Book reviewed in this article: Principles of Biomedical Ethics. By Tom L. Beauchamp and James F. Childress.

This paper presents results found through searching publicly available U.S. data sources for information about how to handle incidental fndings (IF) in human subjects research, especially in genetics and genomics research, neuroimaging research, and CT colonography research. We searched the Web sites of 14 federal agencies, 22 professional societies, and 100 universities, as well as used the search engine Google for actual consent forms that had been posted on the Internet. Our analysis of these documents showed that there is very (...) little public guidance available for researchers as to how to deal with incidental fndings. Moreover, the guidance available is not consistent. (shrink)

Despite calls by some commentators for disclosing incidental fndings in genetics research, several factors weigh in favor of caution. The technology of genetics has the power to uncover a vast array of information. The most potent argument for restraint in disclosure is that much research is pursued without consent so that the individual participant may not know that research is being conducted at all. Often the work is done by investigators and at institutions with which the person has no prior (...) contact. Past practice is also relevant; genetics researchers historically have chosen not to disclose incidental fndings, of which misattributed paternity and pleiotropic alleles such as ApoE have been the most common. Many people choose not to have genetic tests when given a choice. It may be desirable to discuss the topic of incidental fndings when consent for research is obtained, but given the risk of unwanted surprise when there has been no prior discussion, the potential utility of incidental fndings should be very high before they are even ofered to individuals. (shrink)

No consensus yet exists on how to handle incidental fnd-ings in human subjects research. Yet empirical studies document IFs in a wide range of research studies, where IFs are fndings beyond the aims of the study that are of potential health or reproductive importance to the individual research participant. This paper reports recommendations of a two-year project group funded by NIH to study how to manage IFs in genetic and genomic research, as well as imaging research. We conclude that researchers (...) have an obligation to address the possibility of discovering IFs in their protocol and communications with the IRB, and in their consent forms and communications with research participants. Researchers should establish a pathway for handling IFs and communicate that to the IRB and research participants. We recommend a pathway and categorize IFs into those that must be disclosed to research participants, those that may be disclosed, and those that should not be disclosed. (shrink)

The approach to incidental research fndings in children emerges by considering the child-parent relationship and balancing divergent interests and preferences. Incidental fndings with clear and proximate clinical importance should be disclosed to both. We recommend that particularly sensitive or private information should be disclosed to the adolescent frst, while particularly serious information should frst be disclosed to the parent. These approaches allow the researcher to form an alliance with one party prior to engaging the other. However, unlike clinical settings, where (...) there may be presumptive expectations of confdentiality about sharing information within the family, in most research settings it is reasonable to plan to disclose such information to both parties. It is important to communicate this plan during the informed consent process separately to adolescents to avoid enrolling adolescents when sensitive incidental fndings such as pregnancy and drug use may be detected. The approach to incidental fndings without clear and proximate beneft is challenging. Researchers should plan more limited disclosure of such incidental fndings for pediatric participants than for adult participants. (shrink)

Incidental research findings, as defined in this symposium’s consensus paper, are unexpected findings discovered in the course of research but “beyond the aims of the study.” These include findings generated by research methodology, such as imaging or genetic analysis, findings related to clinical screening for inclusion or exclusion, or direct observations of physical abnormalities or behavior. Decisions about managing incidental research findings involve important ethical considerations regarding a researcher’s obligations to provide care, minimize harms, and respect research participants’ wishes. When (...) the research participant is a child, the triadic relationship between the researcher, child participant, and parent makes these considerations more complicated. (shrink)

Researchers do not owe their subjects the same level of care that physicians owe patients, but they owe more than merely what the research protocol stipulates. In keeping with the dynamics of the relationship between researcher and subject, they have limited but substantive fiduciary obligations.

The possibility of generating incidental findings — in both research and clinical contexts — has long been regarded as a risk of these enterprises. Should incidental findings in research also be regarded as potential benefits? At first glance, it would seem they ought to be. After all, in particular circumstances or given a particular set of values, any piece of information can be beneficial. Therefore, it may seem incoherent or unduly paternalistic to regard IFs only as risks. Moreover, developments in (...) science and technology increasingly transform what was once of uncertain meaning and dubious value into information that is likely to have clear meaning and potential personal value, if not obvious clinical utility. For these reasons, it would seem that in the future, IFs should be treated as potential benefits in the design and regulation of research. (shrink)

This paper argues against considering incidental fndings as potential benefts of research when assessing the social value of proposed research, determining the appropriateness of a study's risk/beneft ratio, and identifying and disclosing the risks and benefts of participation during informed consent. The possibility of generating IFs should be disclosed during informed consent as neither a risk nor beneft, but as a possible outcome collateral to participation. Whether specifc IFs will be disclosed when identifed is a separate question whose answer is (...) material to determining whether IFs constitute a risk or a potential indirect beneft of participation. Finally, three types of IF should be distinguished and treated diferently during informed consent: those that will be routinely generated , those that can reasonably be characterized in terms of their nature and frequency of generation , and those of unpredictable nature and frequency that can be characterized only in general terms. Research protocols should provide a rationale for sharing or not sharing IFs of these three types with participants. Regulatory review of such plans should not, however, be confused with regarding IFs as potential benefts when assessing the study's risk/beneft ratio or merit. (shrink)

Researchers in the health sciences regularly discover information of potential health importance unrelated to their object of study in the course of their research. However, there appears to be little guidance available on what researchers should do with this information, known in the scientific literature as incidental findings. The study described here was designed to determine the extent of guidance available to researchers from public sources. This empirical study was part of a larger two-year project funded by the National Human (...) Genome Research Institute to generate guidance on how incidental findings should be managed in human subjects research, especially genetics, genomics, and imaging research. We generated empirical analysis of publicly available guidance and consent forms to help guide a multidisciplinary Working Group of experts in their formulation of normative recommendations reported in this symposium. (shrink)

Human clinical research trials, by which corporations, universities, and research scientists bring new drugs, devices, and procedures into the practice and marketplace of medicine, have become a huge business. The National Institutes of Health doubled its spending over the past five years, while in the private sector the top twenty pharmaceutical companies have more than doubled their investment in research and development over a roughly comparable period. To date, some twenty million Americans have participated in clinical research trials that now (...) are as common in the private practice setting as in academia.For many years human clinical trials received relatively little public attention. In the wake of several well-publicized research abuses, Congress created in 1974 the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research to formulate recommendations to protect human research subjects. The Commission’s 1979 Belmont Report helped to guide the Institutional Review Boards that review the ethics of federally funded research. (shrink)

Human clinical research trials, by which corporations, universities, and research scientists bring new drugs, devices, and procedures into the practice and marketplace of medicine, have become a huge business. The National Institutes of Health doubled its spending over the past five years, while in the private sector the top twenty pharmaceutical companies have more than doubled their investment in research and development over a roughly comparable period. To date, some twenty million Americans have participated in clinical research trials that now (...) are as common in the private practice setting as in academia.For many years human clinical trials received relatively little public attention. In the wake of several well-publicized research abuses, Congress created in 1974 the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research to formulate recommendations to protect human research subjects. The Commission’s 1979 Belmont Report helped to guide the Institutional Review Boards that review the ethics of federally funded research. (shrink)

Human subject research involving brain imaging is likely to reveal signifcant incidental fndings of abnormal brain morphology. Because of this fact and because of the fduciary relationship between researcher and subject, board-certi-fed or board-eligible radiologists should review the scans to look for any abnormality, the scans should be conducted in accordance with standard medical practice for reviewing the clinical status of the whole brain, and the informed consent process should disclose the possibility that incidental fndings may be revealed and what (...) consequences will follow. In the event such fndings are revealed, qualifed physicians should explain to the subject the signifcance of the fndings and the alternatives available. (shrink)

There are countless variations on this theme. The call can come from one of your own physicians who was called by the investigator. Your physician may or may not be well informed on what the reported finding about Disease Y means or how to respond. DNA testing can reveal more than susceptibility to disease. People can learn that they do not have the biological connections — parentage or evidence of ethnic origin — that they thought they did.Colleagues who serve on (...) the Institutional Review Board in my institution tell me that they currently do not permit “cold calls” of the type portrayed in the opening paragraph. Such direct contacts have, however, occurred in the past, with or without the blessing of an IRB. Sharing findings with the individual’s physician, who is then supposed to serve as a learned and wise intermediary, is not without problems either, given that many physicians understand little about complex genetics. Yet the very existence of this project on managing incidental findings in research demonstrates that some people believe that some research findings ought to be available to participants. (shrink)

Human genetic and genomic research can yield information that may be of clinical relevance to the individuals who participate as subjects of the research. It has been common practice among researchers to notify participants during the informed consent process that no individual results will be disclosed, “incidental” or otherwise. However, as genetic information obtained in research becomes orders of magnitude more voluminous, increasingly accessible online, and more informative, this precedent may no longer be appropriate. There is not yet consensus on (...) the responsibilities of researchers to disclose individual research results to research participants. Empirical research suggests that participants want to know individual research results. On the other hand, the increased resolution and power aforded by new genomic analyses may lead to fndings of statistical, but not necessarily clinical, signifcance. This paper addresses the issues to be considered in deciding whether and how to disclose “incidental” fndings or other fndings of clinical signifcance that arise in the course of human genomic and genetic research. What research results should be ofered, and what should not be ofered? For which research should individual results be ofered to research participants, when should they be ofered, how, and to whom? (shrink)

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. 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. (shrink)