Motivating factors for physician ordering of Factor V Leiden genetic tests

Abstract

Background

The Factor V Leiden (FVL) genetic test is used by many physicians despite its uncertain clinical utility. This study investigated whether self-reported motivations and behaviors concerning FVL genetic testing differed between two groups of primary care physicians defined by frequency of prior FVL test use.

Methods

In January 2007, 112 primary care physicians (60 frequent, 52 infrequent FVL test users) at Group Health, a large health care delivery system, were surveyed. Survey content areas included: primary reasons and motivating factors for ordering FVL; likelihood of ordering FVL for hypothetical patients; potential barriers to genetic testing, and practices and skills regarding FVL test ordering.

Results

Responses between groups agreed concerning most clinical- or patient-related factors. Frequent-FVL physicians were more likely than infrequent-FVL physicians to report ordering FVL for hypothetical patients with mesenteric venous thrombosis (adjusted OR 4.57, 95% CI 1.55, 13.53) or venous thrombosis following hospital discharge (adjusted OR 3.42, 95% CI 1.30, 8.95). Frequent-FVL physicians were also less likely to agree with several potential barriers to genetic testing and more likely to report high confidence in interpreting and explaining FVL test results.

Conclusions

Generally, both groups of physicians reported similar motivating factors for ordering FVL, and reported behaviors were consistent with existing guidelines. More striking differences were observed for measures such as barriers to and confidence in using genetic tests. Though additional research is necessary to evaluate their impact, these results inform several knowledge-to-practice translation issues that are important to the successful integration of genetic testing into primary care.

Introduction

Factor V Leiden (FVL) is a genetic variant that confers resistance to activated protein C and a predisposition to venous thromboembolism (VTE). At present, evidence for the clinical utility of the FVL test is limited¹. Among those who carry the FVL variant, the risk of a first VTE is increased², but the implications for risk of VTE recurrence or patient management are less clear^{3, 4}. Current recommendations suggest evaluation on a case-by-case basis. Two U.S. working groups, the College of American Pathologists and the American College of Medical Genetics, have released consensus statements related to the appropriate clinical use of FVL testing ^5-7. Indications for FVL testing are generally the same as for other thrombophilias and include recommendations based on age, site and presence of precipitating factors (previous VTE, strong family history, pregnancy, exogenous hormone use) for patients with VTE and unexplained late pregnancy loss in women. The clinical goal of testing is not specified in these guidelines.

FVL is the third most readily available genetic test in the United States, as judged by the number of laboratories that offer FVL testing ⁸. Genetic tests are predicted to become an increasingly important component of clinical care, on the presumption that genetic susceptibility information will guide prevention and clinical management. Primary care practitioners may well be early adopters or gatekeepers of this technology. However, data on factors influencing FVL testing in clinical practice are limited. Previous studies have observed that primary care physicians are generally supportive of integrating genetics into clinical care but may be hesitant to go beyond traditional roles such as specialty referral, taking a family history, and supportive counseling^9-11. Additionally, physician confidence in performing these roles is not high⁹. Assessing motivating factors for and potential barriers to ordering genetic tests such as FVL may be early but necessary steps in the process of translating of genetic knowledge to clinical care, especially in the context of uncertain clinical utility. Practically, this understanding could inform development of practice guidelines or help individual physicians decide how best to integrate genetics into their own practices.

The primary objective of this study was to determine whether self-reported motivations for ordering a FVL genetic test differed among groups of primary care physicians defined by prior clinical use of the test at Group Health (GH), a large integrated health care delivery system based in Western Washington. At GH, venous thrombosis treatment guidelines recommend FVL testing for female VTE patients who are pregnant and that FVL testing be considered for patients under the age of 50 with an idiopathic VTE or who have a strong family history of VTE¹². These guidelines acknowledge that the appropriateness of such testing has yet to be clarified but may inform patient-physician discussions regarding prognosis and duration of anticoagulation. Physicians from two groups defined by their FVL test ordering experience were sampled separately. We hypothesized that prior clinical use of FVL testing is associated with: differences in the perceived purpose and motivating factors for test ordering; the likelihood of ordering a FVL test for a hypothetical patient; more favorable attitudes towards genetic testing, and greater confidence in using the test.

Methods

Study setting and participants

GH serves as the setting for several case-control studies of heart disease among persons with pharmacologically treated hypertension or among postmenopausal women^{13, 14}. Medical records and an automated laboratory database were used to identify which primary care physicians had ever ordered a FVL test for any of these case-control study participants. We then divided physicians into two groups: physicians who had ever ordered a test for a participant in our case-control studies (n = 69) and physicians who had never ordered a FVL test at GH (n = 39). To increase study power, we supplemented the first group with 16 additional physicians who most frequently ordered FVL within the 12 months preceding the survey (December, 2005 to December, 2006; range, 2-4) and the second group with 46 additional physicians who had not ordered a test at GH during that same period and had the fewest number of FVL tests ever ordered (range, 1-3). For ease of reference, we refer to the first group as frequent FVL test use (frequent-FVL) and the second group as infrequent FVL test use (infrequent-FVL). Physicians were unaware of the intentional sampling on prior test use. Primary care was defined as any of the following categories: internal medicine, family medicine, or other (obstetrics/gynecology or gerontology/geriatrics; a total of three physicians). Physicians who were retired, lacked a contact address, or were specialists were ineligible. The study was approved by the Group Health Institutional Review Board and physicians who returned surveys gave implicit informed consent.

After the initial population was supplemented, a total of 170 physicians (85 in each group) were selected to receive surveys. One hundred and fourteen physicians responded (67%). Following exclusion of two responders (one retiree and one essentially blank survey), the analysis included 60 frequent-FVL and 52 infrequent-FVL physicians.

Survey instrument and data collection

The survey instrument, available as supplementary material, comprised nine pages and took approximately 20 minutes to complete. The survey was divided into six content sections with differing response formats (some questions had multiple parts): 1) nine questions on primary reasons for ordering the FVL test (checkbox); 2) fourteen questions on importance of motivating factors (five-point scale); 3) thirteen questions on likelihood of ordering FVL for hypothetical patients (five-point scale); 4) eleven questions on potential barriers to genetic testing (five-point scale); 5) three questions on confidence in practices and skills related to FVL test ordering (five-point scale); and 6) eight questions on provider characteristics (combination of open and closed questions). For several sections, participants were asked similar questions about testing for lupus anticoagulant or anticardiolipin; these results are not reported here.

Physicians received up to five interoffice mailings: 1) an introductory letter; 2) a survey packet that included an incentive (bookstore gift card); 3) a reminder letter for nonrespondents, after two weeks; 4) an additional copy of the survey for nonrespondents after two additional weeks; and 5) a thank-you letter to participants. Responses were double-entered into an electronic database by abstractors who were blinded to a physician’s FVL test use group. The dataset was closed 8 weeks after the last reminder letter was mailed.

Statistical analysis

Statistical analyses were performed in Intercooled STATA 8 (STATA, College Station, Texas). Statistical significance was declared at p ≤ 0.05 (two-sided). Responses phrased on a five-point scale (e.g., very high, high, fair, low, very low) were dichotomized for analysis (e.g., very high/ high versus fair / low / very low). Responses at the positive end of the scale (e.g., high, important, or agree) were considered affirmative. Between-group differences in the proportion of affirmative responses were assessed using a chi-squared test (unadjusted). Multivariate logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) after adjustment for self-reported age, gender, specialty and number of VT patients per year.

Rasch analysis was used to estimate the tendency for positive response across all items in a section while accounting for physician-specific variation in the degree of affirmative response¹⁵. Questions within each section can be ranked according to the logit term for each item, yielding a relative ordering from highest to lowest tendency for an affirmative response. An interaction model suggested that the overall response to all items within a table did not differ significantly between frequent-FVL and infrequent-FVL physicians (Rasch interaction test p-values > 0.11). Thus, Rasch model parameters are reported for the combined population.

Results

The two physician groups did not differ significantly according to age, gender, time spent in practice, research, or teaching, or graduation from a U.S. medical school (Table 1). However, compared with infrequent-FVL physicians, more frequent-FVL physicians reported practicing internal medicine and fewer reported practicing family medicine. Frequent-FVL physicians were also more likely to spend less time in administration, report seeing more venous thrombosis patients per year, order the FVL test at GH in the 12 months preceding the survey and at any time. The mean number of FVL tests ever ordered was higher in the frequent-FVL group (7.8 versus 1.1). Among the various specialties comprising primary care and adjusted for FVL test use group, internal medicine physicians were likely to report an average of 13.8 more venous thrombosis patients (95% CI 9.8 to 17.8) in a typical year compared with family medicine physicians. “Other” physicians reported approximately the same number of venous thrombosis patients as family medicine physicians (adjusted mean difference -1.7, 95% CI -11.0 to 7.7).

Table 1.

Characteristics of physician participants.

Category	Infrequent-FVL	Frequent-FVL
	N = 52	N = 60
Age, years (SD)	51.4 (7.6)	49.8 (8.3)
Female, %	40.4	35
Specialty, %
Family medicine	90.4	66.7*
Internal medicine	9.6	28.3*
Other	0	5
Time spent (%)
in practice	87.5	93.7
in research	0	2.2
in administration	9.3	1.6*
in teaching	2.4	0.8
Venous thrombosis patients per year, mean (SD)	7.3 (6.5)	11.6 (11.5)*
Ever ordered test, %	61.5	100*
Number of tests ever ordered, mean (SD)	1.1 (1.1)	7.8 (1.0)*
Ordered test in 12 months prior to survey, %	0	61.7*
Medical school in US, %	96.2	88.1

^*p < 0.05.

Among both frequent-FVL and infrequent-FVL groups, more than half of the participants identified the following primary reasons for ordering FVL: advise patients about risk of recurrence, make treatment decisions, make clinical decisions about prevention, or explain the occurrence of venous thrombosis (Table 2). A higher proportion of the frequent-FVL compared with the infrequent-FVL group tended to identify each reason but responses did not differ significantly between the two groups when adjusted for age, gender, specialty and number of venous thrombosis patients. A family history of venous thrombosis, personal history of venous thrombosis, and consultation with a specialist were patient- and clinical care-related factors that were identified by a majority of physicians (Table 3). After adjustment, frequent-FVL physicians were less likely to identify the inclusion of FVL on a thrombophilia panel as important (adjusted OR 0.38, 95% CI 0.14, 0.97).

Table 2.

“In clinical practice, what would be your primary reasons for ordering the Factor V Leiden test in the context of venous thrombosis?”

Statement	Logit (SE)	Infrequent- FVL, %	Frequent- FVL, %	Adjusted OR (95% CI)
Advise patients about risk of recurrence	-6.7 (0.76)	82.7	91.7	2.42 (0.68 to 5.21)
Make treatment decisions	-5.9 (0.72)	75	85	1.88 (0.68 to 8.53)
Make clinical decisions about venous  thrombosis prevention	-4.9 (0.69)	67.3	68.3	1.06 (0.45 to 2.49)
Explain the occurrence of venous thrombosis	-4.9 (0.69)	57.7	75	1.78 (0.76 to 4.13)
Satisfy a patient request	-3.0 (0.66)	28.8	38.3	1.61 (0.68 to 3.78)
Make a diagnosis of venous thrombosis	0 (ref.)	3.8	10	2.94 (0.54 to 16.10)
Teach medical students residents etc	0.72 (0.72)	3.8	5	0.96 (0.13 to 7.08)

Responses are ordered from highest to lowest tendency for an affirmative response on a logit scale.

OR’s are adjusted for age, gender, specialty and number of VT patients per year.

Table 3.

“When deciding whether to order a Factor V Leiden test, how important would the following factors be to you?”

Factor	Logit (SE)	Important (%)		Adjusted OR (95% CI)
		Infrequent- FVL	Frequent- FVL
Family history of venous thrombosis	-3.5 (0.52)	88.5	91.7	1.76 (0.40 to 7.79)
Personal history of venous thrombosis	-3.0 (0.44)	84.6	90	1.63 (0.47 to 5.61)
Consultation with a specialist	-0.92 (0.29)	61.5	60	1.27 (0.55 to 2.91)
Presence of established risk factors for  venous thrombosis	-0.29 (0.29)	50	45	0.70 (0.31 to 1.62)
Age	0 (ref.)	42.3	40	0.78 (0.34 to 1.81)
Site	0.39 (0.30)	34.6	31.7	1.15 (0.49 to 2.69)
Group Health guidelines	0.48 (0.30)	30.8	31.7	1.34 (0.54 to 3.32)
Family history of arterial thrombosis	0.48 (0.30)	34.6	28.3	0.83 (0.35 to 1.97)
Professional society guidelines	0.53 (0.30)	30.8	30	0.85 (0.35 to 2.04)
Inclusion of FVL test on a thrombophilia  panel	0.73 (0.31)	36.5	18.3*	0.38 (0.14 to 0.97)
Patient preference or request	0.93 (0.31)	19.2	26.7	2.01 (0.74 to 5.45)
Patient access to genetic counseling	1.6 (0.35)	13.5	15	1.34 (0.42 to 4.23)
Gender	2.3 (0.43)	9.6	6.7	0.95 (0.22 to 4.05)

Responses are ordered from highest to lowest tendency for an affirmative response on a logit scale.

OR’s are adjusted for age, gender, specialty and number of VT patients per year.

^*p < 0.05

Thirteen hypothetical clinical scenarios were presented (Table 4). The four scenarios with the strongest tendency for FVL ordering were a young man diagnosed with testicular cancer, a man with mesenteric VTE, a young woman on oral contraceptives, and a female relative of a FVL heterozygote. More than half of the physicians in either group were likely to order the test for these hypothetical patients. After adjustment, frequent-FVL physicians were significantly more likely than infrequent-FVL physicians to order the test for a man with mesenteric venous thrombosis (adjusted OR 4.57, 95% CI 1.55, 13.53), and for a young man diagnosed with lower extremity deep vein thrombosis a week after discharge from an extended hospital stay (adjusted OR 3.42, 95% CI 1.30, 8.95).

Table 4.

“Please estimate the likelihood that you would order a Factor V Leiden test for [each hypothetical clinical scenario].”

	Logit (SE)	Likely to order (%)		Adjusted OR (95% CI)
		Infrequent- FVL	Frequent- FVL
A 45 yo man is diagnosed with testicular cancer and is scheduled to receive  chemotherapy	-2.4 (0.37)	80.8	83.3	1.19 ( 0.43 to 3.31)
A 67 yo man is diagnosed with mesenteric vein thrombosis	-1.9 (0.34)	65.4	85*	4.57 ( 1.55 to 13.53)
A 32 yo woman on oral contraceptives is diagnosed with deep vein thrombosis	-1.6 (0.33)	65.4	76.7	2.23 ( 0.88 to 5.63)
A healthy 29 yo woman reports that her 35 yo sister was found to be  heterozygous for FVL. She would like to know if she also carries the  mutation	-1.6 (0.33)	67.3	75	1.42 ( 0.59 to 3.44)
A 68 yo man is diagnosed with deep vein thrombosis. He frequently travels on  long flights and wants to know whether he should be tested	-0.34 (0.31)	44.2	53.3	1.47 ( 0.64 to 3.38)
A 55 yo woman without any known predisposing risk factors is diagnosed with  idiopathic venous thrombosis	-0.10 (0.31)	36.5	51.7	1.94 ( 0.85 to 4.40)
A pregnant 35 yo woman is diagnosed with lower extremity deep vein  thrombosis	0 (ref.)	34.6	50	1.77 ( 0.74 to 4.22)
A 45 yo man is diagnosed with lower extremity deep vein thrombosis a week  after discharge from an extended hospital stay	0.20 (0.32)	26.9	50*	3.42 ( 1.30 to 8.95)
A 77 yo man is diagnosed with pulmonary embolism and reports that his father  had venous thrombosis at age 48	0.25 (0.32)	32.7	43.3	1.56 ( 0.65 to 3.77)
An asymptomatic 75 yo man with a family history of venous thrombosis is  scheduled for elective surgery	2.0 (0.38)	9.6	16.7	1.50 ( 0.44 to 5.17)
A 57 yo woman with a history of deep venous thrombosis is considering  hormone therapy for postmenopausal symptoms	2.3 (0.41)	11.5	10	0.79 ( 0.22 to 2.78)
A 65 yo woman is diagnosed with a second occurrence of deep vein thrombosis	3.7 (0.64)	0	6.7	NE
A 70 yo woman is diagnosed with pancreatic cancer	4.9 (1.0)	0	3.3	NE

Responses are ordered from highest to lowest tendency for an affirmative response on a logit scale.

OR’s are adjusted for age, gender, specialty and number of VT patients per year.

Note: “Likely to order” denotes whether the likelihood of ordering the FVL test was “Very High” or “High.”.

NE = not estimable.

^*p < 0.05

Among possible barriers to the integration of genetic testing in routine clinical care, lack of availability of genetic counseling services, uncertainty about impact on patient management, and the low number of applicable patients were ranked as the three most affirmative statements (Table 5). More than half of physicians in both groups agreed with the lack of availability of genetic counseling as a potential barrier. After adjustment, several statements were more likely to reflect a significantly lower proportion of frequent-FVL compared with infrequent-FVL physicians in agreement. These included lack of genetic counseling services (adjusted OR 0.37, 95% CI 0.15, 0.93), few number of relevant patients (adjusted OR 0.24, 95% CI 0.10, 0.60), and lack of professional society guidelines in favor of genetic testing (adjusted OR 0.13, 95% CI 0.03, 0.59).

Table 5.

“A range of opinions exists about possible barriers to integration of genetic testing in clinical care. Please check the appropriate box.”

Statement	Logit (SE)	Agree(%)		Adjusted OR (95 % CI)
		Infrequent- FVL	Frequent- FVL
Genetic counseling services are not well integrated into my practice	-1.5 (0.32)	76.9	53.3*	0.37 (0.15 to 0.93)
It is unclear whether the test result would alter patient management	-0.27 (0.30)	42.3	38.3	0.76 (0.35 to 1.71)
I don’t see enough patients for whom genetic testing would be applicable	0 (ref.)	50	21.7*	0.24 (0.10 to 0.60)
Current guidelines at GHC do not encourage genetic testing	0.60 (0.32)	28.8	20	0.66 (0.25 to 1.69)
I am concerned about potential genetic discrimination based on my patients’  genetic test results	0.66 (0.32)	23.1	23.3	1.05 (0.41 to 2.69)
I am concerned about my patients’ privacy/ confidentiality of genetic test  results	1.0 (0.34)	21.2	15	0.48 (0.16 to 1.44)
Current guidelines from professional societies do not encourage genetic  testing	1.3 (0.36)	23.1	6.7*	0.13 (0.03 to 0.59)
It is inconvenient (for either patients or practitioners) to obtain the test	1.3 (0.36)	17.3	11.7	0.77 (0.24 to 2.45)
Sensitivity or specificity of the test are too low	1.8 (0.40)	13.5	6.7	0.46 (0.12 to 1.79)
Patients must first express an interest in the test	2.0 (0.42)	13.5	3.3*	0.29 (0.05 to 1.55)
Genetic testing is not necessary because a family history tells me similar  information	2.9 (0.57)	7.7	0*	NE

Responses are ordered from highest to lowest tendency for an affirmative response on a logit scale.

OR’s are adjusted for age, gender, specialty and number of VT patients per year.

“Agree” denotes whether the participant designated the corresponding factor as “Strongly Agree” or “Agree.”

NE = not estimable.

^*p< 0.05.

Finally, a greater proportion of frequent-FVL physicians reported high confidence in interpreting and communicating FVL test result (Table 6). Following adjustment for age, gender, specialty and number of venous thrombosis patients, these associations were not statistically significant (OR 1.96, 95% CI 0.73, 5.31 and OR 2.20, 95% CI 0.80, 6.04, respectively). The results differed according to specialty: a greater proportion of internal medicine compared with family medicine physicians expressed high confidence in interpreting results (infrequent-FVL: 40% versus 15%; frequent-FVL: 59% versus 28%) and in communicating results to patients (infrequent-FVL: 60% versus 11%; frequent-FVL: 53% versus 28%). Notably, fewer than 40% of physicians in either FVL group expressed high confidence in any of the three areas.

Table 6.

Physician confidence in ordering FVL tests.

Question	Logit (SE)	High(%)		Adjusted OR (95% CI)
		Infrequent -FVL	Frequent- FVL
How would you rate your confidence in interpreting the results of Factor V Leiden  tests?	-2.0 (0.58)	17.3	36.7*	1.96 (0.73 to 5.31)
How would you rate your confidence in communicating information about the  results of Factor V Leiden tests to your patients?	-1.7 (0.56)	15.4	35*	2.20 (0.80 to 6.04)
How would you rate your confidence in determining when it is appropriate to test  for Factor V Leiden?	0 (ref.)	7.7	16.7	0.77 (0.17 to 3.51)

Responses are ordered from highest to lowest tendency for an affirmative response on a logit scale.

OR’s are adjusted for age, gender, specialty and number of VT patients per year.

“High” denotes whether the participant rated the corresponding question as “Very High” or “High.”

^*p < 0.05.

Analyses excluding the supplemental physicians yielded similar results, though confidence intervals were very wide due to limited power and multivariate adjustment was not possible for several items.

Discussion

In this survey of practicing primary care physicians, we identified several clinical, patient- or physician-related factors associated with FVL test ordering. These differences between groups were generally small in magnitude. FVL test ordering status was associated with increased likelihood of ordering of FVL for two hypothetical scenarios: mesenteric venous thrombosis in a 67 year-old man and deep vein thrombosis following an extended hospital stay in a 45 year-old man. Larger differences between FVL groups were observed for other features of the survey. FVL ordering status was associated with more favorable attitudes toward genetic testing. Frequent-FVL doctors were less likely to agree with perceived barriers to genetic testing, though a substantial proportion of both groups agreed that genetic counseling services and unclear impact on patient management were potential barriers. A greater proportion of frequent-FVL physicians expressed high confidence in communicating and interpreting FVL test results, though these results were not statistically significant after adjustment.

Physician responses to the motivating factors and clinical vignettes were generally consistent with existing recommendations based on expert clinical opinion^{5, 6}. A majority of physicians were likely to order the FVL test in the context of VTE that presents at an unusual site (mesenteric venous thrombosis) or concurrently with oral contraceptive use. Physicians in both groups were also likely to order the test for asymptomatic patients if there was an affected relative or if cancer developed at an early age, contexts for which recommendations in the CAP, ACMG, or Group Health guidelines are less clear. Only 50% of frequent-FVL and 35% of infrequent-FVL physicians said that they would be likely to order FVL for the young pregnant woman, the only scenario on the list included in Group Health guidelines.

Though most physicians in both groups did not agree with any of the eleven potential barriers to integrating genetic tests into clinical care (except for genetic counseling), the level of confidence in interpreting and communicating test results was low even within the frequent-FVL group. That frequent-FVL physicians were less likely to agree with several potential barriers to genetic testing and were more confident in using FVL test results than infrequent-FVL physicians suggests some internal consistency among this group of physicians. These data are consistent with reports that physicians are open to the integration of genetics into primary care, though they may need additional training^{9, 10, 16-18}

A key strength of this study was the selection of comparison groups based on prior clinical use of the FVL test, allowing us to evaluate which factors were important to either group as well as those that differed between groups. However, several limitations deserve mention. The two FVL test use comparison groups reflect a low level of difference in the self-reported number of VTE patients seen annually and likely, a low level of variability in test ordering experience. This may explain the lack of association between FVL ordering group and the clinically-motivated factors for ordering the test. We controlled for the self-reported number of VTE patients, but residual confounding due to a specific mix of patients may have remained (e.g., frequent-FVL physicians may have tended to see the most compelling VTE patients). Additionally, we queried physicians about possible and likely actions, which may not reflect actual behavior or predict future behavior. The survey was lengthy, and false positive results are possible. In light of the hypothesis-generating nature of this study, we did not statistically control for multiple comparisons and our results should be interpreted accordingly.

Our results suggest several areas for future research focusing on the translation of knowledge to practice. First, regardless of FVL test use group, most of the doctors in our study ordered the FVL test at some point in time, even though the average number of yearly venous thrombosis patients was low and despite a generally low confidence level in their own ability to interpret or communicate test results. The two groups ranked the clinical indications for testing similarly and in a manner that does not correspond precisely to recommendations of professional societies or even their own clinical group. That FVL test use groups were similar with respect to clinical- and patient-centered motivational factors but differed according to measures such as perceived barriers to genetic testing or confidence is striking. Not all guidelines are evidence-based, but even when sufficient scientific knowledge is available to make a best-practice recommendation or guideline, integration of genetic testing into clinical care requires both physician awareness and support to achieving best practices. Understanding why physicians do or do not comply with clinical guidelines is a first step; adherence to practice guidelines is itself known to be influenced by many factors¹⁹. Our results suggest that the availability of counseling or other referral services, frequency of relevant presenting patients, and a clinician’s ability to explain results are all important to primary care physicians. Our study suggests that confidence levels may vary by specialty within primary care, an observation that requires further investigation. Additional research is needed to determine whether interventions or updated practice guidelines targeting areas identified by our survey, such as providing access to specialty referral or education, will improve physician performance and patient health. A key question will be how to achieve both higher levels of confidence and better performance, and studies identifying such translational factors are needed for the successful deployment of genetic tests in primary care. Ultimately, primary care physicians and their patients will benefit if physicians have the confidence and skills to use these tests properly.