title: Application of the case-crossover design to reduce unmeasured confounding in studies of condom effectiveness.
abstract: This analysis examined how unmeasured confounding affects estimates of the effectiveness of condoms in preventing sexually transmitted infections. Data were analyzed from a prospective cohort study of 1,122 female sexually transmitted disease clinic patients in Alabama (1992-1995), wherein participants were evaluated for sexually transmitted infections at six 1-month intervals. Associations between condom use and incident gonorrhea and chlamydia infection were compared between case-crossover and cohort analyses. In a case-crossover analysis of 228 follow-up visits ending in gonorrhea/chlamydia ("case intervals") and 743 self-matched follow-up visits not ending in gonorrhea/chlamydia ("noncase intervals") (183 women), consistent condom use without breakage or slippage was associated with significantly reduced risk of infection relative to nonuse (adjusted risk odds ratio = 0.49, 95% confidence interval: 0.26, 0.92). Conversely, a cohort analysis of 245 case intervals and 3,896 noncase intervals (919 women) revealed no significant reduction in infection risk from consistent use of condoms (adjusted risk odds ratio = 0.79, 95% confidence interval: 0.53, 1.17). Dose-response relations between the number of unprotected sex acts and infection were stronger in the case-crossover analysis (p for trend = 0.009) than in the cohort analysis (p for trend = 0.18). These findings suggest that epidemiologic studies confounded by unmeasured differences between condom users and nonusers underestimate condom effectiveness against these infections. The case-crossover method provides an additional technique for reducing unmeasured confounding in studies of condom effectiveness.
authors.affiliation: National Center for Chronic Disease Prevention and Health Promotion, Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA. dlw7@cdc.gov
authors.forename: Lee
authors.initials: L
authors.lastname: Warner
authors.forename: Maurizio
authors.initials: M
authors.lastname: Macaluso
authors.forename: Harland D
authors.initials: HD
authors.lastname: Austin
authors.forename: David K
authors.initials: DK
authors.lastname: Kleinbaum
authors.forename: Lynn
authors.initials: L
authors.lastname: Artz
authors.forename: Michael E
authors.initials: ME
authors.lastname: Fleenor
authors.forename: Ilene
authors.initials: I
authors.lastname: Brill
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Newman
authors.forename: Edward W
authors.initials: EW
authors.lastname: Hook
mesh_terms: D000328:Adult; D000407:Alabama / Q000453:epidemiology; D002690:Chlamydia Infections / Q000453:epidemiology / Q000517:prevention & control; D015331:Cohort Studies; D017280:Condoms; D015986:Confounding Factors, Epidemiologic; D018592:Cross-Over Studies; D005260:Female; D006069:Gonorrhea / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D011446:Prospective Studies; D015231:Sexually Transmitted Diseases, Bacterial / Q000453:epidemiology* / Q000517:prevention & control*; D013997:Time Factors