IRB Review of

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IRB Review of Studies Involving IND/IDEs
Michael Linke, PhD Chair, UC Medical IRBs
University of Cincinnati
Human Research Protection Program Institutional
Review Boards
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Learning Objectives

• Describe the role of the IRB in review of
  protocols involving IND/IDEs
• Specify the information and materials that the
  IRB requires to conduct its review of protocols
  involving IND/IDEs
• Discuss the distinction between therapy and
  research in protocols involving IND/IDEs

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Human Research Protection Program Policy Number
III.08 Review of the use of Investigational
Agents in Human Subjects Research
It is the policy of the University of Cincinnati
that the use of Investigational Agents be
reviewed and approved for use in accordance with
Federal Regulations
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• In order for an investigational drug, agent,
  biologic or device to be used in clinical
  research at UC, an Investigational New Drug (IND)
  or Investigational Device Exemption (IDE) must be
  on file with the FDA and an IND number granted
  when required by Federal Regulations.

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• Exemption from IND requirements
• investigation of a drug or biologic that is
  lawfully marketed and
• (i) 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
• (ii) the drug is lawfully marketed as a
  prescription drug product and its proposed use
  is not intended to support a significant change
  in the advertising for the product
• (iii) 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
• (iv) it is conducted in compliance with the
  requirements for IRB review and informed
  consent21CFR parts 56 and 50, respectively
• (v) it is conducted in compliance with the
  requirements concerning the promotion and sale of
  drugs 21CFR312.7 and
• must not intend to invoke an exception from
  informed consent for emergency research
  21CFR50.24.

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When is an IND not required?

• Not intended to be reported to the FDA to
  support
• a new indication for use
• any other significant change in the labeling
• a significant change in the advertising for the
  product

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When is an IND not required?

• It does not involve a factor that significantly
• increases the risks
• decreases the acceptability of the risks
• route of administration
• dosage level
• subject population

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When is an IND not required?

• It is conducted in compliance with the
  requirements for
• IRB review 21 CFR parts 50
• informed consent 21 CFR part 56
• the promotion and sale of drugs 21 CFR 312.7.

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IRB Review of Exemption Requests Review to
determine whether they meet the exemption
criteria If the IRB determines that the
exemption criteria are not met investigator will
be asked to submit an IND or have the FDA make a
determination on the requirement for an IND.
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• IRB Regulatory Analysts will confirm that the
  submission is complete and accurate
• Required Forms
• Sponsor Statement FDA form 1571
• Investigator Statement FDA form 1572
• Document that the IND or IDE number is valid
• Sponsor-protocol or letter verifying the number
• Sponsor-Investigator studies, a letter from the
  FDA is required

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• IRB Regulatory Analysts will confirm that the
  submission is complete and accurate
• Review any other supplemental Information
• Investigators Brochure
• Grant
• Subject informational material

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• Protocol reviewed per
• UC Policy III.01 REVIEW BY THE INSTITUTIONAL
  REVIEW BOARD OF HUMAN SUBJECTS RESEARCH
• distinction between therapy and research is
  maintained
• make significant/non-significant device
  determinations

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IRB must ensure that the distinction between
therapy and research is maintained.

• "therapeutic misconception"
• the misconception that participating in
  research is the same as receiving individualised
  treatment from a physician.
• participants fail to appreciate that
• the aim of research is to obtain scientific
  knowledge
• any benefit to the subject is a by-product of
  that knowledge

Appelbaum PS, Roth L, Lidz CW. The therapeutic
misconception informed consent in psychiatric
research. Int J Law Psychiatry 1982531929
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• Distinction between therapy and research is
  maintained.
• Investigator must ensure that the participants
  understand that the investigational agent
• is experimental
• not been proven to be beneficial

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• Distinction between therapy and research is
  maintained.
• Investigator/Primary Care Physician
• recognize that the physician is fulfilling a dual
  role
• roles must be harmonized
• consider the need to inform the patient

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Information Sheet Guidance For IRBs, Clinical
Investigators, and Sponsors Significant Risk
and Nonsignificant Risk Medical Device Studies
U.S. Department of Health and Human Services
Food and Drug Administration Center for Devices
and Radiological Health (CDRH) January 2006
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Significant/Non-Significant Device Determinations

• Three types of device studies
• significant risk (SR) device studies
• non-significant risk (NSR) device studies
• exempt studies

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Significant/Non-Significant Device Determinations

• Significant Risk Devices
• present a potential for serious risk to the
  health, safety, or welfare of a participant
• implants
• supporting or sustaining human life
• diagnosing, curing, mitigating, or treating
  disease or otherwise preventing impairment of
  human health
• sutures, cardiac pacemakers, orthopedic implants

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Significant/Non-Significant Device Determinations

• IRBs do not have to make the determination if FDA
  has already made the risk determination.
• Review of before FDA approval
• FDA may not approve the IDE
• FDA may request significant changes to the
  research protocol
• the IRB may need to re-evaluate the study

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Significant/Non-Significant Device Determinations

• Non-significant risk determination
• the sponsors description
• does the proposed research study meet the
  definition of significant risk
• the proposed use of the device
• any protocol related procedures and tests
• additional information from the sponsor
• most daily-wear contact lenses and lens
  solutions, ultrasonic dental scalers, and foley
  catheters

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• Non-significant risk determination
• If an IRB finds that an investigational medical
  device study poses a NSR, the sponsor does not
  need to submit an IDE to FDA before starting the
  study.
• If an IRB determines that an investigation,
  presented for approval under as a non-significant
  risk device involves a significant risk device,
  it notifies the investigator and, where
  appropriate, the Sponsor.

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• IDE Exempt Investigations
• a legally marketed device when used in accordance
  with its labeling
• a diagnostic device if it complies with the
  labeling requirements in 809.10(c) and if the
  testing
• is noninvasive
• does not require an invasive sampling procedure
  that presents significant risk
• does not introduce energy into a subject
• is not used as a diagnostic procedure without
  confirmation by another medically established
  diagnostic product or procedure

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• IDE Exempt Investigations
• consumer preference testing,
• testing of a modification/combination of devices
• legally marketed devices
• testing is not for the purpose of determining
  safety or effectiveness
• does not put subjects at risk

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• IDE Exempt Investigations
• a device intended solely for veterinary use
• a device shipped solely for research with
  laboratory animals and contains the labeling
  "CAUTION Device for investigational use in
  laboratory animals or other tests that do not
  involve human subjects."

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