Investigators and institutional review boards should integrate plans about the appropriate disclosure of individual genetic results when designing research studies. The ethical principles of beneficence, respect, reciprocity, and justice provide justification for routinely offering certain results to research participants. We propose a result-evaluation approach that assesses the expected information and the context of the study in order to decide whether results should be offered. According to this approach, the analytic validity and the clinical utility of a specific result determine whether (...) it should be offered routinely. Different results may therefore require different decisions even within the same study. We argue that the threshold of clinical utility for disclosing a result in a research study should be lower than the threshold used for clinical use of the same result. The personal meaning of a result provides additional criteria for evaluation. Finally, the context of the study allows for a more nuanced analysis by addressing the investigators' capabilities for appropriate disclosure, participants' alternative access to the result, and their relationship with the investigators. This analysis shows that the same result may require different decisions in different contexts. (shrink)

Determining what constitutes an anticipatable incidental finding from clinical research and defining whether, and when, this IF should be returned to the participant have been topics of discussion in the field of human subject protections for the last 10 years. It has been debated that implementing a comprehensive IF-approach that addresses both the responsibility of researchers to return IFs and the expectation of participants to receive them can be logistically challenging. IFs have been debated at different levels, such as the (...) ethical reasoning for considering their disclosure or the need for planning for them during the development of the research study. Some authors have discussed the methods for re-contacting participants for disclosing IFs, as well as the relevance of considering the clinical importance of the IFs. Similarly, other authors have debated about when IFs should be disclosed to participants. However, no author has addressed how the “actionability” of the IFs should be considered, evaluated, or characterized at the participant's research setting level. This paper defines the concept of “Actionability at the Participant's Research Setting Level” for anticipatable IFs from clinical research, discusses some related ethical concepts to justify the APRSL concept, proposes a strategy to incorporate APRSL into the planning and management of IFs, and suggests a strategy for integrating APRSL at each local research setting. (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)

The National Institutes of Health and other federal health agencies are considering establishing a national biobank to study the roles of genes and environment in human health. A preliminary public engagement study was conducted to assess public attitudes and concerns about the proposed biobank, including the expectations for return of individual research results. A total of 141 adults of different ages, incomes, genders, ethnicities, and races participated in 16 focus groups in six locations across the country. Focus group participants voiced (...) a strong desire to be able to access individual research results. Recognizing the wide range of possible research results from a large cohort study, they repeatedly and spontaneously suggested that cohort study participants be given ongoing choices as to which results they received. (shrink)

Introduction Biobank-based research is growing in importance. A major controversy exists about the return of aggregate and individual research results. Methods The authors used a mixed-method approach in order to study parents' attitudes towards the return of research results regarding themselves and their children. Participants attended four 2-h, deliberative-engagement sessions held on two consecutive Saturdays. Each session consisted of an educational presentation followed by focus-group discussions with structured questions and prompts. This manuscript examines discussions from the second Saturday which focused (...) on the benefits and risks of returning aggregate and individual research results regarding both adults (morning session) and children (afternoon session). Attitudes were assessed in pre-engagement and post-engagement surveys. Results The authors recruited 45 African-American adults whose children received medical care at two healthcare facilities on the South Side of Chicago that serve different socioeconomic communities. Three dominant themes were identified. First, most participants stated that they would enrol themselves and their children in a biobank, although there was a vocal minority opposed to enrolling children, particularly children unable to participate in the consent process. Second, participants did not distinguish between the results they wanted to receive regarding themselves and their children. Supplemental survey data found no attitudinal changes pre-engagement and post-engagement. Third, participants believed that children should be allowed access to their health information, but they wanted to be involved in deciding when and how the information was shared. Discussion Participant attitudes are in tension with current biobank policies. An intensive educational effort had no effect on their attitudes. (shrink)

Over the past decade, there has been an extensive debate about whether researchers have an obligation to disclose genetic research findings, including primary and secondary findings. There appears to be an emerging (but disputed) view that researchers have some obligation to disclose some genetic findings to some research participants. The contours of this obligation, however, remain unclear. -/- As this paper will explore, much of this confusion is definitional or conceptual in nature. The extent of a researcher’s obligation to return (...) secondary and other research findings is often limited by reference to terms and concepts like “incidental,” “analytic validity,” “clinical validity,” “clinical relevance,” “clinical utility,” “clinical significance,” “actionability,” and “desirability.” These terms are used in different ways by different writers to describe obligations in different sorts of cases. -/- Underneath this definitional confusion is a general notion, supported by much of the literature, that findings only need to be disclosed when they surpass certain presumably objective or measureable thresholds, such as medical importance or scientific reproducibility. The problem is that there is significant variability in the way that these terms and concepts are used in the literature and, as such, in defining the scope of an obligation to return findings that surpasses the relevant thresholds. -/- The goal of this paper is to analyze the definitional muddle underlying the debate about returning genetic research findings, with the hope of answering a few questions. First, what is the range of definitions being used in this debate? Based on an extensive literature review, Part 1 will lay out a range of articulated definitions for each relevant term, with the goal of categorizing them into a handful of distinct types. Part 2 explains the definitional redundancy and confusion in the current literature, and, drawing from the terminological patterns identified in Part 1, outlines more cohesive building blocks to inform the development of future disclosure frameworks.Our minimum goal in articulating these conceptual building blocks is to promote clearer articulations of, and distinctions between, future disclosure frameworks. More ambitiously, we suggest which definitions and conceptualizations we consider most appropriate to use in future disclosure frameworks. Here, we seek to balance benefits to participants through the disclosure of important information with the minimization of undue burdens on individual researchers and the research enterprise more generally. -/- Our analysis builds upon the central philosophical distinction between concepts and conceptions. The basic idea is that the “concept” of X refers to the general (and relatively uncontroversial) structure/shape of X, while various “conceptions” of X are more particular, filled out, and controversial elaborations of the concept. In other words, “concepts” of X will be formal representations of X, while “conceptions” of X will be substantive interpretations of the key elements and relationships operating within that formal framework. (Implicit in this distinction is an important point about the nature of disagreement – namely, that in order for two or more parties to “disagree” about X as opposed to simply talk past one another, there must be at least enough shared agreement about X to know that the parties are referring to the same thing. A concept of X provides this point of common agreement, while competing conceptions of X mark the areas where disagreement arises.) In this paper, we will employ this distinction in a fundamental way to clarify exactly where the primary disagreements arise in the debate over disclosing genetic research findings. -/- We propose that, underlying all the seeming confusion and disagreement, there are three central and widely agreed upon concepts at work in this debate—validity, value, and volition. The first two concepts concern the nature of the information itself. An obligation to disclose only exists when findings are valid and have value but there are competing conceptions of how to determine or define validity and valuableness. The third concept—volition—pertains not to the information but rather to the person to whom it will be disclosed. Does that person want or not want the information, and what is the best way of determining this? Here, too, competing conceptions arise. Our key point, though, is that almost all of the ethical disagreement arises because of competing conceptions of these three concepts. Understanding and appreciating this key point can help to refocus the substantive debate by providing some common ground to start from in determining how best to interpret these shared concepts. This refocusing can, ideally, produce more productive debate and facilitate some progress in resolving it. (shrink)

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)