Given the definition of an IF as “a finding concerning an individual research participant that has potential health or reproductive significance and is discovered in the course of conducting research but is beyond the aims of the study,” it is possible to distinguish three types of IFs.27
First, there are findings that will be routinely generated during the conduct of the study but that are not findings responsive to the study aims. Examples include findings related to the study's inclusion or exclusion criteria. These constitute IFs because, although they are discovered in the course of the study, such information is not responsive to the study's aims; the discovery of this information is not an aim of the study, but a collateral event. The possibility of these types of IFs should be disclosed to prospective participants. Whether the protocol should include plans to disclose (or offer to disclose) such an IF, however, depends on a variety of factors, including the nature of the IFs themselves. Although the details will affect these disclosure plans, it is possible to sketch a spectrum of IFs and their disclosure implications.
At one end might be a finding of an infection or high blood pressure that postpones an experimental surgical intervention, or results of a pregnancy test conducted to determine study eligibility. A protocol might reasonably include a plan to disclose such findings. These findings have clinical utility and, moreover, are generated by standard clinical tests. During informed consent, prospective subjects would need to consent to the possibility of learning such information.
At the other end of the spectrum might be discovery of symptoms of mild cognitive impairment (MCI), used as an exclusion criterion for a late-life mood disorder study. Evaluation and a finding of impairment that warrants study exclusion may not be equivalent to a clinical diagnosis of MCI. Moreover, the clinical utility of a MCI diagnosis has not been established. Indeed, its diagnostic criteria are not consistently utilized, and relevant clinical communities cannot agree on the meaningfulness of a finding of MCI.28
Some people would be very disturbed to learn that they have cognitive deficits, however mild or early. In addition, learning such information could impair their ability to purchase long-term care insurance or health insurance. Even if some prospective subjects would welcome learning of their quasi-diagnosis of MCI for use in personal planning, it may be reasonable for a research protocol to plan not
to inform subjects of a specific finding of MCI, but instead to simply advise such subjects that they are not eligible for the study.
Although plans to disclose this class of IFs may differ by protocol, the fact that such findings will be routinely generated (e.g., pregnant/not-pregnant, blood pressure normal or not) should be disclosed during informed consent. Moreover, although regulations guiding informed consent and consent forms tend to divide possible outcomes and findings into either risks or potential benefits of participation, it would seem preferable to present the prospect of such findings being generated in a more neutral way. For example, a prospective subject can decide, in light of her circumstances and values, whether the prospect of learning she is pregnant or has high blood pressure constitutes a potential benefit, a risk, or a reason to refuse to enroll.
A second class of IFs is comprised of those that can reasonably be expected to arise because of the nature of the research being pursued, although unlike findings generated as part of the eligibility evaluation or adjunctive medical care, their generation is not an explicit part of the research protocol. Instead, they may be findings that frequently — or, as it may turn out, even necessarily — accompany the specifically sought research findings. This may be because the research modality frequently generates them (e.g., suspicious findings in neuroimaging or CT colonography studies outside the study's aims, or misattributed parentage in genetic studies) because of pleiotropy (as with Alzheimer disease risk and cardiovascular risk), or because a particular research finding is associated with a health condition not under study (e.g., when a finding of male infertility suggests previously undiagnosed cystic fibrosis). Although such findings will not be generated in the case of each participating subject, their nature can be characterized and their frequency estimated. The nature and probability of generating these types of findings should be disclosed to prospective subjects during informed consent, along with plans for their management, including plans for disclosure or nondisclosure, recording, and privacy protection. When reasonable people can be said to disagree about whether learning such information would constitute a benefit or a harm, it would be preferable not to describe the possible generation (and disclosure) of such IFs as either risks or potential benefits of participation. Instead, describing them more neutrally, as possible consequences of participation, would be more accurate. When the precise nature of the possible finding can be characterized and plans are made to offer to disclose it, for example misattributed parentage or an established instance of pleiotropy, it may be advisable to use language such as the following: “Many people find learning of [the IF] disruptive or disturbing, but others find it useful to know. You should think about what learning such information would mean to you, and also remember there is a [characterize the likelihood] chance of learning such information.”
Of course, even when information will not be disclosed to subjects, its management is still material to them. This is true in part because of the risk that third parties will learn the information. Moreover, even if the discovery of IFs presents little risk — for example, because they will be recorded anonymously — subjects still have interests regarding the management of such information. They might, for example, object to the collection of this information, and thus might choose not to participate in the study. Personal risk is not the only reason to refuse study participation. Just as people may refuse to participate because they do not endorse a study's aims — in effect, they do not wish to contribute to the discovery of particular sorts of information — the same concern might apply to information beyond the study's aims whose discovery is nevertheless anticipated in the course of the study (e.g., because of pleiotropy). For these reasons, whether information about IFs will be collected, and whether and how it will be recorded (e.g., with or without identifiers), is relevant. These plans should be delineated during informed consent.
Finally, a study may generate IFs of an as yet unpredictable nature and frequency that can be characterized only in general terms as part of the informed consent disclosure. This third class of IFs will be the most difficult to explain during informed consent and may be impossible for subjects to evaluate as likely to either harm or benefit them. An example would be possible, but as yet uncharacterized pleiotropy: without specific details about what condition will be revealed, individuals would be unable to evaluate the personal relevance of such a finding. Nevertheless, the possibility of generating such IFs should be disclosed, along with a statement of the circumstances, if any, under which such findings would be offered to participants.
Elaboration of the criteria that should guide such offers of disclosure is beyond the scope of this discussion; however, a conservative approach seems warranted. The likelihood of any particular participant benefiting from the generation of an IF whose nature and probability cannot be characterized at the outset is quite remote, especially if criteria for disclosing IFs are stringent (i.e., at minimum requiring that the finding have clinical utility, and perhaps requiring that learning the information through study participation be the only reasonable path to its acquisition). Thus, especially for this type of IF, the possibility of their generation and disclosure should not be characterized as a potential benefit of participation. If there is the possibility that such findings would be disclosed to participants, however, then that should be stated as a possible consequence and perhaps even characterized as a risk of participation. The role of informed consent in the protection of human subjects — i.e., to afford subjects the information necessary to avoid risk of harm — justifies this asymmetrical treatment of these IFs as risks, but not as potential benefits of research.