There are conditions in which genetic results should be offered to research participants. The decision to report genetic results should not depend solely upon the discretion of the investigator, but should include a broader range of perspectives as is found in Institutional Review Boards. When genetic research results are under consideration for reporting, standard criteria/guidelines should be developed and followed that include careful consideration of the risks and benefits to participants. While returning research results may serve a number of significant functions, it is important to keep the subject's best interests in mind. Returning information that is preliminary and not validated by other studies should be approached with extreme caution.
When returning genetic research results, if a genetic counselor is not available, personnel who explain the genetic results should have training and experience in human genetics and counseling. Also, concise and accurate written information should accompany the results. Consent forms as well as post-study information provided to research participants should include a section that addresses the future personal and/or reproductive implications for the participant and his/her family.
The NHLBI Working Group on Reporting Genetic Results in Research Studies was convened to consider the existing literature, as summarized above, and provide recommendations for guidelines on reporting individual results to research participants in heart, lung, blood, and sleep studies. These recommendations are generalized for wider application.
Under what circumstances should genetic results be offered to research participants?
- Genetic results should be offered to study participants if they meet the following criteria:
- There is established analytic validity.2
- The associated risk for the disease is replicable and significant, e.g. relative risk >2.0. Variants with greater penetrance or associated with younger age of onset should receive priority.
- The disease has important health implications, such as premature death or substantial morbidity.
- Proven therapeutic or preventive interventions are available. Research results on genetic diseases or traits that do not affect the participants' health but carry significant reproductive risks for disease among offspring should be considered for reporting to study subjects.
- In general, genetic test results should not be withheld if they meet the criteria described above, assuming that participants have agreed to receive results. Results should never be forced on research participants. Examples of current genetic tests meeting these criteria include homozygous Factor V Leiden, cystic fibrosis transmembrane conductance regulator (CFTR) and breast cancer BRCA1/BRCA2 mutations.
- A list of genetic tests that meet these criteria, such as the list included in the appendix of the working group report (www.nhlbi.nih.gov/meetings/workshops/gene-results.htm), should be reviewed to identify tests appropriate for consideration for reporting. Note that practically all of the more than 250 tests listed in that table relate to specific mutations of monogenic diseases and do not include polymorphisms that are usually investigated in genetic epidemiologic population studies. No such list can be considered exhaustive, given the changing nature of the field, but should provide examples and guidance for deciding which tests should be offered to participants. These suggested tests should be reviewed by investigators from individual studies for appropriateness for reporting in their study. The process of creating the list of available genetic tests should be repeated on a periodic basis by a group with sufficient expertise to judge the evolving scientific foundation for reporting these results.
- Decisions regarding reporting of research results should not be made by the investigator alone, and should be done only with IRB approval after careful consideration of risks and benefits.
When should genetic results be offered to research participants?
- Genetic research results should be offered and, if accepted, shared with participants as soon as possible after determining that the genetic test(s) performed in the study are analytically and clinically valid, e.g. manuscript with associated relative risks of genetic variant accepted in a peer-reviewed journal, results are replicated by other studies, etc.
How should genetic results be offered to research participants?
- Genetic research results meeting the criteria outlined in #1 should be offered as part of the original consent process. Research study participants should be given the opportunity to decline receiving genetic results and remain eligible for participation if receiving the results is not central to the conduct of the research.
- Consent forms should address results with personal health implications, implications for family members, and reproductive implications separately, as by a two-part question such as, “We will be studying genes that affect cardiovascular disease but may find other genetic disorders. Do you want results reported that have significant health implications for yourself or your family members? Reproductive implications for yourself or your family?” Consent forms should note that the confirmation of the genetic research results in a clinical setting and psychosocial and/or medical care that may be needed will be the responsibility of the participant. People administering informed consent for genetic tests should be trained to explain the personal, familial, and reproductive implications of reporting.
- At the time of consent, a counselor/consultant should be provided to explain the nature of the study, implications of participation, and the potential relevance of the genetic results, including any risks of harm or potential for benefits for participants, their families or communities; this person need not be a certified/licensed genetic counselor, but must have training and experience in human genetics and counseling to execute this responsibility appropriately.
- Results may be returned by letter or in person by a qualified person (see recommendation #8). If results are disseminated by letter, access to genetic counseling should be included. Follow-up by telephone may be needed to confirm the receipt of results and make sure the participant comprehends the information. Legitimate and brief information, preferably on a single page, should accompany test results to inform clinicians about what to do with the genetic test/marker results. Ideally, these information sheets should be standardized and available from a responsible source, perhaps as part of a website relating this information. Findings with reproductive implications, including implications for the relatives or offspring of the subject, should follow the same guidelines.
- Referrals for appropriate medical and psychosocial care should be available to research participants. Attempts should be made to identify accessible resources for uninsured participants.
How can a standard approach for reporting genetic results in research studies be established?
- A process should be developed for educating non-geneticist members of the research team (investigators, IRB members, subject advocates, etc.) on the difference between highly penetrant monogenic genetic diseases as compared to genes of small effect contributing to complex polygenic traits. Such understanding is required to assess the risks and benefits of reporting or not reporting results to participants.
- Recommendations regarding reporting of genetic results arising from this NHLBI working group should be coordinated and harmonized across agencies involved in conducting such research, if possible.
- Consensus panels by professional organizations (American College of Medical Genetics, American Society of Human Genetics, National Society of Genetic Counselors, International Genetic Epidemiology Society, etc.) may be valuable in assessing these criteria and/or establishing additional guidelines, so that recommendations developed by specific organizations are not viewed as designed to serve their own agenda.
- Based on our recommendations and the results of the consensus panels of relevant organizations, formal, uniform guidance should be issued for IRBs, institutions, investigators and sponsors with respect to best practices for testing and reporting genetic results in human research studies.
It is hoped that these recommendations will serve as the first steps toward establishing formal guidelines on reporting genetic results in research studies. In addition to the development of guidelines, there is a need for constant monitoring of progress in the field to address the evolving nature of genetic research. More research is needed on gene-gene and gene-environment interactions to enable better application of genomic information in the development of diagnosis, prevention, and treatment strategies. Research is also needed on the potential ethical, legal, and social implications of reporting genetic results to research study participants. Finally, the effects of reporting results on recruitment should be studied.