The IRB What Lies Ahead Your Questions, My Answers

1
The IRB - What Lies Ahead Your Questions, My
Answers
Wake Forest University School of
Medicine Research Administrators 1000 am
Thursday, September 6, 2001 Commons Conference
Room 3.

• Wesley Byerly, Pharm.D.
• Director, Institutional Review Board

2
New IRB OperationalPolicies and Procedures

• Effective September 1, 2001
• Copies are available on the IRB web page
• Expand on the general IRB Policy and Procedure
• Questions related to IRB policies and procedures
  should be directed to the IRB Office at 716-4542
• Web page updated
• membership list available for printing
• deadlines and meeting dates
• forms
• policy and procedures
• information and guidelines
• education

3
New IRB OperationalPolicies and Procedures

• Research Related Injury
• Provides standard language and guidance for
  investigators and sponsors on the provision of
  medical treatment and compensation for research
  related injury.
• Advertisements
• Describes required elements for advertisements.
• The BG number and the advertisement approval date
  must appear on all advertisements.
• An Advertisement Submission Form must accompany
  all advertisements.

4
New IRB OperationalPolicies and Procedures

• Adverse Event Reporting
• Provides operational detail for adverse event
  reporting.
• An Adverse Event Report Cover Sheet will be
  required for all adverse events submitted to the
  IRB.
• Amendments to Previously Approved Research
  Studies
• Additions, deletions and other changes to the
  informed consent document must be indicated by
  red lining.
• A rational supporting all additions, deletions or
  other changes to the informed consent, protocol,
  and other IRB approved study documents must be
  provided.
• A completed Amendment Request Form must accompany
  all requests for changes in previously approved
  research studies.

5
Hot Buttons in Human Subjects Protection

• Discrepancies between protocol and consent form
  regarding purpose, risk and/or benefits
• Children participating in non-therapeutic,
  greater than minimal risk research
• Auditing the IRB and the Research Process
• Need for an IND
• Collecting and Retaining Biological Material for
  Future Research
• Principal Investigator Leaving the Institution
• Use of Placebo
• Need for an adequate number of IRBs

6
Types of INDs

• "Commercial INDs" are applications that are
  submitted primarily by companies whose ultimate
  goal is to obtain marketing approval for a new
  product.
• Noncommercial INDs, filed for noncommercial
  research
• Investigator INDs
• submitted by a physician who both initiates and
  conducts an investigation, and under whose
  immediate direction the investigational drug is
  administered or dispensed
• may be for unapproved drug, or an approved
  product for a new indication or in a new patient
  population

7
Types of INDs (cont.)

• Emergency Use INDs
• allows the FDA to authorize use of an
  experimental drug in an emergency situation that
  does not allow time for submission of an IND in
  accordance with (21 CFR 312.23 or 312.34)
• Treatment INDs
• submitted for experimental drugs showing promise
  in clinical testing for serious or immediately
  life-threatening conditions while the final
  clinical work is conducted and the FDA review
  takes place
• "Compassionate" INDs
• Used to mean Emergency Use IND or Treatment IND
• "Compassionate" is not in the IND regulations.

8
When is an IND needed?

• A sponsor shall submit an IND to FDA if the
  sponsor intends to conduct a clinical
  investigation with an investigational new drug
• When the principal intent of the investigational
  use of a test article is to develop information
  about the product's SAFETY or EFFICACY,
  submission of an IND may be required.
• Investigational use suggests the use of an
  approved product in the context of a clinical
  study protocol
• The clinical investigation of a marketed drug or
  biologic does not require submission of an IND if
  certain conditions are met

9
An IND is NOT Required if

• (1) it is not intended to be reported to FDA in
  support of a new indication for use or to support
  any other significant change in the labeling for
  the drug
• (2) it is not intended to support a significant
  change in the advertising for the product
• (3) it does not involve a route of administration
  or dosage level, use in a subject population, or
  other factor that significantly increases the
  risks (or decreases the acceptability of the
  risks) associated with the use of the drug
  product

10
An IND is NOT Required if (cont.)

• (4) it is conducted in compliance with the
  requirements for IRB review and informed consent
  21 CFR parts 56 and 50, respectively
• (5) it is conducted in compliance with the
  requirements concerning the promotion and sale of
  drugs 21 CFR 312.7 and
• (6) it does not intend to invoke 21 CFR 50.24,
  Exception from informed consent requirements for
  emergency research.

11
Retaining Biological Specimens or Data for Future
Research Use

• Participation in therapeutic research can not be
  made contigent upon releasing biological
  specimens for future research.
• A separate consent form or NIH/NCI check box type
  option in the main consent form must be used.
• Obtaining biological specimens for future use
  (i.e. banking or developing a repository) must be
  supported by a protocol not just requested in the
  consent.
• The same concepts hold true for retaining data or
  developing a data repository for future research
  use

12
Retaining Biological Specimens or Data for Future
Research Use

• Where will the specimens be stored?
• Physical location of the repository
• Name of the responsibility individual
• Name of the oversighting IRB
• How will specimens be obtained and processed?
• How will specimens are distributed?
• Who decides?
• What is the application process?
• Who can access the specimens?
• How the secondary distribution of specimens will
  be controlled?
• What security measures will be used to protect
  the repository?

13
Retaining Biological Specimens or Data for Future
Research Use

• How will specimens be labeled? (anonyomus vs.
  subject identifier)
• Will clinical or identifying data be collected?
• What will be collected and how?
• How will it be associated with the specimen?
• What steps will be used to maximize the
  confidentiality of linked identifiers?
• If, in the future a subject request there
  specimen to be withdrawn and destroyed how will
  this be done and documented?
• Assurance that specimens will not be released
  without IRB approval for each individual project
• Assurance that the oversighting IRB has auditing
  capability

14
An Algorithm for IRB Evaluation of Studies That
Involve Placebo

• Is placebo being used in place of standard
  therapy?
• Is standard treatment considered to be effective?
• Is the toxicity of standard therapy such that
  patients routinely refuse treatment?
• Could the use of placebo instead of standard
  treatment cause irreversible health problems of
  extreme suffering?
• Is it possible to predict the placebo response
  rate in this study with a reasonable degree of
  accuracy?
• Could this trial benefit future subjects to the
  point that a reasonable person with an average
  degree of altruism and risk-aversiveness would
  consent to being randomized in this trial?
• RJ Amdur. An algorithm for evaluating the ethics
  of placebo-controlled clinical trials. Presented
  at ARENA Conference, IRBs New Directions in
  2000. Oct. 31, 2000. San Diego, CA

15
Responsibility for Protocols Remaining Open
following the Departure of the PI from the
Institution

• When an individual leaves the institution, the
  IRB considers that individual's Department
  Chairman, Section Head or equivalent person
  responsible for reassigning or closing all the
  departing individuals open protocols.
• Closing an open protocol must be done in a manner
  that ensures the rights, welfare and safety of
  all subjects still participating in the research
  study
• Until a protocol is reassigned or closed the
  Department Chairman, Section Head or equivalent
  person responsible for
• the conduct of all ongoing research studies
• the protection of the rights, welfare and safety
  of consented research participants
• Department Head or similar individual for the
  Hospital - i.e. the person who signed off on the
  protocol review form.

16
Multiple WFUSM IRBs

• A Draft Proposal
• Four IRBs
• Meet four times per month
• Each able to review most types of research
• Exceptions
• Research involving children
• Oncology
• Research involving persons with a diminished
  capacity to consent
• Social Medicine
• Some triage by the IRB Office

17
What Else Is Ahead?

• Revised Protocol Review Form
• Revised Informed Consent Template
• Standardized Continuing Review Submission
• FWA
• Changes in required human subjects education
• Stay Tuned!