Ethical and Practical Guidelines for Reporting Genetic Research Results to Study Participants

Whether individual results of genetic research studies ought to be disclosed to study participants has been debated in recent decades. Previously, the prevailing expert view discouraged the return of individual research results to participants because of the potential lack of analytic validity, questionable clinical validity and medical actionability, and questions about whether it is the role of research to provide participants with their data. With additional knowledge of participant perspectives and shifting views about the benefits of research and respect for participants, current expert consensus is moving toward support of returning such results. Significant ethical controversies remain, and there are many practical questions left to address, including appropriate procedures for returning results and the potential burden to clinicians when patients seek guidance about the clinical implications of research results. In this review, we describe current views regarding the return of genetic research results, including controversies and practical challenges, and consider the application of these issues to research on apolipoprotein L1 (APOL1), a gene recently associated with health disparities in kidney disease. Although this case is unique, it illustrates the complexities involved in returning results and highlights remaining questions.

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3409 The Power of Phenotypic Extremes in Detecting Novel Genetic Modifiers of Hemophilia

Journal of Clinical and Translational Science ◽

10.1017/cts.2019.57 ◽

2019 ◽

Vol 3 (s1) ◽

pp. 23-24

Author(s):

Ohad Shimshon Bentur ◽

Barry S. Coller

Keyword(s):

Informed Consent ◽

Genetic Information ◽

Genetic Modifier ◽

Genetic Research ◽

Informed Consent Process ◽

Consent Process ◽

Genetic Modifiers ◽

Research Results ◽

Study Participants ◽

Actionable Variants

OBJECTIVES/SPECIFIC AIMS: 1. To identify novel genetic modifiers that result in a mild bleeding phenotype in patients with FVIII <1%. 2. To examine the feasibility of a practice model that incorporates the principles and methods for both obtaining consent for NGS and returning individual research results from the sources described above. METHODS/STUDY POPULATION: 1. We plan a 3-step approach for identifying novel genetic modifiers of hemophilia: a. Obtain samples from individuals with an extremely mild bleeding phenotype: The study will be narrowed to patients with confirmed FVIII <1%, a null mutation in the gene for FVIII, and a mild bleeding phenotype according to a detailed bleeding history. b. Identify variants that modify phenotype: Whole exome sequencing will be performed, followed by a focused analysis of genes known or suspected to be involved in thrombosis and hemostasis and prediction of variant impact using algorithms that account for conservation and deleteriousness of all variants. c. Verify the impact of novel variants in independent samples: In silico (analyze genetic databases for suspected variants), in vivo (assess bleeding in animal models of hemophilia after introducing presumed modifier variants). 2. We will employ a model for obtaining informed consent and communicating individual genetic research results and results with potential clinical impact to research participants: a. The informed consent process will be performed after potential participants read a pamphlet entitled “Genetic Research at The Rockefeller University Hospital and Center for Clinical and Translational Science.” The pamphlet includes 16 questions that the potential participants are urged to ask the investigator, including, “What will you look for in my genetic information?”, “Will I receive results from this study?”. Potential participants will also be informed of the meaning of clinically actionable variants, either pathogenic variants related to phenotype or secondary (“incidental”) findings (i.e. variants unrelated to phenotype, the knowledge of which could lead to actions that may improve health). Participants who do not want to receive information about potentially actionable variants will be excluded from the study to avoid a situation where the investigator has clinically important information that cannot be shared with the participant. b. Genetic testing will be performed in a CLIA-certified lab to allow investigators to share the results with the study participants. c. Results will be reported to study participants according to a standard operating procedure (SOP) that classifies the report of variants according to the relation to phenotype and the pathogenic potential. d. Participant satisfaction with the informed consent process and the return of results will be assessed by a questionnaire for obtaining participants’ perceptions of their research experience, based on a standard set of validated research participation experiences measures (Kost RG et al, J Clin Transl Sci. 2018;2:31). RESULTS/ANTICIPATED RESULTS: Samples from individuals with severe null mutation hemophilia and a mild bleeding phenotype will be enriched in genetic modifier variants. After completing participation, participants will express satisfaction with the informed consent process and the results of the return of genetic information. DISCUSSION/SIGNIFICANCE OF IMPACT: Genetic risk assessment to predict bleeding risk has the potential to provide hemophilia patients with tailored therapy, allowing for very early initiation of treatment (prophylactic thrice weekly IV administration of FVIII) in patients with a high bleeding risk and deferring this costly and burdensome treatment in patients who are expected to be mild bleeders. Genetic modifier variants of hemophilia may be found to predict thrombosis in non-hemophiliac patients and profoundly impact the treatment of venous thrombosis. A structured process for obtaining consent for NGS and return of genetic results to study participants can protect them from uncertain genetic information. Moreover, this process will prevent a situation in which investigators have knowledge about clinically actionable variants but they are not allowed to report them to the participants or do not have a process for doing so. Sharing individual research results and results with clinical significance with participants of studies that involve whole exome sequencing can promote transparency and engagement of participants throughout the research enterprise.

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Solutions for Unexpected Challenges Encountered when Integrating Research Genomics Results into the EHR

ACI Open ◽

10.1055/s-0040-1719059 ◽

2020 ◽

Vol 04 (02) ◽

pp. e132-e135

Author(s):

Luke V. Rasmussen ◽

Christin Hoell ◽

Maureen E. Smith ◽

Rex Chisholm ◽

Justin Starren ◽

...

Keyword(s):

Genetic Research ◽

Lessons Learned ◽

Return Of Results ◽

Patient Portal ◽

Test Results ◽

Research Results ◽

Genetic Test Results ◽

Future Return ◽

New Research ◽

Genetic Results

Abstract Background While there have been published reports detailing technical challenges of incorporating genetic test results into the electronic health record (EHR) with proposed solutions, less has been published about unanticipated sociotechnological or practical communication challenges involved in this process. Objectives This study was aimed to describe unanticipated issues that arose returning genetic research results through the EHR as part of the National Human Genome Research Institute (NHGRI)-funded electronic Medical Records and Genomics (eMERGE) 3 consortium, and provide lessons learned for future implementations Methods We sequenced 3,000 participants on a 109-gene panel and returned genetic results initially in person and/or by letter, with a later release directly into the EHR and patient portal. Results When results were returned through the EHR, multiple participants expressed confusion and contacted the health system, resulting in our institution temporarily freezing our return of research results. Discussion We determined the likely causes of this issue to be (1) the delay between enrollment and results return, (2) inability to personalize mass e-mail messages announcing new research test results in the EHR, (3) limited space for description of test results in the EHR, and (4) the requirement to list an ordering physician for research results in the EHR. For future return of results, we propose sending preparatory e-mails to participants, including screenshots of how they can expect to see their results presented in the EHR portal. Conclusion We hope our lessons learned can provide helpful guidance to other sites implementing research genetic results into the EHR and can encourage EHR developers to incorporate greater flexibility in the future.

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Automatic Placement of Genomic Research Results in Medical Records: Do Researchers Have a Duty? Should Participants Have a Choice?

The Journal of Law Medicine & Ethics ◽

10.1111/jlme.12323 ◽

2015 ◽

Vol 43 (4) ◽

pp. 827-842

Author(s):

Anya E.R. Prince ◽

John M. Conley ◽

Arlene M. Davis ◽

Gabriel Lázaro-Muñoz ◽

R. Jean Cadigan

Keyword(s):

Medical Record ◽

Medical Records ◽

Genomic Research ◽

Research Results ◽

Research Participants ◽

Difficult Question ◽

Automatic Placement ◽

Study Participants ◽

Research Studies

The growing practice of returning individual results to research participants has revealed a variety of interpretations of the multiple and sometimes conflicting duties that researchers may owe to participants. One particularly difficult question is the nature and extent of a researcher’s duty to facilitate a participant’s follow-up clinical care by placing research results in the participant’s medical record. The question is especially difficult in the context of genomic research. Some recent genomic research studies — enrolling patients as participants — boldly address the question with protocols dictating that researchers place research results directly into study participants’ existing medical records, without participant consent. Such privileging of researcher judgment over participant choice may be motivated by a desire to discharge a duty that researchers perceive themselves as owing to participants. However, the underlying ethical, professional, legal, and regulatory duties that would compel or justify this action have not been fully explored.

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Return of Research Results to Study Participants

JAMA ◽

10.1001/jama.2018.7898 ◽

2018 ◽

Vol 320 (5) ◽

pp. 435 ◽

Cited By ~ 28

Author(s):

Charlene A. Wong ◽

Adrian F. Hernandez ◽

Robert M. Califf

Keyword(s):

Research Results ◽

Return Of Research Results ◽

Study Participants

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Expectation versus Reality: The Impact of Utility on Emotional Outcomes after Returning Individualized Genetic Research Results in Pediatric Rare Disease Research, a Qualitative Interview Study

PLoS ONE ◽

10.1371/journal.pone.0153597 ◽

2016 ◽

Vol 11 (4) ◽

pp. e0153597 ◽

Cited By ~ 12

Author(s):

Cara N. Cacioppo ◽

Ariel E. Chandler ◽

Meghan C. Towne ◽

Alan H. Beggs ◽

Ingrid A. Holm

Keyword(s):

Rare Disease ◽

Genetic Research ◽

Qualitative Interview ◽

Interview Study ◽

Research Results ◽

Disease Research ◽

Emotional Outcomes ◽

Qualitative Interview Study ◽

The Impact

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Returning Individual Genetic Research Results to Research Participants: Uptake and Outcomes Among Patients With Breast Cancer

JCO Precision Oncology ◽

10.1200/po.17.00250 ◽

2018 ◽

pp. 1-24 ◽

Cited By ~ 2

Author(s):

Angela R. Bradbury ◽

Linda Patrick-Miller ◽

Brian L. Egleston ◽

Kara N. Maxwell ◽

Laura DiGiovanni ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Susceptibility ◽

Genetic Counselor ◽

Genetic Research ◽

Informed Choice ◽

Multiple Primary Cancers ◽

Research Results ◽

Cancer Susceptibility Genes ◽

Cancer Multiple ◽

To Receive

Purpose Understanding the outcomes of returning individual genetic research results to participants is critical because some genetic variants are found to be associated with health outcomes and have become available for clinical testing. Materials and Methods BRCA1/2-negative women with early-onset breast cancer, multiple primary cancers, or a family history of breast cancer who participated in a gene discovery cancer registry were offered the opportunity to learn their individual genetic research results of 24 breast cancer susceptibility genes with a genetic counselor after predisclosure genetic counseling. Outcomes included uptake of research results, knowledge, informed choice, psychosocial adjustment, uncertainty, satisfaction, and uptake of clinical confirmation testing. Results Four hundred two potential participants were contacted. One hundred ninety-four participants (48%) did not respond despite multiple attempts, and 85 participants (21%) actively or passively declined. One hundred seven participants (27%) elected for predisclosure counseling and were more likely to be younger, married, and white. Ninety percent of participants who had predisclosure counseling elected to receive their genetic research results, and 89% made an informed choice. Knowledge increased significantly after predisclosure counseling, and anxiety, intrusive cancer-specific distress, uncertainty, and depression declined significantly after receipt of results. General anxiety and intrusive cancer-specific distress declined significantly for both participants with a positive result and those with a negative result. Sixty-four percent of participants had clinical confirmation testing when recommended, including all participants with a mutation in a high-penetrance gene. Conclusion Uptake of genetic research results may be lower than anticipated by hypothetical reports and small select studies. Participants who elected to receive research results with genetic providers did not experience increases in distress or uncertainty, but not all patients return for confirmation testing.

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Do solidarity and reciprocity obligations compel African researchers to feedback individual genetic results in genomics research?

BMC Medical Ethics ◽

10.1186/s12910-020-00549-4 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Dimpho Ralefala ◽

Mary Kasule ◽

Ambroise Wonkam ◽

Mogomotsi Matshaba ◽

Jantina de Vries

Keyword(s):

Genetic Research ◽

Research Participation ◽

Ethical Question ◽

Group Discussions ◽

Future Studies ◽

Research Results ◽

Genomic Study ◽

Genomics Research ◽

Depth Interviews ◽

Parents And Caregivers

Abstract Background A key ethical question in genomics research relates to whether individual genetic research results should be disclosed to research participants and if so, which results are to be disclosed, by whom and when. Whilst this issue has received only scarce attention in African bioethics discourse, the extension of genomics research to the African continent has brought it into sharp focus. Methods In this qualitative study, we examined the views of adolescents, parents and caregivers participating in a paediatric and adolescent HIV-TB genomic study in Botswana on how solidarity and reciprocity obligations could guide decisions about feedback of individual genetic research results. Data were collected using deliberative focus group discussions and in-depth interviews. Results Findings from 93 participants (44 adolescents and 49 parents and caregivers) demonstrated the importance of considering solidarity and reciprocity obligations in decisions about the return of individual genetic research results to participants. Participants viewed research participation as a mutual relationship and expressed that return of research results would be one way in which research participation could be reciprocated. They noted that when reciprocity obligations are respected, participants feel valued and not respecting reciprocity expectations could undermine participant trust and participation in future studies. Conclusions We conclude that expectations of solidarity and reciprocity could translate into an obligation to feedback selected individual genetic research results in African genomics research.

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