Ethics and the Emergency Exception from Informed Consent (EFIC)

1
Ethics and the Emergency Exception from Informed
Consent (EFIC)

• Arthur R. Derse, MD, JD, FACEP
• Director for Medical and Legal Affairs,
• and Associate Director
• Center for the Study of Bioethics
• Professor of Bioethics and Emergency Medicine
• Medical College of Wisconsin

2
Point(s) of View

• Ethics, Law and Emergency Medicine
• MCW emergency research ethics consultant
• Member of public community that benefits from
  emergency research

3
Consent for Research

• The voluntary consent of the human subject is
  absolutely essential.
• Nuremberg Code 1947
• Respect for persons
• And their autonomous choices
• Belmont Report 1979

4
Emergency Exception History (1)

• 1981 Common Rule
• No exceptions for emergencies
• Emergency research finessed through
• Waived consent - by IRBs
• Deferred consent
• - ask patient or surrogate afterward
• Ignoring consent requirement

5
Emergency Exception History (2)

• 1993 FDA halts emergency research without
  informed consent (except minimum risk)
• 1995 Coalition Conference of Acute Resuscitation
  Researchers
• Proposed standard - Appropriate incremental
  risk
• Amount of increment in risk an IRB believes
  would be acceptable to potential patient, AND
• Studies should support a realistic possibility of
  a benefit over standard care
• Biros MH, Lewis RJ, Olson CM, Runge JW, Cummins
  RO, Fost N. Informed consent in emergency
  research. Consensus statement from the Coalition
  Conference of Acute Resuscitation and Critical
  Care Researchers. JAMA. 1952731283-1287.

6
Emergency Exception History (3)

• 1996 FDA HHS issue Exception From Informed
  Consent (EFIC)
• Life-threatening situation
• Available treatments are unproven or
  unsatisfactory
• Participation in the research holds out the
  prospect of direct benefit to the subjects
• The clinical investigation could not practicably
  be carried out without the waiver
• Requirements of community consultation and public
  disclosure
• FDA Final Rule 21 CFR 50.24

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For Research with EFIC

• Research Imperative
• Dire outcomes for emergent medical conditions
• Societal demand for benefit from improved
  emergency medical care
• No other way to improve patient care without
  emergency research with consent exception
• Contra a prospective opt-in directive for
  research
• But impractical
• Patients who wish to forgo research can refuse by
  using an opt-out bracelet or other refusal
  indication
• Patients and families want access to promising
  treatments for dire conditions
• E.g. surveys, HIV trials, Abigail Alliance
  (access to developmental cancer drugs and other
  drugs for serious life-threatening illnesses)
• Contra Therapeutic misconception - These are
  research trials, not uniform administration of
  promising therapy
• But these trials are based on preclinical studies
  potential for the intervention to provide a
  direct benefit to the individual subjects
• Future benefit of all patients potentially at risk

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Against Research with EFIC

• Rights of those who may not want to be research
  subjects should trump those who may
• Future benefit of patients at risk for the
  medical problem should not trump autonomy of
  current patients autonomy
• Let other societies make progress and learn from
  their experience
• Even if circumscribed, researchers will expand to
  other conditions
• "This just seems like lazy investigators not
  wanting to try to get informed consent in
  situations where it is difficult to get it, so
  they say it is impossible. I don't think we
  should use people like this.
• George J. Annas, Boston University bioethicist,
  commenting on Resuscitation Outcomes Consortium,
  quoted in Stein R. Critical Care Without Consent
  Ethicists Disagree On Experimenting During
  Crises. Washington Post Sunday, May 27, 2007 pA01

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Public Perception

• Surveys
• 70 of public, under some circumstances, would be
  wiling to participate in a study without giving
  consent
• McClure KB, Delorio NM, Gunnels MD, Ochsner MJ,
  Biros MH, Schmidt TA. Attitudes of emergency
  department patients and visitors regarding
  emergency exception from informed consent in
  resuscitation research, community consultation
  and public notification. Acad Emerg Med.
  200310352-359.
• Vs. UK- 84 Emergency research should start in
  the absence of consent but should be obtained as
  soon as possible from the nearest relative.
• Booth MG, Read E, Kinsella J. Public perception
  of emergency research a questionnaire. European
  J Anaesthesiology (2005), 22 933-937.
• Media
• Stein R. Critical Care Without Consent Ethicists
  Disagree On Experimenting During Crises.
  Washington Post Sunday, May 27, 2007 pA01
• Ostrom CM. You May Become Medical Guinea Pig
  Without Knowing It. Seattle Times. Jun. 3, 2007.

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Effect of EFIC on Research

• Human Cardiac Arrest Research Reports
• Absolute number decreased
• 1990-1993 46 vs. 1997-2000 13
• Hiller KM, Haukoos JS, Heard K, Tashki JS,
  Paradis NA. Impact of the Final Rule on the rate
  of clinical cardiac arrest research in the United
  States. Acad. Emerg Med. 2005121091-8.
• Cardiac Arrest Studies
• Absolute number arrest studies dec. 15 annually
  vs. no ? for a. fib
• Arrests cases, A. Fib controls 1992-2002
  57/197
• Conclusion Implication that rule restricted US
  trials
• Nichol G., Huszti E, Rokosh J, Dumbrell A,
  McGowan J, Becker L. Impact of informed consent
  requirements on cardiac arrest research in the
  United States exception from informed consent or
  from research. Resuscitation. 2004623-23.
• Cited, along with anecdotal reports, in, Mosseso
  Jr. VN, Cone DC. Using the exception from
  informed consent regulations in research. Acad.
  Emerg Med. 2005121040-1039.
• Exception may have changed the spectrum of
  research toward smaller numbers of trials needing
  greater resources
• McClure KB, Delorio NM, Gunnels MD, Ochsner MJ,
  Biros MH, Schmidt TA. Attitudes of emergency
  department patients and visitors regarding
  emergency exception from informed consent in
  resuscitation research, community consultation
  and public notification. Acad Emerg Med.
  200310352-359.

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Community Consultation

• Small number of published studies using EFIC
  required community consultation
• Scope and breadth wide, and effectiveness not
  adequately evaluated
• Baren JM, Biros MH. The research on community
  consultation an annotated bibliography. Acad.
  Emerg Med. 200714346-352.
• FDA Draft Guidance for IRBs Researchers on EFIC
  (8/29/06)
• Including Community Consultation definition,
  timing, content, type frequency, and roles of
  sponsor, investigator IRB
• MCWs share of experience

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Keeping the Exception from Undermining the Rule

• E.g. Controversy re Phase III RCT using
  Polymerized Human Hemoglobin - Pyridoxylated
  (PolyHeme) in hypotensive trauma
• Utilizing EFIC
• Pre-hospital phase - Polyheme vs. Saline
• In-hospital phase - Polyheme vs. Blood
• Question If in-hospital administration of blood
  is standard therapy,
• And has 75 efficacy in saving lives (i.e. 25
  mortality)
• Does the in-hospital portion of the trial
  comparing Polyheme to blood comport with the
  Federal requirement that current therapies be
  unproven or unsatisfactory?
• Derse AR. Emergency Research and Consent Keeping
  the Exception from Undermining the Rule. Am. J.
  Bioethics. 20066(3)36-37.
• Burton TM. Amid Alarm Bells, Blood Substitute
  Keeps Pumping. Wall Street Journal. Vol. 80 No. 6
  Feb. 22, 2006 pA1

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Proposals for EFIC Expansion

• Definition of life-threatening condition should
  be broadly interpreted to include serious
  disability as well as death
• E.g. disability from stroke
• Existing therapies should be considered
  unsatisfactory, even if partially effective,
  when
• serious risk of morbidity or mortality remains
  even with the best available treatment, or
• when the adverse effects of the best available
  treatments are serious
• AEM Consensus Conference on Ethical Conduct of
  Resuscitation Research Breakout Session
• Waters D, Sayre MR, Silbergleit R. Research
  conditions that qualify for emergency exception
  from informed consent. Acad. Emerg Med.
  2005121040-1044.

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An EFIC Tale

• PAD (Public Access Defibrillation) Trial
• CPR vs. CPR Publicly Accessible Automated
  External Defibrillators (AEDs)
• EFIC including community consultation
• Outcome Almost double survivors to discharge
  with CPRAED (vs. CPR)
• As a result, AEDs now commonplace in public
  settings
• Personal experience
• Oct. 2, 2007, Mitchell International Airport
• Effectiveness of AEDs in community setting could
  not have been evaluated without the EFIC

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Conclusions

• It is ethical under carefully circumscribed
  circumstances to conduct emergency research using
  an exception to the requirement for informed
  consent (EFIC)
• Some ethicists have concerns about current use
  and expansion
• Public perception is an important factor
• Researchers and IRBs should adhere to the letter
  and spirit of the regulations, including
  qualifying conditions for EFIC and requirements
  for community consultation and notification