Disclosure of Research Results from Cancer Genomic Studies: State of the Science

Abstract

Although the cancer research community has supported a ''nondisclosure'' position about the return of individual results to research subjects, new technologies, such as genome wide association studies, will reveal clinically relevant findings, some of which cannot be ignored. What recommendations exist that can guide researchers and Institutional Review Boards (IRBs) about this issue? This article summarizes the relevant public documents about the disclosure of individual research results to inform policy development. Four stakeholder groups were selected to make this comparison: federal, professional, advisory, and advocacy groups. Regardless of a group's position on disclosure, there was consensus that if research results were to be disclosed under any condition, the results must be analytically and clinically validated and that the researcher should not make this decision alone, but in conjunction with the IRB. There was no consensus, however, on the specific determinants for disclosure or what constitutes clinical validity. Although sufficient agreement exists to begin developing general guidelines about the process for disclosure of individual research results, the actual determinants with which to guide this decision remain challenging. An alternate framework that addresses the threshold of uncertainty a stakeholder is willing to accept, the positive predictive value of the research finding, and the magnitude of harm of returning results may be more effective to guide decision making. These assessments, along with what is considered useful information, requires the involvement of the research subject community to inform decision-making and move the policy process forward. Setting the StageThe recent NIH Policy for GWAS suggests that the researcher and her/his IRB or designated institutional official are expected to devise a plan to address the possibility of revealing clinically relevant information identified through the course of genomic research.1,2 This suggestion has moved the controversial issue of disclosure of individual research results to the forefront of cancer research, not only for GWAS but for the entire spectrum of cancer research studies. Currently, many issues remain unclear, including the conditions that warrant disclosure of individual versus aggregate research results, how to handle findings unrelated to the original research, who should make these decisions, and who should be responsible for communicating findings to the research subject. Researchers and IRBs need guidance to help address these issues and develop responsible, consistent policies to protect the rights and welfare of research subjects, and to engender the public's trust in the research enterprise. For more than a decade, many professional, federal, advisory, and advocacy groups have presented guidelines or recommendations to address issues of disclosure of individual research results. What can we learn from these efforts? The purpose of this article is to review and comment on results from a systematic analysis ...

Intentions to receive individual results from whole-genome sequencing among participants in the ClinSeq study

“…13 Recommendations for return of individual WGS results have generally focused on the clinical utility of the results. 11,14,15 Kohane and Taylor 13 call for a new paradigm for return of findings from genome sequencing, which considers preferences of research participants who may be seeking to learn 'personal' information. By this, they mean health information that are valued, even when it may not be actionable or meet standards for clinical utility.…”

How do researchers manage genetic results in practice? The experience of the multinational Colon Cancer Family Registry

“…We have compiled a set of suggestions for future researchers based on our own experience of returning results to research participants. Our consensus suggestions are designed to be used to supplement guidelines that are currently available (Botkin et al 2010;Fabsitz et al 2010;Bookman et al 2006;Dressler 2009). We have also described the disclosure protocols used by registries in order to increase the information available to research consortia managing clinically relevant genetic results on participants.…”

“…Since then, genetic counseling has become a significant component in the provision of multidisciplinary cancer risk assessment for clinical practice. Unlike the relatively routine use of genetic testing in medical practice, the management of clinically significant genetic results generated in the course of research has been inconsistent across countries and across different studies (Ravitsky and Wilfond 2006;Dressler 2009;Affleck 2009;Miller et al 2008;Kollek and Petersen 2011). Institutional Review Boards (IRBs) in the USA previously adopted the stance that only summary outcomes of research results need be provided to participants, rather than individual results (Affleck 2009;Beskow et al 2001;Partridge and Winer 2002).…”

“…More recently, consensus is emerging among US bioethicists and researchers that research participants should be offered the opportunity to receive personal genetic results when there are clinical implications (Dressler 2009), and there is increasing discussion about whether incidental findings as well as expected genetic findings should be returned (Wolf et al 2012;Green et al 2012). Survey results show that nearly all research participants expect researchers to return clinically useful information (Meulenkamp et al 2010;Kaufman et al 2008;Ceballos et al 2008).…”

“…While there are some agreed upon ethical principles for the return of genetic results in epidemiological research studies (Bookman et al 2006;Roberts et al 2010;Dressler 2009), there is little practical information to guide researchers on implementing these principles. Kollek and Petersen (2011) have presented a series of challenges to be addressed in order to return individual research results to participants.…”