Genomic research—including whole genome sequencing and whole exome sequencing—has a growing presence in contemporary biomedical investigation. The capacity of sequencing techniques to generate results that go beyond the primary aims of the research—historically referred to as “incidental findings”—has generated considerable discussion as to how this information should be handled—that is, whether incidental results should be returned, and if so, which ones.Federal regulations governing most human subjects research in the United States require the disclosure of “the procedures to be followed” in (...) the research as part of the informed consent process. It seems reasonable to assume—and indeed, many commentators have concluded—that genomic investigators will be expected to inform participants about, among other procedures, the prospect that incidental findings will become available and the mechanisms for dealing with them. Investigators, most of whom will not have dealt with these issues before, will face considerable challenges in framing meaningful disclosures for research participants.To help in this task, we undertook to identify the elements that should be included in the informed consent process related to incidental findings. We did this by surveying a large number of genomic researchers (n = 241) and by conducting in‐depth interviews with a smaller number of researchers (n = 28) and genomic research participants (n = 20). Based on these findings, it seems clear to us that routine approaches to informed consent are not likely to be effective in genomic research in which the prospect of incidental findings exists. Ensuring that participants’ decisions are informed and meaningful will require innovative approaches to dealing with the consent issue. We have identified four prototypical models of a consent process for return of incidental findings. (shrink)

Technology has outpaced the capacity of researchers performing research on human participants to interpret all data generated and handle those data responsibly. This poses a critical challenge to existing rules governing human subjects research. The technologies used in research to generate images, scans, and data can now produce so much information that there is significant potential for incidental findings, findings generated in the course of research but beyond the aims of the study. Neuroimaging scans may visualize the entire brain and (...) even the entire head; computed tomography colonography research may visualize the entire torso, from the base of the lungs to the pubis; genetics studies may reveal “extra” and sometimes unwanted information about the family, such as misattributed paternity and undisclosed adoption; and genomic microarray research increasingly involves whole-genome analysis revealing an individual’s complete genotype, with enormous potential for uncovering unexpected information about an individual’s genetics and risks of developing future conditions. (shrink)

Background Genomic research is challenging the tradition of informed consent. Genomic researchers in the USA, Canada and parts of Europe are encouraged to use informed consent to address the prospect of disclosing individual research results (IRRs) to study participants. In the USA, no national policy exists to direct this use of informed consent, and it is unclear how local institutional review boards (IRBs) may want researchers to respond. Objective and methods To explore publicly accessible IRB websites for guidance in this (...) area, using summative content analysis. Findings Three types of research results were addressed in 45 informed consent templates and instructions from 20 IRBs based at centres conducting genomic research: (1) IRRs in general, (2) incidental findings (IFs) and (3) a broad and unspecified category of ‘significant new findings’ (SNFs). IRRs were more frequently referenced than IFs or SNFs. Most documents stated that access to IRRs would not be an option for research participants. These non-disclosure statements were found to coexist in some documents with statements that SNFs would be disclosed to participants if related to their willingness to participate in research. The median readability of template language on IRRs, IFs and SNFs exceeded a ninth-grade level. Conclusion IRB guidance may downplay the possibility of IFs and contain conflicting messages on IRR non-disclosure and SNF disclosure. IRBs may need to clarify why separate IRR and SNF language should appear in the same consent document. The extent of these issues, nationally and internationally, needs to be determined. (shrink)

The debate on the ‘right to know’ has simmered on for over 30 years. New examples where a right to be informed is contrasted to a right to be kept in ignorance occasionally surface and spark disagreement on the extent to which patients and research subjects have a right to be self-determining concerning the health related information they receive. Up until now, however, this debate has been unsatisfactory with regard to the question what type of rights—if any—are in play here (...) and to what extent they can provide a normative basis for informed consent. This paper provides an analysis of informed consent in the context of ‘epistemic interventions’: interventions which involve the communication of information. First, I offer an analysis of the concept of a ‘right not to know’ in the context of consent to epistemic interventions. I argue that the scope of the consent is determined by the extent to which this intervention can be seen as an infringement of the private sphere. After that I show how this analysis affects the scope and standards of informed consent. (shrink)

Growing interest in embedded research approaches—where research is incorporated into clinical care—has spurred numerous studies to generate knowledge relevant to the real-world needs of patients and other stakeholders. However, it also has presented ethical challenges. An emerging challenge is how to understand the nature and extent of investigators’ obligations to patient-subjects. Prior scholarship on investigator duties has generally been grounded upon the premise that research and clinical care are distinct activities, bearing distinct duties. Yet this premise—and its corresponding implications—are challenged (...) when research and clinical care are deliberately integrated. After presenting three case studies from recent pragmatic clinical trials, we identify six differences between explanatory trials and embedded research that limit the application of existing scholarship for ascertaining investigator duties. We suggest that these limitations indicate a need to account for the implications of usual care and to move beyond a narrow focus on the investigator-subject dyad, one that better reflects the team- and institution-based nature of contemporary health systems. (shrink)

Pragmatic clinical trials offer important benefits, such as generating evidence that is suited to inform real-world health care decisions and increasing research efficiency. However, PCTs also present ethical challenges. One such challenge involves the management of information that emerges in a PCT that is unrelated to the primary research question, yet may have implications for the individual patients, clinicians, or health care systems from whom or within which research data were collected. We term these findings as?pragmatic clinical trial collateral findings,? (...) or?PCT-CFs?. In this article, we explore the ethical considerations associated with the identification, assessment, and management of PCT-CFs, and how these considerations may vary based upon the attributes of a specific PCT. Our purpose is to map the terrain of PCT-CFs to serve as a foundation for future scholarship as well as policy-making and to facilitate careful deliberation about actual cases as they occur in practice. (shrink)

The rapid growth of next-generation genetic sequencing has prompted debate about the responsibilities of researchers toward genetic incidental findings. Assuming there is a duty to disclose significant incidental findings, might there be an obligation for researchers to actively look for these findings? We present an ethical framework for analyzing whether there is a positive duty to look for genetic incidental findings. Using the ancillary care framework as a guide, we identify three main criteria that must be present to give rise (...) to an obligation to look: high benefit to participants, lack of alternative access for participants, and reasonable burden on researchers. Our analysis indicates that there is no obligation to look for incidental findings today, but during the ongoing translation of genomic analysis from research to clinical care, this obligation may arise. (shrink)

Clinicians have good moral and professional reasons to contribute to pragmatic clinical trials (PCTs). We argue that clinicians have a defeasible duty to participate in this research that takes place in usual care settings and does not involve substantive deviation from their ordinary care practices. However, a variety of countervailing reasons may excuse clinicians from this duty in particular cases. Yet because there is a moral default in favor of participating, clinicians who wish to opt out of this research must (...) justify their refusal. Reasons to refuse include that the trial is badly designed in some way, that the trial activities will violate the clinician’s conscience, or that the trial will impose excessive burdens on the clinician. (shrink)