Informed Consent Exception for Emergency Research

1
Informed Consent - Exception for Emergency
Research

• Bonnie M. Lee
• Associate Director for Human Subject Protection
  Policy
  
• Office for Good Clinical Practice
• Food and Drug Administration

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Informed Consent - Exception for Emergency
Research

• Briefly What are the regulatory requirements?
• Focus
• Community consultation requirements.
• What you can do
• What we can do

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Important Note

• FDA regulations do not allow IRB waiver of the
  consent requirement or altering of the consent
  procedure.
  
• FDA regulations provide an exception to informed
  consent for
  
• individuals in a life-threatening situation (21
  CFR 50.23)
  
• emergency research (21 CFR 50.24)

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Informed Consent - Exception for Emergency
Research

• 21 CFR 50.24, effective 11/1/96
• Narrow exception to requirement to obtain and
  document informed consent
  
• For a limited class of research involving
  subjects in need of emergency medical
  intervention, who cannot provide informed consent.

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Informed Consent - Exception for Emergency
Research

• Based on a Consensus Statement by the Coalition
  of Acute Resuscitation and Critical Care
  Researchers (JAMA, April 26, 1995)
  
• Needed because deferred consent does not equate
  to informed consent

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Criteria for IRB Approval

• Clinical equipoise (Experts question whether the
  relative benefits and risks of the research
  intervention are equivalent, or better than,
  standard therapy)
• Direct benefit (The intervention must be
  promising, and must hold out the prospect of
  direct benefit to the subjects)
  

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Criteria for IRB Approval

• Subjects are in a life-threatening situation
  requiring intervention
  
• Available treatments unproven or unsatisfactory
• Research is needed to determine safety and
  effectiveness of intervention under study

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Criteria for IRB Approval

• Informed consent is not feasible
• Subjects cannot consent due to their medical
  condition and
  
• Intervention must start before consent from a LAR
  is feasible and
  
• No reasonable way to identify likely subjects
  prospectively
  
• --21 CFR 50.24(a)(2)

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Criteria for IRB Approval

• Study participation holds out prospect of direct
  benefit to the subjects because
  
• Their life-threatening situation necessitates
  intervention
  
• Appropriate animal other preclinical studies
  have been done support the potential for direct
  benefit to the subjects and
  
• Risks are reasonable in relation to the subjects
  medical condition the risks and benefits of
  standard therapy and the proposed intervention.
  
• --21 CFR 50.24(a)(3)

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Criteria for IRB Approval

• The study could not practicably be done without
  the waiver.
  
• Waiver of consent is not appropriate when
• Time is sufficient to obtain LAR consent
• Most subjects have a LAR readily available
• Subject population can be identified, and
  prospective consent obtained, before a
  predictable, life-threatening emergency
  
• --21 CFR 50.24(a)(4)

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Criteria for IRB Approval

• The study plan includes
• A defined potential therapeutic window based on
  scientific evidence
  
• Commitment from the clinical investigator to
• Try to contact each subjects LAR within that
  window to get consent, or a family member who
  could object to subjects participation
  
• Summarize these contact efforts and report them
  back to the IRB at the time of continuing review
  
• --21 CFR 50.24(a)(5) (7)(v)

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Criteria for IRB Approval

• There must be
• Informed consent procedures, and
• An informed consent document to be used where
  feasible for subjects or legally authorized
  representatives, and
  
• Information to be used when providing an
  opportunity for a family member to object to the
  subjects participation in the study.
  
• --21 CFR 50.24(a)(6)

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Criteria for IRB Approval

• There must be procedures
• To inform, asap, each subject, LAR, or family
  member, as appropriate
  
• The details of the study after the subjects
  inclusion in the study
  
• Right to discontinue participation in the study
  without penalty or loss of benefits
  
• Must be disclosed in event of subjects death
• --21 CFR 50.24(b)

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Special Protections

• Independent data monitoring committee to exercise
  oversight of the investigation.
  
• Community consultation
• Public Disclosure to the communities before and
  after the study
  
• --21 CFR 50.24(a)(7)(i), (ii), (iv)

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Requests to Use the Rule

• In 6 years since it was effective
• Approx. 30 requests to use the rule
• Approx. 20 protocols allowed to proceed under the
  rule
  

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Common issues/deficiencies

• Study not appropriate for 50.24 exception
• No informed consent document or procedures
• No procedures for informing LAR or family member
  that subject was enrolled in study (in the event
  of the subjects death)
  
• Minimal or no plans for community consultation
• Minimal or no plans for public disclosure

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Common issues/deficiencies

• Failure to define the therapeutic window
• Independent Data Monitoring Committee

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Initial Community Consultation

• Who?
• Community where research will take place
• Community from which subjects will be drawn
• When? Prior to initiation of the study
• Why?
• Allows the community(ies) to discuss the research
  with the investigators, and to provide feedback
  to the IRB

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Public Disclosure

• Who?
• Same communities (plus research community)
• When and What?
• Before initiation of the study
• Study plans (not usually disclosed by sponsor)
• Informed consent wont be obtained from most
  subjects subjects
  
• After study is completed
• Comprehensive summary data sufficient to apprise
  the communities and researchers of the study
  results
  
• Demographic information about the research
  population

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Consultation Disclosure

• How much is enough?
• One town meeting?
• A legal notice in the local paper?
• Informing hospital staff?
• An ad with a phone number for the public to call
  for more information?

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Consultation

• Rule doesnt dictate how or what to do
• Communities differ N.Y.City v. village
• size, homogeneity of population, languages...
• Effective consultation
• Multifaceted
• Informative to IRBs and communities
• Continuing

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Consultation

• Need to determine the demographics of the
  potential subject population
  
• review demographics of patients previously
  treated for the condition under study
  
• Need to determine the demographics of the
  community in which the research will be conducted
  
  
• geographic region, e.g., city or region

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Consultation

• Go to Gatekeepers to groups to develop plan for
  consultation
  
• Elicit interest newspaper articles, talk shows,
  advertise meetings
  
• Address skepticism/special concerns
• Use existing (better attendance) v. special
  (folks with strong interest) meetings

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Consultation - 2-way Communication

• Inform community
• no informed consent for most subjects
• risks and potential benefits
• right to refuse and how to be excluded
• Community informs IRB
• support for, or concerns about, the research
  activity
  
• Exchange of Information

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Consultation

• IRB must hear/learn of concerns
• IRB may
• approve study or
• change study (e.g., limit enrollment) or
• decide it is inappropriate
• decide more consultation is needed

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Consultation

• Provides sunshine to the research enterprise
• It IS NOT intended to substitute for consent
  (i.e., the community does not vote yea or nay)

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What can you do?

• National EMS Research Agenda calls for
• evaluating current regulatory requirements
• identifying those that are impediments to EMS
  research
  
• then, develop EMS-specific consent strategies
• appropriate revisions to existing regulations

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What can you do?

• Model The Coalition of Acute Resuscitation and
  Critical Care Researchers
  
• evaluate current regulatory requirements
• identify impediments to EMS research
• develop EMS-specific consent strategies
• appropriate revisions to existing regulations
• Reach a consensus

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What can you do re consultation?

• If community consultation and community
  disclosure requirements are a particular
  concern
  
• develop a model for how such requirements ought
  to be fulfilled
  
• a model
• establishes a voluntary standard
• avoids recreating the wheel at each site

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What can you do re consultation?

• Use existing networks to enlist the public
• civic e.g. schools, churches, social clubs
• occupational e.g., businesses, professional
  organizations
  
• informational e.g., media, internet, libraries
• Incorporate public health messages
• how to lower risk of condition/disease

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What can you do re consultation?

• Nurture trust and confidence
• candor
• openness to media
• effective communication
• Consider a citizen advisory panel to plan outreach

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What is FDA doing?

• Developing guidance re informed consent in large
  scale public health emergencies
  
• when informed consent is required
• how to facilitate information dissemination,
  comprehension, voluntariness, and consent
  
• when informed consent is not required
• how the existing exceptions may be applied in
  this situation

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Our Goal

• Protect research subjects
• Improve EMS, patients survival and outcomes
• Not, to necessarily make doing the research easy