Informed Consent Elements Tailored to Genomics Research
The main elements required by federal regulations to be included in a consent form for a research project involving human subjects (i.e. research participants) are listed below. Beneath each element is a discussion of relevant issues to consider in the context of genomics research and example language adapted from existing consent documents developed for various National Institutes of Health (NIH) sponsored research projects.
Genomics studies may involve prospectively collecting new samples and information or using previously collected samples and information. For genomics studies involving the use of previously collected samples and information, re-consent of research participants may be appropriate. Therefore, some of the example language below reflects language that could be used in re-consent forms (see section "Consent Form Examples and Model Consent Language" to view an example of a re-consent form for a genome-wide association study).
These considerations are intended to be complementary to requirements, regulations and guidance documents, including: 45 CFR 46 [access.gpo.gov], 21 CFR 50 [access.gpo.gov], 21 CFR 56 [access.gpo.gov], and other guidance from The Office for Human Research Protections [hhs.gov] and the Food and Drug Administration [fda.gov]
Note: When developing a consent form it is important to use simplified language that is not overly technical and takes into consideration the literacy level of potential research participants. Furthermore, potential participants should be given ample time to consider participating in a project so that they can develop informed questions as their understanding of the research project matures.
Purpose of Research Project
Potential participants should be given a succinct explanation of why they have been approached for the proposed study 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. Use of simplified language that is not overly technical may help potential participants understand the rationale for the study.
Description of the Research Procedures
It is important for potential participants to understand what they will experience as research participants. Dividing the research procedures into stages may make the information easier to understand. The description should cover topics such as:
- The process for the collection of samples (blood or other tissue) and health information.
- How samples and health information will be coded and stored.
- Whether there will be access to a research participant's medical records and, if so, the process for accessing them (e.g., one-time vs. ongoing collection of information from medical records).
- The duration of storage.
- Whether and how samples and health information will be shared with qualified investigators for appropriate research use both during the study period and after the study ends.
- A general description of the types of researchers who will have access to samples and data (e.g., academic, industry, government)
- Whether and how future contact (i.e. re-contact) is planned.
Sharing of data: One of the main factors that distinguishes genomic-related research studies from other studies involving human research participants is that they generate large datasets of genomic and health information that are increasingly being deposited in databases or larger data repositories for sharing with the broad biomedical research community. These databases and data repositories may be fully open or accessible only with the permission of a Data Access Committee (e.g. database of Genotypes and Phenotypes (dbGaP) ), depending on the nature of the data, local policies, and other factors.
Many of these datasets are useful beyond the particular aims of the study for which they were originally collected, especially as various diseases turn out to have mechanisms in common. Thus, the value of these data can increase when they are allowed to be shared with the broader research community and are not restricted in use to particular diseases or for a limited period of time.
This section should describe the mechanism(s) that will be used to store and share the data and should also indicate whether samples and genomic data will be shared with the broader research community both inside and outside the sponsoring institution.
Investigators should note that the NIH GWAS Policy (Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (GWAS) [grants.nih.gov]) states that "for prospective studies, in which GWAS are conceived within the study designs at the time research participants provide their consent, the NIH expects specific discussion within the informed consent process and documentation that participants' genotype and phenotype data will be shared for research purposes through the NIH GWAS data repository" (currently dbGaP [ncbi.nlm.nih.gov]).
Future Contact: This section should clearly outline the investigator's intentions for future contact with the research participant, if any, and how the investigator or other study staff will contact the research participant at a later date.
Financial Compensation, Costs and Commercialization
It is important to communicate to the potential research participant whether there will be any 1) financial compensation for taking part in the research project, 2) costs for taking part in the research project, and 3) compensation for a research-related injury.
Any proposed compensation should not be included in the "Benefits" section of the consent form.
It is possible that some of the genomics research conducted either by the primary investigator or secondary users could eventually lead to the development of new diagnostic tests, new drugs or other commercial products. The section should also indicate that if this should occur, there is no plan for research participants to receive any part of the profits generated from such products.
Potential Benefits of Participating in the Project
Potential benefits to the research participant and to others should be described in the consent form. It is important to include potential benefits for society, but investigators should be careful to distinguish between potential benefits to the individual research participant versus society.
Potential Risks of Participating in the Project
Research participants need to be informed of the risks in any research project, including genomics research projects where large amounts of genomic- and health-related data may be generated, stored, and broadly shared with other qualified investigators for appropriate use. The risks attached to genomics research and the extent to which we understand them need to be clearly articulated to research participants through the informed consent process. Discussing the likelihood of the risk as well as the severity of the risk may help research participants better understand the context of these kinds of risks. Possible risks may vary depending upon the study protocol, but as with most genomics research, the potential risks are centered on psychological and social risks for the research participant and, possibly, their family.
Examples include risks such as:
- Risks related to broad sharing of phenotype and genomic data (e.g. genotype, DNA sequence, expression profiles, etc.).
- Risks of the data sharing model for the study (e.g. the possibility that the coded 1 data may be released to members of the public, insurers, employers, and law enforcement agencies).
- Risks of receiving information that is unwanted by the participant.
- Risks of computer security breaches or other unanticipated distributions arising from maintaining data in an electronic format
- Risks to relatives or identifiable populations or groups.
- The uncertainty of findings related to genetic risk for a given disease or trait.
- Privacy risks, both those known and those unforeseen at this time.
- Any physical risks, such as those associated with collecting blood or other tissues samples.
Recently, federal legislation (The Genetic Information Nondiscrimination Act, or GINA) was passed that will provide baseline protection against discrimination in employment and health insurances decisions across the nation. President Bush signed the act into federal law on May 21, 2008. The parts of the law relating to health insurers will take effect by May 2009, and those relating to employers will take effect by November 2009. Please note that this federal protection may be eclipsed by more extended state privacy or discrimination laws, so it is important to clearly present the issues to consider in the context of where the research is being done.
OHRP has issued the Guidance on the Genetic Information Nondiscrimination Act: Implications for Investigators and Institutional Review Boards regarding consideration of GINA in the review of genetics protocols and informed consent forms.
For a list of frequently asked questions regarding GINA, please refer to the Department of Health and Human Services Information for Researchers and Health Care Professionals.
An individual's participation in a research study could have implications for his/her family members. When appropriate, researchers should try to include willing family members in the consent process through discussion and, if possible, educational materials.
Genome-wide association studies, genome sequencing projects, and related genomics research studies typically generate rich phenotypic and genomic datasets that are often deposited in controlled access databases for storage and wide-spread sharing with the research community. This presents special challenges to privacy and confidentiality protections. For a more detailed discussion of these challenges, see the Lowrance and Collins paper on identifiability in genomics research.2
It is important to address participants' concerns about protection of their identities against undesired intrusions (privacy) and about limiting the access to study information that might identify them (confidentiality). This section of the consent document should describe the level of confidentiality of the research data and the measures planned to ensure that confidentiality is maintained. Participants should know whether their samples will be anonymous/non-identifiable (i.e. personal identifiers will not be kept with their sample and the sample will not have a code number that can be used to identify the participant) or coded and considered de-identified (i.e. any identifying information such as name or SS# will be replaced with a code and only a few authorized people will have access to this code to link samples and data back to personal identifiers).
In special circumstances, such as for reportable conditions like HIV status and child abuse, absolute confidentiality may not be possible. If this or a similar possibility exists, then disclose the conditions under which information must be disclosed and to whom.
Certificates of Confidentiality are an important tool to protect the privacy of research study participants. The NIH encourages their appropriate use and has made information on their applicability and use available to investigators at the Certificates of Confidentiality Kiosk [grants.nih.gov].
Certificates of Confidentiality are issued by the NIH to protect identifiable research information from forced disclosure. They allow the investigator and others who have access to research records to refuse to disclose identifying information on research participants in any civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, or local level. Certificates of Confidentiality may be granted for studies collecting information that, if disclosed, could have adverse consequences for participants or damage their financial standing, employability, insurability, or reputation. By protecting researchers and institutions from being compelled to disclose information that would identify research participants, Certificates of Confidentiality help achieve the research objectives and promote participation in studies by assuring confidentiality to participants.
If a Certificate of Confidentiality is in effect, it should be reflected in the consent form. Participants should be given a fair and clear explanation of the protection that it affords, including the limitations and exceptions noted in the "Extent and Limitations of Coverage" section of Certificates of Confidentiality: Background Information [grants.nih.gov].
Returning Results to Research Participants
The return of individual research results to participants should be carefully considered because the information can have implications for the participant's health and well-being. This information might also increase participants' stress and anxiety. While clinically valid and meaningful results may have a positive impact on an individual's health, harm such as incorrect medical treatment or unnecessary anxiety might occur if research results without documented clinical relevance are provided back to participants or used for medical decision-making.3
Genomics research such as GWA and sequencing studies will find many associations between particular genetic loci and diseases. However, these initial findings will need much additional research before their clinical significance is understood and appropriate actions are determined.
The decision on whether to return research results to participants (either individual research results or general research findings through newsletters, study Web site, etc) should be made by the study investigator in consultation with his/her IRB. This decision, including the format and process for returning results, should be clearly communicated.
In some cases, applicable state or local laws may require the return of specific test results to participants (e.g., the diagnosis of particular communicable diseases). In such cases, a statement to this effect should be included in the consent form.
The National Heart Lung and Blood Institute (NHLBI) convened a Working Group on Reporting Genetic Results in Research studies to discuss if, when, and how genetic information should be reported to study participants. The conference report and recommendations for reporting genetic research results is a useful resource.4
In March 2008, a consensus statement based on an interdisciplinary workshop convened to develop research ethics recommendations for whole-genome research was published.5 Two recommendations address the return of results: (1) "Personal genome projects should have an established process approved by a research ethics committee for evaluating whether findings (incidental or otherwise) meet criteria for offering results to individual participants. This process should be highlighted in the initial consent and should acknowledge the participants' rights not to know certain results." (2) "The process of identifying and disclosing research results should involve professionals with the appropriate expertise required to provide the participant with sufficient interpretive information. In general, the results offered should be scientifically valid, confirmed, and should have significant implications for the subject's health and well-being. Plans to return other forms of data-such as significant non-health-related data-should be built into the study design and governance structure."
Participants have the right to withdraw from the study at any time and the implications and consequences of withdrawal should be discussed in this section of the form and as part of the overall consent process.
For certain genomic studies, complete withdrawal of samples and information may not be possible once samples have been distributed to laboratories and information has been posted for broad data sharing. In such circumstances, a full explanation of the inability to withdraw all samples/information should be provided.
If participant samples are being shared with other investigators and labs or there is the potential for sharing of these samples in the future, the consent form should clearly explain whether or not these samples can be destroyed and what the process will be.
For studies where individual-level genomic, demographic, and health data will be deposited in a public or controlled-access data repository for broad sharing with the research community, the consent form should reflect the data repository policy. For example, a data repository may allow submitting investigators and their institutions to request removal of data on individual participants from the data repository if a research participant withdraws consent. These participants' data can then be excluded from future distributions, but data that have already been distributed for approved research use will not be able to be retrieved.
Alternatives to Participating in the Project
As outlined in 45 CFR 46.116(a), the consent form needs to include a disclosure of appropriate alternative procedures or courses of treatment, if any, that might be available to the participant. For genomics studies this generally means that the individual may choose not to participate in the project.
As outlined in 45 CFR 46.116 (a), this section should convey that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the participant is otherwise entitled, and the participant may discontinue participation at any time without penalty or loss of benefits to which the participant is otherwise entitled.
This section should list whom the research participant should contact for 1) answers to pertinent questions about the research and research participants' rights and 2) in the event of a research-related injury.
Depending on the study population, the contact persons may need to be prepared to respond to research participants in other languages.
Return to Informed Consent for Genomics Research main page
1. Coded means that any identifying information (such as name or social security number) that would enable the investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain has been replaced with a number, letter, symbol or combination thereof (i.e., the code); and a key to the code exists, enabling linkage of the identifying information to the private information or specimens. From Guidance on Research Involving Coded Private Information or Biological Specimens [hhs.gov]
2. Lowrance, W.W. & Collins, F.S. Ethics. Identifiability in genomic research. Science, 317, 600-2. 2007. [PubMed]
3. Excerpted from the NIH Genome-Wide Association Studies Points to Consider for IRBs and Institutions [gds.nih.gov]
4. Bookman, E.B. et al. Reporting genetic results in research studies: summary and recommendations of an NHLBI working group. Am J Med Genet A, 140, 1033-40. 2006. [PubMed]
5. Caulfield, T. et al. Research ethics recommendations for whole-genome research: consensus statement. PLoS Biol, 6, e73. 2008. [PubMed]
Last Updated: March 18, 2014