Sexually Transmitted Diseases:
The Cost-Effectiveness of Screening Men for Chlamydia trachomatis: A Review of the Literature
Gift, Thomas L. PhD*; Blake, Diane R. MD†; Gaydos, Charlotte A. DrPH‡; Marrazzo, Jeanne M. MD, MPH§
From the *Centers for Disease Control and Prevention, Division of STD Prevention, Atlanta, Georgia; †Department of Pediatrics, University of Massachusetts Medical School, Worchester, Massachusetts; ‡Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland; and §Division of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, Washington.
Correspondence: Thomas L. Gift, PhD, Centers for Disease Control and Prevention, 1600 Clifton Road. NE, Mail Stop E-80, Atlanta, GA 30333. E-mail: firstname.lastname@example.org.
Received for publication December 11, 2007, and accepted March 2, 2008.
Background: An important consideration in determining whether to implement or continue a program to screen men for chlamydia is its cost-effectiveness. A review of the literature on the cost-effectiveness of screening men for chlamydia could potentially provide guidance.
Methods: An Ovid Medline search was conducted for articles published between 1990 and July 2007 using terms for cost, chlamydia, and male. This search returned 175 articles; 25 were retained after eliminating those not relevant to cost-effectiveness studies of male chlamydia screening. We added 4 articles that were in-press or are published in this issue, for a total of 29. These articles were examined for common themes and their results summarized.
Results: The reviewed studies examined both proactive and opportunistic screening and included screening of risk groups and of the general population. Some older studies included enzyme immunoassays; more recent studies featured nucleic acid amplification assays. Six studies used dynamic transmission models. Fourteen studies analyzed male and female chlamydia screening interventions. Several contained sufficient data to examine the cost-effectiveness of male screening compared with female screening. Male screening was preferred to expanded female screening in 1 study. In other studies, combined male and female screening programs were cost-saving.
Conclusions: Studies comparing chlamydia screening in men with chlamydia screening in women may be the most useful for guidance to programs. The studies which compare the 2 generally have found that screening men from the general population is not preferred to screening women from the general population, although 1 study found that screening of men from risk groups can be cost-effective compared with screening women from the general population.
CHLAMYDIA TRACHOMATIS IS THE MOST common bacterial sexually transmitted disease and can lead to sequelae such as epididymitis in men and pelvic inflammatory disease (PID) and its sequelae in women,1 although some investigators have questioned the extent to which chlamydia screening prevents PID.2,3 Because the most serious sequelae of chlamydial infection occur in women, chlamydial control efforts in the United States have historically focused on screening women. A recent review found that chlamydia screening in women compares favorably with other clinical preventive services.4 The Centers for Disease Control and Prevention recommends screening sexually active women 25 years of age or younger for chlamydia annually, but does not have a recommendation for screening heterosexual men.5 However, because chlamydial infection in men plays a role in transmission to women and because chlamydial infection in men is often asymptomatic,1 screening men offers the potential to assist in preventing disease in women.6 A recent systematic review of the literature examined the published body of evidence on the effectiveness of chlamydia screening generally.7
To address the issue of screening men for chlamydia, the Centers for Disease Control and Prevention convened an external consultation in March 2006 to examine the published evidence regarding the effectiveness and acceptability of screening men.8 One of the topics reviewed was the cost-effectiveness literature.
Materials and Methods
The consultants considered cost-effectiveness articles that were published between 1990 and January 2006. For the purposes of this report, we reviewed additional articles published since the consultation through August 2007. We conducted an Ovid Medline search using the following terms:
1. Cost or cost-effectiveness (keywords) or the topic of Costs and Cost Analysis, or Cost-Benefit Analysis
2. Chlamydia (keyword) or topics of Chlamydia trachomatis or Chlamydia Infections
We restricted our search to articles on humans and published in English. We retained any articles which contained cost information for implementation of a male screening intervention, but rejected articles that contained only vague or general references to cost, contained cost data for tests or treatment without any other cost information, or contained cost data for nonscreening interventions (such as partner notification without any other information pertaining to a program screening men). We also rejected articles that were reviews, editorials or letters, or that were not devoted to chlamydia in men (some of the latter were studies related to cost of C. pneumoniae or its sequelae).
Literature Search Results and Characteristics of Retained Articles
We found 175 articles that were indexed under all 3 terms described in the Methods section. Of these, we retained 25.9–33 We rejected 150 for the reasons shown in Table 1. We then added 4 additional articles appearing in this issue,34 available as “in-press,”35,36 or in print as of July 2007 but which did not appear in the literature search.37 The final total of articles considered was 179, with 29 retained for this literature review. Retained articles are shown in Table 2, arranged in alphabetical order based on the first author.
Interventions and Populations Screened
Of the retained studies, 15 presented cost or cost-effectiveness analyses of male-only screening interventions (5 of these presented both male and female models that were calculated separately),10,12,16,18–22,24–27,29,30,36 whereas 14 featured male and female screening together.9,11,13–15,17,23,28,31–35,37 One of the latter group included cost data collected from an intervention group that was mostly male (77 men, 2 women),11 whereas another featured a population that was mostly female (13,352 men, 54,059 women),28 but the remainder included populations that were balanced or nearly balanced between sexes. Nine studies were comparisons of testing methodologies only or contained program cost data for only 1 intervention, with no comparison to another intervention or to a baseline.11,13,14,21,23,28–31
Eleven studies analyzed screening in the general population (though this often was restricted to adolescents and young adults),9,11,15,26,28–31,33,35,37 and the other 18 studies analyzed either programs restricted to adolescents exclusively or to high-risk populations (such as STD or HIV clinic patients or men in correctional settings), or both.10,12–14,16–25,27,32,34,36 Some studies examined proactive screening interventions, in which men or women were invited to be screened, and some analyzed opportunistic screening interventions, in which men or women were screened when they visited a venue where screening was offered (such as a school, correctional facility, emergency department, or health care provider). Five studies were of proactive screening interventions.9,11,15,26,35 All of the proactive studies were of screening using home-collected specimens which were mailed for processing. The remaining 24 studies were analyses of opportunistic screening interventions or limited to comparisons of different testing methodologies, as discussed above.10,12–14,16–25,27–34,36,37 Ten studies involved use of leukocyte esterase testing, either alone or to preselect men for additional urine screening with a more sensitive test (generally a nucleic acid amplification test, although some older studies used an enzyme immunoassay).10,12,18–20,25,27,29,30,36 Many of the studies including use of leukocyte esterase are analyzed in detail in a review of the testing literature.38 Only 1 study employed pooling, but did not compare that technique with nonpooled testing for cost-effectiveness purposes.15
Cost Perspectives and Modeling Approaches
The studies employed various cost perspectives. The most limited is the program perspective, which includes costs incurred by the program or entity conducting the screening intervention. These costs typically include those of test kits, treatment, and test processing, plus labor costs. Some program-perspective studies excluded relevant costs, such as labor costs for specimen collection or treatment costs. A broader cost perspective is the health care system perspective, in which direct medical costs of the intervention and sequelae of chlamydial infection (often in patients screened and their partners) are included. Some studies failed to include potentially relevant health care system costs or failed to consider some sequelae. The broadest perspective is the societal perspective, where patient costs for lost productivity because of illness and health care visits are included, as well. Eight studies contained cost data from multiple perspectives—7 of these had program and health care system-perspective analyses,17,19,20,22,24,25,32 whereas 1 featured analyses from the program and societal perspectives.34 Eleven studies had program-perspective analyses11–14,16,21,23,28–31, 3 studies contained health care system-perspective analyses,10,27,36 and 6 had societal-perspective analyses.9,15,18,26,33,35 Because only health care system- or societal-perspective analyses generally include consideration of averted sequelae costs, only analyses from these perspectives were likely to show that an intervention was cost-saving (i.e., it averted more sequelae costs than it incurred in the implementation of the intervention). Typical averted costs considered included those for epididymitis, those for acute chlamydia in female partners, and sequelae in partners: PID, its sequelae, neonatal conjunctivitis, and neonatal pneumonia. Only 2 studies attributed any cost savings from averted HIV infections.17,22
Transmission models can attribute reduced PID in females to male screening interventions 2 ways, by treatment of direct partners of male index cases and through reduced population prevalence. Six of the studies were dynamic models.9,15,33–35,37 In contrast, static models generally assume a constant population prevalence. The static models in this review that included averted PID costs typically assumed some form of partner notification to treat female partners of male index cases.9,10,18–21,26,33–37 Some of these studies based on static models (and others from Table 2) also made projections about reduced near-term transmission (because of curing cases in men, who would therefore not infect new or prior but uninfected female partners during the time period in which they would otherwise have been infectious).10,27,32,36 However, these models did not assume that the screening programs would reduce prevalence in the population, thus reducing the risk of infection beyond the current and near-term partners of those screened.
Study Findings on the Cost-Effectiveness of Male Chlamydia Screening
Nine of the 18 studies that showed either health care system or societal-perspective cost results found 1 or more interventions to be cost-saving at baseline assumptions: 4 found screening of both men and women to be cost-saving,9,17,32,33 whereas 5 found screening of women to be cost-saving,22,24,25,33,36 and 4 found screening of men to be cost-saving10,24,25,36 (some studies found multiple interventions to be cost-saving, and other studies that did not find screening interventions to be cost-saving at the baseline did find that they could be cost-saving in sensitivity analyses).
All but 1 of the dynamic transmission model-based studies contained enough data to directly compare the impact of screening men for chlamydia with the impact of screening women.9 Some of the remaining models, such as those that calculated the cost-effectiveness of male and female screening programs separately, had sufficient information to compare the relative cost-effectiveness of male and female screening programs by comparing the average cost-effectiveness ratios. In instances where male and female screening could be directly compared, only 2 studies found screening of men and women to be more cost-effective than screening women alone.34,37 One of these was limited to considering only targeted male screening,34 whereas the other examined male screening on a population-wide level (restricted only by age).37In other studies, when combined male/female screening programs were cost-saving, cost savings from the female screening component were typically larger than the net costs attributable to the male screening portion of the intervention, leaving combined intervention to be cost-saving.32,33 In 1 intervention, it was not possible to determine the relative contribution that male and female screening made to the overall cost-effectiveness, although, the combined screening program became cost-saving after the second year.9 Another study that considered male and female screening programs separately found both to be equally cost-saving.36
Many of the studies reviewed here are confined to comparing different tests or testing algorithms. That is helpful in determining how to screen men, but less useful in deciding whether to screen men. For those that consider alternative screening strategies, some general principles emerge.
Cost-effectiveness studies have consistently indicated that the cost of PID and the rate at which it develops in women with chlamydia are the primary factors influencing whether any chlamydia screening program of men or women is cost-effective or cost-saving. The studies we reviewed made different assumptions about these variables. That accounts for much of the observed differences in cost per case of PID avoided or cost per quality adjusted life year gained. Another source of different conclusions among studies is inflation and exchange rate differences, for which we did not correct. Thus, the relative cost-effectiveness of the interventions included in each study may be a more meaningful indication for program guidance than the net cost or cost savings per averted case or gained quality adjusted life year. However, for cost-effectiveness studies to be of the most use to programs, they must consider male screening in a context of existing (or potential alternative) programs that screen women. Relatively few cost-effectiveness studies have done this. Moreover, many studies that have considered screening women have not fully evaluated implications of transmission from infected men to women, although some have included the impact on new sex partners following soon after screening, or included an effect attributable to notification and treatment of partners. Hogben and Kissinger39 reviewed the literature on partner notification elsewhere in this issue and concluded that self-referral was more viable than health department-initiated partner notification.
Another important factor influencing the cost-effectiveness of a screening program—and how a given study is interpreted—is the population screened. All but one34 of the transmission model-based studies assumed that men and women screened would come from the general population, although all studies assumed that persons screened would be adolescents and young adults (typically up to 24 or 25 years of age, although 1 study37 examined the impact of screening men or women up to 40 years of age among the alternatives considered). The models based on drawing from the general population have generally found male screening to be relatively less attractive than screening women, with one exception.37 However, in some special populations or venues, screening men may have a meaningful impact.10,32,34,36 A literature review by Rietmeijer et al.40 running in this issue found that chlamydia positivity in correctional settings were higher than in other venues, but that many settings yielded higher chlamydia positivity than the general population. This finding of identifiable higher-prevalence venues was supported by a review of surveillance data by Satterwhite et al.41 that is published in this issue.
In summary, studies comparing the cost-effectiveness of chlamydia screening in men with chlamydia screening in women may provide useful for guidance to public health programs. Most studies reported that the approach of screening men from the general population was not preferred to screening women from the general population, although 1 study found that screening men from high-risk groups could be cost-effective in this context. The decision to screen men for chlamydia ultimately depends on many factors including local population prevalence of chlamydia in men, as well as women, targeted high-risk groups, and availability of resources for this purpose.
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