Why is informed consent required?
Several regulations and policies stipulate the information that must be given to research participants prior to their enrolling in a study.
The Big Picture:
- Informed consent is crucial in research as it ensures individuals have an informed choice about whether to participate in a research study.
- In the United States, the requirements for obtaining informed consent from research participants are stipulated by several regulations and policies.
- U.S. regulations may not require informed consent for all kinds of genomics research (e.g., if the samples or data are de-identified); however, there may be other policy or ethical reasons for conveying that such research might or will be done.
Why is informed consent important?
The origin of the modern regulations for informed consent in the U.S. date back to the 1930s, when Nazi physicians conducted horrific experiments on human subjects without their consent before and during WWII. After the war, from the Nuremberg Trials came the Nuremberg Code, a set of 10 ethical principles for physicians and researchers to follow when conducting experimentation on humans, one of which was informed consent. The egregious actions taken by the U.S. Government during the Tuskegee Syphilis Study from 1932-1972 without the consent of the men involved in the study led to the creation of National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research in 1974. Four years later, this commission published the Belmont Report, which laid out the essential need for informed consent in human research. In the 1980s, the U.S. Department of Health and Human Services (HHS) operationalized the findings of Belmont Report into a set of guidelines and principles for research and specific requirements for informed consent that we now refer to collectively as the “Common Rule.”
Informed consent demonstrates respect for personal autonomy (“Respect for Persons” in the Belmont Report) and is an important ethical requirement in research. The consent process clarifies to participants that research is distinct from clinical care, as the purpose is to benefit society rather than solely the individual. Even if consent is not legally required in a specific circumstance, researchers should consider what information is important to convey to ensure respect for participant autonomy.
Which U.S. regulations determine informed consent requirements?
With limited exceptions, the Common Rule (45 CFR 46) mandates that researchers obtain informed consent for federally funded research that involves "a living individual about whom an investigator (whether professional or student) conducting research:
- Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or
- Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens."
Food and Drug Administration (FDA) regulations also require informed consent for both private and federally funded clinical research involving drugs, biological products and devices. FDA regulations and requirements regarding informed consent align closely to the Common Rule regulations with a few differences, including specific situations under which consent may be waived. Some of these situations include research involving military personnel or data that would be identifiable only by linking it to the consent form. The FDA provides comparison chart between current FDA and HHS human subject protection regulations.
The Health Information Portability and Accountability Act (HIPAA) Privacy Rule mandates that individuals or organizations who meet the definition of a HIPAA ”covered entity” obtain patient/participant authorization to use or disclose individually identifiable health information for purposes other than clinical care or billing. Some human subjects research is conducted at institutions that are not subject to HIPAA (including federal labs), but portions of the HIPAA Privacy Rule may still apply. Researchers should check with institutional officials about their HIPAA requirements.
Are there instances where it might be appropriate to obtain informed consent even if regulations do not require it?
Not all research that involves human samples or data requires informed consent. According to the current definition of "human subject" in the Common Rule, informed consent is not required for use of samples and data that do not identify the person/donor (such as those stored in biobanks and data repositories for future research use) or for use of samples and data from people who are deceased.
While informed consent is not required by federal regulations for research with de-identified samples and data, it may still be appropriate to obtain consent for using the samples for certain purposes. In accordance with the NIH Genomic Data Sharing (GDS) policy, researchers who intend to use human-derived biospecimens or cell lines collected or created after January 25, 2015, to derive genomic data may only do so when the original informed consent processes for collecting the biospecimens explicitly discuss future research use and broad data sharing, even if the data will be generated from de-identified specimens. The NHGRI Informed Consent Resource also describes some special considerations for genomics research, which might also be helpful to convey during the informed consent process.
Additionally, HIPPA and the Common Rule permit research on information from deceased individuals who did not provide consent before death. However, under the Privacy Rule a legally defined personal representative must authorize disclosure of individual health information, including individual research results.
It is ethically appropriate to continue to respect any known preferences of a research participant (e.g., as articulated in an advance directive) and/or conditions that were described in a consent form, even after that research participant has died. Researchers should consider:
- whether prior consent or consent from surrogates can and should be sought, even if they are not explicitly required by regulations.
- how the interests of participants and surviving relatives will be protected if informed consent cannot be obtained.
Also, in some cases, IRBs — the ethical oversight bodies for the research — can waive or alter the requirement for obtaining informed consent in research using samples and data from human subjects. IRBs can grant waivers when certain conditions are met, such as if the research poses minimal risks and if seeking consent is impractical. The HHS Office for Human Research Protections developed decision trees to help determine whether consent requirements may be waived.
What is the difference between “opt-in” and “opt-out” types of approaches?
Samples, genomic data and health information collected during routine clinical care are often stored and used for research, consistent with the current requirements of the Common Rule. Typically, research requires participants to actively choose to participate, or "opt-in" through a robust consent process. However, "opt-out" approaches assume a default of inclusion, in which people must actively decline to have their data and information stored or shared in order to not be included. In some opt-out structures, patients are given the option to decline to have their de-identified clinical samples used in research, though this is not required by regulations. Whether an opt-in consent process or an alternative opt-out process is used, the plans for future use and governance over research use of human clinical specimens should be transparent.
Last updated: January 3, 2022