Required Elements of the Consent Form

Regulations require "a statement that the study involves research, an explanation of the purposes of the research..." - 45 CFR 46.116

Potential participants should be given a succinct explanation that the proposed study involves research, why they have been approached about participation, and who is sponsoring the project. This section should include topics such as a brief description of the underlying genomic science, the study design, the diseases(s) or condition(s) being studied, and the immediate and long-term goals of the study.

Regulations require information about "the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental." - 45 CFR 46.116

When appropriate, the following are also required: "the approximate number of subjects involved in the study" and "anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent" - 45 CFR 46.116

Potential participants should be given information about what they will experience as research participants. The description should cover topics such as:

• The process for the collection of samples (blood or other tissue) and health information.

• Whether researchers will have access to a research participant's medical records and, if so, who and through what process (e.g., one-time versus ongoing collection of information from medical records).

• What DNA sequence or other experimental data will be generated.

• Information related to storing, sharing, and future use of data and samples (see Confidentiality (including privacy and identifiability), and Data and Sample Sharing Through Data Repositories and Biobanks for discussion and sample language).

• What the plans are for dissemination of summary-level research results and possible return of individual research results (see Return of Results to Participants).
   

Regulations require "a description of any reasonably foreseeable risks or discomforts to the subject." - 45 CFR 46.116 

When appropriate, regulations also require "a statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable." - 45 CFR 46.116

Research participants need to be informed of the risks associated with genomics research, including of course risks related to projects in which large amounts of genomic data and health information may be collected, stored, and broadly shared with other investigators. Discussing the likelihood of the risks in the context of the particular study, as well as their potential severity, may help research participants better understand the nature of the various risks. However, it is also important that researchers not overstate the risks when there is little or no evidence that they actually occur or cause harm. Researchers should describe the measures they are taking to reduce risks and the protections from risk that are in place. Discussion of risks should be balanced with discussion of the potential benefits of research participation, which are described in the section Potential benefits.

Potential risks may arise from:

• Physical exposures during the course of the study, such as collecting blood or other tissue samples. In clinical trials guided by genetic information, additional risks could arise from interventions that are different from standard of care. Physical risks are minimal for most genomics research.
   
• Psychological or social risks could occur through receiving information that is unexpected or unwanted by the participant. If results are to be returned, the uncertainty of findings, and personal and sensitive information about disease and disability risk, paternity, or ancestry may be difficult for participants to understand and may sometimes be upsetting to participants.
   
• Privacy breaches due to possible re-identification or other losses of confidentiality.
   
• Unauthorized use of data due to computer security breaches or other unanticipated distributions.
   
• Information about participants in some cases might extend to relatives or identifiable populations or groups, the latter of which could contribute to potential discrimination or stigmatization. (See Considerations for Families and Considerations for Identifiable Populations for more information on how genomics research affects families and communities).
   

Protections from risks:

• The Common Rule regulations, the Office of Human Research Protections (OHRP), institutional human research protection programs, database or biobank governance policies, and Institutional Review Boards all serve to protect research participants from foreseeable risks. Study-specific protections should be articulated through the informed consent process and in the consent form. For specific discussion regarding protection from privacy risks, see the section on Confidentiality (including privacy and identifiability)
   

Regulations require "a description of any benefits to the subject or to others, which may reasonably be expected from the research." - 45 CFR 46.116

Potential benefits of the research findings to participants and society should be described in the consent form and informed consent process. Participants may or may not receive any direct benefits as a result of participating in research. A direct benefit is generally viewed as a benefit gained from an intervention that is being tested in the research that has the prospect of being an effective treatment or informing treatment selection. However, the primary purpose of research is to provide benefits to society by advancing science or contributing to advances in health, so the social value of the research should be discussed in consent forms as an indirect benefit. Other indirect benefits to individuals that are part of study procedures may include the opportunity to receive specialized care or genetic counseling, and learning about their genomes (though the amount and type of results that participants might receive is often unpredictable).

Compensation for participation, if any, should be addressed in a different section.

"A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject." - 45 CFR 46.116

Regulations require "a statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained." - 45 CFR 46.116

Sharing individual and even summary-level genomic data carries some degree of privacy risk to study participants. When data will be shared, researchers should explain how privacy and confidentiality will be protected. See Data and Sample Sharing through Data Repositories and Biobanks for additional information.

A primary privacy concern in genomics research is re-identification. Researchers have shown that subjects can be re-identified by combining de-identified genomic information with other information types that are publicly available, and that individual subjects sometimes can be distinguished even in summary-level genomic data. Current federal regulations do not classify genomic information as "identifiable."

Data repositories may protect against the possibility of re-identification by controlling access to the data and requiring data users to agree not to attempt to re-identify research participants. However, it is not possible to eliminate completely the risk of re-identification. Researchers should explain this risk to participants' privacy and confidentiality and note whether there may be related unanticipated risks in the future.

Legal Protections:

• Researchers may wish to include information in the informed consent process about legal protections for participants' genomic data, including protection against genetic discrimination.
   
• At the federal level, the Genetic Information and Nondiscrimination Act of 2008 (GINA) prohibits the use of genetic information, including family history, for most health insurance and employment purposes. Some states have additional protections against discrimination for other types of insurance (life insurance, disability insurance, or long-term care insurance). GINA's insurance protections do not apply to some Federal programs (though these programs may have internal policies that prohibit or minimize genetic discrimination). Information on GINA is available at the NHGRI website, and OHRP has published GINA guidance for investigators and Institutional Review Boards (IRB).
   
• In addition, the Affordable Care Act of 2010 (ACA) prohibits insurers from refusing coverage to patients or altering their premiums because they have "pre-existing conditions," including genetic diagnoses. The Congressional Research Service has published a report on the complementarity of GINA and ACA, each of which offers some distinct protections against genetic discrimination for health insurance and employment purposes.
   
• Certificates of Confidentiality (CoCs) are another mechanism to promote data confidentiality protection by prohibiting researchers from disclosing identifiable information about their research participants. As of October 2017, CoCs are automatically issued for all NIH-funded research continuing or beginning on or after December 13, 2016. These certificates apply in civil, criminal, administrative, legislative, or other proceedings, whether at the federal, state, or local level. However, certificates do not protect against other types of intentional or unintentional breaches of confidentiality. Non-federally funded investigators can also apply to obtain a CoC. NIH has compiled information for investigators, institutional officials, and IRB members who wish to apply for a CoC, including instructions on how to do so and what information about CoCs should be included in informed consent forms.
   

"For research involving more than minimal risk, an explanation as to whether any compensation or any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained." - 45 CFR 46.116

"An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject." - 45 CFR 46.116

Regulations require "a statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled." - 45 CFR 46.116

In some instances, a research study may contain genomic analyses as one component of a broader research study. Depending on the nature of the research question, the genomics portion of a study may be essential or optional for individual participants. Regardless, the choice to enroll in a study is still voluntary.

Regulations require:

One of the following statements about any research that involves the collection of identifiable private information or identifiable biospecimens: (i) A statement that identifiers might be removed from the identifiable private information or identifiable biospecimens and that, after such removal, the information or biospecimens could be used for future research studies or distributed to another investigator for future research studies without additional informed consent from the subject or the legally authorized representative, if this might be a possibility; or (ii) A statement that the subject’s information or biospecimens collected as part of the research, even if identifiers are removed, will not be used or distributed for future research studies. (45 CFR 46.116)

When collecting identifiable data or biospecimens, researchers should explain whether the data will be de-identified and shared for future research uses without additional informed consent.

Regulations require describing "any additional costs to the subject that may result from participation in the research." - 45 CFR 46.116

Any compensation, including reimbursement, that will be provided to participants or expenses that might be incurred by participants as a result of their involvement in research should be clearly explained in the informed consent process. Financial reimbursement for participation in research is common, as are modest financial incentives, but researchers and IRBs should consider the risk of undue influence of such compensation on research participation. Participants should be told whether there may be any future commercial use of their samples or genomic data, or production and distribution of derivatives, like cell lines, and that it is unlikely that participants will receive any future profits if the research results in products that are eventually developed and sold for commercial purposes. Possible commercial uses of samples and data may include: distribution of cell lines derived from tissue samples (possibly for the study of a specific genetic disorder), or the commercial development of genetic tests or algorithms based on genetic information of people affected by a genetic disorder. It is fine to state that compensation will not be provided, but it is important not to state that participants have rights to compensation that they must waive, which is known as "exculpatory language." See examples of prohibited exculpatory language and acceptable language.

"The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject" - 45 CFR 46.116

"A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject" - 45 CFR 46.116

Participants have the right to withdraw from a research study at any time. The ability of research participants to discontinue their involvement in research is an important mechanism for ensuring the voluntariness of participation and respecting participant autonomy throughout the conduct of ongoing research. However, as in other research contexts, there are likely to be practical limits on the ability of participants to withdraw samples, genomic data, or health information that have been contributed to genomics research. The potential limitations and consequences of withdrawing samples and data from research should be discussed in the consent form and as part of the consent process.

For genomic studies that involve biobanked samples or storage of individual-level genomic, demographic, or health data in unrestricted or controlled-access databases, complete withdrawal of samples and data may not be possible once samples or data have been distributed to other laboratories. However, it may be possible to withdraw samples or data from future distributions. In such circumstances, the consent form and the informed consent process should include a full explanation of the extent to which withdrawal of samples or data is possible or not possible and what the process is.

OHRP and the FDA have both provided guidance related to withdrawal from research. Guidance from both agencies states that investigators are permitted to retain and analyze already collected data relating to any participant who chooses to withdraw from further participation in a research study, provided such analysis falls within the scope of the analysis described in the IRB-approved protocol. The FDA guidance also states that destruction of samples that have already been collected is not required if a participant withdraws from a study, so the samples could continue to be used, but no further sample collection would be allowed. However, institutional policies may differ and individual IRBs might require plans to destroy samples — or at least to offer choices about the disposition of samples — when participants withdraw from research. This issue should also be considered with regard to research involving certain populations that may have cultural values and beliefs regarding samples or genomic data. In summary, it is essential that participants understand their right to withdraw, including what withdrawal would mean for samples and data that have already been distributed, and whether any samples or data will continue to be used for research.

If relevant, regulations require, “a statement that the subject’s biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit.”

Research participants should be informed about whether there may be any future commercial use of their biospecimens and about the potential that they will or will not receive financial benefit from these activities.

If relevant, regulations require, “a statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions.”

Regulations require that prospective participants be informed about whether clinically relevant research results will be provided. The NHGRI Special Considerations for Genomics Research page has more information on generating a plan for returning research results and incidental findings to participants.

For research involving biospecimens, regulations require informing participants “whether the research will (if known) or might include whole genome sequencing (i.e., sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen).”

Participants must be informed if their biospecimens will or might be used to generate whole genome sequencing data, which is defined to also include whole exome sequencing. It may be helpful to distinguish between different types of genetic testing that one might be familiar with and to describe the implications of large-scale sequencing.

The NIH Genomic Data Sharing (GDS) Policy also requires that NIH-funded investigators seek consent for “future research use and broad data sharing” when investigators generate large-scale genomic data. The NIH Guidance on Consent for Future Research Use and Broad Sharing of Human Genomic and Phenotypic Data Subject to the NIH Genomic Data Sharing Policy outlines the elements of consent that are important to capture when describing the sharing of large-scale genomic data via data repositories to participants (See Data and Sample Sharing Through Data Repositories and Biobanks for relevant sample language on genomic data sharing).