National Institute of Environmental Health Sciences, National Institutes of Health, Box 12233, Mail Drop CU 03, Research Triangle Park, NC, 27709, USA, firstname.lastname@example.org
“In this article I defend a rule utilitarian approach to paternalistic policies in research with human participants. Some rules that restrict individual autonomy can be justified on the grounds that they help to maximize the overall balance of benefits over risks in research. The consequences that should be considered when formulating policy include not only likely impacts on research participants, but also impacts on investigators, institutions, sponsors, and the scientific community. The public reaction to adverse events in research (such as significant injury to participants or death) is a crucial concern that must be taken into account when assessing the consequences of different policy options, because public backlash can lead to outcomes that have a negative impact on science, such as cuts in funding, overly restrictive regulation and oversight, and reduced willingness of individuals to participate in research. I argue that concern about the public reaction to adverse events justifies some restrictions on the risks that competent, adult volunteers can face in research that offers them no significant benefits. The paternalism defended here is not pure, because it involves restrictions on the rights of investigators in order to protect participants. It also has a mixed rationale, because individual autonomy may be restricted not only to protect participants from harm but also to protect other stakeholders. Utility is not the sole justification for paternalistic research policies, since other considerations, such as justice and respect for individual rights/autonomy, must also be taken into account.”
The Law of Incidental Findings in Human Subjects Research
Establishing Researchers’ Duties
Susan M. Wolf, J.D., Jordan Paradise, J.D., and Charlisse Caga-anan
“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.1 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 (IFs), findings generated in the course of research but beyond the aims of the study.2 Neuro-imaging scans may visualize the entire brain and even the entire head; computed tomography (CT) 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 (WGA) revealing an individual’s complete genotype, with enormous potential for uncovering unexpected information about an individual’s genetics and risks of developing future conditions.
Generating massive amounts of information by sophisticated research technologies raises questions about how this information should be managed. Jack Balkin and others have written about the rise of the surveillance state created by computer technology, producing vast amounts of information about individuals’ phone calls, spending habits, and computer searches.3 Yet this is nothing compared to the capacity of genomic microarrays to sequence the three billion base pairs in your genome or full-body magnetic resonance imaging (MRI) to generate a detailed scan of the inside of your entire body. Generating this kind of biomedical information raises a fundamental question: what duties do researchers owe to human subjects in the discovery and management of data generated by research? We focus on a crucial aspect of this issue: how should researchers handle incidental findings of potential clinical or reproductive importance?
Current law and federal regulations offer no direct guidance on how to deal with IFs in research, nor is there adequate professional or institutional guidance.4 The problem of IFs in research was little recognized and seldom discussed until recently. Yet studies report that neuroimaging reveals IFs in up to 47 percent of supposedly normal adult control research participants,5 though the prevalence of IFs varies with the population examined.6 CT colonography reveals extracolonic findings in about half of scans in asymptomatic participant populations.7 Genetic family studies are estimated to reveal misattributed paternity in about 10 percent of research participants in the general population, though this percentage is difficult to verify.8
Despite the potential to generate IFs during the course of research, researchers, Institutional Review Boards (IRBs), and universities have been conducting research with no agreement that they have any responsibility to address and report IFs. Research currently proceeds with no consensus that researchers have duties to analyze anomalies spotted, secure a clinical consult to verify the existence of these IFs, and offer to disclose verified IFs of likely importance to the research participant. Research protocols may
Research currently proceeds with no consensus that researchers have duties to analyze anomalies spotted, secure a clinical consult to verify the existence of these IFs, and offer to disclose verified IFs of likely importance to the research participant. Research protocols may thus fail to address the problem of IFs at all, much less set up a pathway for handling them should they arise, and IRBs, funders, and relevant professional societies seem to offer little guidance.
thus fail to address the problem of IFs at all, much less set up a pathway for handling them should they arise, and IRBs, funders, and relevant professional societies seem to offer little guidance.9
Against this background, this article attempts a leap forward. We argue that researchers owe research participants duties that are both ethical and legal obligations: to disclose in the informed consent process the possibility of discovering IFs and the plan for management; to recognize an IF that arises during the course of research; to verify the presence of the IF and evaluate its probable importance, obtaining expert consultation if necessary; and to offer to disclose an IF of likely clinical or reproductive importance to the research participant. These duties should apply even in large-scale human subjects research using genomic microarrays and in reanalysis of archived data sets when the research participant is identifiable.
Our analysis focuses on genetic and genomic research as well as imaging research, two research domains in which IFs are emerging, raising pressing questions of how to handle them. To explore these broad research domains, we examine functional magnetic resonance imaging (fMRI) research, CT colonography research, genetic family studies, and research using genomic microarrays. We examine the problem of IFs across these four research approaches in imaging and genetics/genomic because they span a spectrum of research contexts, research participant populations, and data types. They also pose the potential for banking samples, images, or data for future studies that may themselves yield IFs. Although we focus on these four areas, we generate an analysis that can and should be applied more broadly. We advocate researcher duties that should be applied to any human subjects research generating IFs.
This article first offers background by defining “incidental findings,” illuminating underlying concepts critical to the discussion. Part II traces the ethical and legal theories supporting our finding of an overarching duty on the part of researchers to manage IFs. Part III then specifies researcher duties to manage IFs: to develop a plan for management in the research protocol, discuss the possibility of and management plan for IFs in the informed consent process, as well as address, evaluate, and offer to communicate IFs of likely clinical or reproductive significance to research participants when they arise. We recommend a pathway to be followed in handling IFs in research and unpack the implications — a new vision of researcher duties and research participant rights in the age of powerful research technologies routinely generating IFs. Our recommendations challenge the traditional research/clinical divide, advocating a set of researcher duties based on law and ethics.”