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  1. Returning Individual Research Results: The Five Questions You Should Ask

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    Should research participants receive the results of tests that occur as part of a study? Not long ago the presumed answer was no; returning individual results seemed impractical and participants had no reason to expect to learn anything about their own health through the study. Expectations, however, are evolving, and the standard answer to that question might be, too.

    At this year’s SCOPE Summit conference, Kinetiq’s Executive Vice President James Riddle chaired a keynote discussion about returning individual results. The presentation urged sponsors, CROs, investigators, and IRBs to address questions of returning individual results during study design, instead of after a study begins. To continue the discussion started at SCOPE, this blog reviews some ethical and regulatory fundamentals regarding the return of individual test results to research participants.

    Ethical Issues

    People now can access—and demand—more health information about themselves than ever before. Increased access to electronic health records, a proliferation of wearable health monitors, the popularity of personal genetic tests, and the availability of medical information online has fostered our appetite for individualized and patient-centric health information. This has implications for human research, too, where research participants may want personal results from the tests they undergo.

    The crux of whether to provide those results typically lies in the healthcare/research dichotomy. Unlike clinical care, where the focus is on what benefits the patient, research focuses on contributions to generalizable knowledge. A research study may not present any direct benefit to a participant, and study-related tests may not be designed for individual results. A study objective such as preserving a study’s blind actually may work against providing an individual’s results. Ethical justifications for non-disclosure include the duty to avoid harm by providing results of uncertain value, and contributing to the “therapeutic misconception” that individual care is a researcher’s main concern.

    At the same time, other ethical principles can favor the return of individual results. The principle of respect for persons suggests that participants are equitable partners in the success of research and also suggest an investigator should inform participants of medical findings incidentally discovered during the course of the study that require action to avoid harm, and similar arguments can be made for providing planned research test results. Another justification—the principle of reciprocity, which originates from the duty to respect persons–acknowledges participants as partners in the research enterprise who are entitled to choose whether they receive potentially useful test results. When assessing whether it is appropriate to return individual research test results, sponsors, CROs, investigators, and IRBs can consider several questions:

    1. Do the test results have clinical or reproductive significance, and is the test result clinically actionable?

    There may be an ethical obligation to provide individual test results if an effective intervention is available for the discovered condition and if that intervention could prevent serious harm.

    2. Has the test’s analytic and clinical validity been established?

    If the accuracy of the test is unknown, there may be limited benefit and potential harm in releasing the results. A major consideration is the test’s analytic validity (specificity and sensitivity) and clinical validity (causal association between finding and condition).

    The Centers for Medicare & Medicaid Services (CMS) regulates laboratory testing through the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The CLIA program ensures that clinical labs meet standards for accuracy and reliability. Research laboratories, however, can be “excepted” from CLIA certification requirements if they do not report patient-specific results “for the diagnosis, prevention, or treatment of any disease or impairment of, or the assessment of the health of individual patients.” Using a non-CLIA laboratory for research therefore might preclude the return of a participant’s individual results from a non-CLIA certified research laboratory, or increase the risks associated with providing test results of uncertified accuracy and reliability.

    3. What is the magnitude of potential harm if the results are not disclosed?

    Even if some test results are not clinically actionable, the results might reveal the potential of a serious medical condition. Participants might value that knowledge.

    4. Does the informed consent process discuss the possibility of disclosing test results?

    As of January 2019, informed consent documents for research conducted under the Common Rule must state whether participants will receive clinically relevant research results. (See for example, 45 CFR 46.116(c)(8).)

    5. Does disclosing the test results comply with applicable law?

    Some regulatory issues related to providing individual research test results are discussed below.

    In a 2017 editorial, the Journal of the American Medical Association (JAMA) argued that at least one study should have returned individual results. JAMA criticized the study of testosterone’s effect on anemia because it did not include a mechanism for alerting participants to a possible worsening of anemia. In this case, the study plan itself complicated the possibility of returning results, as the anemia test results were blinded, analyzed away from the study sites, and found after the study procedures had ended.

    Ideally, researchers and IRBs will prospectively establish plans for returning results and document that plan in the protocol and consent forms. In some cases, however, the question whether a specific result should be returned can arise after a study begins. This raises another set of questions for consideration:

    • Was the participant given the option of receiving test results?
    • If given an option, did the participant choose to receive results?
    • Was the consent form silent on the issue of returning results?
    • Did the consent state that no results would be disclosed?

    Researchers also should consider whether disclosing results complies with applicable law.

    Regulatory Issues

    As mentioned above, the 2018 Requirements of the Common Rule necessitate that the informed consent document state whether results will be returned. Other than that, the federal human subject protection regulations are largely silent regarding the return of individual results. The rules do, however, indirectly affect the issue.

    Regulatory requirements related to informed consent state that the consent process must provide adequate information to a potential subject about the reasonably foreseeable risks and benefits of the research. Participants must also be told of any significant new findings developed during the course of the research that might relate to their willingness to continue participation. Some research test results, both planned test results and incidental findings, could be viewed as a benefit or risk of the study and thus the possibility of such findings and any policy for their return needs to be disclosed in the consent discussion and in the consent form.

    The Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule also impacts the regulatory question of when test results should be returned to research participants. The Privacy Rule establishes standards for protecting the privacy of individually identifiable health information and confers specific rights on individuals, including the right to access and amend certain health information. Generally, if research test results are included in a participant’s medical record or otherwise used to make decisions about them, those results become part of the designated record set and subject to an individual’s right of access. In other words, if a participant requested access to those test results, an entity covered by HIPAA would be obligated to provide them. While the Privacy Rule does not involve IRBs in the process of reviewing and honoring an individual’s request to access research test results, IRBs, institutions, and investigators should understand this right and ensure that the protocol and informed consent documents do not contain information contrary to the Privacy Rule.

    It is important to note some regulatory uncertainty regarding the interaction between the Privacy Rule and the CLIA laboratory requirements mentioned earlier. Recent amendments to both rules broaden an individual’s ability to access laboratory test reports directly, but some commentators interpret these revisions as conflicting with each other. Specifically, if a research laboratory is a HIPAA-covered entity and research test results are considered part of the designated record set, then participants have a legal right to receive these results. But if this same research laboratory is excused from CLIA requirements, it cannot comply with the Privacy Rule’s access provisions without violating the prohibition against returning individual results from a non-CLIA certified laboratory.

    Several factors can influence whether the HIPAA and CLIA regulations actually conflict. For example, there is ambiguity regarding the scope of research laboratory test results that would be considered part of a designated record set. It is also unclear whether CMS interprets providing test results per an individual’s request under the Privacy Rule as a violation of the CLIA regulations.

    Learn more about HIPAA and CLIA considerations for research—and earn continuing education credits–through an on-demand webinar by Kinetiq, the research and technology consulting division of Quorum.

    Conclusion

    It no longer seems enough to say the returning of results is impractical, or that the study design precludes it. As patient access to individual health information increases, more research participants will expect to see their research test results, including exploratory tests that may have un-established accuracy and reliability. The traditional stance prohibiting the return of individual research results is arguably evolving into a “translational research” model where researchers have a limited duty to provide results to their participants. SACHRP’s 2018 memo to the Secretary of Health and Human Services suggests how norms around returning results may be evolving:

    “SACHRP believes that there should be due consideration of whether to return individual research results during the design, conduct, and oversight of research, with a general but rebuttable presumption towards disclosure.”

    As the SCOPE Summit keynote presentation suggested, sponsors, CROs, investigators, and IRBs should work together to ensure that any decision regarding the return of individual results minimizes risks and maximizes benefits to the participant.