Advances in genomic technology and analytical tools are enabling discoveries that enhance our understanding of the impact of genomic variants on health and disease. It is now possible to sequence an individual's whole exome or genome to identify variants associated with disease, investigate how genomic variants interact with environmental factors, and learn how genomic variation is distributed among populations. Increasingly, research participants' samples, genomic data, and associated health information are being stored and shared to maximize the benefit achieved through research.

Overview

Scientific research depends on the contributions of research participants. It is essential that the rights and interests of research participants (i.e., human subjects) who contribute samples and health-related information to these projects are respected throughout the research process.

The nature of genomic data requires that several specific considerations be kept in mind. In addition to being personal and unique to each individual, genomic data may, for example:

  • Be stored and used indefinitely.
  • Inform individuals about susceptibility to a broad range of conditions (some of which are unexpected given personal or family history).
  • Carry with them risks that are uncertain or unclear.
  • Be reinterpreted and change in relevance over time.
  • Raise privacy concerns (in part because of the risk of re-identification).
  • Be relevant for family members and reproductive decision-making.

In designing an effective informed consent process for genomics research, researchers should consider the information participants might need in order to understand risks and potential benefits of participating in the study, with attention to cultural context or other special circumstances of the participants (including language, literacy, and attitudes about consent and research participation). To ensure adequate protections for research participants, additional elements of the consent form may be required by state or local laws, biobanks and data repositories, or IRBs.

The informed consent process in most genomics research, as with any type of research, should be a dynamic interaction that focuses on information that researchers, IRBs, and participants themselves think would be most useful for participants as they decide whether or not to participate in a given study. Some concepts that arise in genomics research, such as results related to increased risk (but not diagnoses) or the long-term storage and use of data, can be particularly challenging to convey and may require additional time. Involving genetic counselors in the informed consent process may be useful (either communicating directly with potential subjects or as advisors on the consent process) because of the complexities of communicating the potential risks and benefits of genomics research; however, it may not be practical or necessary for many studies.

For some research, while informed consent is not required by federal regulations, it may still be appropriate. Institutions, IRBs, federal funding agencies, or other governance bodies may require or expect consent in some of these cases. In particular, NIH, under the NIH Genomic Data Sharing (GDS) policy, expects that researchers generating large-scale human genomic data use specimens or cell lines for which consent was obtained for future research purposes and broad sharing.

Why is informed consent required?

Informed consent shows respect for personal autonomy and is an important ethical requirement in research. Even if consent is not legally required in a specific circumstance, researchers should consider the best way to engage participants in order to respect their autonomy.

With limited exceptions, the Common Rule mandates that researchers obtain informed consent for federally funded research involving "a living individual about whom an investigator conducting research obtains data through direct intervention or interaction with the individual, or identifiable private information." Research funded by the United States Department of Health and Human Services (HHS) is also subject to the remaining portions of 45 CFR 46, which pertain to pregnant women, fetuses and neonates (Subpart B), prisoners (Subpart C), children (Subpart D) and Institutional Review Boards (IRBs) (Subpart E).

In addition, the Food and Drug Administration (FDA) regulations require informed consent for private and federally funded clinical research involving drugs, biological products, and devices. FDA regulations and requirements regarding informed consent closely align 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 involving data that would be identifiable only by linking data to the consent form. The FDA provides a comparison chart of the FDA and current HHS human subject protection regulations.

The Health Information Portability and Accountability Act (HIPAA) Privacy Rule mandates that researchers working within HIPAA 'covered entities' 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 there are portions of the Privacy Rule that may apply; to understand how the Privacy Rule might apply, researchers should check with institutional officials.

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 for use of de-identified samples and data (such as those that are often stored in biobanks and data repositories for unspecified future research use), or for stored samples and data from people who are deceased is not required.[1] Also, in some cases, the requirement for informed consent for research using samples and data from human subjects may be waived. IRBs can grant waivers when certain conditions are met, including that the research poses minimal risks or seeking consent is impractical. The HHS Office for Human Research Protections (OHRP) has developed useful decision trees for determining whether consent requirements may be waived.

For some research, while informed consent is not required by federal regulations, it may still be appropriate. Institutions, IRBs, federal funding agencies, or other governance bodies may require or expect consent in some of these cases. In particular, NIH, under the NIH Genomic Data Sharing (GDS) policy, expects that researchers generating large-scale human genomic data use specimens or cell lines for which consent was obtained for future research purposes and broad sharing.

Additionally, research on information from deceased individuals who did not provide consent before death is legally permissible under HIPAA and the Common Rule.[2] However, the Privacy Rule requires authorization by a legally defined personal representative for disclosure of individual health information, including individual research results. It is generally viewed as 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. It is important to consider whether prior consent or consent from surrogates can and should be sought, even if not explicitly required by regulations, and how the interests of participants and surviving relatives will be protected if informed consent cannot be obtained.

Often, samples, genomic data, and health information collected during routine clinical care are stored and used for research, consistent with the current requirements of the Common Rule. Typically, research requires participants to choose to participate actively ("opt-in"). However, "opt-out" approaches assume a default of inclusion, whereby people must actively decline in order to not be included. In some opt-out structures, patients are actively given the option to decline to have their de-identified clinical samples used in research, though this is not required by regulations. Education and notification serves to promote participant autonomy. Whether the consent process is opt-in or opt-out, the plans for future use, and governance over research use of clinical specimens should be transparent.

Before proceeding with your research, you should confirm the relevant expectations for informed consent with your local institutional review board.

The Informed Consent Process

Informed consent involves two fundamental components: a dialogue or process, and a form.

  • The informed consent process consists of interactions between a qualified member of the research team and the potential participant. This process provides research participants with information that will help them make voluntary, informed decisions about whether to begin or continue participating in a research project. The researcher and potential participants should discuss the study and the content of the consent form, and the researcher should answer any questions the participants may have. Informed consent is achieved through dynamic interactions and in some scenarios it may be an ongoing process, rather than a one-time informational session.
  • The consent form is a component of the informed consent process that provides a written summary of the research project (including the study's purpose, research procedures, potential risks and benefits, etc.) and explains the individual's rights as a research participant.

Advances in genome sequencing technology, evolution in our understanding of the genome, the increased power of data storage and sharing, and varying attitudes about genomic privacy necessitate a flexible approach to communicating with prospective participants during the informed consent process and within the consent form.

The informed consent process in most genomics research, as with any type of research, should be a dynamic interaction that focuses on information that researchers, IRBs, and participants themselves think would be most useful for participants as they decide whether or not to participate in a given study. Some concepts that arise in genomics research, such as results related to increased risk (but not diagnoses) or the long-term storage and use of data, can be particularly challenging to convey and may require additional time.

When developing an informed consent process and consent form, researchers should use language, videos, and/or other educational materials that take into consideration the literacy level (including genetic/scientific literacy), language, and cultural expectations of potential research participants. Ideally, written materials should use the simplest language that accurately describes the concepts, be as short as possible, and avoid being overly technical.[3] Readability calculators can be a good initial test of language complexity, and unfamiliar terms should be explained or defined.

Genomics research often requires large numbers of participants and participants who are geographically dispersed. In part to overcome the challenge of reaching many people across large distances, some or all of the informed consent process may be carried out remotely by phone, videoconference, or web-based methods.

Furthermore, potential participants should be given time to consider whether or not to participate in a project so that, as their understanding of the research project matures, they can develop informed questions. How much time participants will need to understand and consent to research participation will vary. What is essential is that participants understand that they do not have to make a decision immediately.

Comprehension is a critical component of informed consent and it could also be useful to include a plan for assessing minimum understanding as part of the consent process. For example, researchers could ask participants to explain the salient parts of the consent and correct any misconceptions, or researchers could define minimum comprehension thresholds and require that participants be able to adequately answer specific questions before obtaining consent.[4] For materials to support participant understanding in genomics research, see Educational Tools and Resources for Participants.

Large-Scale Genomic Data

Studies that include whole genome sequencing (WGS), whole exome sequencing (WES), epigenetic profiles, microbiotic profiles, and related forms of in-depth extra-genomic data generate immense amounts of personal information about participants. It is important to draw a distinction between targeted genetic research and broader sequencing protocols, so that participants understand the scope of data generation.

As with any study involving genetic or genomic analyses, the informed consent process for "whole genome" studies should inform participants of the following:

  • What might be learned from the data collection.
  • How the data will be stored and shared.
  • Whether participants will receive any individual results from current or future studies using their samples or data.
  • What would happen if they decide to stop participating in the study or after they are deceased.
  • The risks (including privacy risks and psychosocial risks) and potential benefits of generating large-scale genomic data.

These topics are covered in detail throughout this resource, and each topic includes sample language that can be used and modified for the consent process. It should be noted that wherever the term "genomic data" is used, the considerations discussed apply to any genomics research, including whole genome analyses.

The following considerations are not comprehensive but are intended to be complementary to federal and institutional requirements, regulations, and guidance documents. For research that includes international sites, consent forms may be subject to additional regulatory guidelines and may need to be approved by multiple IRBs. Study investigators can include additional information in the consent form beyond what is required by federal regulations.

Last updated: January 8, 2018