Attitudes of Researchers to the Return of Incidental and Targeted Genomic Findings Obtained in a Research Setting to Participants

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2069-2069
Author(s):  
Conrad V Fernandez ◽  
Denise Avard ◽  
Bartha Knoppers ◽  
Colleen O'Connell ◽  
David Malkin ◽  
...  
Keyword(s):  
Genetic Counselling ◽  
Incidental Findings ◽  
Clinical Utility ◽  
Genomic Research ◽  
Data Set ◽  
Research Results ◽  
Ethics Review ◽  
Institutional Ethics ◽  
Wide Range ◽  
Genomic Results

Abstract Abstract 2069 Background: The use of genomic research has exploded in recent years. Various guidelines recommend disclosure of significant, clinically validated findings to participants. Continued debate in this area has led to calls for stakeholder involvement to inform policy. In particular, the attitudes of genomics researchers are salient yet relatively unexplored with respect to how the sharing of both targeted and incidental findings should be accomplished. Methods: All 107 researchers affiliated with two large-scale Genome Canada projects [Canadian Pediatric Cancer Genome Consortium (CPCGC) and the Finding of Rare Genes Canada Consortium (FORGE)] were surveyed using a mailed, validated 32-item questionnaire that had been pilot tested with genomics researchers. The survey was designed to cover a wide range of topics including attitudes of researchers to the return of incidental and targeted research results, the need for genetic counselling, responsibilities to participants over time, to child participants and to siblings of participants, and institutional ethics review. Two reminders were sent to non-respondents. Data were analyzed with descriptive statistics. Results: 74/107 (69%) responded. Most were between 41–55 yr of age (n=40, 54%) and had their most senior training inNorth America (n=67, 91%). The majority were experienced researchers (n=58, 78%) and felt comfortable in discussing genomic results with participants (n= 66, 89%). Respondents did not feel a strong responsibility to look for meaningful incidental results in the genomic data set they created (n=27, 37%). However, once potentially significant results were identified, researchers indicated that participants had a strong or very strong right to receive analytically validated genomic results irrespective of whether these results were incidental findings (n= 50, 68%) or primary targets of the research (n= 64, 87%). Most indicated that results with clinical utility that were actionable should be offered to participants (n=54, 73%) although some indicated that research results should not be returned under any circumstances (n=6, 8%). The majority felt that a research result should be confirmed in a clinical lab prior to return to participants (n=51, 69%). Most indicated that genetic counselling should be provided either almost always or frequently prior to genomic research participation (n=48, 64%). Respondents indicated that siblings of genomic research participants had a strong or very strong right to be informed of results (n=46, 62%), and this was especially true if an intervention to ameliorate the identified condition is feasible (n=56, 76%). A minority of researchers felt personal responsibility to ensure genomic research results obtained on a child of potential clinical utility were eventually communicated to him/her when the child became an adult (n=10, 14%). A slim majority felt the parents or health care provider should be responsible (n=38, 51%). Some researchers reported encountering incidental findings of clinical utility (n=25, 34%) and had offered them to participants. However, the minority reported that their institutional ethics review boards either always (n=10, 14%) or sometimes (n=24, 32%) required an offer of results. Only 16 (22%) indicated that their ethics board had a detailed process on how to do so. Conclusions: Researchers in general support the offer of return of targeted and incidental genomic research results to participants. A minority strongly oppose such action. There is typically a high degree of support for the offer of genomic research findings to siblings, especially if actionable. Given the new developments in genomics and resulting incidental findings, researchers describe little specific guidance about the process that should be followed in returning results to participants. Greater policy guidance would be of assistance in providing a consistent approach to the offer of incidental or targeted genomic research results. Acknowledgments: Funded by Genome Canada and the Canadian Institutes of Health Research. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Returning a Research Participant's Genomic Results to Relatives: Analysis and Recommendations

2015 ◽  
Vol 43 (3) ◽  
pp. 440-463 ◽  
Author(s):  
Susan M. Wolf ◽  
Rebecca Branum ◽  
Barbara A. Koenig ◽  
Gloria M. Petersen ◽  
Susan A. Berry ◽  
...  
Keyword(s):  
Incidental Findings ◽  
Genomic Research ◽  
Research Results ◽  
Health Implications ◽  
Multiple Contexts ◽  
Important Health ◽  
Reproductive Concerns ◽  
Genomic Results ◽  
Individual Research Results ◽  
Genetic Results

The debate about how to manage individual research results and incidental findings in genetic and genomic research has focused primarily on what information, if any, to offer back to research participants. However, increasing controversy surrounds the question of whether researchers have any responsibility to offer a participant’s results (defined here to include both individual research results and incidental findings) to the participant’s relatives, including after the participant’s death. This question arises in multiple contexts, including when researchers discover a result with potentially important health implications for genetic relatives, when a participant’s relatives ask a researcher whether any research results about the participant have implications for their own health or reproductive planning, when a participant’s relative asks whether any of the participant’s results have implications for a child’s health, and when the participant is deceased and the participant’s relatives seek information about the participant’s genetic results in order to address their own health or reproductive concerns.

scholarly journals Understanding Incidental Findings in the Context of Genetics and Genomics

2008 ◽  
Vol 36 (2) ◽  
pp. 280-285 ◽  
Author(s):  
Mildred K. Cho
Keyword(s):  
Incidental Findings ◽  
Human Subjects ◽  
Association Studies ◽  
Human Migration ◽  
Genomic Research ◽  
Human Subjects Research ◽  
Research Results ◽  
Yield Information ◽  
Individual Research Results ◽  
Genetics And Genomics

Human genetic and genomic research can yield information that may be of clinical relevance to the individuals who participate as subjects of the research. However, no consensus exists as yet on the responsibilities of researchers to disclose individual research results to participants in human subjects research. “Genetic and genomic research” on humans varies widely, including association studies, examination of allele frequencies, and studies of natural selection, human migration, and genetic variation. For the purposes of this article, it is defined broadly to include analysis of DNA collected from humans that has implications for human health (even if the purpose of the study is not medical). This paper addresses both research results of individual research participants that may be an intended product of the research, as well as unanticipated, “incidental” findings.

scholarly journals Managing incidental findings and research results in genomic research involving biobanks and archived data sets

2012 ◽  
Vol 14 (4) ◽  
pp. 361-384 ◽  
Author(s):  
Susan M. Wolf ◽  
Brittney N. Crock ◽  
Brian Van Ness ◽  
Frances Lawrenz ◽  
Jeffrey P. Kahn ◽  
...  
Keyword(s):  
Incidental Findings ◽  
Genomic Research ◽  
Data Sets ◽  
Research Results ◽  
Archived Data

scholarly journals Practices and Attitudes toward Returning Genomic Research Results to Low-Resource Research Participants

2021 ◽  
pp. 1-12
Author(s):  
Megan B. Raymond ◽  
Kayla E. Cooper ◽  
Lisa S. Parker ◽  
Vence L. Bonham
Keyword(s):  
Low Income ◽  
Clinical Care ◽  
Genomic Research ◽  
Research Results ◽  
Low Resource ◽  
Research Participants ◽  
Research Programs ◽  
Ancillary Care ◽  
Genomic Results ◽  
Resource Research

<b><i>Introduction:</i></b> Many research programs are challenged to accommodate low-resource research participants’ (LRRP) ancillary care needs when returning genomic research results. We define LRRP as those who are low income, uninsured, underinsured, or facing barriers to act upon the results returned. This study evaluates current policies and practices surrounding return of results (RoR) to LRRP, as well as the attitudes of investigators toward providing ancillary care to LRRP. <b><i>Methods:</i></b> A semi-structured interview study was conducted with representatives of 35 genomic research programs nationwide. Eligible programs were returning, or planning to return, medically actionable genomic results to participants. <b><i>Results:</i></b> Three content categories emerged from this study, including: (1) RoR structures, (2) barriers to RoR to LRRP, and (3) solutions to meet community and LRRP needs. Three major structures of RoR emerged: (1) RoR Embedded in Clinical Care, (2) RoR Independent of Clinical Care, and (3) Reliance on Clinical Partnerships to Facilitate RoR. Inadequacy of program resources to address the needs of LRRP was commonly considered a significant obstacle. The attitudes and views of informants regarding responsibility to provide ancillary care for LRRP receiving genomic results were highly varied. Some informants believed that genomic sequencing and testing was not a priority for LRRP because of other pressing issues in their lives, such as housing and food insecurity. Research programs differ regarding whether clinical and social support for LRRP is considered within the purview of the research team. Some programs instituted accommodations for LRRP, including social work referral and insurance enrollment assistance. <b><i>Conclusion:</i></b> Support to access downstream treatment is not readily available for LRRP in many genomic research programs. Development of best practices and policies for managing RoR to LRRP is needed.

scholarly journals International Policies on Sharing Genomic Research Results with Relatives: Approaches to Balancing Privacy with Access

2015 ◽  
Vol 43 (3) ◽  
pp. 576-593
Author(s):  
Rebecca Branum ◽  
Susan M. Wolf
Keyword(s):  
Genetic Risk ◽  
Incidental Findings ◽  
Research Community ◽  
Genomic Research ◽  
Return Of Results ◽  
Research Results ◽  
International Policies

Debate over return of results and incidental findings to participants in genetic and genomic research has exploded over the last decade. At this point, there is wide agreement that investigators have a responsibility to anticipate discovery of findings that may warrant return, to incorporate in protocols a plan for evaluating such findings, and to offer at least some of these results to participants consenting to such return. However, the issue of how to handle questions from a participant’s genetic relatives about their own risk, or whether investigators should alert relatives to a genetic risk they may share, has garnered much less attention. Only recently has the genomic research community begun to debate these questions and offer recommendations.

scholarly journals Considerations for Returning Research Results to Culturally Diverse Participants and Families of Decedents

2015 ◽  
Vol 43 (3) ◽  
pp. 569-575
Author(s):  
Nanibaa' A. Garrison
Keyword(s):  
Culturally Diverse ◽  
Genomic Medicine ◽  
Research Participant ◽  
Genomic Research ◽  
Special Focus ◽  
Ethical Considerations ◽  
Research Results ◽  
Diverse Backgrounds ◽  
Considerable Debate ◽  
Genomic Results

As genomic medicine advances and immense amounts of data are generated that may potentially affect human health, there is increasing concern around which of these results matter to participants. There has been considerable debate on which research results to return to participants and when those results should be returned. To date, however, the debates around the return of genomic results have not focused on how those results should be returned, especially when the results come from minority and/or culturally diverse participants. This commentary explores cultural and ethical considerations, and shares insight from my own Navajo background, around returning genomic research results to participants and potentially to families of culturally diverse backgrounds, with a special focus on considerations when the research participant is deceased, and raises points for further discussion.

scholarly journals Clinical application of fetal genome-wide sequencing during pregnancy: position statement of the Canadian College of Medical Geneticists

2021 ◽  
pp. jmedgenet-2021-107897
Author(s):  
Joanna Lazier ◽  
Taila Hartley ◽  
Jo-Ann Brock ◽  
Oana Caluseriu ◽  
David Chitayat ◽  
...  
Keyword(s):  
Genetic Counselling ◽  
Incidental Findings ◽  
Clinical Utility ◽  
Genetic Diagnosis ◽  
Position Statement ◽  
Current Evidence ◽  
Chromosomal Microarray Analysis ◽  
Fetal Anomalies ◽  
Genome Wide ◽  
Monogenic Diseases

Purpose and scopeThe aim of this position statement is to provide recommendations for Canadian healthcare professionals regarding the use of genome-wide sequencing (GWS) in the context of diagnostic testing of the fetus during pregnancy. This statement was developed to facilitate clinical translation of GWS as a prenatal diagnostic test and the development of best practices in Canada, but the applicability of this document is broader and aims to help professionals in other healthcare systems.Methods of statement developmentA multidisciplinary group was assembled to review existing literature on fetal GWS for genetic diagnosis in the context of suspected monogenic diseases and to make recommendations relevant to the Canadian context. The statement was circulated for comments to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors on 19 February 2021.Results and conclusionsThe use of prenatal GWS is indicated for the investigation of multiple fetal anomalies. Its use in the context of isolated fetal anomaly should be guided by available resources and current evidence, which is continually changing. During pregnancy, GWS should be ordered by, or in collaboration with, a medical geneticist. It should be used following detailed phenotyping to interrogate known disease genes, preferably using a trio approach, following detailed fetal phenotyping. Testing should be done with an overall aim to help in the management of the pregnancy, delivery and postnatal care. It should be guided by personal utility of the test for the pregnant person and clinical utility for pregnancy and birth management, as outlined herein. Genetic counselling is crucial in making the parental decision an informed decision. Chromosomal microarray analysis should be completed in parallel or prior to GWS and should be preceded by Quantitative Fluorescent PCR (QF-PCR) for detection of common aneuploidies. In normal circumstances, only pathogenic and likely pathogenic variants with a high likelihood of being associated with the identified fetal anomalies should be reported. Reporting of secondary findings, defined as purposeful analysis of variants in a set of medically actionable genes, should not, by default, be performed in the prenatal context. Laboratories should only report incidental findings that reveal risk of a significant Mendelian condition during infancy and childhood. Should a laboratory have a policy for reporting incidental findings in medically actionable adult-onset conditions, they should only be reported with explicit opt-in consent signed by the tested individuals. Genetic counselling is crucial in disclosing the test results and the implications the results may have for the fetus. It should be emphasised that negative results do not rule out a genetic diagnosis nor guarantee a good prognosis. Postnatal phenotyping and reanalysis of existing data should be considered. Families should be given the opportunity to participate in research studies as appropriate. These recommendations will be routinely re-evaluated as knowledge of the diagnostic and clinical utility of fetal GWS during pregnancy improves.

scholarly journals Preferences regarding Return of Genomic Results to Relatives of Research Participants, Including after Participant Death: Empirical Results from a Cancer Biobank

2015 ◽  
Vol 43 (3) ◽  
pp. 464-475 ◽  
Author(s):  
Carmen Radecki Breitkopf ◽  
Gloria M. Petersen ◽  
Susan M. Wolf ◽  
Kari G. Chaffee ◽  
Marguerite E. Robinson ◽  
...  
Keyword(s):  
Incidental Findings ◽  
Genetic Research ◽  
Research Participant ◽  
Potential Health ◽  
Research Results ◽  
Health Significance ◽  
Genomic Results ◽  
Individual Research Results ◽  
The Individual ◽  
Archive Data

Biobank data and samples frequently endure beyond the life of the individual who provided the sample; this is particularly true for biorepositories that archive data and samples from cancer patients. Those data and samples may be used for research, including after the death of the individual. When the research produces genetic research results (a term used here to include incidental findings and individual research results) that have potential health or reproductive importance for the individual who provided the sample, the results may also have importance for blood relatives. This raises the question of whether the research results should be shared with relatives, at their request or at the initiative of the researchers. The issues are complex even when the research participant is alive, but are particularly challenging after the death of the individual whose data and sample are archived, as the individual may not have been asked their preferences about sharing with family, including after death. Even if the individual’s preferences on sharing have been elicited, investigators and biobank directors may be concerned about withholding genetic research results from relatives that are of potential health significance.

Structure Guided Molecular Docking Assisted Alignment Dependent 3DQSAR Study on Steroidal Aromatase Inhibitors (SAIs) as Anti-breast Cancer Agents

2019 ◽  
Vol 16 (7) ◽  
pp. 808-817 ◽  
Author(s):  
Laxmi Banjare ◽  
Sant Kumar Verma ◽  
Akhlesh Kumar Jain ◽  
Suresh Thareja
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Aromatase Inhibitors ◽  
Direct Synthesis ◽  
3D Qsar ◽  
Chemotherapeutic Agents ◽  
Modeling Tools ◽  
Data Set ◽  
Wide Range ◽  
Steroidal Aromatase Inhibitors

Background: In spite of the availability of various treatment approaches including surgery, radiotherapy, and hormonal therapy, the steroidal aromatase inhibitors (SAIs) play a significant role as chemotherapeutic agents for the treatment of estrogen-dependent breast cancer with the benefit of reduced risk of recurrence. However, due to greater toxicity and side effects associated with currently available anti-breast cancer agents, there is emergent requirement to develop target-specific AIs with safer anti-breast cancer profile. Methods: It is challenging task to design target-specific and less toxic SAIs, though the molecular modeling tools viz. molecular docking simulations and QSAR have been continuing for more than two decades for the fast and efficient designing of novel, selective, potent and safe molecules against various biological targets to fight the number of dreaded diseases/disorders. In order to design novel and selective SAIs, structure guided molecular docking assisted alignment dependent 3D-QSAR studies was performed on a data set comprises of 22 molecules bearing steroidal scaffold with wide range of aromatase inhibitory activity. Results: 3D-QSAR model developed using molecular weighted (MW) extent alignment approach showed good statistical quality and predictive ability when compared to model developed using moments of inertia (MI) alignment approach. Conclusion: The explored binding interactions and generated pharmacophoric features (steric and electrostatic) of steroidal molecules could be exploited for further design, direct synthesis and development of new potential safer SAIs, that can be effective to reduce the mortality and morbidity associated with breast cancer.

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