Ethical Foundation of Informed Consent
In the United States, federal regulations for protecting the rights, interests, and welfare of human subjects who participate in research are based on the Belmont Report, which articulates three ethical principles that always warrant consideration in research:
- Respect for persons
- Individuals should be treated as autonomous agents
- Those with diminished autonomy are entitled to protection
- Obligation to do no harm
- Maximize possible benefits and minimize possible harm
- The benefits and burdens of research are distributed fairly
The Belmont Report lists 3 important components of informed consent:
Information. The consent process should include information about the research procedure, the purpose of the research, risks and anticipated benefits, alternative procedures and a statement offering the subject the opportunity to ask questions and to withdraw at any time from the research.
Comprehension. The information should be conveyed in a manner and context that promotes understanding of the information.
Voluntariness. Consent is valid only if it is voluntarily given.
Current Regulatory Requirements (for Whom, When, What to Disclose)
The current regulatory requirements are based on the Common Rule, which applies to most federally funded research (or research conducted in federally funded institutions that elect to follow these rules for all research conducted within their institution; see list of the departments and agencies that adhere to the Common Rule). The Common Rule defines research as “a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.” §46.012 The rule outlines the basic requirements for Institutional Review Boards (IRBs), including provisions related to obtaining and documenting informed consent.
According to 45 CFR 46 section .116 (General requirements for consent), an investigator must obtain legally effective informed consent to involve a human being as a subject in research so that the prospective subject can be given sufficient opportunity to decide whether or not to participate. Under certain circumstances, an IRB may approve a consent procedure which alters or waives the requirements for informed consent, and this is described in more detail in Sections 3: Alternative Approaches to Disclosure and Authorization.
The Common Rule defines a human research subject as “a living individual about whom an investigator (whether professional or student) conducting research obtains
(1) Data through intervention or interaction with the individual, or
(2) Identifiable private information.” §46.012
Future Regulatory Requirements
On January 19, 2017, the Department of Health and Human Services (DHHS) and 15 other agencies published revisions to the Common Rule, and some of the most significant changes are aimed at enhancing the informed consent process for research (Sugarman 2017).
The original compliance date for most of the provisions of this rule was January 19, 2018, but on January 17, 2018, the Interim Final Rule announced a delay until July 19, 2018, with the option for further delay, to give institutions additional time to prepare to implement the revisions. Before July 19, 2018, institutions may only begin implementing provisions of the revised Common Rule that do not conflict with the pre-2018 Common Rule. The compliance date for cooperative research (and use of a central or single IRB) has not changed and is still January 20, 2020.
A notice of proposed rulemaking (NPRM) is also in development to seek public comment on a proposal for further delay in the required implementation of the revised Common Rule (for example, until January 21, 2019). A decision will be made after considering public comments.
If the proposed changes to the Common Rule go into effect, the definition of human subject will change:
Human subject “means a living individual about whom an investigator (whether professional or student) conducting research: (i) Obtains information or Biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or (ii) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.” §__.102.e
The rule includes new requirements regarding the information that must be given to patients as part of the informed consent process:
- The rule specifies that the informed consent process must begin with a summary of the main reasons why a person might or might not want to participate in the research.
- It must start with “a concise and focused presentation of the key information that is most likely to assist a prospective subject or legally authorized representative in understanding the reasons why one might or might not want to participate in the research.” This part of the informed consent must be organized and presented in a way that facilitates comprehension.” §__.116.a.5.i
- Key information that is most important to the subject and likely to help a patient (or legal representative) make a decision about participation must be provided. The approach should emphasize the fostering of overall understanding and comprehension
- “Informed consent as a whole must present information in sufficient detail relating to the research, and must be organized and presented in a way that does not merely provide lists of isolated facts, but rather facilitates the prospective subject’s or legally authorized representative’s understanding of the reasons why one might or might not want to participate.” §__.116.a.5.i
- The prospective participant should also be provided with an opportunity to discuss the information
There are also additional disclosure requirements including some for research that involves the collection of identifiable private information or identifiable biospecimens. There must be either be
- A statement that identifiers might be removed so the information or biospecimens could be used for future research, OR
- A statement that, even if identifiers are removed, the information or biospecimens will not be used or distributed for future research studies. §__.116.b.9
To facilitate transparency, at least one IRB-approved version of the consent form for a given clinical trial must be posted on the Federal Website “after the trial is closed to recruitment and no later than 60 days after the last study visit by any subject.” §__.116.h
- Introduction Consent, Disclosure, and Non-disclosure
- Informed Consent
- Alternative Approaches to Disclosure and Authorization
- Non-disclosure of Research Activities
- Data on Different Approaches to Disclosure
- Appendix: US Regulatory Agencies
- Appendix: Regulatory Frameworks
- Appendix: Institutional Regulatory Oversight
- Appendix: Emerging Regulatory Issues
Proposed revisions to the Common Rule.
For a detailed information on the theoretical and regulatory foundations of informed conset, what should be disclosed as part of the consent process, and a discussion of the controversies that arose with consent and the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial (SUPPORT; ClincalTrials.gov #NCT00233324) see the white paper: Informed Consent.