       Clinical Trials and Contracts
          What is a Clinical Trial?

   A clinical trial is a type of study designed
   to determine whether a drug, device,
   biologic or procedure can be used safely
   and effectively in the treatment,
   prevention, or detection of human illness.


K 30 Feb 2011
           It’s important to know….


   UCLA defines clinical trials as those
    studies funded by for-profit entities
    (e.g. Pharmaceutical, Biotech
    companies)



K 30 Feb 2011
                Sponsor-Initiated
                  Clinical Trial
   Sponsor authors the protocol
   Sponsor holds the IND/IDE
   Sponsor covers all cost of the study
   Sponsor assumes all liability
   Indirect Cost Rate of 26% for industry-funded
    studies
   Multi-center publication typically written by
    sponsor (authorship does not typically contribute
    to academic advancement)
   Subject to sponsor and federal oversight
K 30 Feb 2011
                  The Process-
                Sponsor-Initiated

                    CDA Process (CTCU)
                    Thorough Protocol Review
                     Initial “Go”/ “No-Go” Decision
                    Budget Development and Negotiation




                     Regulatory Approval(s) Submission
                     Clinical Trial Agreement (CTA)
                     Negotiation



K 30 Feb 2011
                “Go”/“No-Go” Decision
                      Requires:

     Protocol Feasibility Assessment
     Available Subject Population
     Available Resources:
          Personnel (PI and staff time)
          Space
          Other ancillary support
             Pharmacy
             GCRC


K 30 Feb 2011
                Investigator-Initiated
                    Clinical Trial
   Investigator authors the protocol
   Investigator usually holds the IND/IDE
   Sponsor may only cover some cost of the study
   University generally assumes all liability
   Indirect cost rate depends upon funding entity
   Publications (academic advancement)
   Subject to federal oversight and registration on
    clinicaltrials.gov




K 30 Feb 2011
                   The Process –
                Investigator Initiated
                      Write protocol
                      Identify potential sponsor/submit idea
                      Contact OCGA/CTCU
                      Budget Development




                       Submit budget for sponsor approval
                       Submit sponsor agreement/budget
                       to appropriate UCLA office
                       Regulatory Approval(s) Submission

K 30 Feb 2011
                Budgeting: A Process
   Careful consideration of standard of care (routine and
    billable to subjects insurance) versus research related
    costs.

   Necessary pre-approval/pre-authorizations for
    devices/certain standard of care charges.

   Budget approval by someone with fiduciary responsibility
    or as required by department.
   Determination of the true cost to perform clinical trial at
    UCLA.
    (So you don’t end up in the RED)
K 30 Feb 2011
  Can the Budget pull the weight???




K 30 Feb 2011
    Develop A Budget That Covers All
                Costs
   Understand the protocol and the detail
   Differentiate between standard of care (Routine) and
    research costs
   Analyze Costs: Personnel, Hidden costs,
    Administrative
   Patient Care, Indirects
   Develop appropriate payment terms and schedule


K 30 Feb 2011
 Contracts – For Profit (industry)

   Limited budget guidance available
   Budget development/negotiation often
    lengthy
   Start-up funds limited to small % of
    agreed upon costs
        Earnings based on subject enrollment
   Contractual terms negotiated separately

K 30 Feb 2011
                Contracts – Non-profit

   Budget restraints often in place
   Contracts negotiations may be lengthy
   Payment terms restrictive
   Indirect cost rate the same as grant
    (54%)



K 30 Feb 2011
          Clinical Trials Contracting
   Clinical trial agreements/contracts contain many
    important legal terms & conditions
   Authority to sign a contract is restricted to certain
    University officials to protect both you, the PI, and
    the institution
   Signing of a contract is contingent upon final IRB
    approval



K 30 Feb 2011
                Financial Regulations -

   Idea
       plus
   Funding source
      equals
   Implications!!


K 30 Feb 2011
                     Implications
   for the PI
   for the university
   for the sponsor of the study
   Examples:
        Indirect cost rate
        Intellectual property rights
        What can be done with the results/data
        Who is responsible if things go wrong
         (indemnification and subject injury)
        Financial conflicts of interest
K 30 Feb 2011
 Financial Disclosure Process & CIRC
                (Conflict in Research Committee)

 Form                700U              700U          740
                                     Addendum



 Required By         State of          UCLA         Federal
                 California Form       Form          Form



 Who                Principal        PI & Other     PI & Key
 Discloses        Investigator     Investigators   Personnel

 What to
 Disclose           $500+             $500+        $10,000+


            Positive Disclosure       Supplement      CIRC Review


CIRC must review and approve disclosures prior to contract sign-off.
K 30 Feb 2011              K-30 February 2010
      Financial Disclosure Process &
                   CIRC
     Important Facts to Note:

          Disclosure of financial interest is effective for only a 12-
           month period (700U = report 12 months prior, 740 = report
           12 months prior & future)

          CIRC Meeting & Submission Deadlines
                  http://cf.research.ucla.edu/circ/circfuturemeetings.cfm
               Contract Officers need all financial disclosure documents
                no less than two business days before the CIRC case
                submission deadline
               Missed deadline can cause a significant delay (30 days
                minimum)
K 30 Feb 2011
                Financial Regulations -
     Why do we need financial disclosure
                 forms?

   It’s the law!!

   Institution must manage financial interests

   Positive disclosure may affect language in
    ICF
K 30 Feb 2011
The Regulatory Process at UCLA
          Requires:

 IRB/ARC Review & Approval
 Other Institutional Approvals

 Financial Disclosures (700U, 700U
  Addendum & 740)


K 30 Feb 2011
          Human Subjects Protection

   UCLA Institutional
    Review Board (IRB)
        Functions under
           Federal Guidelines (CFR)

           Federal-wide Assurance (FWA)

           UCLA policy and guidelines

           UC policy and guidelines

           Committee’s own decisions



K 30 Feb 2011
        Other Institutional Approvals
       Some examples:
          Financial Disclosure/CIRC

          Environment, Health & Safety (EH&S)

             Medical Radiation Safety Committee
                        Research use of isotopes or radiation machines in
                         humans
                   Institutional Biosafety Committee
                        Research use of infectious substances
                        Research use of recombinant DNA
            Internal Scientific Peer Review Committee
             (ISPRC)
               Cancer and cancer prevention studies


K 30 Feb 2011
         Required Research Training at
                    UCLA
        http://www.citiprogram.org
             Human Research: Biomedical Researchers & Staff
             Human Research: Social & Behavioral Researchers & Staff
             Human Research: Basic Scientist Group
             Animal Research Group
             Optional, but recommended training
                 Responsible Conduct of Research

                 Good Clinical Practices

             HIPPA Research Training Course
                   (human research only)




K 30 Feb 2011                       K-30 February 2010
    Other helpful research training
   Recruiting & Consenting Research Participants
   Research Subject Advocacy & the Informed Consent
    Process
   Research with Children & Minors
   Using Investigational Drugs & Devices in Clinical Research
   What to Do After the IRB Approval:
      Post IRB Approval Requirements
   Good Clinical Practices:
      Source Documentation & Data Management
   Data & Safety Monitoring in Clinical Research
        http://map.ais.ucla.edu/go/1002345

K 30 Feb 2011             K-30 February 2010
        Here are some tips to help
        you navigate the research
           processes at UCLA.




K 30 Feb 2011    K-30 February 2010
                     Key Elements
    First – contact your fund manager for
     guidance
    Simultaneous processing of documents
         IRB, other regulatory, budget & contract
    Know your contacts
         Maintain communication, keep the ball rolling
    Proactive completion of paperwork
         Initial vs Final


K 30 Feb 2011
            Top Reasons for Delays in
               Contract Execution
   Incomplete and/or Missing Forms
        Financial Disclosure Forms (700U/740)
        Supplement (for positive disclosure)
        Goldenrod (Request for Proposal Approval and Submission)
        P.I. Exception Letter
   Budget
        Missing Budget
        Investigator Approval of the Budget
K 30 Feb 2011
Top Reasons for Delays in Contract
           Execution:
   Incorrect F&A Cost Rate (54% vs 26%)
   Study Type Not Correctly Identified
     (e.g. is it a clinical trial vs. research agreement)
   Missing IRB or other Approvals
   Late CIRC Review & Approval
   Missing Signatures


K 30 Feb 2011
       After IRB approval and before
          contract execution: Trial
                Registration
   Law 110-85 ( http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-014.html
    was enacted on September 27, 2007 to expand the scope of clinical trials that must
    be registered at www.clinicaltrials.gov.
   Registration is not limited to “industry-funded” trials only, but applies to studies
    regardless of sponsorship (including those with no external support)

   The definition of an applicable clinical trial is based on the Public Law definition and
    not the UCLA definition of a clinical trial. Clinical trials (regardless of sponsorship)
    that must be registered generally include: (1) Trials of Drugs and
    Biologics: Controlled, clinical investigations, other than Phase 1 investigations, of a
    product subject to FDA regulation; and (2) Trials of Devices: Controlled trials with
    health outcomes, other than small feasibility studies, and pediatric postmarket
    surveillance.

   Note: For PI-initiated studies (regardless of sponsorship), the PI has the
    primary responsibility for assuring trial registration. Click here to download
    key information about the requirements.




K 30 Feb 2011
              After IRB approval and
               contract execution…
        Running the study
               Subject recruitment and screening
                    How; where do you find the subjects?
               Study visits
                    Where are study visits conducted?
               Data management
                    Who will maintain required documentation?
               Regulatory compliance
                    On-going communication with IRB and ARC
                          Amendments, continuation review
                          Adverse event reporting
               Financial Management
                    Set up accounts, monitor expenditures, invoice sponsor


K 30 Feb 2011
   Study Begins!



K 30 Feb 2011

				
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