Delivery of Genomic Medicine for Common Chronic Adult Diseases

Abstract

The greatest public health benefit of advances in understanding the human genome may be realized for common chronic diseases such as cardiovascular disease, diabetes mellitus, and cancer. Attempts to integrate such knowledge into clinical practice are still in the early stages, and as a result, many questions surround the current state of this translation.
To synthesize current information on genetic health services for common adult-onset conditions by examining studies that have addressed the outcomes, consumer information needs, delivery, and challenges in integrating these services.
MEDLINE articles published between January 2000 and February 2008.
Original research articles and systematic reviews dealing with common chronic adult-onset conditions were reviewed. A total of 3371 citations were reviewed, 170 articles retrieved, and 68 articles included in the analysis.
Data were independently extracted by one reviewer and checked by another with disagreement resolved by consensus. Variables assessed included study design and 4 key areas: outcomes of genomic medicine, consumer information needs, delivery of genomic medicine, and challenges and barriers to integration of genomic medicine.
Sixty-eight articles contributed data to the synthesis: 5 systematic reviews, 8 experimental studies, 35 surveys, 7 pre/post studies, 3 observational studies, and 10 qualitative reports. Three systematic reviews, 4 experimental studies, and 9 additional studies reported on outcomes of genetic services. Generally there were modest positive effects on psychological outcomes such as worry and anxiety, behavioral outcomes have shown mixed results, and clinical outcomes were less well studied. One systematic review, 1 randomized controlled trial, and 14 other studies assessed consumer information needs and found in general that genetics knowledge was reported to be low but that attitudes were generally positive. Three randomized controlled trials and 13 other studies assessed how genomic medicine is delivered and newer models of delivery. One systematic review and 19 other studies assessed barriers; the most consistent finding was the self-assessed inadequacy of the primary care workforce to deliver genetic services. Additional identified barriers included lack of oversight of genetic testing and concerns about privacy and discrimination.
Many gaps in knowledge about organization, clinician, and patient needs must be filled to translate basic and clinical science advances in genomics of common chronic diseases into practice.

Full text

CLINICIAN’S CORNER
REVIEW
Delivery of Genomic Medicine
for Common Chronic Ad ult Diseases
A Systematic Review
Maren T. Scheuner, MD, MPH
Pauline Sieverding, MPA, JD, PhD
Paul G. Shekelle, MD, PhD
T
HE GREATEST PUBLIC HEALTH BEN-
efit of advances in understand-
ing the human genome will
likely occur as genomic medi-
cine expands its focus from rare genetic
disorders to inclusion of more common
chronic diseases, such as coronary heart
disease, stroke, diabetes mellitus, and
cancer. These diseases are generally due
to complex interactions between varia-
tions in multiple genes and the environ-
ment and only rarely are due to single-
gene forms of the disease. With genomics
discoveries relating to common chronic
diseases, numerous genetic tests may
emerge that hold promise for signifi-
cant changes in the delivery of health care,
particularly in preventive medicine and
in tailoring drug treatment.
Attempts to integrate genetic/
genomic knowledge of common chronic
conditions into clinical practice are in the
early stages, and as a result, many ques-
tions surround the current state of this
translation. These questions include,
what are the outcomes of genomic medi-
cine? What is the current level of con-
sumer understanding about genomic
medicine, and what information do con-
sumers need before they seek services?
How is genomic medicine best deliv-
ered? What are the challenges and bar-
riers to integrating genomic medicine
into clinical practice? By examining stud-
ies relevant to these questions, this sys-
tematic review attempts to synthesize
available information on the delivery of
genomic medicine for common adult-
onset conditions.
CME available online at
www.jamaarchivescme.co m
and questions on p 1373.
Author Affiliations: RAND Corporation, Santa Monica,
California (Drs Scheuner and Shekelle); Department
of Veterans Affairs, Health Services Research and De-
velopment Service, Washington, DC (Dr Sieverding);
and VA Greater Los Angeles Healthcare System, Los
Angeles, California (Dr Shekelle).
Corresponding Author: Maren T. Scheuner, MD, MPH,
RAND Corporation, 1776 Main St, Santa Monica, CA
90401 (scheuner@rand.org).
Context The greatest public health benefit of advances in understanding the hu-
man genome may be realized for common chronic diseases such as cardiovascular dis-
ease, diabetes mellitus, and cancer. Attempts to integrate such knowledge into clini-
cal practice are still in the early stages, and as a result, many questions surround the
current state of this translation.
Objective To synthesize current information on genetic health services for common
adult-onset conditions by examining studies that have addressed the outcomes, con-
sumer information needs, delivery, and challenges in integrating these services.
Data Sources MEDLINE articles published between January 2000 and February 2008.
Study Selection Original research articles and systematic reviews dealing with com-
mon chronic adult-onset conditions were reviewed. A total of 3371 citations were re-
viewed, 170 articles retrieved, and 68 articles included in the analysis.
Data Extraction Data were independently extracted by one reviewer and checked
by another with disagreement resolved by consensus. Variables assessed included study
design and 4 key areas: outcomes of genomic medicine, consumer information needs,
delivery of genomic medicine, and challenges and barriers to integration of genomic
medicine.
Data Synthesis Sixty-eight articles contributed data to the synthesis: 5 systematic
reviews, 8 experimental studies, 35 surveys, 7 pre/post studies, 3 observational stud-
ies, and 10 qualitative reports. Three systematic reviews, 4 experimental studies, and
9 additional studies reported on outcomes of genetic services. Generally there were
modest positive effects on psychological outcomes such as worry and anxiety, behav-
ioral outcomes have shown mixed results, and clinical outcomes were less well stud-
ied. One systematic review, 1 randomized controlled trial, and 14 other studies as-
sessed consumer information needs and found in general that genetics knowledge was
reported to be low but that attitudes were generally positive. Three randomized con-
trolled trials and 13 other studies assessed how genomic medicine is delivered and newer
models of delivery. One systematic review and 19 other studies assessed barriers; the
most consistent finding was the self-assessed inadequacy of the primary care work-
force to deliver genetic services. Additional identified barriers included lack of over-
sight of genetic testing and concerns about privacy and discrimination.
Conclusion Many gaps in knowledge about organization, clinician, and patient needs
must be filled to translate basic and clinical science advances in genomics of common
chronic diseases into practice.
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METHODS
Data Sources and Study Selection
A review of articles published in peer-
reviewed journals between January
2000 and February 2008 was con-
ducted using MEDLINE. Searches were
conducted independently by 1 of us
(M.T.S.) and a professional librarian
using the following Medical Subject
Headings: genetics/genomics AND, out-
comes, patient information needs/
willingness to participate, delivery of ser-
vices, workforce manpower issues, role
of primary care, privacy issues, includ-
ing insurance and employment issues.
Reference mining of retrieved articles
from these searches was used to iden-
tify additional articles.
Only original research articles and
systematic review articles were re-
viewed. Systematic reviews were de-
fined by having described a search for
literature using computerized data-
bases (eg, MEDLINE) and the presen-
tation of findings in a systematic way.
If we identified an article as already
summarized in an accepted system-
atic review, we excluded it to avoid
double-counting data. Commentar-
ies, essays, legal analyses, consensus
statements, and editorials were ex-
cluded. Delivery of genetic services and
the associated issues were different in
developed as compared with develop-
ing countries; therefore, we excluded
articles about developing countries.
Because we were interested in ge-
netic services for adults who have or
who are at risk for common chronic dis-
eases, such as cancer, diabetes, and
coronary heart disease, we only in-
cluded articles concerning these types
of conditions, including multifacto-
rial forms of common chronic dis-
eases, and single-gene disorders that
typically present in adulthood and fea-
ture common chronic diseases, such as
breast and ovarian cancer due to BRCA1
and BRCA2 gene mutations or iron
overload due to HFE gene mutations.
This means we excluded articles that
dealt with children or adolescents; ge-
netic disorders that generally manifest
in childhood (eg, neurofibromatosis or
sickle cell anemia); rare genetic disor-
ders that manifest in adulthood (eg,
Huntington disease); reproductive is-
sues; animal studies; genetically modi-
fied foods; research that did not per-
tain to clinical genetic services (eg,
genetic association studies or studies de-
scribing participation in basic genet-
ics research); and genetics educa-
tional resources, materials, curricula, or
educational interventions for health
professionals or the public.
Data Extraction and Synthesis
Data were extracted (M.T.S.) and
checked (P.G.S.) with disagreement re-
solved by consensus. Variables as-
sessed included study design and top-
ics within 4 key areas based on the key
questions. We encountered 2 in-
stances of potential overlap between
topic categories and elected to resolve
them as follows: we considered stud-
ies describing consumer educational
needs as information needs rather than
a barrier to integration of genetic ser-
vices, and articles assessing use of fam-
ily history in practice were classified as
barriers to integration of genetic ser-
vices rather than a model of integra-
tion into primary care, since these ar-
ticles uniformly described inadequacies
of most physicians in collecting and as-
sessing familial risk.
Frequencies of data were tabulated
and articles were grouped into topic cat-
egories. Evidence tables were created
for each key area, and a narrative syn-
thesis was performed. Because of the
heterogeneous nature of the studies, we
could not justify statistical pooling.
RESULTS
The literature searches and reference
mining yielded 10 866 titles. After re-
moval of duplicates and clearly irrel-
evant titles, 3371 citations were re-
viewed, and from these, 68 articles were
selected and retrieved (F
IGURE).
The number of articles in each cat-
egory and topic according to type of
study are presented in T
ABLE 1. The most
common study designs were cross-
sectional surveys and qualitative or de-
scriptive studies. There were 5 system-
atic reviews and 8 experimental studies.
Outcomes of Genomic Medicine
We identified 16 articles that de-
scribed outcomes resulting from ge-
nomic medicine. These studies were
further categorized as relating to psy-
chological, affective, and cognitive out-
comes; behavioral outcomes; or clini-
cal outcomes (T
ABLE 2).
Psychological, Affective, or Cogni-
tive Outcomes. We identified 7 articles
that assessed psychological, affective, or
cognitive outcomes, including 2 system-
atic reviews, 2 randomized controlled
trials (RCTs), 1 survey, and 2 pre/post
studies. One systematic review ad-
dressed the perceived risks and psycho-
logical and behavioral impacts of ge-
netic testing in adults with a family
history of disease.
1
A total of 35 articles
involving 30 studies met criteria for this
review. Only 1 RCT was included, 2 were
cross-sectional studies, and the remain-
der had prospective designs.
Sixteen studies described outcomes
for hereditary breast and ovarian can-
cer, 11 for hereditary nonpolyposis co-
lorectal cancer, 1 for both hereditary
breast and ovarian cancer and heredi-
tary nonpolyposis colorectal cancer, and
2 for Alzheimer disease. The majority
of the studies reported negative effects
on affective outcomes for individuals
found to carry genetic susceptibility
mutations—but these effects were gen-
erally short-lived, and there were gen-
erally no differences between carriers
and noncarriers with respect to per-
ceived risk 12 months after genetic test-
ing. An increase in screening behavior
was observed in carriers, but the change
was less than expected.
We identified another systematic re-
view that addressed the effects of ge-
netic counseling and testing for breast
cancer susceptibility.
2
This review iden-
tified 15 studies, which were mostly ob-
servational in design, and concluded
that, in general, counseling and test-
ing was not associated with increased
psychological distress and was associ-
ated with some improvements in de-
creased worry, anxiety, and depression.
One RCT involving obese individu-
als found that consultation that in-
cluded genetics content did not have
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negative effects on self-efficacy, self-
control, or increase in body weight af-
ter 6 months. In addition, the individu-
als with a family history of obesity who
received consultation with genetics con-
tent reported significant improvement of
negative mood after 6 months.
3
An-
other RCT r epor ted that education and
personalized prevention recommenda-
tions increased the accuracy of risk per-
ception without increasing worry in adult
nondiabetic offspring of diabetic parents.
4
The importance of risk perception as-
sociated with family history was de-
scribed in a survey of patients with and
without a family history of colorectal
cancer. Being screened appropriately
was significantly associated with a high
perception of risk for colorectal can-
cer among those with a family his-
tory.
5
The remaining identified studies
were pre/post in design, assessing psy-
chological or affective outcomes in pa-
tients before and after genetic counsel-
ing, and reported improvements in
satisfaction, knowledge, and reduc-
tions in worry.
6,7
Behavioral Outcomes. We identi-
fied 5 articles relating to patient or cli-
nician behavioral outcomes resulting
from genetic services. A systematic re-
view of 11 studies assessing patients’ be-
havioral responses to genetic risk infor -
mation relating to cancer and heart
disease concluded that results were
mixed, with some studies showing no
change in behavioral outcomes, wher eas
other studies reported increased moti-
vation to participate in cancer screening.
8
Results from a survey of US physi-
cians about exposure to and attitudes to-
ward advertisements for genetic tests for
inherited cancer susceptibility found that
27% had received advertising for ge-
netic susceptibility tests and 25% felt that
such advertising would be important in
their decision-making to recommend
testing.
9
Another survey of primary care
clinicians in the United States assessed
factors influencing whether these phy-
sicians would order a genetic test to in-
dividually tailor smoking-cessation treat-
ment. The study found that the most
important factors for ordering such a test
included the ability to more precisely tar -
get smoking-cessation treatment and to
encourage patients with the knowledge
that their treatment was tailored. How-
ever, concerns about genetic discrimi-
nation were an important barrier.
10
A survey of Massachusetts family phy-
sicians found that physicians expected
their patients to be more likely to get
screened for cancer and make lifestyle
and behavioral changes if genetic test-
ing identified them as at increased risk.
11
Survey data from 65 patients with his-
tory of depression found that de-
pressed patients r epor ted that they were
Figure. Literature Flow
16 Articles on outcomes of
genomic medicine
3 Systematic reviews
4 Experimental studies
9 Other
16 Articles on delivery of
genomic medicine
3 Randomized controlled
trials
13 Other
20 Articles on barriers and
challenges to integration
of genomic medicine
1 Systematic review
19 Other
16 Articles on consumer
information needs
1 Systematic review
1 Randomized controlled
study
14 Other
68 Articles included in analysis
3371 Titles and abstracts reviewed
170 Articles selected and retrieved
for further review
10
866 Titles identified in literature
search and reference mining
7495 Duplicate and clearly irrelevant titles excluded
3161 Titles excluded
40 Unable to retrieve articles
102 Excluded
8 Not clinical genetics research
4 Included in systematic review
32 Nonsystematic review
35 Commentary, essay, editorial, or legal analysis
7 Economic or decision analyses
1 Wrong setting (developing country)
4 Pediatric genetic focus
3 Reproductive genetic focus
8 Educational materials or interventions
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willing to pay for impr ovements in tr eat-
ment response to antidepressant medi-
cation, and their stated willingness to pay
for a 5% improvement in treatment re-
sponse exceeded the price of a pharma-
cogenetic test.
12
Clinical Outcomes. We identified 4
studies that assessed clinical out-
comes. A pre/post study assessed
women with BRCA mutations and re-
ported that after counseling, 15% and
50% underwent risk-reducing surgery
for breast and ovarian cancer, respec-
tively, and 4 early stage cancers were
identified. Among women who did not
undergo prophylactic surgery, recom-
mended cancer screening increased.
13
A nonrandomized comparison of
Greek patients who had at least 2 un-
successful attempts at weight loss com-
pared conventional diet and nutrition
counseling with nutrition counseling
informed by a nutrigenomics test re-
sult. For the first 300 days, weight loss
between groups was not statistically dif-
ferent, but among the 50% of patients
with more than 300 days of follow-up,
there was a statistically significant dif-
ference of about 5 kg, with the test
group weighing less on average.
14
We identified only 1 RCT of a ge-
netic testing intervention for a com-
mon condition that measured a clinical
outcome.
15
In this trial, 200 adults re-
quiring warfarin anticoagulation were
randomized to standard dosing vs a dos-
ing schedule determined from a for-
mula that takes into account CYP2CP and
VKORC1 genotypes. During the time to
achieve a stable maintenance dose, there
was no difference between groups in the
primary outcome of the percentage of in-
ternational normalized ratios outside the
therapeutic range (31% in the pharma-
cogenetic group and 33% in the stan-
dard dosing group). Patients in the phar -
macogenetic group did have significantly
fewer dose adjustments and fewer blood
samples drawn for testing international
normalized ratios.
One study reported possible harms
from genetic testing. Among 24 pa-
tients who had BRCA testing and were
found to have an unclassified variant
(meaning the result of the test was un-
informative), semistructured inter-
views revealed that 19 interpreted this
information as “pathogenic” and 10
went on to undergo preventive sur-
gery. None of the 5 patients who inter-
preted this test result as uninforma-
tive had preventive surgery.
16
Consumer Information Needs
We identified 16 articles describing con-
sumer information needs, including 1
systematic review, 1 RCT, 10 surveys,
2 pre/post studies, and 2 qualitative
studies. Five articles addressed con-
sumers’ knowledge, attitudes, and be-
liefs about genetics and the other 11 ad-
dressed the intention to seek or
participate in genetic services, includ-
ing uptake of genetic testing (T
ABLE 3).
Five surveys from the United States
and the Netherlands assessed consum-
ers’ knowledge, attitudes, and beliefs, and
generally they all found that genetic
knowledge was low, but attitudes about
genetics were positive. However, there
were concerns about genetic discrimi-
nation.
17-21
Two surveys from the United
States investigated knowledge and atti-
tudes of Hispanic participants regard-
ing cancer genetic services, found inter-
est in such services,
20
and found that
acculturation factors related to lan-
guage may affect awareness.
21
Six articles focused on the intention
to seek genetic services, including
Table 1. Characteristics of 68 Genomics Health Services Articles Included for Review
Category/Topic
Type of Study
Systematic
Review Experimental Survey
Pre/
Post Observational
Qualitative/
Descriptive
Outcomes
Psychological, affective, cognitive 2
a
212
Behavioral 1 4
Clinical 21 1
Consumer information needs
Knowledge, attitudes, and beliefs 5
Intention to seek genetic services 1 4 1
Participate in genetic services 1 1 1 2
Delivery of genetic services
Existing genetics services and the genetics workforce 4
b
1
c
Integrating genetics into primary care practice 1 1 2 2
New models of genetic services 2 2 1
Barriers to integration of genetic services
Health professionals’ knowledge, attitudes, beliefs, and abilities 1 10 2 2
d
Lack of oversight of genetic testing 1
Privacy and discrimination concerns 2 2
e
Total 5 8 35 7 3 10
a
One review also included behavioral outcomes.
b
Qualitative technique was also used (interviews) in 1 study.
c
Descriptive study.
d
Included 1 medical record review.
e
Qualitative comparative studies.
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Table 2. Evidence Table of Studies of Outcomes of Genetic/Genomic Health Services
Source Study Type (Location, y) Target Population Study Goals Selected Findings
Psychological or Cognitive Outcomes
Heshka et al,
1
2008
Systematic literature
review (2000-2006)
Adults with family history of any
multifactorial adult-onset
disorder who had
undergone genetic testing
Review perceived risks and
psychological and behavioral
effects of genetic testing for
common chronic diseases
1 RCT, 2 cross-sectional studies, 27
prospective studies: short-lived negative
psychological effects and modest increases
in screening for carriers, no differences
in perceived risk after testing for carriers
or noncarriers
Butow et al,
2
2003
Systematic literature
review (1980-2001)
Women with family history of
breast cancer who had
genetic counseling or testing
Review the perceived risks and
psychological effects of genetic
counseling and testing
1 RCT, no differences in outcomes; 1 RCT,
significantly less breast cancer–specific
stress at 3 mo; 13 pre/post studies, mostly
no changes or some improvements in
perceived risk, worry, anxiety, or
depression
Rief et al,
3
2007 RCT (Marburg, Germany)
a
410 Obese (BMI ⱖ30) patients;
intervention groups, 145 and
146; controls, 116
Patients received consultation with
or without genetic information;
controls, no intervention
Patients who received consultation with genetic
information rated it as superior, showed no
negative psychological effects or increase in
weight after 6 mo; those with family history
had lasting psychological benefits
Pierce et al,
4
2000
RCT (south London,
England, 2000)
152 Adult, nondiabetic
offspring of diabetic patients,
105 enrolled; intervention,
43; controls, 62
Patients received interviews with
genetic counseling or interviews
only
Genetic counseling and personalized
prevention recommendations improved
accuracy of risk perception with no increase
in worry, anxiety, or depression
Palmer et al,
5
2007
Cross-sectional survey
(Boston,
Massachusetts, 2004)
1065 Adults aged 35-55 y
enrolled in a multispecialty
practice surveyed by mail,
355 with family history of
colon cancer and 710
without; 833 respondents
Assess health beliefs and attitudes
about colon cancer and their
effects on colon cancer
screening
Patients with greatest familial risk and with
strong perceived risk nearly 3 times more
likely to have been appropriately screened
Collins et al,
6
2000
Pre/post (Australia,
1998-1999)
193 Adult patients with family
history of colorectal cancer;
157 completed preclinic,
127 postclinic
questionnaires
Assess colorectal cancer-related
worries, risk perceptions, their
effects on interest in genetic
testing, overall satisfaction with
clinic
Worry positively associated with younger age,
higher education, higher perceived risk;
colon cancer worry significantly reduced
after genetic consultation
Pieterse et al,
7
2007
Pre/post (Utrecht, the
Netherlands, March
2001 to August 2003)
622 Adult patients with family
history of cancer; 200
completed previsit, 171
postvisit questionnaires
Assess associations between
counselor-patient
communication and patient
satisfaction, cognitions, anxiety,
and perceived control after a
genetic consultation
Receiving medical information increases
patient satisfaction, does not increase level
of anxiety
Behavioral Outcomes
Marteau and
Lerman,
8
2001
Systematic literature
review
a
Evidence about behavioral
responses to genetic risk
information
Review evidence, literature on
behavior; consider how it might
be changed in response to
genetic information
11 Studies described effects on behavior:
genetic risk can increase or have no effect
on motivation to screen for cancer; little
known about effect of genetic test results on
lifestyles
Vadaparampil
et al,
9
2005
Cross-sectional survey
(United States,
1999-2000)
2079 Physicians; 1251
respondents
Assess physicians’ exposure,
attitudes toward advertisements
for genetic tests for cancer
susceptibility
27% Received advertisements; 25%
considered them important in their
recommendations for cancer genetic
susceptibility testing
Levy et al,
10
2007
Cross-sectional survey
(United States, 2002)
2000 Primary care physicians;
562 respondents
Assess training and experience
with genetics, attitudes and
concerns about use of genetic
testing
75% Had training in genetics, 5% confident in
their ability to interpret test results; most
important factors in offering test: ability to
target cessation treatment, ability to
encourage patients with tailored messages
Gramling et al,
11
2003
Cross-sectional survey
(Massachusetts, 2002)
691 Family physicians; 300
respondents
Assess opinions about patients’
motivation to change behavior
based on genetic test results
indicating high risk for cancer
Expected that their patients would be more
likely to screen (89.9%), improve their diet
and exercise (92.5%), or quit smoking
(93.6%)
Herbild et al,
12
2008
Cross-sectional survey
(Denmark, 2002)
89 Patients treated with
antidepressant medications;
65 respondents
Assess willingness to pay for
improvements in treatment
response to antidepressant
medication
Willing to pay for 5% probability of
improvement, which exceeded price of
genetic test that could predict these benefits
Clinical Outcomes
Scheuer et al,
13
2002
Pre/post (Boston,
Massachusetts,
1995-2000)
251 Women with deleterious
BRCA1/2 gene mutations
and tissue at risk for breast
or ovarian cancer
Assess participation in screening
for early detection,
chemoprevention, and
risk-reducing surgery after
receiving cancer prevention
recommendations
14.9% and 50.3% underwent risk-reducing
surgery for breast cancer and ovarian
cancer, respectively; 4 cancers identified;
screening behavior increased in women
who did not undergo risk-reducing
surgery
Arkadianos et
al,
14
2007
Nonrandomized
comparison (Greece)
a
43 Attendees at weight
management clinic matched
to 43 controls on clinical
characteristics
Intervention patients received
dietary instructions informed by
results of a nutrigenetic test;
control patients received
standard diet and exercise
Weight loss not statistically different between
groups up to 300 d; then 22 control patients
gained an average 2.74 kg while intervention
patients lost an average 2.54 kg
(continued)
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motivations for genetic testing. An RCT
randomized 2165 primary care pa-
tients into 2 groups—one offered a
DNA-based test for hemochromatosis
and the other a phenotypic test—and
then assessed the willingness to have
the testing. The authors found that ac-
ceptance of testing was about the same
for both groups (56% for genotypic and
58% for phenotypic testing) and that
reasons for refusal included a need to
talk with a physician (44%), concern
about privacy (32%), and dislike of
blood drawing (29%).
22
Two surveys of patients with colorec-
tal cancer assessed factors contributing
to decision making about genetic test-
ing for hereditary nonpolyposis colorec-
tal cancer, including germline testing
23
and tumor microsatellite instability test-
ing.
24
Among 314 patients, motivations
for germline testing included learning of
increased risk to children and finding out
whether additional screening was
needed. For 125 patients eligible for tu-
mor microsatellite instability testing, the
majority had positive attitudes about the
potential benefits and perceived few bar-
riers to undergoing the test, despite hav-
ing little knowledge about the test. A pre /
post study used interviews and
questionnaires to assess barriers to par-
ticipating in genetic counseling and
BRCA gene testing for patients newly di-
agnosed with breast cancer.
25
Participa-
tion was not influenced by distress,
knowledge about hereditary breast can-
cer, previous genetic testing in rela-
tives, or perceived risk and barriers.
A survey of 187 mothers undergoing
BRCA gene testing who had children
aged 8 to 21 years found that most of
these women were motivated to have
testing for the information it provided to
their children, and they believed that hav-
ing such information could be used to
prevent or control cancer in their chil-
dren. The 2 most common informa-
tional resource needs of these mothers
for discussing their BRCA test results with
their children included reading educa-
tional literature (93%) and speaking with
a family counselor (86%).
26
Another survey of 139 women pre-
viously treated for early stage breast
cancer found that the majority (76%)
would have been interested in genetic
testing to determine risk of recur-
rence with most (84%) wanting to in-
clude information from test results in
decision making about treatment.
27
Five articles addressed patients’ in-
formation needs related to participa-
tion in genetic services. Two articles un-
derscored the importance of eliciting
the patient’s perspective when discuss-
ing risk of chronic disease, particu-
larly in the context of the family his-
tory. A systematic literature review that
included 11 qualitative research stud-
ies found that for individuals with a
family history of cancer, coronary heart
disease, or diabetes, the salience of their
family history was determined by ac-
knowledging that a disease runs in the
family, and this was strongly influ-
enced by the personal experiences of
that illness in relatives. Some of these
factors were the same as the medical fac-
tors used to assess familial risk (ie, the
number of affected relatives and age at
onset), but others were more per-
sonal, such as emotional or physical
closeness of a family member.
28
A quali-
tative study published the following
year delved further into patients’ per-
ceived familial risk and found that a
sense of vulnerability to common
chronic disease depended on the emo-
tional impact of experiencing the ill-
ness in the family, especially if the ill-
ness was sudden, premature, or fatal,
and the nature of personal relation-
ships within the family.
29
A pre/post study from the United
States of women eligible for referral to
cancer genetics consultation found that
after 6 months those who had attended
the consultation were significantly more
knowledgeable, but clinical history, per-
ceived risk, family history, psychologi-
cal state, and anxiety were not associ-
ated with attendance.
30
Two articles addressed the genetic
counselor-patient interaction. A cross-
sectional study of observed behavior from
the Netherlands found that adults re-
ferred for cancer genetics consultation
had a strong psychosocial focus, which
was important to their agenda for the
consult; however, these needs only mini-
mally influenced the interaction during
the visit because patients did not com-
municate their previsit needs.
31
A quali-
tative study from the United States that
interviewed genetic counselors and their
patients found that the goals of genetic
counseling were often unclear to both.
Although counselors objected to stat-
ing goals because doing so implied a
preset agenda, patients were uncertain
about the role of the counselor and the
boundaries of what would be discussed.
Table 2. Evidence Table of Studies of Outcomes of Genetic/Genomic Health Services (cont)
Source Study Type (Location, y) Target Population Study Goals Selected Findings
Clinical Outcomes
Anderson et al,
15
2007
RCT (Salt Lake City,
Utah)
a
200 Adults requiring warfarin
therapy, about 50% male,
and more than half
preoperatively for orthopedic
procedures
Patients were randomized to
conventional warfarin dosing vs
a formula that takes into
account CYP2C9 and VKORC1
genotypes
No statistically significant difference between
groups in the primary study end point,
30.7% INR in intervention group, 33.1% INR
in standard group
Vos et al,
16
2007
Semistructured interviews
(the Netherlands,
1998-2006)
24 Patients who received
BRCA1/2 genetic test
results classified as a variant
of uncertain clinical
significance
Assess recall and interpretation of
result and effects on life
domains
Little change reported to most lives in general;
a third reported large changes in preventive
behaviors; 10 of 19 who had interpreted
their results as pathogenic had preventive
surgery; 0 of 5 who interpreted their results
as uninformative did so
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); INR, international normalized ratio; RCT, randomized controlled trial.
a
Year not stated.
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Table 3. Evidence Table of Studies of Knowledge, Attitudes, and Beliefs About Genetic Services and Informational Needs of Consumers
Source Study Type (Location, y) Target Population Study Goals Selected Findings
Knowledge, Attitudes, and Beliefs About Genetic Services
Morren et al,
17
2007
Cross-sectional survey
(the Netherlands,
2001)
1916 Patients aged ⱖ15 y with
chronic disease; 1496
respondents
Assess perceived knowledge
and attitudes about genetics
10% Reported sufficient genetics knowledge; DNA
testing frightened about 25%; two-thirds wanted
to know if their disease was genetic; 40% would
want to know if they were at risk; about half
concerned about genetic discrimination by
employers and insurers; primary care clinician
preferred source of genetics information
de Vries et al,
18
2005
Cross-sectional survey
(the Netherlands)
a
4000 Adults (aged 18-50 y)
who were not undergoing
cancer treatment; 478
respondents
Assess knowledge, risk
perception, attitudes, and
beliefs about hereditary
cancer
25% Correctly indicated hereditary types of cancer;
two-thirds to three-quarters wanted to know types
with hereditary aspects, how to recognize them,
personal risks, and steps to take; preferred
sources for information were leaflets, general
practitioner, Internet
Peters et al,
19
2004
Cross-sectional survey
(Philadelphia,
Pennsylvania,
December 2001 to
January 2002)
430 African American and
white prospective jurors;
75% response rate, 90%
completion rate
Assess awareness of and
attitudes about genetic
testing for cancer risk
61% Had heard about genetic testing; positive
attitudes were prevalent (⬎80%); lower
awareness, less belief in potential benefits, more
concern about racial discrimination among African
American compared with white participants
Ricker et al,
20
2007
Cross-sectional survey
(Los Angeles County,
2000)
235 Adult Latino attendees of
outpatient clinics, about
98% of eligible participants
Assess personal and family
history of cancer, beliefs
about cancer, screening
behaviors, access to
screening information,
interest in genetic
services
More than 85% expressed interest in information
about risk and motivation to participate in cancer
genetics services; heredity perceived as most
frequent cause of cancer after smoking
Vadaparampil
et al,
21
2006
Cross-sectional survey
(United States, 2000)
4313 US Hispanic respondents
aged ⬎25 y to National
Health Interview Survey
Assess knowledge, attitudes,
and practices related to
cancer prevention and
control
21% Had heard of genetic testing for cancer risk
(highest rates: 27% of Puerto Rican and 14% of
Mexican respondents); completing the interview in
Spanish, having an intermediate or low level of
English-language preference inversely and
significantly associated with test awareness
Intention to Seek Genetic Services
Anderson et al,
22
2005
RCT (United States)
a
2165 primary care patients;
genotype vs phenotype test
randomization intervention,
559 and 538 white, 538 and
530 African American
Assess willingness, knowledge,
attitudes, and beliefs about
phenotypic or genotypic
testing for hereditary
hemochromatosis
Test acceptance associated with interest in knowing
more about health (81%), helping family members
(71%); refusal reasons included need to talk with
physician (44%), concern about privacy (32%),
dislike of blood drawing (29%); African American
respondents in deep South less likely to accept
either test than white or African American
respondents in mid-Atlantic
Esplen et al,
23
2007
Cross-sectional survey
(Ontario, Canada)
a
483 Adult colorectal cancer
patients from
population-based cancer
registry; 314 respondents
Assess motivational factors,
expectations, psychosocial
functioning related to genetic
testing
More than 80% motivated to find out about risk in
children; women significantly more likely to test to
find out if more screening was needed (84% vs
67%) and in response to recommendations from a
health professional (57% vs 45%); women and
younger patients had higher levels of distress
Manne et al,
24
2007
Cross-sectional survey
(United States)
a
173 Adults with colorectal
cancer meeting the Revised
Bethesda criteria for tumor
MSI testing; 125
respondents
Assess knowledge, exposure,
perceived benefits, and
barriers to MSI testing
Average percentage of correct answers, 17.5%
(median, 6%); highest rated benefit, to learn if
children or other relatives were at risk (98.3%);
most frequent barriers, possible insurance
discrimination (32%), uncertainty of test result
(37%); more distressed patients, those who
perceive higher risk for recurrence, those with
metastatic disease less motivated to have MSI
testing
Schlich-Bakker
et al,
25
2007
Pre/post (the Netherlands,
2002-2004)
102 Adults with newly
diagnosed breast cancer
Assess participation in genetic
counseling and BRCA testing
57% Had genetic counseling and BRCA testing; no
differences in psychological distress or knowledge
between patient groups; patients who declined
testing had lower perceived risks; motivation for
testing, information for children, information for
prevention
Tercyak et al,
26
2007
Cross-sectional survey
(United States)
a
187 Women with children aged
8-21 y who had not yet
received BRCA test results;
consent rate of 81%
Assess informational resource
needs, BRCA testing
motivations, decision
making, vigilance, decisional
conflict regarding
communicating test results
to children
80% Reported that learning about their children’s
risks of inheriting mutation “very important”
motivation for testing; 44% believed results could
be used to prevent or control cancer in children;
mothers with greater interest in testing to learn
about their children’s risks, those with more
vigilant decision-making styles, those with higher
decisional conflict had greatest information needs
for communicating results to children
O’Neill et al,
27
2007
Cross-sectional survey
(North Carolina, 2005)
231 Women with early stage
breast cancer; 166
participants, 139 with
complete data
Assess interest in genomic
testing for risk of breast
cancer recurrence and
preferences for incorporating
results into treatment
decisions
Majority would definitely want genetic recurrence risk
testing (76%) and were willing to pay on average
$997; participants significantly more willing to have
chemotherapy if results indicated high recurrence
risk and if physicians advised them to do so;
participants’ worry increased as function of
recurrence risk results
(continued)
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Most patients appreciated the time spent
by genetic counselors and believed that
their physicians could not provide the
service.
32
Delivery of Genomic Medicine
We identified 16 articles that de-
scribed the delivery of genomic medi-
cine. These studies were further clas-
sified as relating to existing genetic
services and the genetics workforce, in-
tegration of genetics into primary care,
and new models of genetic services de-
livery (T
ABLE 4).
Five articles described genetic ser-
vices and the current genetics work-
force: 4 surveys of the genetics work-
force in the United States and 1
descriptive study of regional genetic
health centers in the United Kingdom.
Two surveys used data from a mailed
questionnaire to the 1576 active physi-
cian and PhD members of the Ameri-
can Board of Medical Genetics and found
that 60% of respondents perceived that
there were inadequate numbers of ge-
neticists
33
and that geneticists provid-
ing services for adult-onset diseases rep-
resented the smallest proportion of
geneticists (7%).
34
Another survey ob-
tained data from active members of the
American Academy of Pediatrics Sec-
tion of Genetics and Birth Defects and
physicians certified by the American
Board of Medical Genetics and found that
5% had training in internal medicine, and
adult patients seen for reasons other than
prenatal services represented only 12%
of patients seen by geneticists.
35
The
fourth survey described characteristics
and professional roles of 211 nurse ge-
netics specialists in the United States and
found that most (57%) provided direct
patient care and worked in genetics
(26%) or oncology (22%) settings.
36
The
descriptive study from the United King-
dom found that half of referrals come
from primary care, genetic counselors
were key to providing genetic services,
and genetic testing was primarily for
single-gene disorders.
37
Six articles described the integration
of genetics into primary care. This in-
cluded 1 qualitative study from Canada
that found family physicians anticipate
providing more genetic services, but they
were uncertain and had concerns about
their abilities to do so.
38
The remaining
5 articles were from the United King-
dom and described a range of ap-
proaches to integrating clinical genetic
services into primary care, including 2
pre/post studies, 1 survey, 1 qualitative
study, and 1 cluster RCT.
Three studies (the RCT, the survey,
and a pre/post study) addressed the use
of a nurse genetics specialist within the
primary care setting. Both the RCT and
the survey found that patient satisfac-
tion with the service provided by the
nurse genetics specialist was high and
costs with the new model were less.
39,40
The pre/post study found that physi-
cians believed that contact with a nurse
genetics specialist helped in identifying
patients in need of a genetics referral and
that nurse genetics specialists provided
current genetics information to them.
41
The other 2 studies examined the
effect of referral guidelines for cancer
genetics services among general
Table 3. Evidence Table of Studies of Knowledge, Attitudes, and Beliefs About Genetic Services and Informational Needs of Consumers (cont)
Source Study Type (Location, y) Target Population Study Goals Selected Findings
Information Needs Related to Participation in Genetic Services
Walter et al,
28
2004
Systematic literature
review and
meta-analysis
(1993-2001)
Qualitative studies describing
familial risk for cancer,
coronary heart disease, and
diabetes mellitus for at-risk
individuals
Explore understanding about
familial risk
11 Qualitative studies; features recognized as
contributing to familial risk: number of affected
relatives, age at diagnosis, severity of illness;
premature death or severe disability increased
salience of family history; risk perception
influenced by personal experience with relative’s
disease; ambivalence and uncertainty may be
exacerbated by difficulty in obtaining accurate
information
Walter and
Emery,
29
2005
Qualitative (United
Kingdom, 2002-2003)
180 Adult patients with family
history of cancer, heart
disease, or diabetes
Assess how patients
understand family history
and its influence on
consultations about disease
risk and management
Sense of vulnerability depended on number or sex of
affected family members, age at onset, and
emotional impact of witnessing illness; beliefs
about contributions of nature and nurture can
affect patients’ views on control they can exert
over risk
O’Neill et al,
30
2006
Pre/post (Pennsylvania)
a
43 Women with breast cancer
and at least 10% probability
of having BRCA mutation
Assess referral uptake for
clinical cancer genetic
counseling
Awareness about genetics overall significantly
associated with referral uptake; acceptors and
decliners had significantly better knowledge scores
than intenders; perceived benefits did not influence
referral uptake; most important barriers were
potential for insurance discrimination (77%) and
cost (69%)
Pieterse et al,
31
2005
Cross-sectional study of
observed behavior (the
Netherlands,
2001-2003)
130 Adults aged ⱖ18 y who
were first in their family
referred for cancer genetic
consultation
Describe counselor-patient
interaction and examine
whether communication
reflects patients’ previsit
needs
Patients had strong psychosocial focus; previsit
needs minimally influenced interaction and patients
did not appear to tailor verbal communication to
needs
Bernhardt et al,
32
2000
Qualitative (United States)
a
Genetic counselors and clients
in focus groups (10
counselors, 19 clients) and
telephone interviews (8
counselors)
Assess quality of providing
genetic counseling services
Many counselors objected to stating goals since it
implied preset agenda; clients had few
expectations about how counseling would be
delivered, role of counselor, boundaries of
discussion not clear; most clients believed
physicians could not provide the services
Abbreviations: MSI, microsatellite instability; RCT, randomized controlled trial.
a
Year not stated.
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Table 4. Evidence Table of Studies Assessing How Genetic/Genomic Medicine Is Delivered
Source Study Type (Location, y) Target Population Study Goals Selected Findings
Medical Genetics Workforce
Cooksey et al,
33
2005
Survey (United
States, 2003)
1567 US resident, active
medical geneticists certified
by ABMG; 861 respondents
Describe current models of
providing clinical genetic
services and roles of health
professionals; identify
measures to monitor changes
in demand; establish
description of genetic services
Medical geneticists providing patient care spend 50%
of their time on patient care activities; about 70%
report their practice is full or nearly full; about 60%
report supply of geneticists in community not
adequate for demand
Cooksey et al,
34
2006
Survey and qualitative
study (United
States, 2003)
1567 US resident, active
medical geneticists certified
by ABMG; 861 respondents
Identify clinically relevant
subgroups of geneticists
and assess their genetics
practices, patient care, other
characteristics
Geneticist subgroups included general (36%), pediat-
ric (28%), reproductive (15%), metabolic (14%),
adult (7%); adult geneticists practice almost exclu-
sively in academic medical centers, spend sub-
stantial time in laboratories, spend fewest hours in
patient care
Pletcher et al,
35
2002
Survey (United States,
1997-1998)
735 Active members of
American Academy of
Pediatrics Section of
Genetics and Birth Defects
and physicians certified by
ABMG; 506 respondents
Gather practice information
from practicing geneticists
Most clinical geneticists have training in another spe-
cialty, but only 5% in internal medicine; 81% prac-
tice in urban setting, almost two-thirds at a medi-
cal school; adults comprise 12% of patients seen;
respondents spend 3.1 h with new patients, 1.4 h
for follow-up visit; “suboptimal” reimbursement for
services
Lea et al,
36
2006
Cross-sectional
survey (United
States, 2004)
293 Members of ISONG; 211
respondents
Describe current models of
providing clinical genetics
services and demand for
genetic services
One-third held doctoral degrees, one-third held aca-
demic positions, 57% provided direct patient care,
with most working in genetics (26%) or oncology
(22%)
Donnai and
Elles,
37
2001
Descriptive
(United Kingdom)
a
12 Regional genetic health
centers
Describe genetics services
and workforce
Regional genetic centers provide diagnosis, risk
assessment, counseling, surveillance, support;
about half of referrals come from specialists, other
half from primary care; genetic counselors have
key role in delivery
Integrating Genetics into Primary Care
Carroll et al,
38
2003
Qualitative (Ontario,
Canada)
a
40 Urban and rural family
physicians in 4 focus groups
Explore physicians’ experiences
in dealing with genetic sus-
ceptibility to cancer
Escalating expectations for genetic testing met with
uncertainty, concern, and anxiety as participants
acknowledged inadequacies in current role; about
14% had patients who inquired about inherited
cancers, but only a few had patients who had been
referred for counseling or testing
Holloway et al,
39
2004
Cluster RCT
(United Kingdom,
1998-1999)
374 Women without breast or
ovarian cancer referred for
genetic risk assessment;
189 novel service, 185
standard service
Assess satisfaction with the
new community-based
service model; baseline and
follow-up data compared
between the groups
Satisfaction with both models was high; women with
low familial risk less satisfied; community-based
cancer genetic service about 30% less expensive
in staff and patient costs
Westwood et al,
40
2006
Survey (United
Kingdom,
2002-2003)
64 Patients in primary care
referred to clinical genetics;
45 attended appointments,
34 returned survey
Assess feasibility and patient
satisfaction with genetic
nurse counselor service
Almost half (48%) of patients seen did not need to
attend further appointments;
patients were satisfied with travel time,
distance to clinic; patient costs perceived as low
Drury et al,
41
2007
Pre/post (United
Kingdom, 2003)
17 General practices in central
England; 10 randomly se-
lected, 7 urban, 3 rural
Assess genetic nurse counselor
clinic that acted as liaison be-
tween regional clinical
genetics service
Physicians reported limitations and gaps in current
knowledge; referral guidelines provided by the
nurse gave them more confidence; most felt
contact with genetic nurse helped significantly in
identifying patients whose risk warranted referral
Elwyn et al,
42
2002
Qualitative (United
Kingdom)
a
19 General practitioners in
Wales; 14 attended
Examine physicians’ reactions
to referral guidelines and tele-
phone triage system for
cancer genetics services
Participants had few objections to triage system to
regulate access to scarce specialist service,
thought referral guidelines would help them refer
patients appropriately
Lucassen et al,
43
2001
Pre/post (United
Kingdom)
a
12 General practitioners in
Oxfordshire County,
England
Assess genetics referrals and
risk assessment in primary
care clinicians before and
after dissemination of
guidelines
After guidelines, more referrals from primary care
correctly met criteria, fewer low-risk referrals, and
more informative letters sent to specialists; no
change in referrals from counties that did not
receive guidelines
New Models of Genetic Services
Jenkins et al,
44
2007
RCT (United States)
a
136 English-speaking people
who had consented to
BRCA1/2 gene mutation
analysis; 111 enrolled,
102 completed
Compare psychological
sequelae, knowledge,
satisfaction, preferences, and
cost of telephone vs in-person
disclosure of results
No significant differences in anxiety and general well-
being, similar rates of satisfaction; among those
who did not receive their preferred method of dis-
closure (n = 22), statistically significant tendency to
prefer phone results; greater costs associated with
in-person result disclosure
Lea et al,
45
2005
Survey (Maine)
a
Rural physician practices and
public health nurses: 650
participants in educational
presentations, 85%
response rate; 24 clinics and
125 patients eligible for
satisfaction surveys, 18%
and 25% response rates
Describe 3-y telegenetics pilot
project that provided
educational and clinical
services
Survey evaluations overall very positive; provider and
patient responses regarding satisfaction low but
mean satisfaction scores high; consulting physi-
cians very satisfied overall and confident in evaluat-
ing and managing patients seen via telemedicine
(continued)
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practitioners. The qualitative study
found that physicians appreciated that
referral guidelines would improve
their referral patterns,
42
and the pre/
post study found that guidelines were
associated with improved referral
patterns.
43
Five articles described new models of
genetic services. One experimental study
evaluated telephone disclosure of BRCA
genetic test results compared with tra-
ditional genetic services and found there
were no significant differences in anxi-
ety and general well-being between the
2 groups, and both groups reported simi-
lar rates of satisfaction with the ser-
vices.
44
A survey of rural physician prac-
tices in northern Maine and public health
nurses statewide found that health pro-
fessionals receiving and providing edu-
cational and clinical genetic services via
videoconferencing generally found it to
be a positive and satisfying experi-
ence.
45
One experimental study random-
ized general practice teams in the United
Kingdom to the use of computerized de-
cision support software that aided in fa-
milial risk assessment of breast, ovar-
ian, and colorectal cancer or to a
comparison group that received educa-
tion and guidelines; it found that with
decision support, there were signifi-
cantly more genetics referrals, and these
referrals were more likely to be consis-
tent with referral guidelines.
46
Regarding direct-to-consumer mar-
keting of genetic services, an observa-
tional study that assessed nutrigenom-
ics tests found that the genetic test
results provided little influence on the
assessment and recommendations pro-
vided by the test companies, and test
results frequently included recommen-
dations for the consumer to purchase
costly dietary supplements.
47
A survey
of primary care physicians and con-
sumers in the United States found that
a small percentage (14%) of consum-
ers were aware of nutrigenomic test-
ing and of those who had a nutrige-
nomics test, only 10% had discussed the
results with their physicians.
48
Barriers to Clinical Integration
of Genomic Medicine
We identified 20 articles that de-
scribed barriers to the clinical integra-
tion of genomic medicine. These ar-
ticles were further classified as relating
to health professionals’ knowledge, at-
titudes, beliefs, and abilities; lack of
oversight of genetic testing; and pri-
vacy, confidentiality, and genetic dis-
crimination concerns (T
ABLE 5).
Fifteen articles described health
professionals’ knowledge, attitudes, be-
liefs, and abilities pertaining to medical
genetics. This included 1 systematic re-
view, 10 surveys, 2 observational studies,
1descriptive study, and 1 qualitative study.
The systematic review included 18
studies that dealt with primary care
physicians’ perceived barriers concern-
ing the provision of genetic services.
The studies were published between
1993 and 2001 and included 7 sur-
veys, 4 pre/post tests, 4 qualitative stud-
ies, 1 observational study, and 1 clus-
ter RCT. These studies found that
physicians reported that they lack suf-
ficient knowledge and confidence re-
lating to provision of genetic services
and they have limited time to obtain
family history.
49
These themes were also
identified in the other 14 articles.
The 10 surveys and the qualitative
study we found assessed genetics
knowledge and attitudes of a variety of
health professionals from the United
States, Australia, and the Netherlands,
and these studies found similar re-
sults to the systematic review,
49
with re-
spondents feeling underprepared for as-
sessing and managing genetic issues in
their practice and lacking basic ge-
netic knowledge.
50-60
The 2 observational studies and the
descriptive study we retrieved de-
scribed health professionals’ abilities to
collect, document, and interpret fam-
ily history. These studies found that a
majority of patients with a strong fa-
milial risk for a common disease lacked
documentation of key family history
elements in their medical record, as well
Table 4. Evidence Table of Studies Assessing How Genetic/Genomic Medicine Is Delivered (cont)
Source Study Type (Location, y) Target Population Study Goals Selected Findings
New Models of Genetic Services
Emery et al,
46
2007
Cluster RCT (England)
a
170 General practice teams in
eastern England using the
health service intranet;
intervention group 23,
comparison 22
Evaluate effect of genetic risk
assessment strategy for
familial breast, ovarian, and
colorectal cancer using
computer decision support
system
Significantly more referrals from intervention practices
than comparison practices (6.2 and 3.2 referrals
per 10 000 registered patients per year); referrals
from intervention practices more than 5 times
more likely to be consistent with referral guidelines;
patients referred from intervention practices had
lower cancer worry scores
Kutz,
47
2006 Observational (United
States, 2006)
Direct-to-consumer marketers
of nutrigenomic tests
available from 4 Web sites;
14 fictitious consumers
created
Investigate whether
nutrigenomic tests provide
consumers with information
needed to tailor diet and
exercise according to risks
Results from 2 of 4 Web sites included
recommendations for consumer to purchase
costly dietary supplements; lifestyle information
influenced recommendations more than genetic
test result
Goddard et al,
48
2007
Cross-sectional survey
(United States, 2006)
Consumers participating in
HealthStyles 2006 survey
(5250 respondents, 80%
response rate) and
physicians participating in
DocStyles 2006 survey
(1250 respondents, 52%
response rate)
Assess consumers’ awareness
and use of nutrigenomic
tests and practicing primary
care physicians’ and
pediatricians’ awareness of
nutrigenomic tests
14% of consumers were aware of nutrigenomic
testing; 0.6% report using such tests; of these,
10% discussed result with physicians; 44% of
physicians were aware of nutrigenomics testing;
media are major source of information about
nutrigenomics testing for both consumers and
physicians
Abbreviation: ABMG, American Board of Medical Genetics; ISONG, International Society of Nurses in Genetics; RCT, randomized controlled trial.
a
Year not stated.
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Table 5. Evidence Table of the Challenges or Barriers to the Clinical Integration of Genomic Information
Source Study Type (Location, y) Target Population Study Goals Selected Findings
Health Professionals’ Knowledge, Attitudes, Beliefs, and Abilities
Suther and
Goodson,
49
2003
Systematic literature
review (1991-2001)
Empirical reviews on topics of
genetics and primary care in
peer-reviewed journals
Review primary care physicians’
perceived barriers
concerning provision of
genetic services
Of 18 articles, 12 identified inadequate knowledge as
barrier to providing genetic information or services;
limited time to obtain detailed family history was
barrier in 4, lack of referral guidelines barrier in 3;
3 described decreased confidence with assessing
and referring patients with genetic risks
Lapham et al,
50
2000
Cross-sectional survey
(United States, 1998)
3600 Members of 6 national
health professional
organizations; 1958
respondents
Determine genetics education
needs of dieticians,
occupational therapists,
physical therapists,
psychologists,
speech-language-hearing
specialists, and social
workers
Less than 20% had referred patients for genetic
counseling; 15% referred patients for genetic
testing; 26% had confidence in eliciting genetic
information; only 16% reported having high
confidence in discussing genetic basis of
conditions with patients
Wilkins-Haug
et al,
51
2000
Cross-sectional survey
(United States,
1998-1999)
1248 Fellows of ACOG; 564
respondents
Assess current practice
patterns and opinions on
genetic screening of
gynecologists
Only 24% of respondents did not routinely review
family histories; when genetic testing is called for,
21% provide counseling, 54% refer to geneticist,
22% do both; 21% identified as sole provider of
information and counseling to patients, but most
(65%) note they are not confident of knowledge
Freedman et al,
52
2003
Cross-sectional survey
(United States,
1999-2000)
1763 Physicians; 1251
respondents
Assess attitudes about genetic
testing for cancer
susceptibility among
physicians providing care
for adults in certain
specialties
29% reported feeling qualified to provide counseling
to patients; 40% of primary care physicians felt
qualified to recommend testing to patients
compared with 84% of oncologists; 81% had
concerns about potential insurance discrimination
for patients with positive results; 53% thought
it was difficult to ensure confidentiality of
results
Gramling et al,
53
2004
Cross-sectional survey
(Massachusetts, 2002)
91 Family physicians; 300
respondents
Assess physicians’ attitudes
about predictive genetic
testing for cancer
87% Believe screening for hereditary cancer
susceptibility with family history is important; 62%
confident of ability to recognize patients with
hereditary cancer risk
Maradiegue
et al,
54
2005
Survey (United States)
a
46 Graduate APN students at
2 northeastern US
universities
Assess medical genetic
knowledge and perceptions
34% Stated they felt comfortable speaking with
family diagnosed with genetic condition; 22% felt
they could draw pedigree; 95% reported no prior
training during undergraduate programs regarding
21 common genetic disorders
Chen and
Goodson,
55
2007
Cross-sectional survey
(United States)
a
8058 Public health educators;
1607 respondents
Assess attitudes toward
genomic competencies,
awareness of efforts to
promote genomics,
knowledge of genomics
49% Valued their practice of genomic competencies
proposed for public health educators even though
most (89%) supported these competencies; 51%
of answers to 6 items regarding basic and applied
genomic knowledge were correct
Baars et al,
56
2005
Cross-sectional survey
(the Netherlands
1997-1999)
2377 Medical students
nearing graduation; 291
respondents
Assess medical genetics
knowledge
Mean percentage of correct answers on genetic
examination, 62%; mean score for essential
knowledge that all physicians should know, 71%;
for desirable knowledge, 56%; for specialized
knowledge, 44%
Metcalfe et al,
57
2002
Qualitative study and
survey (Victoria,
Australia, 1999-2000)
Primary care providers: 39
focus group participants and
875 eligible survey
participants; 160
respondents
Assess genetics knowledge
and educational needs
Believe their knowledge is poor and they are
inadequately prepared to manage patients with
genetic conditions; want to know more about
prenatal testing, counseling, and drawing
pedigrees; report low use of genetic services,
that genetics is not very relevant to current
practice, and that referral and management
process is often patient-driven
Doksum et al,
58
2003
Survey (United States,
1998)
2250 Internists,
obstetrician-gynecologists,
oncologists; 803
respondents
Assess nongeneticist
physicians’ knowledge and
experience with BRCA
testing
Only 13% of internists, 21% of
obstetrician-gynecologists, and 40% of
oncologists correctly answered 4 knowledge
questions about genetics of breast cancer and
testing; knowledge only significantly associated
with ordering BRCA testing among
oncologists
Wideroff et al,
59
2003
Cross-sectional survey
(United States,
1999-2000)
1763 Physicians; 1251
respondents
Assess use of genetic testing
for cancer susceptibility
among certain specialties
31% Had ordered cancer susceptibility test
or referred patients in previous 12 mo; testing and
referral significantly associated with practice
location in the Northeast, feeling qualified to
recommend testing, receiving cancer susceptibility
testing advertisements, and having patients
who asked about test
Sandhaus et al,
60
2001
Cross-sectional survey
(Cleveland, Ohio, 2000)
124 Family practitioners,
general internists, and
gynecologists not currently
ordering BRCA1/2 testing;
82 respondents
Assess ability of physicians
to interpret genetic
testing laboratory report
that provided BRCA1/2
genetic test results and
probabilistic information
about cancer risk
32% Did not demonstrate sufficient knowledge
to provide accurate genetic risk assessment;
knowledge of cumulative risk strongly
associated with comprehension of cancer
risk information
(continued)
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as documentation of genetic risk as-
sessment or referral for genetics evalu-
ation.
61-63
A survey of family physi-
cians also found that most (87%)
believed that family history screening
is important; however, only 62% were
confident in the ability to recognize pa-
tients with hereditary risk.
53
One article described oversight of ge-
netic testing. A survey of 190 genetic test-
ing laboratory directors found that most
would support formal registration under
a genetic testing specialty regulated by the
ClinicalLaboratory ImprovementAmend-
ments and that proficiency testing could
improve the quality of genetic testing.
64
Four articles described concerns
about privacy and genetic discrimina-
tion. Two articles used data from the
same qualitative comparative analysis
of states with and without laws pro-
hibiting genetic discrimination by
health insurers. One article found that
there are no well-documented cases of
Table 5. Evidence Table of the Challenges or Barriers to the Clinical Integration of Genomic Information (cont)
Source Study Type (Location, y) Target Population Study Goals Selected Findings
Health Professionals’ Knowledge, Attitudes, Beliefs, and Abilities
Sweet et al,
61
2002
Observational (Ohio,
1999-2000)
Patients at ambulatory cancer
clinic; family-history data
from 362 patients compared
with medical records
Assess medical record
documentation of family
history
Of 69 patients with high familial risk, 14 had records
describing increased familial risk; 7 referred for
genetic consultation; of 8 histories assessed as
potential cancer syndrome, 4 had sufficient family
history in record to corroborate assessment; of 54
patients with no history documented, 15 were
assigned high familial risk based on computer
data entry
Frezzo et al,
62
2003
Observational (Illinois,
2001-2002)
78 patients in internal medicine
practice
Assess the documentation of
family history in medical
records; 2 collection
methods, self-administered
questionnaire and pedigree
interview by genetic
counselor, compared with
medical record
All individuals at increased risk by review of medical
records also identified as having increased risk by
questionnaire or pedigree interview; questionnaires
revealed 32 patients with increased risk compared
with 18 identified with record review; pedigree
analysis identified 30 patients with increased risk
compared with 15 with record review
Murff et al,
63
2004 Descriptive (Boston,
Massachusetts,
2001-2002)
995 Consecutive new patients
seen by primary care
physicians
Determine completeness of
documented cancer family
history information
68% Had some form of cancer family history
information in records; age at diagnosis
documented in 51% of relatives with colon
cancers, 38% with breast cancer, and 27% with
ovarian cancer; 17% of patients who met criteria
for testing referred for services
Oversight and Regulation of Genetic Testing
Hudson et al,
64
2006
Cross-sectional survey
(United States)
a
345 Molecular and biochemical
genetic testing laboratory
directors; 190 respondents
Assess participation in
proficiency testing for genetic
tests and attitudes of
laboratory directors toward
current regulation
84% Indicated that laboratory participated
in some form of external proficiency testing; 60%
found it very useful to improve quality of genetic
testing; 73% agreed that CLIA should create
genetic testing specialty for molecular and
biochemical tests
Privacy and Confidentiality Concerns
Hall and Rich,
65
2000
Qualitative comparative
case study (United
States, 1995-1997)
Representatives from insurance
industry (47), genetics
professionals (29), and
patient advocates (5) from 7
states with laws and 6
states without laws on use
of genetic information in
health insurance
Evaluate whether state laws
reduce extent of genetic
discrimination by health
insurers
No well-documented cases of health insurers either
asking for or using presymptomatic genetic test
results in underwriting decisions, either before or
after laws or in states with or without laws
Hall and Rich,
66
2000
Qualitative-comparative
case study (United
States, 1995-1997)
Representatives from insurance
industry (47), genetics
professionals (29), and
patient advocates (5) from 7
states with laws and 6
states without laws on use
of genetic information in
health insurance
Assess attitudes regarding
genetic discrimination
Patients’ and clinicians’ fear of genetic discrimination
in health insurance exceeds reality, may deter
genetic testing, particularly for costlier tests and
adult-onset diseases; most professionals are
aware of federal and state laws prohibiting
discrimination, but many underestimate
protections
Halletal,
67
2005 Cross-sectional survey
(United States and
Canada, 2001-2003)
86 859 Primary care patients;
78 942 respondents with
complete data
Assess concern about
insurance problems related
to genetic testing for
hemochromatosis
African American and Asian individuals significantly
much less likely and Hispanic more likely than
white individuals to express concern about
insurance discrimination; participants younger than
65 y, US residents (compared with Canadians),
those without high school diploma, and those with
lower mental health scores were substantially
more likely to express concern
Halletal,
68
2007 Survey (United States and
Canada)
1154 Primary care patients
screened for iron overload
phenotypes and HFE
genotypes; 832
respondents
Assess extent of insurance and
employment problems
associated with population
screening for hereditary
hemochromatosis and iron
overload after 1 y
Three respondents (0.4%) had verified insurance or
employment problems that they believed were
related to hereditary hemochromatosis and iron
overload; 2 had problems with life insurance and 1
with long-term care insurance; no problems
verified for health insurance or employment
Abbreviations: ACOG, American College of Obstetricians and Gynecologists; APN, advanced practice nursing; CLIA, Clinical Laboratory Improvement Amendments.
a
Year not stated.
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health insurers either asking for or using
presymptomatic genetic test results for
underwriting purposes.
65
The other
study found that patients’ and clini-
cians’ fears of genetic discrimination in
health insurance exceeds reality, and
this fear may deter genetic testing, es-
pecially for high-cost tests and adult-
onset diseases.
66
A cross-sectional survey of 86 859 pa-
tients in primary care settings participat-
ing in a hemochromatosis screening
study in North America found that Afri-
can American and Asian individuals were
less likely to have concerns about genetic
discrimination, and younger participants,
US residents, and those with less than
a high school education were more likely
to have these concerns.
67
A follow-up sur-
vey of 832 participants from this cohort
who were screened for iron phenotypes
and HFE genotypes associated with he-
mochromatosis found that after 1 year,
none reported problems with health in-
surance or employment and only 3
(0.4%) reported problems with life in-
surance or long-term care insurance.
68
COMMENT
Genomic advances hold the promise to
improve care and prevention of com-
mon chronic diseases. Although that
promise has yet to be fully realized, new
genetic discoveries make the reality of
that promise seem closer than ever before.
However, if past experience with other
health care advances is any guide, patients
will not realize the full benefit of genomic
advances without a thorough under-
standing of the organization, clinician,
and patient needs that are required to
translate these advances into improved
clinical outcomes. Our systematic review
reveals a large gap between what knowl-
edge is available and what health sys-
tems still need to know about the out-
comes, consumer needs, organization of
health services, and barriers, to ensure
appropriate and effective clinical inte-
gration of genomic information and tech-
nologies for common chronic disease.
The most important and consistent
finding from our literature review is that
the primary care workforce, which will
be required to be on the front lines of
the integration of genomics into the
regular practice of medicine, feels woe-
fully underprepared to do so. Reme-
diation of this deficiency should be a
top priority, and more studies are
needed to test models for how this can
be feasibly accomplished.
A second theme we identified is that
consumers have unclear and dissonant
notions about the value of genetic test-
ing for common chronic disease. In gen-
eral, consumers knew little about genet-
ics/genomics but were interested in the
prospect of this technology helping to
better identify diseases for which they and
their family members were at increased
risk. Consumers were also worried about
the possible adverse consequences of
genetic testing, particularly the privacy
issues and discrimination in health insur-
ance and employment. Therefore,
another research need is the develop-
ment and testing of interventions to pro-
mote greater understanding of genomic
medicine among consumers. Such inter-
ventions may need to be tailored for the
needs of specific populations.
A third theme we identified is that
there is a great need to better under-
stand the outcomes of genomic medi-
cine interventions for common chronic
disease. To date most studies have as-
sessed these outcomes using weak pre/
post study designs, and in general these
studies have assessed changes in psy-
chological, affective, and cognitive out-
comes of patients receiving genetic coun-
seling and testing for single-gene
disorders. More research describing clini-
cal outcomes is needed: do patients who
receive counseling and testing have bet-
ter clinical outcomes in terms of mor-
tality, decreases in incidence of disease,
and better clinical responses to pharma-
ceuticals? And at what cost?
We identified other barriers to the
clinical integration of genomic medi-
cine for common chronic disease, in ad-
dition to the perceived inadequacy of the
primary care workforce to participate in
this. The most prominent of these in-
clude health professionals’ lack of ba-
sic knowledge about genetics and their
lack of confidence in interpreting famil-
ial patterns of disease, which limits their
ability to appropriately counsel their pa-
tients, order and accurately interpret ge-
netic tests, and refer their patients for ge-
netics consultation. In addition, there
may not be sufficient numbers of genet-
ics professionals available to meet the de-
mand for genetic services.
Our review has several limitations.
First was the difficulty in identifying
health services studies of genomic medi-
cine for common chronic disease. We
know of no empirical assessments iden-
tifying an optimal search strategy for such
studies as, for example, there exist opti-
mal search strategies to identify RCTs and
studies of risk and prognosis. We
searched MEDLINE using reasonable
search terms, but we acknowledge it is
likely that we have failed to identify some
studies of relevance. However, given the
consistency of the studies we did iden-
tify, we believe it is unlikely that miss-
ing literature would substantially change
our main conclusions.
Second, we did not address the litera-
ture dealing with prenatal genetics, pe-
diatric genetics, genetic conditions with
pediatric onset experienced by adults, or
rare single-gene disorders presenting in
adulthood. Our focus was on the oppor-
tunities and challenges of genomics in-
terventions for common chronic dis-
eases of adulthood. Even then we found
that the evidence regarding these con-
ditions is largely limited to single-gene
disorders that manifest as common dis-
eases in adulthood, particularly cancer.
Third, because this literature was a
heterogeneous combination of study
questions, designs, populations, and
outcomes, synthesizing the study find-
ings involved making a certain num-
ber of judgments on our part. We tried
to be explicit and describe these judg-
ments as fully as possible so readers can
understand what we did.
CONCLUSIONS
In summary, this review of health ser-
vices research studies revealed many
gaps in the organization, clinician, and
patient needs that must be filled to re-
alize the full benefits of genomics. These
studies reported that consumers need
more and better information to under-
GENOMIC MEDICINE IN CLINICAL PRACTICE
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stand the value of genomic medicine for
common chronic diseases; that the pri-
mary care workforce is not prepared to
meet the challenge of integrating com-
mon disease genetics/genomics into the
regular practice of medicine; that the ge-
netics workforce appears to have inad-
equate numbers to respond to genetic
service needs for adult-onset condi-
tions; that few models of integration into
primary care have been successfully
implemented on a wide scale; and that
a host of barriers exist, such as lack of
oversight for genetic testing technolo-
gies and concerns about privacy and dis-
crimination. All of these issues need at-
tention. It will be a lost opportunity if
the health services research compo-
nents of genomic medicine fail to keep
pace with the rapid basic science ad-
vances and clinical discoveries.
Author Contributions: Dr Scheuner had full access to
all of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data
analysis.
Study concept and design: Scheuner, Sieverding,
Shekelle.
Acquisition of data: Scheuner.
Analysis and interpretation of data: Scheuner, Shekelle.
Drafting of the manuscript: Scheuner, Sieverding,
Shekelle.
Critical revision of the manuscript for important in-
tellectual content: Scheuner, Shekelle.
Obtained funding: Sieverding, Shekelle.
Study supervision: Shekelle.
Financial Disclosures: None reported.
Funding/Support: This work was funded by the De-
partment of Veterans Affairs, Veterans Health Ad-
ministration, Health Services Research and Develop-
ment Service, and was conducted by a team that
included Veterans Affairs employees.
Role of the Sponsor: Employees of the Department
of Veterans Affairs were involved in the design and
conduct of the study; in the analysis and interpreta-
tion of the data; and in the preparation and review of
the manuscript.
Disclaimer: The opinions expressed in this article are
those of the authors and do not reflect those of the
Department of Veterans Affairs, the Veterans Health
Administration, or the Health Services Research and
Development Service.
Previous Presentations: Presented at a planning meet-
ing of experts in health services research and genom-
ics and Veterans Affairs policy makers in Washing-
ton, DC; September 2007.
Additional Contributions: We are grateful to Rob-
erta Shanman (RAND Corporation), Brett Munjas (VA
Greater Los Angeles Healthcare System), and David
Adamson, PhD (RAND Corporation), who contrib-
uted to the completion of this article. These individu-
als did not receive compensation for their efforts be-
yond their usual salary.
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