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Issues in Returning Individual Results from Genome Research Using Population-Based Banked Specimens, with a Focus on the National Health and Nutrition Examination Survey: Workshop Summary (2014)

Chapter: 2 Genomics in Population-Based Data Collection: The Example of the National Health and Nutrition Examination Survey

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Suggested Citation:"2 Genomics in Population-Based Data Collection: The Example of the National Health and Nutrition Examination Survey." National Research Council. 2014. Issues in Returning Individual Results from Genome Research Using Population-Based Banked Specimens, with a Focus on the National Health and Nutrition Examination Survey: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18829.
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2

Genomics in Population-Based
Data Collection:
The Example of the National Health
and Nutrition Examination Survey

The National Health and Nutrition Examination Survey (NHANES) is a program of studies designed to assess the health and nutritional status of adults and children in the United States. NHANES is a major program of the National Center for Health Statistics (NCHS), which is part of the Centers for Disease Control and Prevention (CDC) and has the responsibility for producing vital and health statistics for the nation. The NHANES program began in the early 1960s and has been conducted as a series of surveys focusing on different population groups or health topics. In 1999, the survey became a continuous program that has a changing focus on a variety of health and nutrition measurements to meet emerging needs. NHANES is a cross-sectional survey of the U.S. household population with an annual sample size of approximately 5,000 individuals. These persons are located in counties across the country, 15 of which are visited each year.

Information is collected through in-person home interviews and health examinations at mobile examination centers. The NHANES interview includes demographic, socioeconomic, dietary, and health-related questions. The examination component consists of medical, dental, and physiological measurements, as well as laboratory tests administered by highly trained medical personnel. Findings from this survey are used to determine the prevalence of major diseases and risk factors for diseases. Information is used to assess nutritional status and its association with health promotion and disease prevention. NHANES findings are also the basis for national standards for such measurements as height, weight, and

Suggested Citation:"2 Genomics in Population-Based Data Collection: The Example of the National Health and Nutrition Examination Survey." National Research Council. 2014. Issues in Returning Individual Results from Genome Research Using Population-Based Banked Specimens, with a Focus on the National Health and Nutrition Examination Survey: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18829.
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blood pressure. Data from the survey are used in epidemiological studies and health sciences research, which help develop public health policy and design health programs and services for the nation. The NHANES Website (http://www.cdc.gov/nchs/nhanes.htm [June 2014]) has a large amount of information about the survey and related research and results.

In this session of the workshop, Kathryn Porter, NCHS, provided an overview of the NHANES. The overall goal of NHANES is to assess the health and nutritional status of children and adults in the United States. The survey focuses on chronic disease, on measures of environmental toxicants, and on diet and nutrition. Another goal of NHANES, which is the focus of the workshop and this summary, is to create and maintain a nationally representative specimen bank.

To obtain participant permission for specimen collection, NHANES uses a four-consent design as part of its continuous survey. There is consent for a household interview and a separate consent for physical examination. The interview and exam response rates have hovered around 75-77 percent, quite high for a health survey (Zipf et al., 2013). NHANES also asks for consent to store blood and urine for nongenetic future research and asks for a separate consent from participants aged 20 and over to store blood for future genetic research. The latter two consents state that the survey organization does not know what tests will be done on the specimens in the future and that participants will not be contacted with results. About 85-90 percent of adults who agree to the exam also agree to allow NHANES to store specimens for genetic research (McQuillan, Pan, and Porter, 2006).

The NHANES staff processes a wide range of specimens, which are sent to 24 laboratories across the country and become the basis of more than 500 assays. Relatively few of these are reported back to participants, namely, only those that have clinical relevance to participants. Participants receive a final report with a preset number of findings in 12 to 16 weeks after the exam and are urged to discuss results with their doctors. If participants want help on how they should follow up on a condition, or about finding an appropriate clinic, referrals are provided. NHANES does not cover any of the costs of follow-up.

As Porter explained, NHANES seeks to report findings that are valid and obtained by a CLIA-certified laboratory.1 Reportable findings should have significant implications for a participant’s health concerns, and a course of action to ameliorate or treat the concerns should be readily available, both of which are in line with recommendations from the Presi-

__________________

1CLIA refers to regulations established by federal Clinical Laboratory Improvement Amendments; see http://www.cms.gov/Regulations-and-Guidance/Legislation/CLIA/index.html?redirect=/clia/ [June 2014].

Suggested Citation:"2 Genomics in Population-Based Data Collection: The Example of the National Health and Nutrition Examination Survey." National Research Council. 2014. Issues in Returning Individual Results from Genome Research Using Population-Based Banked Specimens, with a Focus on the National Health and Nutrition Examination Survey: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18829.
×

dential Commission for the Study of Bioethical Issues (see http://www.bioethics.gov [June 2014]). Survey participants always have the option to opt out; that is, to say that they do not want to receive any such results. A very small percentage of participants actively opt out.

NHANES DNA specimens have been banked since 1991 and are physically stored at the CDC in Atlanta. From various cycles of NHANES, about 26,000 individuals have given permission to store their specimens in the DNA bank. Data are held within the CDC for confidentiality purposes. No genomic results are allowed into the public domain.

The DNA bank was opened to researchers in 1999 after considerable effort to establish procedures for releasing specimens to researchers while maintaining confidentiality protections promised by law. It was decided that researchers could not investigate genes with clinical relevance because NCHS does not have the capability of providing genetic counseling. Hence, the agency only accepted research proposals that involved candidate genes; that is, single nucleotide polymorphisms (SNPs) of interest. NCHS could critically review these proposals and determine if those SNPs were reportable or not. Most approved research requests involved common gene variants with relatively low associated risk.

As time and science marched on, Porter said, two things changed. First, technology evolved and targeted gene analysis was no longer the standard. NCHS began to receive proposals for genome-wide association studies (GWAS) done with chips with millions of SNPs. Such studies may generate incidental findings, and the question arose as to how potentially reportable gene variants would be handled. The second change involved an evolving ethical context. There was increasing recognition among investigators, institutional review board (IRB) members, and bioethicists that blanket nondisclosure of individual research results and/or incidental findings may be inappropriate in public health research. The acceptability of the NHANES nondisclosure agreements that participants signed in the past came into question.

The NHANES program consulted with review boards and ethicists about how to proceed, and the upshot, Porter explained, was the concept of “binning” the genome, shown in Figure 2-1. Gene variants could be sorted into buckets or bins, with Bin Three having genes of unknown clinical implication and Bin Two containing variants within genes that are clinically valid but not directly actionable. The consensus was that NHANES would not have to act on or report back on items in Bins Two and Three.

Bin One contains variants within genes that have direct clinical utility and for which there are treatment guidelines. The NHANES consultative process recommended that Bin One variants should be reported to participants (Berg, Khoury, and Evans, 2011). This approach was presented

Suggested Citation:"2 Genomics in Population-Based Data Collection: The Example of the National Health and Nutrition Examination Survey." National Research Council. 2014. Issues in Returning Individual Results from Genome Research Using Population-Based Banked Specimens, with a Focus on the National Health and Nutrition Examination Survey: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18829.
×

image

FIGURE 2-1 Binning the genome.
NOTE: An NHANES consultative process recommended that only Bin 1 variants should be considered for reporting.
SOURCE: Adapted from Berg, Khoury, and Evans (2011).

to the NCHS Board of Scientific Counselors, which then called for wider input on how to proceed, not only with regard to NHANES but also because this has become an important issue for many population-based studies.

Suggested Citation:"2 Genomics in Population-Based Data Collection: The Example of the National Health and Nutrition Examination Survey." National Research Council. 2014. Issues in Returning Individual Results from Genome Research Using Population-Based Banked Specimens, with a Focus on the National Health and Nutrition Examination Survey: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18829.
×
Page 5
Suggested Citation:"2 Genomics in Population-Based Data Collection: The Example of the National Health and Nutrition Examination Survey." National Research Council. 2014. Issues in Returning Individual Results from Genome Research Using Population-Based Banked Specimens, with a Focus on the National Health and Nutrition Examination Survey: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18829.
×
Page 6
Suggested Citation:"2 Genomics in Population-Based Data Collection: The Example of the National Health and Nutrition Examination Survey." National Research Council. 2014. Issues in Returning Individual Results from Genome Research Using Population-Based Banked Specimens, with a Focus on the National Health and Nutrition Examination Survey: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18829.
×
Page 7
Suggested Citation:"2 Genomics in Population-Based Data Collection: The Example of the National Health and Nutrition Examination Survey." National Research Council. 2014. Issues in Returning Individual Results from Genome Research Using Population-Based Banked Specimens, with a Focus on the National Health and Nutrition Examination Survey: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/18829.
×
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Population surveys traditionally collect information from respondents about their circumstances, behaviors, attitudes, and other characteristics. In recent years, many surveys have been collecting not only questionnaire answers, but also biologic specimens such as blood samples, saliva, and buccal swabs, from which a respondent's DNA can be ascertained along with other biomarkers (e.g., the level of a certain protein in the blood). The National Health and Nutrition Examination Survey (NHANES), sponsored by the National Center for Health Statistics (NCHS), has been collecting and storing genetic specimens since 1991, and other surveys, such as the Health and Retirement Study (HRS) funded by the National Institute on Aging, have followed suit. In order to give their informed consent to participate in a survey, respondents need to know the disposition and use of their data. Will their data be used for one research project and then destroyed, or will they be archived for secondary use? Sponsors of repeated cross-sectional surveys, such as NHANES, and of longitudinal surveys that follow panels of individuals over time, such as HRS, generally want to retain data for a wide range of secondary uses, many of which are not explicitly foreseen at the time of data collection. They typically inform respondents that their data will be stored in a secure manner and may be provided to researchers with suitable protections against individual identification.

The addition of biologic specimens to a survey adds complications for storing, protecting, and providing access to such data and measurements made from them. There are also questions of whether, when, and for which biologic measurements the results should be reported back to individual respondents. Recently, the cost of full genomic sequencing has plummeted, and research findings are beginning to accumulate that bear up under replication and that potentially have clinical implications for a respondent. For example, knowing that one possesses a certain gene or gene sequence might suggest that one should seek a certain kind of treatment or genetic counseling or inform one's blood relatives. Biomedical research studies, in which participants are asked to donate tissues for genetic studies and are usually told that they will not be contacted with any results, are increasingly confronting the issue of when and which DNA results to return to participants.

Issues in Returning Individual Results from Genome Research Using Population-Based Banked Specimens, with a Focus on the National Health and Nutrition Examination Survey is the summary of a workshop convened in February 2013 by the Committee on National Statistics in the Division of Behavioral and Social Sciences and Education of the National Research Council. This report considers how population surveys, in particular NHANES, should implement the reporting of results from genomic research using stored specimens and address informed consent for future data collection as well as for the use of banked specimens covered by prior informed consent agreements. The report will be of interest to survey organizations that include or contemplate including the collection of biologic specimens in population surveys for storing for genetic research. The issues involved are important for advancing social, behavioral, and biomedical knowledge while appropriately respecting and protecting individual survey respondents.

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