Returning Individual Research Results to Participants Guidance for a New Research Paradigm (2018) / Chapter Skim
Currently Skimming:
Summary
Summary
Pages 1-38
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 1... ...
In the last several decades, questions have been raised about the practice of not returning test results generated in a research study to the study's participants; early on, much of the discussion was focused on returning results from imaging studies, while more recently the focus has moved more to the disciplines of genetics and environmental research. At the same time, the push for increased community and participant engagement across the research study life cycle and the rise of technology-enabled open science and data-sharing movements have added further momentum to the issue.
|
From page 2... ...
asked the National Academies of Sciences, Engineering, and Medicine to conduct a study and generate a report that reviews and evaluates the ethical, societal, regulatory, and operational issues related to the return of individual-specific research results generated from research on human biospecimens. The full Statement of Task for the committee is presented in Box S-2.
|
From page 3... ...
Clinical Laboratory Improvement Amendments of 1988 (CLIA) : Laboratories in the United States that perform tests on human specimens for the purpose of providing information for the diagnosis, prevention, or treatment of a disease or for the assessment of the health of an individual are regulated by CLIA and are required by the Centers for Medicare & Medicaid Services (CMS)
|
From page 4... ...
c HIPAA-covered entities include health plans, health care clearinghouses, and health care providers who transmit health information in electronic form in connection with a covered financial or administrative transactions (e.g., billing transactions)
|
From page 5... ...
• Review the current regulatory environment, including CLIA and any other applicable laws, for conducting tests and returning individual specific research results, including the potential regulatory considerations associated with returning such results. In doing so, the committee will assess how the current regulations ensure or fail to ensure minimization of risks (e.g., erroneous or unreliable results)
|
From page 6... ...
In making the recommendations, the committee will consider and address, as appropriate, º The adequacy of the current CLIA regulations as applied to research laboratories (or subcategories of research testing by such laboratories) that currently return individual-specific results in accordance with CLIA.
|
From page 7... ...
Of note, the committee's charge was not limited to the return of genetic test results, as many other kinds of research are performed on human biospecimens. These include, for example, basic science studies using tumor biopsies to identify a new biomarker for colon cancer, clinical trials that evaluate blood samples for antibody levels induced by a new malaria vaccine, and epidemiological studies measuring the level of a suspected toxin in urine samples for an environmental exposure study -- all of these involve laboratory tests on human biospecimens and are in the scope of this report.
|
From page 8... ...
the offer of unanticipated research results to an individual participant. For the purposes of this report, anticipated results are those results that are actively sought or are expected to arise when using a particular research test on human biospecimens.
|
From page 9... ...
The sponsors indicated to the committee that it would be appro priate to include in its description of the current regulatory environment for the return of individual research results CMS's current interpretation of the scope and applicability of CLIA, which is that "only those facilities performing research testing on human biospecimens that do not report patient-specific results may qualify to be excepted from CLIA certification." Although CMS's current interpretation has been questioned by some legal scholars, the committee was advised that making any comments, analysis, or conclusions regarding the appropriateness of that interpretation would be beyond what was intended in the Statement of Task. Furthermore, the committee was not asked to make recommendations to Congress regarding changes to the CLIA law.
|
From page 10... ...
By its very nature research often produces results that are of uncertain value and, depending on the stage of research, may not be analytically or clinically valid.3 The return of uncertain, poorly validated, or poor-quality results poses a risk that participants will make important clinical or life decisions based on information that subsequently proves to be wrong or is misinterpreted. The risks associated with returning individual research results may be minimized by improving result validity through the adoption of an externally accountable quality system by research laboratories.
|
From page 11... ...
When conducting research involving the testing of human biospecimens, investigators and their institutions should routinely consider whether and how to return individual research results on a study-specific basis through an informed and thoughtful decision-making process. Investigators, with oversight from their IRBs and institutions, will ultimately be responsible for making decisions on a case-by-case basis regarding whether and how to return individual research results, as the decisions require the careful consideration of many factors, which are described below.
|
From page 12... ...
GUIDING PRINCIPLES FOR RETURNING INDIVIDUAL RESEARCH RESULTS The purpose of research is to create generalizable information for the benefit of society, and, unlike clinical care, research is not primarily focused on providing personal benefit for individual participants. Given this perspective, what is the nature of the relationship and expectations between investigators and participants and does our evolving conception of the relationship and expectations require more transparency with respect to individual research results?
|
From page 13... ...
Be cause research results have value to many participants, as a matter of reciprocity, respect, transparency, and trust, the return of results should be routinely considered in the design of research protocols involving human participants.
|
From page 14... ...
QUALITY MANAGMEMENT SYSTEMS FOR LABORATORIES TESTING HUMAN BIOSPECIMENS Establishing laboratory processes to give all stakeholders (investigators, institutions, regulators, and participants) confidence in the validity of the individual research results being returned is critical to ensuring the accuracy of information provided to research participants as well as the quality of the science.
|
From page 15... ...
. BOX S-3 Results Not Intended for Clinical Decision Making in the Study Protocol The committee categorized research test results generated in research laboratories based on how the test results will be used according to the study protocol.
|
From page 16... ...
. In returning the research result with this qualification, the researcher is not providing information for use in clinical decision making on the basis of the research test alone.
|
From page 17... ...
To provide confidence in the quality of research test results disclosed to participants, institutions and their IRBs should permit investigators to return individual research results if A. esting is conducted in a CLIA-certified laboratory; or t B. esults are not intended for clinical decision making in the study r protocol (as defined in Box S-3) and testing is conducted under the externally accountable quality management system for research laboratories once established (see Recommendation 2)
|
From page 18... ...
. NOTE: CLIA = Clinical Laboratory Improvement Amendments of 1988; DRS = designated record set; HIPAA = Health Insurance Portability and Accountability Act of 1996; NIH = National Institutes of Health; QMS = quality management system.
|
From page 19... ...
; B. adopting the externally accountable quality management system for research laboratories once established for relevant laboratories (see Recommendation 2) ; or C. ecoming CLIA certified or facilitating access to core, affiliated, b or third-party CLIA-certified laboratories for sample testing, re testing, or a confirmatory testing process when research results are for use in clinical decision making in a study protocol.
|
From page 20... ...
To clarify, defining value in this way is not meant to imply that each participant needs to be queried regarding the results that would be meaningful to him or her, but it does require the investigator to consider value from the participant perspective rather than from the more traditional clinical perspective. Feasibility is also determined by multiple factors, including potential challenges, the costs and burdens of returning results, whether biospecimens can be linked to a specific participant, and the resources available to communicate the results effectively and appropriately.
|
From page 21... ...
. Ascertaining and incorporating participant needs, preferences, and values into decision-making processes regarding whether or not to return individual research results can be undertaken at the study level but also in the development of policy or guidance.
|
From page 22... ...
Value in this context means the value of a result from the perspective of the participant and might entail clinical utility or personal utility as well as personal meaning. Feasibility is determined by multiple factors, including potential challenges, the costs and burdens of returning results, and whether participants' biospecimens are linked to the participant identity as well as the resources available to communicate the results effectively and appropriately.
|
From page 23... ...
To minimize the burdens on individual investigators, research sponsors and institutions can help investigators understand the preferences and needs of their prospective participants by leveraging their core resources (e.g., Clinical and Translational Science Awards Program cores, community advisory boards) and by engaging community and participant representatives to develop policies and guidance (see Chapter 4 for additional information on the range of engagement in the return of individual research results)
|
From page 24... ...
For all studies using human biospecimens, investigators should rou tinely address their plans regarding the return of individual research results in their funding application or research protocol. The investigator's plan should describe A. hether individual research results will be offered to participants w and, if so, when and how.
|
From page 25... ...
Given the scientific community's general lack of experience with returning individual research results to participants, as well as the complexity and uncertainty inherent in results generated through research, the development of guidance and best practices may help address inconsistency in practices and minimize the risk of harm from the return of research results. To establish an empirical evidence base for the development of best practices, the research community will need to develop a learning system in which processes for returning research results are evaluated for benefits and harms and communication practices are refined.
|
From page 26... ...
In the consent process, investigators should communicate in clear lan guage to research participants A. hich individual research results participants can access, if re w quested, including any results participants have a legal right to access under HIPAA, and how to request these results; and B. hich individual research results, if any, will be offered to par w ticipants and why, and the participant's option to decline to receive their research results. C. If results are going to be offered the following elements should also be communicated during the consent process: 1.
|
From page 27... ...
Recommendation 10: Enable Understanding of Individual Research Re sults by Research Participants. Whenever individual research results are communicated to partici pants, investigators and institutions should facilitate understanding of both the meaning and the limitations of the results by A. ensuring that there is a clear takeaway message and necessary refer ence information to convey what is known and not known about both the meaning of the result and potential clinical implications; B. ommunicating effectively the level of uncertainty in the result c validity; C. roviding mechanisms for participants to obtain additional infor p mation and answers to questions when appropriate and feasible; D. providing guidance for follow-up actions/consultations when appropriate; E. aligning the communication approaches to the particular needs and preferences of the participants and the context of the study; F. providing a written summary of the results and other information communicated to participants for future reference by participants and investigators; and G. everaging existing and emerging health information technologies l to enable tailored, layered, and large-scale communications when appropriate.
|
From page 28... ...
Overall, the current regulatory environment for the return of individual research results is not well aligned with the benefits and risks associated with the practice. The current absolute prohibition of the return of results from non-CLIAcertified laboratories fails to account for several factors, including the high quality maintained by some research laboratories, the value that many participants place on results despite uncertain validity, and the access rights afforded by HIPAA to individual results regardless of quality standards.
|
From page 29... ...
NOTE: CLIA = Clinical Laboratory Improvement Amendments of 1988; DRS = designated record set; HIPAA = Health Insurance Portability and Accountability Act of 1996; NIH = National Institutes of Health; QMS = quality management system.
|
From page 30... ...
should define the DRS to include only individual research results generated in a CLIA-certified laboratory or under the exter nally accountable quality management system for research labora tories (see Recommendation 2) ; B. CR should require all HIPAA-covered entities that conduct re O search on human biospecimens to develop a plan that is reviewed and approved by the IRB for the release of individual research esults in the designated record set to participants in a responsive r manner when requested under HIPAA; C. CMS should revise CLIA regulations such that when there is a legal obligation under the HIPAA access right to return individual re search results, a laboratory will not be considered in violation of CLIA and need not obtain CLIA certification before satisfying this legal obligation; D. MS should revise CLIA regulations to allow research results to C be returned from a non-CLIA-certified laboratory when they are not intended for clinical decision making in the study protocol (as efined in Box S-3)
|
From page 31... ...
The opportunity for change has arisen in response to the evolving relationship between investigators and participants and is supported by an assessment of the potential benefits and risks of returning individual research results. The need for higher standards of quality in many research laboratories is clearly illustrated in this report (see Chapter 3)
|
From page 32... ...
Many institutions and researchers currently lack the experience and resources to return individual research results in a deliberate and effective manner. The committee does not expect that a more widespread return of results will happen immediately.
|
From page 33... ...
TABLE S-1 Recommendations by Stakeholdera STAKEHOLDER RECOMMENDED ACTION HHS RECOMMENDATION 12G – Chapter 6 Refer to research volunteers as participants, not subjects in all regulations relevant to human research CMS RECOMMENDATIONS 12C and D – Chapter 6 Revise CLIA regulations to allow for the return of individual research results from non-CLIA-certified laboratories when results are requested under the HIPAA access right and when the quality of results has been established and they are not intended for use in clinical decision making RECOMMENDATION 12E – Chapter 6 Work with OCR to harmonize definitions of key terms relevant to the return of individual research results in the federal regulations FDA RECOMMENDATION 12H – Chapter 6 Clarify and provide additional guidance regarding how the return of individual research results affects IDE requirements for research studies NIH RECOMMENDATION 2 – Chapter 3 Lead an interagency effort with nongovernmental stakeholders to develop standards for a quality management system for research laboratories testing human biospecimens 33 continued
|
From page 34... ...
34 TABLE S-1, Continued RECOMMENDATION 12F – Chapter 6 Work with OCR and OHRP to harmonize the definitions of key terms relevant to the return of individual research results in the federal regulations OCR RECOMMENDATION 12A – Chapter 6 Revise the definition of the designated record set (DRS) RECOMMENDATION 12B – Chapter 6 Require HIPAA-covered entities that conduct research on human biospecimens to develop a plan for the release of individual research results in the DRS when requested under HIPAA RECOMMENDATIONS 12E and F – Chapter 6 Work with CMS, OHRP, and NIH to harmonize definitions of key terms relevant to the return of individual research results in the federal regulations OHRP RECOMMENDATION 12F – Chapter 6 Work with OCR and NIH to harmonize definitions of key terms relevant to the return of individual research results in the federal regulations Research sponsors and RECOMMENDATION 4 – Chapter 3 funding agencies Ensure adequate resources and infrastructure to generate high-quality individual research results RECOMMENDATION 5 – Chapter 4 Engage community and participant representatives in the development of policy and guidance related to the return of individual research results
|
From page 35... ...
RECOMMENDATION 7 – Chapter 4 Ensure planning for the return of individual research results in applications for funding RECOMMENDATION 11 – Chapter 5 Support research to expand the empirical evidence base relevant to the return of individual research results Research institutions RECOMMENDATION 1 – Chapter 2 Consider whether and how to return individual research results on a study-specific basis RECOMMENDATION 3 – Chapter 3 Ensure the high quality of individual research results that are returned to participants RECOMMENDATION 4 – Chapter 3 Ensure adequate resources and infrastructure to generate high-quality research results RECOMMENDATION 5 – Chapter 4 Enable and facilitate investigator access to relevant community and participant networks, resources, and training RECOMMENDATION 8 – Chapter 4 Develop policies and procedures that support the assessment of plans for the return of individual research results, and ensure that IRBs and research teams have or have access to the necessary expertise and resources to assess plans. continued 35
|
From page 36... ...
TABLE S-1, Continued 36 Research institutions RECOMMENDATION 10 – Chapter 5 Enable the understanding of individual research results by research participants IRBs RECOMMENDATION 3 – Chapter 3 Ensure the high quality of individual research results that are returned to participants RECOMMENDATION 7 – Chapter 4 Review the return-of-results plan and ensure the consent process aligns with it Investigators RECOMMENDATION 1 – Chapter 2 Consider whether and how to return individual research results on a study-specific basis RECOMMENDATION 5 – Chapter 4 Seek information on participant needs, preferences, and values related to return of individual research results RECOMMENDATION 6 – Chapter 4 Include plans for return of individual research results in research protocols RECOMMENDATION 9 – Chapter 5 Ensure transparency regarding return of individual research results in the consent process
|
From page 37... ...
RECOMMENDATION 10 – Chapter 5 Enable understanding of individual research results by research participants Participants RECOMMENDATION 5 – Chapter 4 Engage researchers to ensure that participant needs, preferences, and values are incorporated in decision making about the return of individual research results a An interactive version of this table can be found at http://resources.nationalacademies.org/ReturnofResults/index.html (accessed August 13, 2018)
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.