EXCEPTION FROM INFORMED CONSENT IN CPR DEVICE TRIALS: PROTECTION OF PATIENTS

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EXCEPTION FROM INFORMED CONSENT IN CPR DEVICE
TRIALS PROTECTION OF PATIENTS RIGHTS

• Circulatory System Devices Panel
  Meeting
• September 21, 2004
• Elisa D. Harvey, D.V.M., Ph.D.
• Acting Director, IDE Program
• FDA Office of Device Evaluation

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BACKGROUND

• Informed consent is a fundamental element of
  human subject research protection in clinical
  research
• Declaration of Helsinki
• Belmont Report
• Consent by legally authorized representative
  (proxy) long accepted for research populations
  incapable of providing informed consent
  (e.g., pediatric population, cognitively
  impaired)
• Prior to 1996, NO provision in regulations for
  ANY exception from informed consent requirement
  (individual or by proxy)

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EMERGENCY SITUATIONS

• Medical intervention may be urgently needed in
  situations where individual is unconscious or
  otherwise unable to provide consent HOWEVER,
• Urgency of situation may preclude obtaining
  consent by proxy
• This kind of research is urgently needed

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1996 NEW FDA REGULATION

• Addressed need to permit exception from informed
  consent requirement in specific situations
• Recognized need for additional protection of
  patients rights when research undertaken with
  consent waived
• Regulation developed with substantial input from
  medical community
• Open meetings
• Comment on draft regulation published 1995

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21 CFR 50.24

• Identifies criteria for studies that may be
  conducted with exception from informed consent
• Establishes requirements for study conduct
• Specifies additional steps sponsors must take to
  assure patient protection

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CRITERIA FOR CONDUCTING STUDIES WITH EXCEPTION
FROM INFORMED CONSENT

• Subjects are in life-threatening situation
• Available treatments are unproven and/or
  unsatisfactory
• Participation in study holds prospect of direct
  benefit to patients
• Study could not feasibly be conducted without
  exception from informed consent requirement

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FEASIBILITY

• Too few patients who would be able to provide
  consent, or who would have acceptable proxy
  available to provide consent within reasonable
  time interval
• Not possible to prospectively identify population
  from which study patients would likely be drawn

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STUDY CONDUCT

• Investigators must make every attempt to obtain
  consent from legally authorized representative
  within specified time interval before proceeding
  to enter patient in study
• Investigators must inform patient and/or
  representative about study as soon as possible

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ADDITIONAL PROTECTIONS

• Separate IDE must be submitted to and approved
  by FDA for such studies
• IRB(s) must consult with communities where study
  would be conducted
• Study must be publicly disclosed to these
  communities prior to initiation, and results
  publicly disclosed when study completed
• Study must be overseen by an independent
  data safety monitoring board (DSMB)
• IRBs for study sites must be notified of concerns
  raised by IRBs of other participating sites

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FDA GUIDANCE DOCUMENT

• Draft guidance issued in 2000
• http//www.fda.gov/ora/compliance_ref/bimo/err_gu
  ide.htm
• Attempts to clarify requirements
• Informed by initial experiences conducted under
  21 CFR 50.24
• Public comments on draft identified need for
  further clarifications
• Revisions to guidance are underway

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EXPERIENCE

• Studies have been conducted since 1996 with
  exception to informed consent requirement
• Public Access Defibrillation (PAD) Trial
  (2004 NEJM 3517 637-646)
• Some investigators have described their
  approaches to the regulatory requirements in
  detail
• Such reports helpful in developing more informed
  consensus regarding optimal approaches for these
  studies

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CURRENT STATUS

• Draft guidance being revised to incorporate
  public comments, provide clarification on some
  points
• Past experience should facilitate increased
  efficiency in future investigations done under
  this regulation
• Sponsors, investigators, IRBs and FDA reviewers
  are all still in learning mode with regard to
  best practices

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Questions?

• elisa.harvey_at_fda.hhs.gov
• OR
• edh_at_cdrh.fda.gov
• 301-594-1190 x 154