Screening for Chlamydia trachomatis in Asymptomatic Women Attending Family Planning Clinics: A Cost-Effectiveness Analysis of Three Strategies

In 1996, the Centers for Disease Control and Prevention (CDC) provided $12.9 million for the Infertility Prevention Program [1]. This ongoing project offers financial and legislative support for expanded service delivery within the U.S. Public Health Regions to prevent infertility and other sequelae of chlamydial infection, such as pelvic inflammatory disease and ectopic pregnancy. To ensure the continued success of the Infertility Prevention Program on a national basis, we must be able to cost-effectively identify women at high risk for chlamydial infection for the testing and targeting of prevention and control activities. The CDC recommends testing all women with evidence of mucopurulent cervicitis and all women younger than 20 years of age [2]. They also suggest 1) testing women 20 to 23 years of age who have not consistently used barrier contraception or have had a new sex partner or more than one sex partner during the past 90 days and 2) testing women 24 years of age or older who have not consistently used barrier contraception and have had a new sex partner or more than one sex partner during the past 90 days [2]. Alternatively, it has been suggested that all women younger than 30 years of age who are seen in family planning clinics should be screened [3]. The sequelae of chlamydial infection cost more than $2.7 billion each year [4]. Screening and timely treatment can decrease the incidence of sequelae [1, 5] and the associated medical costs [6]. Universal screening offers the potential to identify and treat as many chlamydial infections as possible, thus decreasing the incidence of future illness and the economic consequences of sequelae [7]. Alternatively, a selective screening program based on the CDC criteria or age could target the portion of the population at highest risk and identify most chlamydial infections without testing all women [8]. To address the question of who should be screened, we applied three screening strategies in a medical cost and outcome decision model to the predominantly asymptomatic population seen at family planning clinics in Baltimore, Maryland. The three strategies were 1) screening women according to the CDC criteria, 2) screening women younger than 30 years of age, and 3) screening all women. We compared each strategy's ability to identify women at risk for chlamydial infection and thus allow the initiation of testing and treatment, decrease the incidence of sequelae, and decrease overall medical costs. Methods Study Sample and Setting We considered 8654 women who attended Baltimore City Health Department (BCHD) family planning clinics between April 1994 and August 1996. As part of the Region III Infertility Prevention Project, these women were tested for Chlamydia trachomatis by polymerase chain reaction (PCR) assays (Roche Diagnostic Systems, Branchburg, New Jersey) that were processed at the Johns Hopkins University Chlamydia Research Laboratory. Women who had at least one clinical sign of chlamydial infection on pelvic examination (mucopus, cervicitis, cervical ectopy, cervical motion tenderness, or friability on cervical contact) and women who presented as the sex partner of a person with chlamydial infection were offered presumptive treatment and were excluded from the study. Women who attended the clinic for reasons that necessitated a pelvic examination (for example, for an annual Papanicolaou test) had PCR testing of cervical specimens. Women who did not need a pelvic examination had PCR testing of urine specimens. Informed consent was obtained from all patients who were attending BCHD family planning clinics to receive standard care. This study was approved by the institutional review board of Johns Hopkins University. Decision Analysis Statistical analysis was done by using Intercooled Stata 4.0 (Stata Corp., College Station, Texas). A decision analytic model (Smltree 2.9, Jim Hollenberg, Roslyn, New York) was developed to analyze a series of possible events associated with each strategy (Table 1). Medical outcomes were defined as prevented cases of pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy, infertility, male urethritis, epididymitis, infantile conjunctivitis, and infantile pneumonia. Economic outcomes were defined as all screening-related program costs and direct medical cost savings of all sequelae (Table 1). Indirect costs were considered in sensitivity analyses. For descriptions of the equations and calculations used in the model, see Appendix. Table 1. Risk for Events and Cost Estimates Modeled in the Reference Case* Overall economic and medical outcomes were compared from the perspective of a health care system to determine which strategy prevented the most disease and had the lowest total costs. Incremental cost-effectiveness ratios (that is, estimates of the additional cost that one strategy requires to prevent one more case of pelvic inflammatory disease than the next most effective strategy) were compared. The reference case estimates were varied in univariate and multivariate sensitivity analyses to determine how changes in estimated values affected the results and to identify break-even prevalence points. Costs were adjusted to 1995 U.S. dollars by using the medical care component of the 1996 consumer price index. Future costs were discounted at an annual rate of 3% [30]. Measurement of Estimated Values Clinic personnel collected demographic, behavioral, and clinical presentation data by using the Region III Infertility Prevention Program Prevalence Study survey. The administrative time associated with the collection of a patient's data was not included as a program cost because the information would have been collected even in the absence of a screening program. The clinician time associated with a full pelvic examination (28 minutes) was estimated by the direct observation of activities in a clinic patient-flow analysis (BCHD. Unpublished data). Begley and colleagues [9] previously estimated the cost of materials for a pelvic examination. The clinician time required for the collection and administrative processing of an additional cervical swab for screening purposes (1.5 minutes) was based on the manufacturer-recommended protocol (Roche Diagnostic Systems). The cost of specimen collection associated with each screening strategy was weighted by the percentage of women who received a pelvic examination for a medical reason other than screening for chlamydial infection. This analysis considered the question of testing cervical specimens by PCR. The sensitivity of PCR (87.6%) was determined by modified meta-analysis of the peer-reviewed medical literature [10-17]. A specificity of 99% was used [12]. The cost of the PCR assay for screening purposes was provided by the Maryland State Health Laboratory and was based on costs of materials, manufacturer quotes for public health testing, and the annualized cost of a thermocycler. The cost of laboratory technician time per specimen was obtained by time-in-motion studies of the laboratory technicians in the Johns Hopkins University Chlamydia Research Laboratory. The follow-up cost of scheduling a return visit for treatment after a positive test result was previously estimated by Begley and colleagues [9]. In the BCHD family planning clinics, approximately 80% of women who are notified of a positive test result return for treatment (BCHD. Unpublished data). The cost of the treatment visit, including administration time, clinician and counseling time, and distribution of doxycycline, was based on clinic records and direct observation of clinician activities (BCHD. Unpublished data). The effectiveness of doxycycline was previously estimated to be 85.7% [18]. Doxycycline causes minor to major side effects in 16% of persons [18], and the cost of treating these side effects was considered a cost of the screening program. An estimated 10% to 40% of women with untreated chlamydial infections develop pelvic inflammatory disease [5, 19-21]. We used an overall probability of pelvic inflammatory disease of 30% and assumed that 40% of these cases would be symptomatic in year 1 [22]. Our reference case-weighted cost of sequelae, which considered the risks for and costs of future sequelae in men, women, and infants, was derived from the research of Washington, Marrazzo, and Haddix and coworkers [4, 22, 23]. Role of the Funding Source The funding source for this study did not play a role in gathering, analyzing, or interpreting the data or in deciding whether to submit the manuscript for publication. Results Reference Case Analysis From April 1994 through August 1996, the BCHD family planning clinics provided services to 8354 women. Approximately 7.6% of these women (n = 638) either had clinical evidence of a chlamydial infection (n = 558) or presented because an infected sex partner had informed them of their possible exposure to chlamydia and had advised them to seek medical care (n = 80). These women were excluded from the study. Of the remaining 7716 women, 17 reported never having had vaginal intercourse. None of these women tested positive for chlamydial infection, and all were dropped from the analysis. Of the remaining 7699 women, most were African American and had no medical insurance (Table 2). The median age was 25 years (range, 11 to 68 years). Many had previously had a diagnosis of a sexually transmitted disease, but few reported having previously had a diagnosis of syphilis. Few women reported having more than one sex partner or having a new sex partner in the 90 days before screening. However, more than half reported inconsistent use of condoms. Table 2. Characteristics of the 7699 Asymptomatic Women Attending Baltimore City Health Department Family Planning Clinics between April 1994 and August 1996* A total of 5173 women received a pelvic examination for routine reproductive care (that is, they would have received a pelvic examination even in the absence of a chlamydial scre