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To estimate the cost and cost-effectiveness of testing sexually transmitted disease (STD) clinic subgroups for antibodies to hepatitis C virus (HCV).
HCV counseling, testing, and referral (CTR) costs were estimated using data from two STD clinics and the literature, and are reported in 2006 dollars. Effectiveness of HCV CTR was defined as the estimated percentage of clinic clients in subgroups targeted for HCV antibody (anti-HCV) testing who had a true positive test and returned for their test results. We estimated the cost per true positive injection drug user (IDU) who returned for anti-HCV test results and the cost-effectiveness of expanding HCV CTR to non-IDU subgroups.
The estimated cost per true positive IDU who returned for test results was $54. The cost-effectiveness of expanding HCV CTR to non-IDU subgroups ranged from $179 to $2,986. Our estimates were most sensitive to variations in HCV prevalence, the cost of testing, and the rate of client return.
Based on national data, testing IDUs in the STD clinic setting is highly cost-effective. Some clinics may find that it is cost-effective to expand testing to non-IDU men older than 40 who report more than 100 lifetime sex partners. STD clinics can use study estimates to assess the feasibility and desirability of expanding HCV CTR beyond IDUs.
Approximately 4.1 million people in the United States (1.6% of the total population) have been infected with the hepatitis C virus (HCV), which is acquired through contact with an infected person's blood.1 Injection drug use behaviors, such as sharing needles or syringes or other injection paraphernalia (e.g., cotton, cookers, water), are the most important behavioral risk factors for HCV infection.1,2 As many as 85% of those infected with HCV develop chronic infection, which may lead to chronic liver disease, cirrhosis, liver cancer, and death.2
The Centers for Disease Control and Prevention (CDC) recommends routine HCV antibody (anti-HCV) testing for high-prevalence groups, particularly people who have ever injected drugs (i.e., injection drug users [IDUs]) or received blood transfusions from infected donors. People who test positive for anti-HCV need follow-up testing for the presence of virus, and to distinguish current from past HCV infection, and are usually referred for follow-up testing as part of medical evaluation. HCV counseling, testing, and referral (CTR) may delay progression of chronic HCV infection and complications because some HCV-infected people change behaviors that speed progression (e.g., alcohol consumption) or are referred for medical evaluation, care, and possible antiviral treatment.3
Public sexually transmitted disease (STD) clinics represent a promising setting for HCV CTR, but few STD clinics currently offer it. (Personal communication, Chris Taylor, NASTAD, August 2006.) Most STD clinics offering HCV CTR services (including the anti-HCV test) target IDUs, but clients may not report injecting drugs, perhaps because of perceived stigma.4–6 For example, in a San Diego STD clinic, Gunn et al.7 found that 40% of HCV-positive clients who initially denied injecting drugs admitted this behavior after diagnosis. For this reason, STD clinics may be reluctant to limit testing to self-reported IDUs (hereafter “IDUs”), but most clinics cannot afford to implement universal testing, and it may be inefficient to do so, even if funds were available. STD clinics need guidance to help them decide how to target HCV CTR services. This article provides estimates of the STD clinic cost per additional positive anti-HCV identified among IDUs and other subgroups potentially at risk for HCV infection. Clinics can use these estimates to inform decisions about whether to offer anti-HCV testing and to whom.
We measured effectiveness of anti-HCV testing as the percentage of STD clinic clients in each subgroup with a true positive HCV test result who returned to receive results, where true positive results captured those individuals who are correctly identified through testing as anti-HCV positive. We measured effectiveness only in subgroups that could be identified based on self-reported information.
We used data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002 to estimate HCV prevalence by subgroup. NHANES is a nationwide household survey that contains laboratory test results for HCV infection for survey participants six years and older, demographic data (age and race/ethnicity), and survey responses about behavioral risk factors for disease. In 1999–2000, 8.8% of respondents had missing HCV tests, and in 2001–2002, 8% had missing tests. Those excluded from HCV testing included hemophiliacs; participants who had received chemotherapy within the past four weeks; and participants with rashes, gauzes, open sores, and other conditions that restricted access to both arms. We estimated HCV prevalence for IDUs and for three subgroups aged 40 and older who did not report injecting drugs (hereafter “non-IDUs”): men who reported 100 or more lifetime sex partners, men who reported fewer than 100 lifetime sex partners, and women (Table 1). People aged 40 or older were selected because HCV prevalence is higher among older age groups. Men were selected because of their higher HCV prevalence. We used 100 or more lifetime sex partners as a risk indicator because HCV may sometimes be sexually transmitted8,9 and because a high number of sex partners could be correlated with injection drug use.
For HCV CTR, STD clinics incur costs for screening and pre-test counseling (including risk assessment), performing a blood test and laboratory analysis for anti-HCV, and post-test counseling. Costs consist of the value of staff time and the laboratory costs for analyzing blood samples. We excluded STD clinic facilities' costs because we assumed they were fixed and would be incurred regardless of whether anti-HCV testing was offered.
We estimated the per-patient cost of each activity by multiplying the staff time required by the staff member's hourly compensation (hourly wage rate plus fringe benefits). The per-patient cost of the laboratory test was estimated by assuming that clinics first use the enzyme immunoassay (EIA), then retest using recombinant immunoblot assay (RIBA) for those with a low EIA signal-to-cutoff ratio (1.0 to 3.8).10 To reduce costs and improve reliability, CDC recommends that RIBA be used only to confirm low-positive EIAs.11
Data were collected on staff time and salaries for the three anti-HCV testing activities from two public STD clinics (Table 2). We used published Medicare reimbursement rates to estimate the laboratory costs of EIA and RIBA tests. Actual clinic payments for these tests were used to establish a range of testing costs. The sensitivity and specificity of the testing protocol were based on Chapko et al.10,12 The percentages of clients who returned for results were obtained from one STD clinic.
We calculated the per-client clinic costs of CTR for four categories of clients: those with positive test results who return to the clinic for results, those with positive test results who do not return, those with negative test results who return, and those with negative test results who do not return. All costs were in 2006 dollars.
The baseline cost-effectiveness analysis combined estimates of CTR costs and effectiveness to calculate the cost per IDU who tested positive for anti-HCV and who returned for results. We then calculated the cost-effectiveness of expanding anti-HCV testing to three additional non-IDU subgroups.
For each of the four subpopulations, we first calculated the per-person cost of CTR as a weighted mean of the costs for positive testers who return (CR+), positive testers who do not return (CN+), negative testers who return (CR−), and negative testers who do not return (CN−). The four weights were the probability of having a positive test outcome multiplied by the probability of returning to receive results (WR+), the probability of having a positive test outcome multiplied by the probability of not returning for test results (WN+), and analogously defined weights for those with negative test outcomes (WR− and WN−).
Per-person costs were calculated as follows:
where each weight is a function of the probability of returning to receive test results, anti-HCV prevalence in the subpopulation, and the sensitivity and specificity of the testing algorithm. Four test outcomes are possible: the probability of a true positive test (PT1), the probability of a false positive test (PF1), the probability of a true negative test (PT2), and the probability of a false negative test (PF2). We estimated the test outcome probabilities as follows:
(R+ is the probability that a positive tester returns to receive results, and R−is the probability that a negative tester returns.)
We estimated the cost-effectiveness of CTR from the STD clinic perspective as the cost per additional client with a true positive test result who returns for results, as follows:
where CER denotes the average cost-effectiveness ratio and R+× PT+ represents the probability that a true positive tester returns to receive results. Average CERs were estimated for each subpopulation.
We analyzed the impact on results of uncertainty in our estimates of costs, anti-HCV prevalence, and the possible future availability and use of a rapid test. For anti-HCV prevalence rates, we recalculated CERs for the lower and upper bounds of the 95% confidence interval for each anti-HCV prevalence estimate. We estimated CTR costs using minimum and maximum values developed from clinic data. We also evaluated a what-if scenario for rapid tests by estimating the likely impact of having a rapid test for anti-HCV. For this scenario analysis, we assumed that such a test would cost the same as the current EIA test ($19.94) but would increase the return rate for results to 100%.
Anti-HCV prevalence among IDUs in the NHANES sample was 57% (Table 1). For non-IDUs older than 40, prevalence was 16% among males with 100 or more sex partners, 2% among males with fewer than 100 sex partners, and 0.9% among females (Table 1).
The estimated cost of pre-test counseling was $1.58 per client (Table 3). Blood draw and testing costs are slightly higher for clients with positive test outcomes because anti-HCV-positive clients are more likely to have a low signal-to-cutoff ratio that requires confirmatory testing. Clients with positive test results have higher post-test counseling costs because staff members usually spend more time with them. The total estimated cost of anti-HCV CTR for positive testers who return for their test results (CR+) was $27.10. For positive testers who do not return, estimated cost (CN+) was $24.60. Estimated costs were $22.70 for negative testers who return (CR–) and $22.30 for negative testers who do not return (CN–).
The testing protocol outcome probabilities varied by subpopulation (Table 4). For IDUs, the probability of a true positive test was 0.53, the probability of a false positive was less than 0.001, the probability of a true negative test was 0.43, and the probability of a false negative test was 0.038. The probability of a false positive test was less than 0.001 even for the subpopulation of women older than 40, whose estimated prevalence of anti-HCV was less than 1%.
For IDUs, the estimated STD clinic costs for CTR were $54 per true positive tester who returned for his or her results (Table 5). The average cost per patient tested in this subpopulation was $25. We estimated that 45.5% of this group who were true positives would return for their results.
The cost of expanding testing from IDUs only to non-IDU men older than 40 with 100 or more sex partners was $179 per positive tester who returns for results. This CER is considerably higher than the estimate for IDUs alone primarily because the proportion of the population that tests as anti-HCV-positive and returns for test results is lower (13.0% vs. 45.5%). The CER for non-IDU men older than 40 with fewer than 100 sex partners was $1,386 and for all non-IDU women older than 40 was $2,986 (Table 5).
For IDUs, the results are relatively insensitive to uncertainty in the estimated prevalence of anti-HCV, with CERs ranging from $45 to $68 (Table 6). For non-IDU women older than 40, CERs vary greatly when uncertainty in estimated anti-HCV prevalence is incorporated ($1,666 to $14,529). Cost-effectiveness estimates for IDUs are sensitive to uncertainty in the estimated cost of anti-HCV testing, but the estimated range for CERs—$28 to $75—suggests that anti-HCV testing for IDUs is highly cost-effective. The availability of a rapid test for anti-HCV infection that would result in return rates of 100% (because results would be available immediately) would lead to more favorable CERs for all subgroups: $47 for IDUs, $155 for non-IDU men older than 40 with 100 or more sex partners, $1,201 for non-IDU men older than 40 with fewer than 100 sex partners, and $2,587 for non-IDU women older than 40.
Our findings provide economic support for recommendations to test IDUs in STD clinics.3,11 The CER for testing IDUs—$54 per true positive tester who receives results—was far below that of any other group. IDUs are widely recognized as the risk group accounting for the greatest proportion of acute and chronic HCV infections and are recommended for testing.3 Many STD clinics offer anti-HCV testing primarily to self-reported IDUs4,5 but still test lower-risk people. For example, data from the Denver STD clinic for 2001–2005 show that more non-IDU clients (887) than IDU clients (540) were tested.4 Clinics may test people who do not report injecting drugs because they are concerned that some clients fail to disclose this behavior.7 Clients and counselors may also mistakenly believe that tattoos/piercings and sexual risks are significant risk factors for HCV infection. In addition, most public STD clinics cannot deny services, including anti-HCV testing, to clients who request them. (Personal communication, Isaac Weisfuse, Deputy Commissioner, Division of Disease Control, New York City Department of Health and Mental Hygiene, October 2006.) Further study should examine why non-IDU clients are tested and create strategies to help clinics target IDUs for testing, including improving methods for getting clients to disclose injection drug use.
An analysis of the cost of CTR per HCV case prevented was beyond the scope of this study. However, if HCV CTR has similar cost-effectiveness to human immunodeficiency virus (HIV) counseling and testing in the STD clinic setting ($82,000 per HIV case averted), then clinic CTR efforts would need to result in one case of HCV infection prevented for every 580 cases that test positive for anti-HCV and return for results.13 In addition, although STD clinics have limited resources, clinic managers may determine that paying an average of $25 per IDU tested is a feasible and worthwhile investment from the clinic perspective. Total CTR costs per 100 IDU clients without known anti-HCV positive status are $2,500 per year, an expense that may seem reasonable to many clinic managers in order to enhance public health.
Because of concerns about nondisclosure of injection drug use, STD clinics may consider offering testing to other subgroups with easily identifiable characteristics or risk behaviors that are associated with higher-than-average anti-HCV prevalence. We found a potentially favorable cost of $179 per additional positive client who returns for test results among non-IDU men older than 40 with 100 or more lifetime sex partners. Expanding testing to all males older than 40 or to all clients older than 40 will not likely be cost-effective for most STD clinics.
Our analysis has several limitations. First, our measure of the effectiveness of HCV testing captures only the identification of anti-HCV and patient notification and not the additional costs or benefits that follow, including actual diagnosis of current infection. As recommended by Haddix et al.14 and Gold et al.,15 cost-effectiveness analyses should ideally capture all future costs and health benefits associated with identifying anti-HCV and notifying clients, including the impacts on health-care utilization and quality and length of life. Accounting for these long-term impacts is challenging because there is no consensus on the expected impact of hepatitis C treatment on future morbidity and mortality.16 Our cost estimates are from the STD clinic perspective and do not include other societal costs, such as travel and time costs for clinic clients.
Second, we were unable to limit our analysis of anti-HCV prevalence to include only those people without known anti-HCV positive status because NHANES did not ask respondents whether they have ever been told by a doctor that they have HCV antibodies. To avoid wasting clinic resources, STD clinics should test only those clients without known anti-HCV positivity. To examine the extent to which this limitation affects our cost-effectiveness results, we excluded from our NHANES sample those people who reported that they had ever been told by a doctor that they had a liver condition. This question is likely to identify individuals with known HCV infection as well as those with other forms of liver disease. Approximately 38% of the IDUs who tested positive for anti-HCV responded “yes” to this question. Once those individuals were eliminated from our analysis, the estimated prevalence of anti-HCV among IDUs was 0.47, and the estimated cost per positive tester who returns was $64.60, as compared to the baseline estimate of $54.40.
For the other subpopulations, the impact of eliminating individuals with a known liver condition reduced anti-HCV prevalence by a small amount that did not substantially alter the cost-effectiveness of testing. For example, for men with more than 100 sex partners, eliminating those who reported a previous liver condition increased the cost-effectiveness from $179 to $186.
In summary, while we obviously do not recommend retesting patients who are aware of their positive anti-HCV status, removing these patients from the analysis is not likely to alter the decision to prioritize testing of those who disclose IDU behaviors but have not been tested before. We were unable to estimate the cost-effectiveness of retesting IDUs who have previously tested negative for anti-HCV because such a question was beyond the scope of our model. However, an evaluation of the cost-effectiveness of HIV screening found that recurrent screening was always less cost-effective than one-time screening but that it became more cost-effective as the annual disease incidence increased.17 Future studies should examine the impact of annual incidence on the cost-effectiveness of recurrent anti-HCV testing.
Third, our estimates of anti-HCV prevalence in each subgroup are from NHANES, which has several limitations that may affect how well the data represent similarly defined subgroups in STD clinics. NHANES excludes groups at especially high risk for HCV infection (e.g., homeless, incarcerated). Additionally, NHANES may understate the prevalence of anti-HCV in STD clinic clients if those clients are more likely than the general population to engage in behaviors that put them at risk for HCV infection. For NHANES respondents with more than 100 sex partners or who report injection drug use, the anti-HCV prevalence estimate may be representative of STD clinic clients who disclose those same behaviors. NHANES is most likely to understate anti-HCV prevalence for STD clinic clients who do not disclose risk behaviors, especially if those clients have riskier lifestyles than the general population.
Fourth, we did not consider females older than 40 with more than 100 sex partners for testing because the NHANES sample of this group was too small to estimate the prevalence of anti-HCV. Because sentinel surveillance information indicates that sexual transmission may be more common among women than men,18 clinics should use available information about risk factors for HCV infection to estimate anti-HCV prevalence among their female clients and develop testing policies accordingly.
Fifth, our estimates assume that the probability of returning for test results is the same for all subgroups. However, it is more realistic to expect return rates to vary by risk group. For example, because they know they are at increased risk for HCV infection, IDUs are generally more likely to return for test results than other targeted subgroups, suggesting that CTR may be more cost-effective for IDUs than our estimates suggest.
Sixth, our sensitivity analyses are limited in that they do not consider the impact of systematically examining the possible range of all values used in the cost-effectiveness model. For example, we did not examine the impact of variations in the sensitivity and specificity of the testing protocol or return rates for test results. Future research will incorporate additional sensitivity analyses, including probabilistic sensitivity analyses to examine which combinations of variables in the model have the greatest impact on cost-effectiveness findings.
Finally, our cost and return rate estimates are based on data from a small number of STD clinics, which may not be representative, and our cost-effectiveness estimates do not capture the challenges that STD clinics are likely to face in limiting testing to specific high-risk subgroups.
Our research suggests that HCV CTR services for IDUs in an STD clinic setting are likely to have an acceptable cost-effectiveness range ($28 to $75). The relatively low cost per positive tester who returns for results supports recommendations for routine anti-HCV testing of IDUs.3
Study estimates also suggest that expanding testing to non-IDU men older than 40 who report 100 or more lifetime sex partners may be cost-effective for some clinics. Based on our estimates, routine testing of other groups in STD clinic settings is not likely to be cost-effective. The cost-effectiveness of HCV CTR would be improved if clinics could better limit anti-HCV testing to high-risk clients and increase return rates for test results.