Michelle Grienauer

by Michelle Grienauer

IRB and Institutional Collaboration in the Return of Incidental Findings

In 2007, Steven Keating—a healthy undergraduate student—participated in an MRI research study where a brain scan revealed an unexpected small abnormality. The researchers were not concerned but still told Keating to “keep an eye on it.” Keating, a soon-to-be MIT mechanical engineering graduate student, was not your typical research volunteer, so “keeping an eye on it” meant researching brain structure and function and, in 2010, scheduling a second MRI (which did not show any change). In 2014, after noticing a recurring phantom vinegar odor and recalling that the abnormality was near his brain’s olfactory center, Keating scheduled a third MRI. This time, the scan revealed a large cancerous tumor, which was removed three weeks later.

Balancing Participant Autonomy and Risk

Although Keating’s professional background makes him unusual (including the ultimate use he has made of his health data), his story is a classic example of an incidental finding— an unexpected result or condition discovered outside of the original purpose for which a test or procedure is conducted. Like Keating, many examples of incidental findings result in life-saving interventions. However, not every finding will have such actionable results.

As a result, the knowledge of the risk and the decision to increase medical monitoring could either empower an individual or result in needless anxiety and stress. Should such a result be disclosed to the individual? If so, under what circumstances? Who should make the decision?

Answering these questions is usually straightforward in the context of clinical care, because a physician’s primary duty is to the patient and, consequently, to explain any options that may provide benefit. Conversely, the goal of research is to contribute to generalizable knowledge, not to benefit a particular subject. Because much genomic research involves test results of unestablished clinical and analytical validity, the historical approach has been to not disclose such results to study participants.

But growing consumer interest in health information and the rise of projects such as Open Humans and Personal Genome Project indicate that promoting data access and control can empower individuals to better monitor their own health. Such access may also encourage innovation by making it easier for individuals to share their data with researchers.

Perplexingly, despite these ethical arguments for returning results, regulatory considerations may sometimes impede disclosure. For example, laboratories without CLIA-certification (many research laboratories) may be prohibited from providing results to the study participant. Because of the complexity of issues, both ethical and legal, much scholarly work has been dedicated to the describing the factors that should be considered when determining whether and how to disclose incidental research findings. Kinetiq previously discussed these considerations in our article and webinar on returning individual results.

The IRB Role

Recent changes in the regulatory landscape have impacted the IRB’s role in returning individual results. The new regulatory framework after the publication of a revised version of the Common Rule includes a requirement that the consent form describe the possibility of disclosing clinically relevant individual research results (which could include certain incidental findings).

Instead of requiring IRB review of the researcher’s plan for return of results, as originally proposed in the NPRM, the final rule only requires the IRB to ensure the research participant is informed of that plan. But practically speaking, an IRB will only be able to assess the adequacy of the informed consent statements by understanding the researcher’s plan.

Thus, while the Common Rule will now require that IRBs confirm the informed consent document discloses the possibility of returning incidental findings, there has been no agency guidance related to the IRB’s responsibilities in the process for returning incidental findings. However, Health and Human Services’ original intention in proposing IRB review of the research plan to return results was based on the growing consensus within the research ethics community that IRBs should act in an oversight capacity.

Specifically, surveys with IRB chairs and recommendations from groups such as Secretary’s Advisory Committee on Human Research Protections (SACHRP), the Presidential Commission for the Study of Bioethical Issues , and the Multi-Regional Clinical Trials (MRCT) Center promote a role where the IRB does not determine whether a particular participant receives a test result, but instead ensures the process for returning results is appropriate.

IRB involvement in reviewing a researcher’s plan for returning results can promote participant rights, safety, and welfare if its role is transparent and based on well-thought out policies and procedures. These policies should provide an overview of the relevant ethical and legal considerations.

For example, IRBs should collaborate with researchers in order to establish and document the institution’s interpretation of the term “clinically relevant” and the factors that go into the assessment (e.g. utility, validity). Institutions, IRBs, and researchers should also wrestle with how to address the difficult, but increasingly common scenario where clinically relevant results are produced in a non-CLIA certified laboratory.

Any plan for returning results should also emphasize the importance of autonomy and recognize the growing public expectation that certain individual results will be made available. Therefore, where possible and appropriate, participants should be given the choice to opt in (or out of) receiving results.

A policy for reviewing plans to return results should also delineate obligations and responsibilities between the IRB and the investigator. Researchers should have the responsibility of anticipating the possibility of discovering clinically relevant incidental findings and ensuring that the protocol and informed consent form describes the plan for handling those results.

The IRB should review this plan for conformance with the considerations established in its policy. A key aspect of the review should be to consider whether the consent document adequately convey:

  • The scope of potential incidental findings
  • Whether such findings will be disclosed
  • The process for disclosing the findings
  • How participants can opt out of receiving certain types of results.

Finally, if the IRB will not make decisions about individual subjects, the policy should be clear that the investigator has the responsibility to determine whether a particular result should be returned to a participant, with IRB consultation available as needed.

The Future of Human Subject Protection is Collaborative

As individuals such as Keating demonstrate, the value of incidental research results continues to grow objectively and subjectively. The great potential for empowering participants, improving health outcomes, and driving innovation forward are strong justifications for moving away from the paternalistic sequestering-of-information approach and towards an open source model of data sharing with participant-collaborators. However, there is also potential for disaster should there be no oversight over the quality of results provided or the process for disclosure.

By creating collaborative and reliable processes that take these factors into consideration, IRBs can play a balanced role in promoting autonomy and innovation, while also protecting participant safety and welfare.

 

Executive Insight

Mitchell Parrish, JD, RAC, CIP, VP of Legal and Regulatory Affairs

 

Physicians are empowered to inform and guide their patients’ healthcare and well-being. With return of incidental research results, investigators may also be empowered, albeit in a more limited sense, to help research participants. Interestingly, this continues to further the growing public debate surrounding the potential for certain clinical research to act as clinical care.

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