Considerations for
Returning Individual
Genomic Results from
Population-Based
Surveys

Focus on the National Health and
Nutrition Examination Survey

__________

Celeste Stone, Rapporteur

Committee on National Statistics

Division of Behavioral and
Social Sciences and Education

Proceedings of a Workshop

NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001

This activity was supported by a contract between the National Academy of Sciences and the Centers for Disease Control and Prevention (75D30121D11240/75D30122F00003). Support of the work of the Committee on National Statistics is provided by a consortium of federal agencies through a grant from the National Science Foundation (award number SES-1560294) and several individual contracts. 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: 978-0-309-70489-2
International Standard Book Number-10: 0-309-70489-8
Digital Object Identifier: https://doi.org/10.17226/27105

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. (2023). Considerations for returning individual genomic results from population-based surveys: Focus on the National Health and Nutrition Examination Survey: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/27105.

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WORKSHOP PLANNING COMMITTEE ON CONSIDERATIONS FOR RETURNING INDIVIDUAL GENOMIC RESULTS FROM POPULATION-BASED SURVEYS WITH A FOCUS ON THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY

JEFFREY R. BOTKIN (Chair), University of Utah, Emeritus

LESLIE G. BIESECKER, National Human Genome Research Institute

NATASHA BONHOMME, Expecting Health

ADAM H. BUCHANAN, Genomic Medicine Institute, Geisinger

DANA C. CRAWFORD, Cleveland Institute for Computational Biology, Case Western Reserve University

DAVID FORSTER, WCG IRB (formerly known as Western Institutional Review Board-Copernicus Group)

INGRID A. HOLM, Harvard Medical School; Boston Children’s Hospital

Staff

BRIAN HARRIS-KOJETIN, Responsible Staff Officer

ALEX HENDERSON, Senior Program Assistant

THERESA PATTEN, Christine Mirzayan Science and Technology Policy Fellow

Consultant

CELESTE STONE, Study Director

COMMITTEE ON NATIONAL STATISTICS

ROBERT M. GROVES (Chair), Georgetown University

LAWRENCE D. BOBO, Harvard University

ANNE C. CASE, Princeton University, Emeritus

MICK P. COUPER, University of Michigan

DIANA FARRELL, JPMorgan Chase Institute

ROBERT GOERGE, University of Chicago

ERICA L. GROSHEN, Cornell University

DANIEL E. HO, Stanford University

HILARY HOYNES, University of California, Berkeley

DANIEL KIFER, The Pennsylvania State University

SHARON LOHR, Arizona State University, Emerita

JEROME P. REITER, Duke University

NELA RICHARDSON, ADP Research Institute

JUDITH A. SELTZER, University of California, Los Angeles

C. MATTHEW SNIPP, Stanford University

ELIZABETH A. STUART, Johns Hopkins Bloomberg School of Public Health

Staff

MELISSA CHIU, Director

BRIAN HARRIS-KOJETIN, Senior Scholar

CONSTANCE F. CITRO, Senior Scholar

Reviewers

This Proceedings of a Workshop 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 proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.

We thank the following individuals for their review of this proceedings:

We also thank staff member DAVID DIERKSHEIDE for reading and providing helpful comments on this manuscript.

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings, nor did they see the final draft before its release. The review of this proceedings was overseen by SUZANNE BAKKEN, Columbia University. She was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteur and the National Academies.

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Acknowledgments

Funding for the workshop was provided by the Centers for Disease Control and Prevention’s (CDC’s) Office of Advanced Molecular Detection as part of a CDC Human Genomics Initiative. The workshop was developed with input from the CDC’s National Center for Health Statistics, Office of Genomics and Precision Public Health, and Office of Science. The committee would like to thank the following staff at the CDC for being generous with their time and attention in answering the committee’s questions and providing information about the National Health and Nutrition Examination Survey program wherever possible: Brian K. Kit, Katherine Kolor, and Jody McLean. The committee is grateful to all the speakers for sharing their experiences and knowledge by developing and providing high-quality and relevant presentations for this workshop. The rapporteur is grateful to Theresa Patten, a Christine Mirzayan Science and Technology Policy Fellow, for contributing her subject matter expertise to the proceedings. Finally, the workshop and proceedings would not be possible without help from knowledgeable and talented National Academies staff who provided guidance, shared best practices, and assisted in navigating institutional processes and procedures.

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Contents

Acronyms and Abbreviations

1 Introduction

ROLE OF THE PLANNING COMMITTEE

ORGANIZATION OF THE PROCEEDINGS

OPENING REMARKS TO THE WORKSHOP

2 NHANES Current Structure and Opportunities for Adding Genomics (Session 1)

OVERVIEW OF THE NHANES RESOURCE

TYPES OF RESEARCH SUPPORTED BY THE CURRENT SURVEY DATA

GENETICS 101/201: UNDERSTANDING THE CURRENT GENETIC TESTING LANDSCAPE

QUESTIONS AND REFLECTIONS FOR SESSION 1

3 Return of Clinically Actionable Genetic Results (Session 2)

WHAT DATA IS BEING GENERATED?: IMPLICATIONS FOR RETURNING RESULTS

ETHICAL ARGUMENTS REGARDING THE RETURN OF RESEARCH RESULTS

CURRENT ACMG LIST, PROCESS, AND ALTERNATIVES

ATTITUDES AND OUTCOMES OF RETURNING RESULTS TO PARTICIPANTS

ISSUES REGARDING DATA REANALYSIS FOR ACTIONABLE VARIANTS

QUESTIONS AND RELFECTIONS FOR SESSION 2

4 Regulatory Issues in the Return of Genetic Results (Session 3)

CLINICAL LABORATORY IMPROVEMENT AMENDMENTS LAB CERTIFICATION AND TEST VALIDATION

POTENTIAL FDA OVERSIGHT AND APPROVAL

NAVIGATING FEDERAL AND STATE-SPECIFIC LAWS GOVERNING GENETIC TESTING AND THE RETURN OF RESULTS

QUESTIONS AND REFLECTIONS FOR SESSION 3

GENERAL END-OF-DAY DISCUSSIONS FOR SESSIONS 1, 2, AND 3

5 Process for the Return of Genetic Results (Session 4)

INFRASTRUCTURE, EXPERTISE, AND OTHER NECESSARY RESOURCES TO COMMUNICATE RESULTS IN A RESEARCH SETTING

COMMUNICATION STRATEGIES IN A CLINICAL RESEARCH SETTING

COMMUNICATION STRATEGIES IN A DIRECT-TO-CONSUMER CONTEXT

SPECIAL ISSUES FOR RETURNS TO PARTICIPANTS IN LOW-RESOURCE COMMUNITIES: LESSONS FROM THE HEALTHY NEVADA PROJECT

SPECIAL ISSUES FOR RETURNS TO PARTICIPANTS IN LOW-RESOURCE COMMUNITIES: LESSONS FROM THE BIOME PROJECT

QUESTIONS AND REFLECTIONS FOR SESSION 4

6 Informed Consent When Considering Returning Genetic Results to Survey Participants (Session 5)

COMMUNITY ENGAGEMENT AND INFORMED CONSENT IN NHANES

INFORMED CONSENT: CONTENT FOR RETURN OF RESEARCH RESULTS AND BIOBANKING

THE INFORMED CONSENT PROCESS FOR RETURN OF RESULTS AND BIOBANKING

QUESTIONS AND REFLECTIONS FOR SESSION 5

GENERAL END-OF-DAY DISCUSSIONS FOR SESSIONS 4 AND 5

7 Considerations in the Return of Genetic Results: Lessons from Other Research Studies (Session 6)

GENOMICS ENGLAND

MILLION VETERAN PROGRAM

ALABAMA GENOMIC HEALTH INITIATIVE

ALL OF US

QUESTIONS AND REFLECTIONS FROM SESSION 6

8 Key Themes and Considerations for Future National Health and Nutrition Examination Survey (NHANES)

RECAP OF WORKSHOP DAYS 1 AND 2

PANEL DISCUSSION

Appendix A Public Meeting Agendas

Appendix B Committee and Speaker Biosketches

Appendix C Public-Facing Background Materials: Glossary of Terms and Acronyms

Appendix D Public-Facing Background Materials: Workshop Primer: Background and Context about the National Health and Nutrition Examination Survey (NHANES)

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Boxes, Figures, and Tables

BOXES

1-1 Statement of Task

4-1 Example of Personnel Needed to Meet Clinical Laboratory Improvement Amendments (CLIA) and Other Regulatory Requirements in a Mid-Sized Genomics Lab

6-1 NHANES Frequently Asked Questions Regarding Results from Future Testing of Specimens

FIGURES

3-1 Timeline of policy positions on genomics return of results

3-2 The spectrum of actionability, with two examples

3-3 Determinants of health and their contributions to premature death

4-1 All of Us Research Program return of genetic results

4-2 State legislation that impacts the return of genetic results

4-3 State legislation that limits insurance use of genetic information

5-1 Electronic health record timelines and survey responses for participants notified of findings (abridged)

5-2 Comparison of Healthy Nevada Project workflow versions 1.0 and 2.0

5-3 Opinions of BioMe Biobank participants and rates of consent to return results, by self-reported race/ethnicity

5-4 BioMe participants’ preferred professional for returning genetic results

6-1 Continuum of how biobanks differ for how much choice participants are given, the granularity of the choices given, and the timing of the choices

7-1 Inputs, considerations, and final model for consent for Genomics England

7-2 Actionability across pharmacogenes meeting Clinical Pharmacogenetics Implementation Consortium level A or B evidence threshold, overall and by ancestry

TABLES

3-1 Summary of File Types and Relative Accuracy for Various Genomic Assays

3-2 File Types and Amount of Data (in MB) Generated by Various Genomic Assays

7-1 Key Features of Two Pilot Studies for Returning Genetic Results in the Million Veteran Program (MVP)

7-2 Genes Currently Defined as Actionable for the Clinical and Population Cohorts of the Alabama Genomic Health Initiative, with Disease Indication, Grouped by Disease Type

Acronyms and Abbreviations

___________________

¹ For more information, see https://www.ncbi.nlm.nih.gov/clinvar/

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