Methods: Analysis of the characteristics of consenting
individuals participating in the National Health and Nutrition Examination
Survey, a nationally representative survey of the US household population.
Results: In 1999, 84% (95% confidence interval 82.4-85.6)
of eligible participants consented to have their blood samples included in a
national repository for genetic research. In 2000, 85.3% (95% confidence
interval 84.0-86.6) consented. Females and black participants in both years
were least likely to consent (1999, 82.2% and 73.2%; 2000, 83.6% and 81.3%,
respectively). An assessment by logistic regression demonstrated that in both
years only non-Hispanic black race/ethnicity was a significant independent
predictor for not consenting to future genetic research.
Conclusion: Although non-Hispanic black individuals have
overall response rates similar to those of the other racial/ethnic groups,
they are less likely to agree to have a blood sample saved for future genetic
research. In balance, however, these findings demonstrate wide acceptance
among survey participants for allowing storage of specimens for future genetic
research across many demographic variables.
Key Words:
informed consent; genetic research; survey;
representative sample; household population
With the recent advances in the understanding of
the human genome, the scientific community has begun to recognize the
importance of stored biologic samples and of population databases with
genetic, phenotypic, and socio-demographic data.
1-4 Such databases may be of
value both for estimating the distribution of various alleles in the general
population and in specific subpopulations as well as for helping to understand
the causal pathways for common diseases that result from complex interactions
between genetic and environmental factors. The addition of the collection and
storage of blood samples for genetic research was proposed to be included in
the current National Health and Nutrition Examination Survey (NHANES)
primarily because the ongoing survey already includes extensive socio-demographic and clinical data. Furthermore, NHANES is the only national
survey that collects biologic specimens from a representative sample of the US
population.
Although there has been research on the public's
attitudes toward the use of biologic samples for genetic research,
5 there is little empirical
evidence on the willingness of research participants from a general population
to consent to have their genetic material included in repositories for
research purposes. Because NHANES used a unique, separate consent procedure to
document consent by participants for the storage and future genetic testing of
blood samples, these data present a unique opportunity to assess the
predictors of consent in a general population to have genetic samples included
in a research repository.
NHANES is a cross-sectional national survey that
is representative of the US civilian non-institutionalized population conducted
by the National Center for Health Statistics (NCHS), Centers for Disease
Control and Prevention (CDC). Although the survey has been conducted
periodically in the past, the current survey will be fielded continuously.
In this study, we analyze data from the 1999 and
2000 NHANES to assess the socio-demographic predictors of the willingness to
participate in genetic research in a diverse, general study population.
Survey design
The NHANES provides national statistics on the
health and nutritional status of the civilian non-institutionalized population
of the United States through household interviews and a standardized physical
examination in special mobile examination centers. Beginning in 1999, NHANES
became a continuous survey with each survey year based on a nationally
representative sample of the US civilian non-institutionalized population. The
procedures followed to select the sample and conduct the interview and
examination were similar to those used in previous years.
6 The goals of NHANES are to
monitor the nation's health by estimating the number and percentage of persons
in the US population and in designated subgroups with selected diseases and
risk factors; monitoring trends in the prevalence, awareness, treatment, and
control of selected diseases; monitoring trends in risk behaviors and
environmental exposures; analyzing risk factors for selected diseases;
studying the relationship between diet, nutrition, and health; exploring
emerging public health issues and new technologies; and establishing a
national probability sample of genetic material for future genetic research.
Data collection for NHANES occurs at three
levels: a brief household screener interview, an in-depth household survey
interview, and a medical examination. Consent for the examination and the
collection of the DNA specimen was obtained after the individual was selected
for participation in the study and the household interview was completed. Only
participants aged 20 or more years were eligible for this collection. Consent
for the collection of the DNA specimen was obtained separately from the
consent for the examination. The NHANES survey and consent documents were
approved by the CDC Institutional Review Board.
The analyses are presented in this report
separately for 1999 and 2000 because small changes were made in the consent
documents after the 1999 data collection (Appendix 1
and 2).
In 1999, the consent form was titled "Consent for Specimen Storage and
Future Research." Although only participants aged 20 or more years were
asked to agree to future genetic research, younger participants and their
parents were asked whether they would agree to the storage of blood or urine
for other research projects (i.e., assessing exposures to environmental
chemicals or infectious diseases). For the 1999 data collection, there were
separate documents for consent, assent (for children older than age 7), and
parental permission. Based on feedback from field staff during 1999, in 2000
these multiple consent documents were combined into one document and the title
was changed to "Consent/Assent and Parental Permission for Specimen
Storage and Continuing Studies." This wording change, made with the
approval of the NHANES Institutional Review Board, was designed to address
concerns raised by the NHANES interviewers that the word "research"
was not well understood by the public. NHANES participants are informed that
all the health data collected will be kept strictly private and that unless
they agree the staff are not allowed to discuss their participation in the
survey under penalty of federal law: Sections 308 (d) of the Public Health
Service Act (42 USC 242 m) and the Privacy Act of 1974 (5USC 552C) (http://www.cdc.gov/nchs/data/nhanes/
99bkpant.pdf). The DNA samples and all
stored specimens and data from the survey cannot be identified by non-staff
researchers or anyone using the data files. Data are re-categorized or
top-coded if there is any potential for identification of participants.
The purpose of the stored specimens was to
provide a resource for new scientific tests including genetic laboratory tests
that were not available when the participant was examined. Therefore, the
participant was informed that no specific studies were currently planned and
that researchers using their samples would not be contacting them for any
additional information. They were also told that NCHS would not contact them
with specific results, but would provide information on the studies being
conducted in a newsletter and that proposals for use of their specimens would
be reviewed for scientific merit and by an institutional review board to
ensure that the proposed research was ethical. Finally, they were also told
they could remove their specimens at any time and were given a toll-free
number to get more information about a particular study.
During 1999, 2721 adults aged 20 years and older
were selected to participate. In 2000, 3680 participants aged 20 years and
older were selected.
Information on race and ethnicity was collected
in two stages, as part of the screener interview and as a part of the in-home
household interview. The race/ethnicity variables in
Table 1 were based on information obtained through a screener, often
provided by a single household member who reported basic demographic data on
persons in the household for the purpose of sample selection. This screening
was based on two questions asked at the door for Mexican American or Hispanic
ethnicity, then the selection of a race category. The race/ethnicity data from
the screener interview differ slightly from the final data obtained from
multiple questions asked of the participant in the interview (13 recoded to
non-Hispanic white in 1999; eight recoded to non-Hispanic white in 2000).
Race/ethnicity was categorized as non-Hispanic
white, non-Hispanic black, and Mexican American. Individuals who did not
self-select into these categories were classified as "other." The
poverty index ratio was calculated by dividing total family income by the
poverty threshold index adjusted for family size at year of interview. All
interviews were translated into either English or Spanish. If another language
was spoken by the participant, a family member or local interpreter translated
the interview into English.
Because the 1999 survey had lower response rates
than usually obtained in NHANES, an extensive public relations campaign was
begun late in 1999 to explain better the survey and to increase public
acceptance. NHANES improved working relationships with local health
departments and local public affairs authorities, enhanced outreach to the
communities through church and community organizations, improved and
simplified consent documents, and developed outreach materials that addressed
specific concerns of segments of the population. These materials included a
brochure designed to address the legacy of the Tuskegee syphilis study which
outlined reforms in human subject protection, fact sheets for Mexican
Americans and African Americans, and a brochure for pregnant women. These
materials were used if a potential participant raised these issues.
Interviewers reported that these materials were very useful answering concerns
and in obtaining respondent cooperation. Although response rates to the survey
increased 8% between 1999 and 2000, the impact of specific efforts could not
be assessed.
The category of future
non-genetic research on the
consent documents was specified so participants could agree to having their
blood kept for other laboratory tests if they were not comfortable with
genetic research. Only 14 individuals in 1999 and 32 in 2000 did not consent
to genetic research while still agreeing to other types of future health
research. In 1999, 96% of interviewed individuals agreed to be examined and
87% of examined individuals aged 20 or more years agreed to phlebotomy. In
2000, 98% of those interviewed agreed to be examined and 88% had phlebotomy.
There were no significant racial/ethnic differences in the examination or
phlebotomy rates in both years.
Statistical analysis
These analyses are based on data used to monitor
the survey operations. Rates are therefore not weighted to produce national
estimates. Consent rates, 95% confidence intervals, and logistic regression
analysis were computed with SAS version 8.2 (SAS Institute, Inc., Cary, NC).
Comparisons were performed with the χ2
test. All P values quoted are two-tailed. The "other"
racial group was deleted from the logistic regression because of the small
sample size and the diverse composition of the group. The language of
interview could also not be modeled, as it was not evenly distributed among
the three racial/ethnic groups.
Table 1 presents the overall response rates to the household interview in
1999 and 2000 for individuals aged 20 or more years. Although survey response
rates exceeded 70% in 1999, response was significantly higher in 2000. This
increase was seen in every race, sex, and age group. The largest increases in
response were for non-Hispanic whites and participants under the age of 40
years.
Of the 2721 individuals aged 20 or more years
selected for the survey in 1999, 1947 (71.6%) completed the interview and were
eligible to sign the consent for storage of their DNA for future genetic
studies. Of these, 1635 (84.0%) agreed to the collection of the DNA specimen (Table
2). In 2000, of the 3680 individuals in this age group selected,
2933 (79.7%) completed the interview, and of these, 2501 (85.3%) agreed to the
DNA specimen collection.
Table 2
presents the characteristics of those eligible to sign the
genetic consent document by demographic categories for 1999 and 2000. The
lowest consent rates were for non-Hispanic blacks in both years, although the
response was significantly higher for blacks in 2000 compared with 1999. In
both years females were significantly less likely to consent (P <
0.05) than males. This gender difference was seen in both years for all
racial/ethnic groups except "others" but was only significant (P
< 0.05) for non-Hispanic whites
(data not shown). In both years the youngest and oldest age groups had the
lowest genetic consent rates. Consent rates were more variable by demographic
categories in 1999 compared with 2000, but indicators of economic status,
education, and poverty level were not significantly associated with
differences in either year.
A logistic regression was performed to determine
which factors independently contributed to a willingness to consent in the two
study years (Table 3). Only non-Hispanic black race/ethnicity remained associated with
an unwillingness to consent to genetic research in both years. In 2000 Mexican
Americans were also less likely to consent.
NHANES is the only national survey that collects
biologic samples on a representative sample of the US population. The debate
on the appropriate consent for genetic research is not a new one for the
program. Blood lymphocytes were collected in the previous survey (NHANES III,
1988-1994) in anticipation of advances in genetic research. Although the
consent document used in that survey informed participants that some of the
blood collected would be stored for future testing, genetic research was not
specifically mentioned. This collection and the ethical issues of using the
stored samples resulted in a workshop and consensus statement addressing the
need for specific consent for genetic studies.
7 This context was the basis for
the development of the informed consent documents for future research from
specimens collected in the current survey. The assessment of acceptance of
this collection is important because of the value of a nationally
representative repository of genetic material and ability to generalize the
knowledge gained from survey participants.
There has been speculation about the willingness
of the general population to agree to participate in genetic research,
5 although most studies
addressing this issue have looked at participation in clinical settings and
are based on genetic testing of members of high-risk families or on the
storage of samples related to a specific disorder.
2, 7-12 A
recent study in Sweden demonstrated high response rates (93%) when a randomly
selected sample were recontacted and asked whether blood previously collected
could be used for academic genetic research.
13 One of the challenges for
NHANES was to develop a "Future Genetic Research" consent document
that provided sufficient information for individuals to make an informed
decision on the future use of their blood specimen for the broad category of
health research. The survey is a general health study that covers a variety of
topics; therefore, we did not want to restrict this national resource by
limiting the future research to topic areas that might be outdated even before
the resource could be used.
14
Consent for the collection of a DNA specimen
among those who agreed to the interview increased in all demographic groups
between 1999 and 2000, possibly related to greater outreach activities as
described in the "Methods" section. Despite these increases, there
continued to be less acceptance of genetic research by females in every
racial/ethnic group and non-Hispanic blacks in general. In both years, the
NHANES program separated the consent for future nongenetic research from
consent for genetic research to allow participants who were not comfortable
with the concept of genetic research to have their biologic specimens to be
kept for other research projects. This option was generally ignored by
participants. They agreed to the storage of specimens and future research
including genetic research as one concept with about 1.0% in both years
checking the box for future research but not the box for genetic research.
Presenting the consent document and the fact
sheet on genetic research to NHANES participants differs from recruitment and
consent issues in other genetic research studies, and therefore these results
might not be directly relevant to more targeted study populations.
Participants in NHANES are not selected on the basis of any known disease or
condition, but are representative of the US population as defined by age,
race, and sex. The broad-based goals of the survey do not provide a motivation
based on personal or familial interest in a disease. As many as 11 examination
components, 40 separate questionnaire sections, and more than 200 laboratory
tests are performed on participants depending on their age. Topic areas cover
diverse areas of health research such as cardiovascular disease or sexually
transmitted diseases.
Recent advances in molecular genetics and human
genome research have provided new scientific tools but have also raised issues
concerning the ethics of such research.
15, 16 In
addition, DNA sampling and storage from populations has also been criticized,
17 although this concept also
has its supporters who believe that such collections are necessary to
determine allele frequencies in populations to better understand disease and
to develop potential interventions.
2, 3 Finally,
concerns about inclusion of all Americans in research, including minorities,
has also received attention, especially with the US government efforts to
include all racial/ethnic groups in human research.18
The results of this study suggest that there is
broad-based general acceptance across the demographic groups for participation
in genetic research such as that proposed for the NHANES genetic repository.
There was some variation in acceptance in subgroups of participants, with
lower response among blacks and females. The participation of African
Americans in medical research has been widely discussed in the medical
literature because of the historical relative absence of racial/ethnic
minorities in medical research and the recent government encouragement for
their inclusion in all human subject research.
8, 9, 18,
19 The studies that have explored the
concerns of African Americans about participating in clinical trials and
familial cancer research have concluded that trust and community involvement
are essential for adequate participation.
8-10 Our results demonstrate that
NHANES has overcome the barriers of African American participation in the
survey, but a higher percentage than the other racial/ethnic groups opted out
of the storage of blood for genetic research. Despite this disparity,
combining data from 1999 and 2000, almost 80% of African Americans agreed to
have their genetic samples included in a research repository. The general
acceptance of the collection of a blood sample for genetic research encourages
us that the program can continue to gain the trust necessary to reduce any
disparities in genetic consent rates.
The lower percentage of females providing consent
was surprising because studies on genetic testing in families with hereditary
diseases have generally shown equal or more acceptance by women.
11, 12
Further research needs to be conducted to determine why this discrepancy
exists.
There is increasing recognition of the need for
population-based data to understand the public health implications of genetic
discoveries by determining the genetic variations across differing populations
and ethnic groups. 3,
5, 20 The availability
of other biologic and environmental measures collected in NHANES increases the
benefit of this resource. The challenge is to provide sufficient information
so that participants can make an informed decision on their willingness to
participate in the survey and to allow their blood to be stored for future
genetic studies. Data from NHANES 1999-2000 provide empirical evidence that
people will agree to genetic research even without the incentive of
determining their own susceptibility for disease. The relative success of
NHANES and the increase in consent rates between 1999 and 2000 demonstrate
that with appropriate operations and outreach efforts, population-based
genetic studies can achieve high consent rates in a general population.
The lack of differences with regard to
participation in the interview, examination, and phlebotomy but the presence
of a racial/ethnic difference in the consent for future studies also suggests
that researchers cannot assume consent for future genetic research among
individuals participating in research projects. Specific consent must be
obtained if an individual's autonomy is to be respected in all aspects of the
research, both current and future.
Acknowledgement
US government funds were used to support the
operation of the survey and these analyses.
Tables
Appendix
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