Philippe R. Bauer, MD, PhD, FCCM; Judith A. Tate, PhD, RN
The Belmont Report, published in 1979, outlines the basic ethical principles for research with human subjects, which include respect for persons, beneficence, and justice.1 Respect for persons requires that subjects, to the degree that they are capable, be given the opportunity to choose what shall or shall not happen to them.1 This opportunity is provided when adequate standards for informed consent are satisfied.1 The consent process contains three elements: information, comprehension, and voluntariness.1 Obtaining informed consent for participation in research reinforces the ethical principle of autonomy by providing the opportunity for individuals to make a voluntary choice to participate. Informed consent is also a legal doctrine based on the Common Rule. The Common Rule, published in 1991, is a set of federal regulations for ethical conduct of research with human subjects.2 Title 45 CFR part 46 of the U.S. Department of Health and Human Services (HHS) regulations outlines the basic provisions for institutional review boards (IRBs), informed consent, and assurances of compliance.3
Controversy prevails over the nature and possibility of informed consent,1 especially in emergency situations. The HHS Office for Human Research Protections4 made clear that emergency medical care for patients may be provided without regard to IRB review and approval. It also required IRB review and approval prior to initiation of research involving human subjects; therefore, whenever emergency care is initiated without prior IRB review and approval, the patient may not be considered to be a research subject. Such emergency care may not be claimed as research, nor may the outcome of such care be included in any report of a research activity.4 It is, however, possible to waive the informed consent requirement when conducting research in an emergency setting. In 1996, the HHS secretary announced, under 45 CFR part 46.101(i), a waiver of the applicability of the regulatory requirement for obtaining and documenting informed consent for a strictly limited class of research; that is, research that may be carried out in human subjects who are in need of emergency therapy and for whom, because of the subjects’ medical condition and the unavailability of their legally authorized representatives, no legally effective informed consent can be obtained. This waiver applies to research involving adults or children but does not apply to research involving other vulnerable subjects.5
The Final Rule, or Revised Common Rule, published in 2017, implemented new steps to better protect human subjects involved in research while facilitating valuable research and reducing burden, delay, and ambiguity for investigators.6 The preamble of the Final Rule places the emphasis on life support and the best interests of the patient. Critical care researchers routinely reach out to surrogates to provide consent for study participation, even for studies carrying minimal risk, because critically ill patients are often sedated or confused or have difficulty vocalizing due to endotracheal intubation. These conditions prevent the patient from fully participating in informed consent because their impaired decisional capacity violates the elements of comprehension and voluntarism. When clinical research studies are timesensitive and the patient’s situation is life-threatening, the immediate unavailability of a surrogate may impede enrollment of patients into studies. In order to balance voluntarism with the potential benefits of a research intervention to the patient or to other patients, waivers of informed consent may be obtained to proceed with research in emergency situations, as outlined by HHS and the Food and Drug Administration (FDA) in the Final Rule.6 Implementing this waiver does not violate the principle of autonomy since the life-threatening event makes it difficult to determine the patient’s preferences.
Waiver of Informed Consent
IRBs may grant a waiver of informed consent for emergency research provided the study meets the following criteria7 :
- The participant has a life-threatening condition that necessitates the engagement of the experimental protocol.
- The participant has impaired decisional capacity.
- There is no time to obtain surrogate consent.
- Alternative treatments would not offer the participant any advantage and the research intervention offers a chance of benefit.
- Community consultation has been implemented
In order to facilitate emergency protocols, it is recommended that the interpretation of a life-threatening condition include any physiologic or anatomic derangement that could result in loss of life or serious disability.
The research protocol must define the timing of the potential therapeutic window during which the investigator should make any effort to reach the patient’s legally authorized representative or family member and document the attempt. An independent data and safety monitoring board should oversee the research. Consultation and public disclosure of the study plan, including risks and expected benefits, should be made with representatives of the community from which the subjects will be drawn. Opt-out mechanisms and procedures to inform the patient or the patient’s legally authorized representative or family member should be available, and every effort should be made to contact a family member and ask whether he/she objects to the patient’s participation in the study.
The IRB will review and approve study protocol, the informed consent procedure, consent documentation, procedure for determining any family objections and documenting those objections, and additional protection of the rights and welfare of the study subjects (community consultation activities, compliance with FDA regulations).
- U.S. Department of Health and Human Services. Office for Human Protections. Belmont Report. April 18, 1979. https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/read-the-belmont-report/index.html#xbasic. Accessed May 25, 2018.
- U.S. Department of Health and Human Services. Office for Human Protections. Federal Policy for the Protection of Human Subjects (‘Common Rule’). https://www.hhs.gov/ohrp/regulations-and-policy/regulations/common-rule/index.html. Content last reviewed March 18, 2016. Accessed May 25, 2018.
- U.S. Department of Health and Human Services. Office for Human Protections. Title 45 CFR Part 46. Protection of Human Subjects. https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html. Revised January 15, 2009. Effective July 14, 2009. Accessed May 25, 2018.
- U.S. Department of Health and Human Services. Office for Human Protections. Emergency Medical and Research: OPRR Letter (1991). https://www.hhs.gov/ohrp/regulations-and-policy/guidance/emergency-medical-care-and-research/index.html. Content last reviewed March 21, 2016. Accessed May 25, 2018.
- U.S. Department of Health and Human Services. Office for Human Protections. Informed Consent Requirement in Emergency Research (OPRR Letter, 1996). https://www.hhs.gov/ohrp/regulations-and-policy/guidance/emergency-research-informed-consent-requirements/index.html. Content last reviewed March 21, 2016. Accessed May 25, 2018.
- U.S. Department of Health and Human Services. Office for Human Protections. Revised Common Rule. https://www.hhs.gov/ohrp/regulations-and-policy/regulations/finalized-revisions-common-rule/index.html. Content last reviewed January 19, 2017. Accessed May 25, 2018.
- U.S. Department of Health and Human Services. Food and Drug Administration. Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors. Exception from Informed Consent Requirements for Emergency Research. https://www.fda.gov/downloads/Regulatoryinformation/Guidances/UCM249673.pdf. March 2011. Updated April 2013. Accessed May 25, 2018.