The question of whether and how to return individual research results to subjects has been an ongoing area of uncertainty for investigators and research institutions. Often, experimental results are not validated, and disclosure could lead to harmful decisions on the part of the subject. Nevertheless, many subjects want and expect to receive their personal results after being involved in clinical research, and the return of results is emerging as an important strategy to improve transparency and engagement with research. The recent report from the National Academies of Science, Engineering, and Medicine (NASEM), Return of Individual-Specific Research Results to Participants: Guidance for a New Research Paradigm, offered recommendations for “a process-oriented approach to returning individual research results that considers the value to the research subject, the risks and feasibility of return, and the quality of the research laboratory.”
On October 3, 2018, PRIM&R hosted a webinar to summarize the recommendations of the report, and provide guidance specifically on its potential implications for IRBs. The panel featured two members of the NASEM committee, Jeffrey Botkin, MD, MPH, professor of pediatrics at the University of Utah, and Amy McGuire, JD, PhD, Leon Jaworski Professor of Biomedical Ethics and director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine.
After the webinar, Dr. Botkin and Dr. McGuire responded to some of the attendee questions time didn’t permit us to address live. We’re pleased to share those responses with the readers of Ampersand.
Why do you think this question of the return of individual results has arisen now?
Amy McGuire (AM): I don’t think this is a new issue, but it has gained more attention in recent years for at least a few reasons. First, the proliferation of genetic and genomic research and our increased understanding about the genetic basis of disease has amplified the discovery of clinically significant findings during the course of research on human biospecimens. Traditionally, research protocols and consent forms, to the extent they addressed the return of results, typically specified that research results would not be returned. Yet, I have heard many investigators share stories of findings they discovered during the course of research that they felt morally obligated to disclose because of their potential clinical significance. Second, individuals have so much more access to information, including information about themselves, now. Between the internet, wearable devices, direct-to-consumer testing, etc., there seems to be an insatiable appetite among some people for information and knowledge. In this context, research results have become somewhat of a commodity, and offering participants access to individual-level results from research is seen as a way to show respect, provide reciprocity for their participation, and potentially benefit them with information that could be clinically important. Finally, there is a tension between the autonomy and rights-based claim on information about oneself and the beneficence-based desire to protect individuals from information that may not be valid or reliable. We see this tension being played out in the regulatory space and it has been recognized that existing regulatory inconsistencies cannot be resolved until this underlying moral tension is negotiated.
What do you think are the primary challenges in moving forward with the committee’s recommendations?
AM: The committee recognizes that implementing their recommendations will require resources, political will, legislative action, and time. It will also require a cultural shift among researchers and IRBs, where participant values and perspectives are systematically taken into consideration when making decisions about return of results. Change is never easy, and unfunded mandates that create additional responsibilities for already busy professionals can be especially difficult to implement.
What if returning the results might result in a vital decision on the part of participants, such as ending their pregnancy (abortion) or something of that nature? What is the legal risk?
AM: There is legal risk associated both with the return of results and with the decision not to return results. If an investigator does not return information that is potentially clinically relevant and that could have led to an intervention that helped the patient prevent or treat an illness, then the investigator may be exposed to liability for failing to disclose that information. On the other hand, if the investigator discloses something that is later discovered to be wrong or inaccurate, and the participant acts on that information, the investigator could be exposed to liability for negligent disclosure. In either case, the participant would have to prove that the investigator had a duty to do something (based on what the standard of care is), that that duty was breached, and that the breach of that duty caused some damages to the participant. The committee addressed this by recommending that the disclosure of research results include a disclaimer about the limited validity and reliability of research findings and that there always be a recommendation for follow-up clinical validation and counseling.
In terms of the regulation: do the tests merely need to be performed in a CLIA-certified lab? There are tests that a lab may perform that are not yet officially certified (are not on their test menu); or, the analyte may be on the test menu, but the lab may be using a method (like a research method) that is not yet validated…
Jeff Botkin (JB): Correct. The stipulation from CMS/CLIA is that results cannot be returned from non-CLIA certified labs, but this does not mean that every test conducted in a CLIA certified lab has been validated. For this reason, if an investigator proposes to return results, it will be important to have a description of the test and the results with respect to validity, whether or not the lab is CLIA certified.
Have you received any responses from the entities on your recommendations? And have they heard back from NIH regarding developing a quality management system (QMS)?
JB: We had the opportunity to present our report to a meeting at the NIH that included Francis Collins and senior staff from FDA, CMS, and OCR. We also presented the report at two meetings with congressional staff who support committees with interest in CLIA and HIPAA. We have not had any specific responses yet to the report. I will imagine that the agencies are unlikely to get back to us or the National Academies so we will have to keep an eye on the agencies.
What about letting participants know that an unanticipated finding was seen in a non-CLIA lab result, so we recommend they follow up with their doctor to get a CLIA-certified test?
JB: Yes, this approach is exactly what we hope to enable. At the present time, CMS prohibits this approach because any communication about results is considered a return of results. There are complexities to this approach because the clinical test might be expensive, leading participants to rely on the non-CLIA lab result rather than spend the money.
Can you say something more about what nonclinical interests participants might have in receiving results? What kinds of interests should investigators be open to considering?
JB: Because our focus was on biospecimen research, most research results will have some health implication. However, some biobanks are using heritage markers to supplement the participant’s self-report of race/ethnicity. This type of result would be of interest to many people. There are also quasi-clinical findings such as exposure to a pesticide for field workers. Here they may be no clinical response to the results unless they are at an alert level, but people would like to know. We might also imagine that people would be curious about results from pharmacokinetics studies just to learn about their bodies and how their response to a drug differs from others. Another quasi-nonclinical result is normal laboratory results from screening tests. Some investigators might just return results when they are abnormal but participants often would appreciate all results. For non-biospecimen research, participants might want to know how they scored on knowledge/attitude/behavior tests compared to others.
PRIM&R thanks Dr. Botkin and Dr. McGuire for sharing their expertise.
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