This section discusses basic elements of informed consent that are required by the Common Rule (45 CFR 46, Subpart A) and that are relevant to genomics. It also provides sample language that can be used as a guide when crafting informed consent forms.
The required elements for the consent form are:
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.
The choice to participate in this research by contributing your samples, genomic data and health information is completely up to you. No matter what you decide to do, your decision will not affect the medical care or benefits to which you are otherwise entitled.
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.
You are invited to take part in a research study by [insert researcher and institution]. This study is part of [insert consortium or initiative if applicable] and is sponsored by the [insert funder]. [Institution] is one of many institutions involved in this project.
You can learn more about the [initiative], including major findings resulting from this research, on the project website, [insert URL].
Why is this research study being done?
We are asking for your permission to collect samples and health information from you for a research study on [specific topic].
[OR] We are asking for your permission to collect samples and health information to be stored in a research biobank and used for many studies.
[OR] We are asking for your participation in a study involving samples and health information you provided for [insert name of previous project or biobank].
Your blood and tissue samples contain DNA, which makes up the genes that serve as the "instruction book" for the cells in our bodies. Your samples and health information will help us study how genes play a role in diseases such as cancer, heart disease, diabetes and glaucoma.
[If applicable] The specific purpose of this study is to learn about [insert specific topic of the study]. The study includes both healthy volunteers and people who have [condition, if applicable].
We will store your samples, genomic data, and health information, and share them, now and in the future, with researchers who are studying a variety of different topics or diseases.
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)
Collection of Samples and Medical Information
If your doctors collected a blood sample (or other tissue sample) as part of your medical care, we will study some of this blood (or other tissue) and genetic material (for example, DNA) that already may have been extracted from this blood (or other tissue).
If blood or tissue sample is not already available for this project, we will use a needle to draw about 4 tablespoons of blood from a vein in your arm. If you object to having blood drawn, we can instead swab cells from the inside of your cheeks.
We will ask for information related to your health and/or disease history [directly as part of the study/from your medical records]. [Insert if biobank or other ongoing data collection: We will look at your medical record from time to time to update this information. This will take place indefinitely for as long as your information and samples are stored in the biobank, unless you tell us to stop].
DNA Sequence Analysis
Using DNA from your blood or tissue sample, researchers will study your entire genetic sequence, known as your genome. The genome sequence will be read and this information will be stored.
Your genomic data will be used to find differences and similarities among people related to disease or other health traits.
Your genomic data and health information will be studied along with information from other participants in this study, and it will be stored for future studies by this and other research teams.
Coding of Tissue Samples and Medical Information
Your blood (or other tissue) sample, genomic data and health information will be labeled with a code, and your name and other information will be removed.
We will keep a master list that links those codes to your samples and data. Only certain project staff can access this master list. We will keep the samples in locked freezers. We will keep genomic data and health information on secure computers. These computers have many levels of protection.
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 sectionPotential 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).
The most common risk of having blood drawn is mild pain, bleeding, bruising, and infection (rare).
If your tissue is collected through a skin biopsy, you will experience some discomfort at the biopsy site, which is usually mild and goes away in a few minutes. It can be treated with minor pain relievers. Normally, the risks include a reaction to the local anesthetic (very rare), bleeding (occasional), infection (rare), and scarring at the biopsy site (always).
If part of your clinical tissue biopsy is used for research, there will be no risks in addition to the regular risk of surgery.
Psychological or Social Risks Associated with Return of Research Results
[If individual results are returned] As part of the research study, it is likely that you will learn that you have genetic risks for disease or disability. This may be upsetting and, depending on what you learn, might create a need to make challenging decisions about how to respond.
Although your genomic information is unique to you, you share some genomic similarities with your children, parents, brothers, sisters, and other blood relatives. Therefore, learning your research results could mean something about your family members and might cause you or your family distress. Before joining the study, it may be beneficial to talk with your family members about whether and how they want you to share your results with them. [See Considerations for Families]
Psychological or Social Risks Associated with Disclosure to Third Parties
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.
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.
Privacy and re-identification risks:
Through all stages of sample and data collection, storage, sharing, and analysis, your privacy and confidentiality will be protected. Exception: the research team is required to report child abuse and neglect, or substantial risk of harm to self or others to state or local authorities.
While neither the public nor the restricted-access databases developed for this project will have information such as your name, address, telephone number, or social security number, it may be possible to identify you based on the information in these databases and other public information (including information you tell people or post about yourself). The risk of this happening is currently very low.
Although your genomic information is unique to you, you do share some genomic information with your children, parents, brothers, sisters, and other blood relatives. Consequently, it may be possible that genomic information from them could be used to help identify you. Similarly, it may be possible that genomic information from you could be used to help identify them.
It is possible also that someone could get unauthorized access or break into the system that stores information about you. Every precaution will be taken to minimize this risk.
If your genomic information is linked back to you, someone might use this information to learn something about your health.
There also may be other privacy risks that we have not foreseen.
Protections against misuse of genetic information:
Since some genetic variations can help to predict future health problems for you and your relatives, this information might be of interest to health care providers, life insurance companies, and others. However, Federal and State laws provide some protections against discrimination based on genetic information. For example, the Genetic Information Nondiscrimination Act (GINA) makes it illegal for health insurance companies, group health plans, and most employers to discriminate against you based on your genetic information. However, it does not prevent companies that sell life insurance, disability insurance, or long-term care insurance from using genetic information as a reason to deny coverage or set premiums.
Additional privacy protections:
[If applicable] To help us protect your privacy, we have obtained a legal document called a Certificate of Confidentiality. The Certificate of Confidentiality helps us to protect your information from most subpoenas or other legal demands. With your permission, your genomic data and health can still be shared for purposes you agree to, such as with other researchers for research purposes.
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.
Are there any benefits to participating in the project?
Your participation will help medical researchers better understand various diseases and develop better treatments, which may help others like you in the future.
[Potential statements regarding benefits to individuals as relevant-state the likelihood of any potential benefits]
You will not benefit directly from participating in this project.
It is likely that you will receive some results about your genomic information that is personally interesting to you. You may learn that you have risk factors for certain diseases and disorders, and you may learn that you are at low risk for other diseases and disorders.
Through participation in this study, you may receive a diagnosis for your condition or have genetic confirmation of a suspected diagnosis based on your clinical symptoms.
It is likely that you will learn something about your health through the initial screening procedure and ongoing follow-up screening. For example, you will be told results of blood pressure tests and changes in your blood pressure over time.
The treatment you receive as part of the trial based on your genomic information may improve your symptoms, [such as xxx].
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 here.
By consenting to participate, you authorize the use of your samples, genomic data and health information for the research described above.
There are no costs to you or your insurance for taking part in this study.
You will not be compensated for taking part in this study.
[OR] You will receive [monetary incentive] for your participation in this study.
We will reimburse your costs for transportation and parking [etc.].
We will use your sample and data only for research. We will not sell them. However, the results of this research might someday lead to the development of products (such as a commercial cell line, a medical or genetic test, a drug, or other commercial product) that could be sold by a company. You will not receive money from the sale of any such product
"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.
Withdrawal from the Project
You may stop your participation in this study at any time. If you decide to withdraw from the study or part of the study, you can contact [Insert Name & Contact Information of Principal Investigator] at [Insert Name of Institution] and he/she will destroy any of your remaining tissue samples and any research data stored at the biobank. The biobank will no longer send out your samples or data. If cell lines have been derived from your samples, we will destroy the remaining cell lines stored in the biobank. However, the samples, cells, and data generated from your samples that have already been sent to other researchers or placed in research databases cannot be withdrawn.
Required Elements of the Consent Form That Do Not Have Genomics-Specific Considerations
"A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject." - 45 CFR 46.116
"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
 Henderson GE, Wolf SM, Kuczynski KJ, Joffe S, Sharp RR, Parsons DW, Knoppers BM, Yu JH, Appelbaum PS. The challenge of informed consent and return of results in translational genomics: empirical analysis and recommendations. J Law Med Ethics. 2014 Sep;42(3):344-55. [PubMed]
 Homer N, Szelinger S, Redman M, Duggan D, Tembe W, Muehling J, Pearson JV, Stephan DA, Nelson SF, Craig DW. Resolving individuals contributing trace amounts of DNA to highly complex mixtures using high-density SNP genotyping microarrays. PLoS Genet. 2008 Aug 29;4(8):e1000167. [PubMed]
Last Updated: January 10, 2018