National Academies Press: OpenBook
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R1
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R2
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R3
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R4
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R5
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R6
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R7
Page viii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R8
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R9
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R10
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R11
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R12
Page xiii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R13
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R14
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R15
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R16
Page xvii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R17
Page xviii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R18
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R19
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R20
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R21
Page xxii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R22
Page xxiii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R23
Page xxiv Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: 10.17226/25094.
×
Page R24

Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Returning Individual Research Results to Participants: Guidance for a New Research Paradigm Jeffrey R. Botkin, Michelle Mancher, Emily R. Busta, and Autumn S. Downey, Editors Committee on the Return of Individual-Specific Research Results Generated in Research Laboratories Board on Health Sciences Policy Health and Medicine Division A Consensus Study Report of PREPUBLICATION COPY: UNCORRECTED PROOFS

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001 This activity was supported by contracts between the National Academy of Sciences and the Centers for Medicare & Medicaid Services, the Food and Drug Administration, and the National Institutes of Health (HHSN26300117). Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project. International Standard Book Number-13: 978-0-309-XXXXX-X International Standard Book Number-10: 0-309-XXXXX-X Digital Object Identifier: https://doi.org/10.17226/ Library of Congress Control Number: Additional copies of this publication are available for sale from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu. Copyright 2018 by the National Academy of Sciences. All rights reserved. Printed in the United States of America Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/. PREPUBLICATION COPY: UNCORRECTED PROOFS

The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president. The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. C. D. Mote, Jr., is president. The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president. The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine. Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org. PREPUBLICATION COPY: UNCORRECTED PROOFS

Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process and it represents the position of the National Academies on the statement of task. Proceedings published by the National Academies of Sciences, Engineering, and Medicine chronicle the presentations and discussions at a workshop, symposium, or other event convened by the National Academies. The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies. For information about other products and activities of the National Academies, please visit www.nationalacademies.org/about/whatwedo. PREPUBLICATION COPY: UNCORRECTED PROOFS

COMMITTEE ON THE RETURN OF INDIVIDUAL-SPECIFIC RESEARCH RESULTS GENERATED IN RESEARCH LABORATORIES JEFFREY R. BOTKIN (Chair), Associate Vice President for Research and Professor of Pediatrics, The University of Utah School of Medicine PAUL S. APPELBAUM, Elizabeth K. Dollard Professor of Psychiatry, Medicine, and Law, Columbia University SUZANNE BAKKEN, Professor of Biomedical Informatics, Columbia University CHESTER BROWN, Professor and the St. Jude Chair of Excellence in Genetics for the Department of Pediatrics, University of Tennessee Health Science Center WYLIE BURKE, Professor Emeritus, University of Washington RICHARD FABSITZ, Adjunct Faculty, George Mason University VANESSA NORTHINGTON GAMBLE, University Professor of Medical Humanities, The George Washington University GREGG GONSALVES, Assistant Professor, Yale School of Public Health RHONDA KOST, Director, Clinical Research Support Office, Co-Director Community Engaged Research Core, Associate Professor of Clinical Investigation, The Rockefeller University Center for Clinical and Translational Science DEBRA G. B. LEONARD, Professor and Chair of Pathology and Laboratory Medicine, Robert Larner, M.D. College of Medicine, University of Vermont, University of Vermont Health Network AMY MCGUIRE, Leon Jaworski Professor of Biomedical Ethics, Baylor College of Medicine JAMES H. NICHOLS, Professor of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine BRAY PATRICK-LAKE, Director of Stakeholder Engagement, Duke Clinical Research Institute CONSUELO H. WILKINS, Associate Professor of Medicine, Vanderbilt University Medical Center and Meharry Medical College BRIAN J. ZIKMUND-FISHER, Associate Professor, University of Michigan Study Staff MICHELLE MANCHER, Study Director AUTUMN S. DOWNEY, Interim Study Director EMILY R. BUSTA, Associate Program Officer OLIVIA C. YOST, Research Associate CAROLINE M. CILIO, Senior Program Assistant DANIEL BEARSS, Senior Research Librarian ANDREW M. POPE, Director, Board on Health Sciences Policy Consultants REBECCA DAVIES, Associate Professor, University of Minnesota CHRISTI GUERRINI, Assistant Professor, Baylor College of Medicine E. HAAVI MORREIM, Professor, University of Tennessee Health Science Center PREPUBLICATION COPY: UNCORRECTED PROOFS v

Reviewers This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We thank the following individuals for their review of this report: BARBARA E. BIERER, Harvard Medical School and Brigham and Women’s Hospital JULIA GREEN BRODY, Silent Spring Institute ELLEN WRIGHT CLAYTON, Vanderbilt University Medical Center BARRY S. COLLER, The Rockefeller University CRISPIN GOYTIA-VASQUEZ, Mount Sinai Health System ALBERTO GUTIERREZ, NDA Partners LLC KATHY L. HUDSON, People-Centered Research Foundation DEVEN MCGRAW, Ciitizen J. STEPHEN MIKITA, Spinal Muscular Atrophy Foundation ELLEN PETERS, The Ohio State University HEIDI REHM, Massachusetts General Hospital MARK E. SOBEL, American Society for Investigative Pathology SUSAN M. WOLF, University of Minnesota BARBARA A. ZEHNBAUER, Emory University School of Medicine MARK L. ZEIDEL, Harvard Medical School and Beth Israel Deaconess Medical Center Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by LYNN R. GOLDMAN, The George Washington University, and JOSHUA M. SHARFSTEIN, Johns Hopkins Bloomberg School of Public Health, responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies. PREPUBLICATION COPY: UNCORRECTED PROOFS vii

Preface There is a long-standing tension in biomedical research arising from 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. Traditionally, the balance has been tipped toward the latter resulting in what has been termed “helicopter research.” The notion here is that investigators drop into communities or people’s lives, engage with them in often very personal ways, and then take off, never to be heard from again. Yet people are curious about themselves, particularly about their health and their family’s health, leaving a sense of frustration and loss when investigators take but do not share. Studies show that many participants want and expect their personal results. They often have these expectations regardless of what the consent discussion promised. Experimental results are often uncertain and disclosure of unvalidated results can, in some circumstances, lead to harmful medical or life decisions. But, of course, investigators are confident enough in experimental results to publish their work, suggesting that individual data points are sufficiently meaningful to contribute to generalizable knowledge. A participant might ask, “If the findings are good enough to publish, why can’t my results be shared with me?” This conflict in values is central to this report. In struggling with the complex and competing considerations, we have attempted to achieve a new balance, one that leans toward communication of results while seeking to enhance the quality of results emerging from research laboratories. Our push toward more disclosure, we believe, is part and parcel of the larger cultural transition toward more engagement, collaboration, and transparency between investigators and research participants. Our committee has had the opportunity to work together for a year to produce this Report, with strong support from the extraordinary staff at the National Academies of Sciences, Engineering, and Medicine. We have achieved consensus on a number of core issues. We are recommending a transition away from firm rules, such as those embodied in current interpretations of the Clinical Laboratory Improvement Amendments (CLIA) and the Health Insurance Portability and Accountability Act (HIPAA) regulations, that stipulate when results must or cannot be disclosed toward a process-based approach. In many circumstances, and on a study-by-study basis, we recommend a peer-review process to assess the risks and benefits of results disclosure with careful attention to laboratory quality. Establishing supporting processes will require motivation, resources, and time. This report is the product of a wonderful collaboration between a diverse set of committee members who came to the task with divergent viewpoints about core issues. Through PREPUBLICATION COPY: UNCORRECTED PROOFS ix

extended discussions, mutual respect, and multiple iterations of the language, we achieved a remarkable degree of consensus. This is a testament to the integrity, scholarship, and humility of the dedicated people who agreed to serve on the committee. We were also privileged to work with the outstanding staff of the National Academies who were unfailingly creative and supportive. We are deeply grateful to Michelle Mancher, Autumn Downey, Emily Busta, Caroline Cilio, Olivia Yost, and Andrew Pope for their expertise, hard work, and insights. We also benefited greatly from consultants to the project including Christi Guerrini, E. Haavi Morreim, and Rebecca Davies and to those who testified to the committee and submitted comments to enrich our understanding and deliberations. Our hopes and expectations are that this report will provide a roadmap toward better and more collaborative and transparent research practices that will benefit participants, investigators and society more broadly. Jeffrey R Botkin, Chair Committee on the Return of Individual-Specific Research Results Generated in Research Laboratories PREPUBLICATION COPY: UNCORRECTED PROOFS x

Acknowledgments This consensus study report reflects contributions from a number of individuals and groups. The committee takes this opportunity to recognize those who so generously gave their time and expertise to inform its deliberations. To begin the committee would like to thank the individuals who attended and presented at their open-session meetings and webinars and the many individuals and organizations who submitted written comments to the committee (see Appendix A). The committee greatly benefited from the opportunity for discussion with these individuals and is appreciative for their many contributions. The committee also thanks the participants who graciously gave their time, knowledge, and perspectives through interviews with the committee. Their thoughtful remarks enriched the committee’s understanding of the complex issues and informed their deliberations (see Appendix B). Many others provided support to this project in various ways. We thank Paul Bachner, University of Kentucky College of Medicine, Karen Dyer, The Centers for Medicare & Medicaid Services, Michael P. Ryan, New York State Department of Health, and David E. Sterry, Clinical and Laboratory Standards Institute, for their technical review. Finally, our gratitude to Casey Weeks for his creative efforts in our graphic design process and Robert Pool for his editorial assistance in preparing this report. PREPUBLICATION COPY: UNCORRECTED PROOFS xi

Contents ACRONYMS AND ABBREVIATIONS xix ABSTRACT xxi SUMMARY S-1 1 INTRODUCTION 1-1 Study Scope and Key Terminology, 1-4 Study Context, 1-6 Study Approach, 1-11 Organization of the Report, 1-12 References, 1-13 2 PRINCIPLES FOR THE RETURN OF IDIVIDUAL RESEARCH RESULTS: ETHICAL AND SOCIETAL CONSIDERATIONS 2-1 Ethical Considerations for the Return of Individual Results in Human Participant Research, 2-1 Societal Considerations for the Return of Individual results in Human Participant Research, 2-7 Recommendations and Guiding Principles for the Return of Individual Research Results, 2-18 References, 2-22 3 LABORATORY QUALITY SYSTEMS FOR RESEARCH TESTING OF HUMAN BIOSPECIMENS 3-1 The Spectrum of Translational Research, 3-1 The Importance of Analytic and Clinical Validity of Research Results, 3-3 Laboratory Quality Systems to Increase Confidence in the Validity of Research Results, 3-7 CLIA, 3-8 Addressing Resource and Infrastructure Needs in Research Laboratories to Enable Return of High-Quality Individual Research Results, 3-23 References, 3-32 4 PROCESSES TO ENABLE APPROPRIATE DECISION MAKING REGARDING RETURN OF INDIVIDUAL RESEARCH RESULTS 4-1 Dimensions to Consider in Decisions on Returning Individual Research Results, 4-1 A Decision-Making Framework for the Return of Individual Research Results, 4-16 Planning for the Return of Individual Research Results, 4-24 Conclusion, 4-29 References, 4-29 PREPUBLICATION COPY: UNCORRECTED PROOFS xiii

5 ADVANCING PRACTICES FOR RETURNING INDIVIDUAL RESEARCH RESULTS 5-1 Opportunities to Improve the Return of Research Results: Learning From Current Practices, 5-2 Setting Participant Expectations in the Consent Process and Beyond, 5-11 Effectively Communicating Individual Research Results to Participants, 5-18 Developing a Learning Process to Improve the Return of Research Results, 5-34 References, 5-35 6 RESHAPING THE LEGAL AND REGULATORY LANDSCAPE TO SUPPORT RETURN OF INDIVIDUAL RESEARCH RESULTS 6-1 Legal and Regulatory Protections in Relation to the Benefits and Risks of Returning Individual Research Results, 6-1 Creating a Regulatory environment Better Aligned with the Benefits and Risks of the Return of Individual Research Results, 6-16 Final Thoughts, 6-23 References, 6-27 APPENDIXES A STUDY APPROACH AND METHODS A-1 B MEETING AGENDAS B-1 C LEGAL ANALYSIS SUPPLEMENTAL PAPER C-1 D ETHICAL PRINCIPLES PAPER D-1 E COMMITTEE MEMBER BIOGRAPHIES E-1 PREPUBLICATION COPY: UNCORRECTED PROOFS xiv

Boxes, Figures, and Tables BOXES S-1 HIPAA, CLIA, and the Common Rule, S-2 S-2 Statement of Task for the Committee on the Return of Individual-Specific Research Results Generated in Research Laboratories, S-3 S-3 Results Not Intended for Use in Medical Decision Making in the Study Protocol, S-12 S-4 Individual Research Results That Should and Should Not Be Returned to Participants, S-15 1-1 Statement of Task for the Committee on the Return of Individual-Specific Research Results Generated in Research Laboratories, 1-3 1-2 The Imperative for Participant-Centered Research in Name and Action, 1-7 1-3 Precision Medicine, 1-9 3-1 Results Not Intended for Use in Clinical Decision Making in the Study Protocol, 3-11 3-2 European Initiatives for Laboratory Quality, 3-15 3-3 Informed Consent Oversight Boards, 3-19 3-4 Quality Assurance and Quality Control Essentials, 3-20 3-5 Lessons in QMS Implementation from Johns Hopkins Hospital, 3-24 4-1 Establishing Clinical Utility, 4-3 4-2 Previous Expert Groups and the Return of Research Results, 4-4 4-3 Community-Based Participatory Research: Community Members as Research Partners, 4-7 4-4 Challenges in Reporting Back Personal Exposure Results, 4-12 4-5 Individual Research Results That Should and Should Not Be Returned to Participants, 4-17 4-6 Memorial Sloan Kettering Cancer Center’s Genomic Advisory Panel, 4-27 5-1 Select Engagement and Communication Practices for the Return of Research Results in Environmental Health, 5-9 5-2 Best Practices for Health-Literate Informed Consent Related to Return of Individual Research Results, 5-15 5-3 Presenting Laboratory Results to Consumers—Experiences of the Food and Drug Administration, 5-18 5-4 Types of Reference Information, 5-20 PREPUBLICATION COPY: UNCORRECTED PROOFS XV

5-5 Examples of Visualizations Relevant to Results Reporting, 5-29 5-6 Standards That Support Integration of External Resources with Electronic Health Records and Patient Portals and Are of Relevance to Return of Research Results, 5-32 6-1 Overview of Federal and State Laws and Regulations Relevant to the Return of Individual Research Results, 6-2 FIGURES S-1 Determining whether laboratory quality is sufficient for investigators to return individual research results, S-13 S-2 A conceptual framework for decisions on returning individual research results, S-16 S-3 Determining whether participants have the right to access their individual research results under HIPAA, S-22 3-1 Diagram of pre-analytic to post-analytic phases of research, 3-3 3-2 Determining whether laboratory quality is sufficient for investigators to return individual research results, 3-23 3-3 Costs, infrastructure, and resources needed to implement a quality management system, 3-25 3-4 Opposing forces encountered by investigators when considering implementing a quality management system, 3-26 3-5 Systematic benefits of standards, 3-27 4-1 A conceptual framework for decisions on returning individual research results, 4-16 6-1 Investigational device exemption (IDE) process for research studies, 6-10 6-2 Determining whether participants have the right to access their individual results under HIPAA, 6-29 TABLES S-1 Recommendations by Stakeholder, S-25 3-1 Quick-Reference Biospecimen Reporting for Improved Study Quality Summary/Checklist: Tier 1 Items to Report If Known and Applicable, 3-14 3-2 Common Elements of Quality Systems, 3-30 4-1 The Range of Engagement in the Return of Individual Research Results, 4-8 5-1 Potential Advantages and Disadvantages of Models of Consent to Return of Incidental Findings, 5-16 6-1 CLIA Categories of Laboratories, 6-4 6-2 Legal Obligations Related to Individual Access to Laboratory Test Results, 6-7 PREPUBLICATION COPY: UNCORRECTED PROOFS xvi

6-3 Recommendations by Stakeholder, 6-24 PREPUBLICATION COPY: UNCORRECTED PROOFS xvii

Acronyms and Abbreviations ACA Patient Protection and Affordable Care Act of 2010 ACMG American College of Medical Genetics and Genomics AIDS acquired immunodeficiency syndrome AV analytic validity BRISQ Biospecimen Reporting for Improved Study Quality CBPR community-based participatory research CDC Centers for Disease Control and Prevention CDS clinical decision support CIOMS Council for International Organizations of Medical Sciences CLIA Clinical Laboratory Improvement Amendments of 1988 CLIAC Clinical Laboratory Improvement Advisory Committee CMS Centers for Medicare & Medicaid Services CSER Clinical Sequencing Exploratory Research consortium CTSA Clinical and Translational Science Awards Program CU clinical utility CV clinical validity DNA deoxyribonucleic acid DRS designated record set DTC direct-to-consumer EHR electronic health record eMERGE Electronic Medical Records and Genomics Network EPA Environmental Protection Agency FDA Food and Drug Administration FHS Framingham Heart Study GAP Genomic Advisory Panel GINA Genetic Information Nondiscrimination Act of 2008 HHS Department of Health and Human Services HIPAA Health Insurance Portability and Accountability Act of 1996 HIV human immunodeficiency virus IDE investigational device exemption IDIOM Scripps Idiopathic Diseases of Man Study IF incidental finding PREPUBLICATION COPY: UNCORRECTED PROOFS xix

IND investigational new drug IRB institutional review board ISO International Organization for Standardization KKI Kennedy V. Krieger Institute LDT laboratory developed test MRCT Multi-Regional Clinical Trials Center of Harvard and Brigham and Women’s Hospital NBAC National Bioethics Advisory Commission NCI National Cancer Institute NDA new drug application NGS next-generation sequencing NHGRI National Human Genome Research Institute NIEHS National Institute of Environmental Health Sciences NIH National Institutes of Health OCR Office for Civil Rights OHRP Office of Human Research Protection PCB polychlorinated biphenyl PCORI Patient-Centered Outcomes Research Institute PGT personal genetic test PHI personal health information PI principal investigator PU personal utility QA quality assurance QC quality control QMS quality management system RCT randomized controlled trial REVEAL Randomized EValuation of the Effects of Anacetrapib Through Lipid- modification clinical trial RoR return of individual research results SOP standard operating procedure VUS variant of unknown significance WHO World Health Organization PREPUBLICATION COPY: UNCORRECTED PROOFS xx

Abstract When is it appropriate to return individual research results to participants? The immense interest in this question has been fostered by the growing movement toward greater transparency and participant engagement in the research enterprise. Yet, the risks of returning individual research results—such as results with unknown validity—and the associated burdens on the research enterprise are competing considerations. A committee of the National Academies of Sciences, Engineering, and Medicine reviewed the current evidence on the benefits, harms, and costs of returning individual research results, while also considering the ethical, social, operational, and regulatory aspects of the practice. The committee’s report includes 12 recommendations directed to various stakeholders—investigators, sponsors, research institutions, institutional review boards (IRBs), regulators, and participants—and are designed to help (1) support decision making regarding the return of results on a study-by-study basis, (2) promote high-quality individual research results, (3) foster participant understanding of individual research results, and (4) revise and harmonize current regulations. SUPPORT DECISION MAKING REGARDING THE RETURN OF RESULTS ON A STUDY-BY-STUDY BASIS Decisions on whether to return of individual research results will vary depending on the characteristics of the research, the nature of the results, and the interests of participants. The justification for returning results becomes stronger as both the potential value of the result to participants and the feasibility of return increase. Investigators should not make assumptions about the kinds of results that participants may value and should incorporate participant needs, preferences, and values into their decision-making process. The responsible return of individual research results requires careful forethought and preparation. Thus, the committee recommends that investigators include plans in study protocols that describe whether results will be returned and, if so, when and how and that research sponsors and funding agencies require that applications for funding consistently address the issue. Additionally, institutions and IRBs should develop policies to support the review of plans to return individual research results. PREPUBLICATION COPY: UNCORRECTED PROOFS xxi

xxii RETURNING INDIVIDUAL RESEARCH RESULTS TO PARTICIPANTS PROMOTE HIGH-QUALITY INDIVIDUAL RESEARCH RESULTS Confidence in the validity of individual research results is critical to decisions about whether to return results to participants. Requirements established by the Clinical Laboratory Improvement Amendments of 1988 (CLIA) were designed to ensure the quality of results from clinical laboratories and are not appropriate or feasible for all research laboratories. However, no alternative exists that defines basic quality standards for research laboratories in the United States. To promote the quality of results returned and to improve the reproducibility of science, the committee recommends that the National Institutes of Health (NIH) lead an effort to develop a quality management system (QMS) for research laboratories testing human biospecimens. When individual research results are intended for clinical decision making in the study protocol, investigators must continue to perform tests only in laboratories that are CLIA certified. However, when results are not intended for clinical decision making in the study protocol, IRBs should permit the return of results under the recommended QMS—once developed—or after determining that the laboratory analysis is sufficient to provide confidence in the result, the value to participants outweighs the risks, and appropriate disclaimer information on the limitations of the validity and interpretation of the individual’s result is provided. FOSTER PARTICIPANT UNDERSTANDING OF INDIVIDUAL RESEARCH RESULTS Once the decision is made to return individual research results to participants, investigators and institutions should communicate those results in a manner that conveys the key takeaway messages and fosters participants’ understanding. Doing so requires providing contextualizing information and explanations that convey what is known and unknown about the meaning and potential clinical implications of the results, including the level of uncertainty in the results’ validity. Communications should be appropriate for participants with different needs, capabilities, resources, and backgrounds. The development of evidence-based best practices, which will require the systematic evaluation of the effectiveness of various approaches, will improve the quality of the process of returning individual research results. REVISE AND HARMONIZE CURRENT REGULATIONS As currently written and implemented, the regulations governing access to research laboratory test results are not harmonized: they afford inconsistent and inequitable access for participants, and regulatory conflicts create dilemmas for laboratories, investigators, and institutions. For example, the Centers for Medicare & Medicaid Services (CMS) prohibits the return of results from laboratories that are not CLIA-certified, but in some circumstances the Health Insurance Portability and Accountability Act of 1996 (HIPAA) may require the return of results requested by a participant, regardless of whether they were generated in a CLIA-certified laboratory. Accordingly, the committee recommends that regulators revise and harmonize the relevant regulations in a way that respects the interests of research participants in obtaining individual research results and appropriately balances the competing considerations of safety, quality, and burdens on the research enterprise. For example, CMS should revise CLIA PREPUBLICATION COPY: UNCORRECTED PROOFS

ABSTRACT xxiii regulations to allow for the return of results from non-CLIA certified laboratories when results are requested under the HIPAA access right and also when an IRB process determines it is permissible. However, the Office for Civil Rights of the Department of Health and Human Services should limit access to individual research results under HIPAA to those generated in a CLIA-certified laboratory or in a research laboratory compliant with the recommended externally accountable QMS for research laboratories. Taken together, the recommendations in this report promote a process-oriented approach to returning individual research results that considers the value to the participant, the risks and feasibility of return, and the quality of the research laboratory. The committee expects that adoption of its recommendations will lead to an increase in the return of individual research results over time, but it also acknowledges that this will create new demands on the research enterprise that cannot be addressed overnight. The recommendations in this report are intended to help stakeholders discuss and prepare for these responsibilities and to develop the necessary expertise, infrastructure, policies, and resources. The initial investments will likely be significant, but ultimately the return on those investments in terms of increased participant trust and engagement with the research enterprise and higher quality standards for research laboratories will be worthwhile. PREPUBLICATION COPY: UNCORRECTED PROOFS

Next: Summary »
Returning Individual Research Results to Participants: Guidance for a New Research Paradigm Get This Book
×
Buy Prepub | $94.00 Buy Paperback | $85.00
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

When is it appropriate to return individual research results to participants? The immense interest in this question has been fostered by the growing movement toward greater transparency and participant engagement in the research enterprise. Yet, the risks of returning individual research results—such as results with unknown validity—and the associated burdens on the research enterprise are competing considerations.

Returning Individual Research Results to Participants reviews the current evidence on the benefits, harms, and costs of returning individual research results, while also considering the ethical, social, operational, and regulatory aspects of the practice. This report includes 12 recommendations directed to various stakeholders—investigators, sponsors, research institutions, institutional review boards (IRBs), regulators, and participants—and are designed to help (1) support decision making regarding the return of results on a study-by-study basis, (2) promote high-quality individual research results, (3) foster participant understanding of individual research results, and (4) revise and harmonize current regulations.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  6. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  7. ×

    View our suggested citation for this chapter.

    « Back Next »
  8. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!