In the course of research based on a biobank population occasionally a condition may be revealed in a particular individual, which was not known before the study, and for which the study was not explicitly designed. This is known as an incidental finding. Within the confines of regulation, the question then becomes how best to relay this information to the individual, if at all.
Fortunately, researchers are not overwhelmed with such occurrences as incidental findings are “so rare, we need to hunt for them” according to Eva Winkler, MD, PhD, Head of NCT- Bioethics Programme EPOC: Ethics and Patient Oriented Care in Oncology; University of Heidelberg, Germany. Patient or donor consent forms should anticipate incidental findings and include return of result options. More broadly, the degree to which study participants should have individual level access to the data generated from their donations is a subject of debate, and worldwide legal heterogeneity.
In considering the return of personal research results to study participants three groups emerge, the general public with no direct connections with the studies under consideration, medical professionals working on the studies, and study participants. The public and medical professionals generally consider only clinically actionable results relevant, whereas evidence suggests that study participants are interested in receiving as much information as possible. [Husedzinovic]
Clinically actionable results are confirmatory of medical conditions, known in the clinical sphere, for which there are regulatorily approved treatments or lifestyle changes are known to modify the condition. It is usually deemed inappropriate to inform a patient of a condition they are already living with for which there is no treatment and no actions on the part of the patient can modify the conditions either in the present or longer term.
The position of patients and the position of clinicians reflects a conflict in core values—the desire to respect the interests and desires of research participants by communicating results contrasted with the responsibility to protect participants from uncertain, perhaps poorly validated information.
The majority of respondents (n = 2,549) to a recent representative survey of the United States indicated that they saw value in receiving research results about themselves (79%), thought it should be standard practice (72%), would make them more likely to participate in studies (72%), and trust researchers more (70%). Of those surveyed 16% had previously received genetic results from a research study. [Wilkins] It is important to remember that many study participants hold these values irrespective of what the consent form they actually sign says.
This highlights an important point that consent forms should consider the possibility of incidental findings from the outset and state policy regarding return of results explicitly so that patients can make an informed decision.
The majority rated how they may respond to some medications, closely followed by how their genetics affects their risk of medical conditions as the most valuable forms of genetic information they could receive. When asked directly which was the most valuable the majority indicated their risk of medical conditions. In contrast receiving financial compensation for participating ranked 7th out of 12. [Wilkins]
Guidance from the US National Academies of Sciences, Engineering, and Medicine leans toward communication of results while seeking to enhance the quality of results emerging from research laboratories. [Botkin]
One consideration for the return of results discussed by Botkin et al. is the difference between results generated in a research laboratory and a Clinical Laboratory Improvement Amendments (CLIA) certified clinical laboratory. As research laboratories implement novel and innovative protocols and generally deal in statistical averages (deidentified groups of patients), rather than individual patients, a “clinically actionable” result for an individual patient should be interpreted with caution until it has been reproduced under standardized and regularly audited protocols in a clinically certified laboratory.
Return of results is plagued by legal and compliance uncertainty. The desire of patients to receive as much information as possible is contrasted by US federal law, which does not confer a fundamental right to access research results generated from biospecimens. [Botkin] The perception among some individuals that they continue to own their biospecimens and any personal data generated from them is in fact not supported by US law. Given that many research studies involve international collaboration, the regulatory obligations become even less clear, leading to calls for harmonization. [Thorogood]
Comparatively, the US’s return policy is very conservative and is predicated on clinically validated results. Other countries particularly in the EU emphasize the return of any results, clinically validated or not, that may have “health relevance”, in some cases even overriding consent forms, as in Spain. [Thorogood] Again these differences represent the conflict core values between clinicians who have a duty to only provide information that could be used to improve a patient’s health and study participants who desire all information.
The best approach to the return of results may be a matter of finding the right balance between information provision and information validation. A policy that is light on validation requires a high level of understanding on the part of the general public about the conclusions they can and cannot draw from the data they receive. Changes to the school level education curriculum may be beneficial or necessary.
The issues involved are complex so return of results are handled by dedicated institutional review boards (IRBs) / independent ethics committees as they come up, providing a centralized but local guidance system for researchers if they uncover an incidental finding during the course of their work.
Botkin, JR., et al. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. The National Academies Press, 2018. https://doi.org/10.17226/25094
Husedzinovic, A., et al. “Stakeholders’ Perspectives on Biobank-Based Genomic Research: Systematic Review of the Literature.” European Journal of Human Genetics, vol. 23, no. 12, Apr. 2015, pp. 1607–1614., https://doi.org/10.1038/ejhg.2015.27
Thorogood, A., et al. “Return of Individual Genomic Research Results: Are Laws and Policies Keeping Step?” European Journal of Human Genetics, vol. 27, no. 4, Aug. 2019, pp. 535–546., https://doi.org/10.1038/s41431-018-0311-3
Wilkins, CH., et al. “Understanding What Information Is Valued By Research Participants, And Why.” Health Affairs, vol. 38, no. 3, 2019, pp. 399–407., https://doi.org/10.1377/hlthaff.2018.05046