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Screening for Chlamydia trachomatis in Women 15 to 29 Years of Age: A Cost-Effectiveness Analysis

Delphine Hu, MD, MPH; Edward W. Hook III, MD; and Sue J. Goldie, MD, MPH
[+] Article and Author Information

From Harvard School of Public Health, Boston, Massachusetts, and University of Alabama at Birmingham, Birmingham, Alabama.


Acknowledgments: The authors thank Karen Kuntz for guidance on probabilistic sensitivity analysis and Steven Sweet for technical advice and help with manuscript preparation.

Grant Support: By Agency for Healthcare Research and Policy Fellowship Award (Dr. Hu).

Potential Financial Conflicts of Interest:Consultancies: E.W. Hook (Abbott Laboratories, Gen-Probe); Honoraria: E.W. Hook (Abbott Laboratories, Gen-Probe); Other: E.W. Hook (Abbott Laboratories; Roche Molecular Systems, Inc.; Gen-Probe; Becton, Dickinson, and Co).

Requests for Single Reprints: Sue J. Goldie, MD, MPH, Department of Health Policy and Management, Harvard School of Public Health, 718 Huntington Avenue, 2nd Floor, Boston, MA 02115-5924.

Current Author Addresses: Drs. Hu and Goldie: Department of Health Policy and Management, Harvard School of Public Health, 718 Huntington Avenue, 2nd Floor, Boston, MA 02115-5924.

Dr. Hook: Department of Medicine, University of Alabama at Birmingham, 703 19th Street South ZRB 242, Birmingham, AL 35294-0007.

Author Contributions: Conception and design: D. Hu, S.J. Goldie.

Analysis and interpretation of the data: D. Hu, E.W. Hook, S.J. Goldie.

Drafting of the article: D. Hu, S.J. Goldie.

Critical revision of the article for important intellectual content: D. Hu, E.W. Hook, S.J. Goldie.

Final approval of the article: D. Hu, E.W. Hook, S.J. Goldie.

Statistical expertise: S.J. Goldie.

Administrative, technical, or logistic support: S.J. Goldie.


Ann Intern Med. 2004;141(7):501-513. doi:10.7326/0003-4819-141-7-200410050-00006
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Before evaluating alternative screening strategies, we sought to validate the model by comparing projected outcomes with independent data not used for initial variable estimation. The model predicts age-specific test positivity for chlamydial infection within a plausible range of values reported by family planning clinics in 50 U.S. states participating in the 2000 CDC Chlamydia Prevalence Monitoring Project (78)(Figure 1, top). The projected cumulative incidence of symptomatic acute pelvic inflammatory disease is also similar to published estimates for self-reported pelvic inflammatory disease (79) adjusted for the proportion attributable to chlamydial infection, which is estimated to be 85% (80)(Figure 1, bottom).

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Figures

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Figure 1.
Positive chlamydia screening test results and cumulative incidence of symptomatic pelvic inflammatory disease.

The age-specific test positivity for predicted by the model (circle) falls within the range reported by the Centers for Disease Control and Prevention Prevalence Monitoring Project data in 2000 (dotted line) (78). The cumulative incidence of symptomatic pelvic inflammatory disease predicted by the model (circle) closely approximates data for self-reported pelvic inflammatory disease from the 1988 National Survey of Family Growth (NSFG) (bara) (79). The vertical columns are the range of values reported by the NSFG adjusted for the 85% of pelvic inflammatory disease that is estimated to be attributable to chlamydial infection(80).

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Figure 2.
Average per-person lifetime costs for selected screening strategies.

The costs attributable to pelvic inflammatory disease and its sequelae progressively shift to those associated with screening and treatment as screening efforts are intensified. *Every 6 months if previously infected.

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Figure 3.
Sensitivity analysis.

The effect of varying selected model variables on the estimated incremental cost-effectiveness ratio for the strategy of annual screening in women 15 to 29 years of age followed by semiannual screening for those with a history of infection. Values in parentheses are the baseline values for each variable and the plausible range used in sensitivity analysis. The bars indicate the variability of the cost-effectiveness ratio caused by changes in the value of the indicated variable, all other variables being held constant. The dotted vertical line indicates the incremental cost-effectiveness ratio under baseline assumptions. *Applies to women younger than 20 years of age. †Associated with a threshold value beyond which this strategy is cost-saving, relative to no screening. ‡Applies to women 20 years of age or older. §Applies to women with a history of chlamydial infection. QALY = quality-adjusted life-year.

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Figure 4.
Two-way sensitivity analyses simultaneously varying the probability of persistent infection (0%, 15%, 30%, and 45%) and the relative risk for recurrent infection (1.0, 2.0, and 3.0).

Many scenarios produce results for age-specific test positivity (top) and cumulative incidence of symptomatic pelvic inflammatory disease (bottom) that are within the range of published data from the Centers for Disease Control and Prevention Chlamydia Prevalence Monitoring Project in 2000 (78) and the National Survey of Family Growth (79), respectively.

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Figure 5.
Reduction in future chlamydia prevalence.

The reduction in future chlamydia prevalence predicted by the model (circles) approximates data reported in areas with broad-based screening programs sponsored by the Centers for Disease Control and Prevention (CDC) and public health departments (triangles). *Data from CDC-sponsored, regional screening programs participating in the National Infertility Prevention Program (1, 5, 65). †Data from women attending reproductive health care clinics in Birmingham, Alabama, between 1995 and 1998 (82). ‡Data from the Chlamydia Prevention Program in Wisconsin (1987–1991) (83). §Data from women participating in the National Job Training Program from May 1990 to June 1996 (66).

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Relative CE of different Chlamydia tests
Posted on October 28, 2004
Brian R Jackson
University of Utah Department of Pathology
Conflict of Interest: None Declared

To the editor:

I read the cost-effectiveness analysis for Chlamydia trachomatis screening by Hu et al.(1) with great interest. One topic not explicitly covered in this article, but that could easily be addressed by the same decision model, is the relative cost-effectiveness of different laboratory tests for Chlamydia trachomatis detection. Nucleic acid amplification methods, which were used by Hu et al. in their analysis, are substantially more sensitive than nonamplified DNA methods, which in turn are much more sensitive than the older enzyme immunoassay methods.(2,3) From the individual patient perspective, then, the amplified tests are clearly optimal. However, many laboratories continue to offer these other less sensitive tests,(4) a phenomenon that appears to be driven by cost. If it could be demonstrated that amplified DNA tests were cost-effective (or even better, cost-saving) versus non-amplified tests from a health system perspective, then perhaps payers could be convinced to cover the modestly increased cost of amplified testing for Chlamydia trachomatis. This would in turn benefit both individual patients and the public health.

Brian Jackson, MD University of Utah Department of Pathology and ARUP Laboratories Salt Lake City, UT

1. Hu D, Hook EW, Goldie SJ. Screening for Chlamydia trachomatis in women 15 to 29 eyars of age: a cost-effectiveness analysis. Ann Int Med. 2004;141(7):501-513. 2. Black CM, Marrazzo J, Johnson RE, Hook EW 3rd, Jones RB, Green TA, et al. Head-to-head multicenter comparison of DNA probe and nucleic acid amplification tests for Chlamydia trachomatis infection in women performed with an improved reference standard. J Clin Microbiol. 2002;40:3757-63. 3. Watson EJ, Templeton A, Russell I, Paavonen J, Mardh PA, Stary A, et al. The accuracy and efficacy of screening tests for Chlamydia trachomatis: a systematic review. J Med Microbiol. 2002;51:1021-31. 4. College of American Pathologists. Surveys 2003. Northfield IL; 2003.

Conflict of Interest:

The author is employed by ARUP Laboratories, which performs testing for Chlamydia trachomatis.

Cost-effectiveness of chlamydia screening has not been demonstrated
Posted on December 9, 2004
Pelham M Barton
University of Birmingham, UK
Conflict of Interest: None Declared

Screening for genital chlamydia is intended to reduce the incidence of severe complications of chlamydia infection in women. Chlamydia screening programmes should also aim to eradicate this curable preventable infectious disease by preventing transmission. We believe that the static modelling approach and the assumptions made in article by Hu et al. do not necessarily mean that opportunistic screening is cost-effective [1].

The authors' attempt to incorporate the transmission dynamics of chlamydia in a state-transition model might well have produced misleading results: sexual behaviour is not random so the use of average numbers of sexual contacts fails to capture the highly skewed distribution of sexual partnerships and differential sexual mixing patterns that are crucial to determining the distribution of sexually transmitted infections [2]. Partner notification does not appear to have been considered and, as pointed out in the accompanying editorial, the incidence of complications has probably been overestimated. Furthermore, the assumption of 100% annual screening coverage of women in the base case is unrealistic. Although this was reduced to 60% in sensitivity analysis, the model does not reflect the impact of differential coverage according to sexual behaviour.

Hu et al. justify their static modelling approach by claiming that cohort models nearly always underestimate cost-effectiveness [3]. In fact, Edmunds et al. show that this is only true under certain conditions, which have not been met by Hu et al. First, the reproductive number for chlamydia is not high [4] Second, chlamydia does not confer lasting immunity; treatment restores women to a susceptible state. Edmunds et al. conclude that avoiding a proper population perspective, "is to avoid a fundamental process"¦ for the sake of being able to complete an incorrect analysis" [3].

The use of a dynamic modelling approach does not, as Hu et al. claim, preclude a comprehensive cost analysis. In the Chlamydia Screening Studies (ClaSS) Project we used detailed cost data collected alongside prospective epidemiological, laboratory, and social studies in a transmission dynamic model using discrete event simulation [5]. We will be comparing our results directly with those of a static model. We think that our approach will provide a more realistic view of the population effects of chlamydia screening and hence a cost-effectiveness analysis that will be of greater relevance to policy makers.

Conflict of Interest:

None declared

In response:
Posted on December 9, 2004
Delphine Hu
Harvard School of Public Health
Conflict of Interest: None Declared

We appreciate Dr. Jackson's interest and comment. We believe that this model has the potential to help inform a number of questions relating to chlamydial screening and chose to start by exploring the impact of different approaches to routine screening for young women from a long- term, societal perspective. Our analysis was intended to inform broad recommendations for national screening guidelines with particular emphasis on the optimal target age range and frequency for screening. At the same time, a wide variety of diagnostic tests are available for C. trachomatis detection, including cell culture, antigen-detection tests, nucleic acid hybridization tests, and most recently nucleic acid amplification tests (NAATs). Compared to non-amplified tests, NAATs have been demonstrated to have superior sensitivity and greater acceptability among adolescents and young adults [1-3], although at a higher cost. As pointed out in Stamm's commentary [4], many public health based screening programs have limited resources and consequently are able to offer screening to less than half the target population. This fact illustrates an important distinction between the cost-effectiveness (i.e., "value for money") of an available technology from a societal perspective and the affordability of that technology from the perspective of one particular payor (e.g., public health clinic). An analysis that comparatively evaluates a wide array of available screening tests and that considers a shorter time horizon, while explicitly taking into account the available budget, would be useful for regional and local decision making. Such analyses are complex since to accurately reflect the tradeoffs associated with different tests in such an analysis, one would require data on the likelihood of compliance with different tests, and correlation between compliance and preferences. We agree such an analysis is of high priority.

Delphine Hu, Edward W. Hook III, and Sue J. Goldie

References

1. Watson EJ, Templeton A, Russell I, Paavonen J, Mardh PA, Stary A, et al. The accuracy and efficacy of screening tests for Chlamydia trachomatis: a systematic review. J Med Microbiol. 2002;51:1021-31.

2. Nsuami M, Cohen DA. Participation in a school-based sexually transmitted disease screening program. Sex Transm Dis. 2000;27:473-9.

3. Wiesenfeld HC, Lowry DL, Heine RP, Krohn MA, Bittner H, Kellinger K, et al. Self-collection of vaginal swabs for the detection of chlamydia, gonorrhea, and trichomoniasis: opportunity to encourage sexually transmitted disease testing among adolescents. Sex Transm Dis. 2001;28:321 -5.

4. Stamm WE. Chlamydia Screening: Expanding the Scope. Ann Intern Med. 2004; 141: 570 - 572.

Conflict of Interest:

Dr. Hook has received research support from Abbott Laboratories, Roche Molecular Systems, GenProbe Inc., and Becton Dickonson, and honoraria from Abbott and GenProbe.

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Summary for Patients

The Cost-Effectiveness of Screening for Chlamydia in Women 15 to 29 Years of Age

The summary below is from the full report titled “Screening for Chlamydia trachomatis in Women 15 to 29 Years of Age: A Cost-Effectiveness Analysis.” It is in the 5 October 2004 issue of Annals of Internal Medicine (volume 141, pages 501-513). The authors are D. Hu, E.W. Hook III, and S.J. Goldie.

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