Cost Effectiveness of the Reverse Sequence Algorithm Compared With the Traditional Algorithm for Syphilis Screening Among Pregnant Women

Abstract

Objective: The traditional syphilis screening algorithm, which involves a nontreponemal assay followed by confirmatory treponemal testing, has been challenged by an alternative approach known as the reverse sequence algorithm. The latter reverses the order of the tests and incorporates a second treponemal test for discordant results. Although the reverse sequence may offer operational advantages, there is a need for formal cost-effectiveness analyses to compare these two syphilis screening alternatives.

Methods: We conducted cost-effectiveness analyses from the health care sector perspective to compare the reverse sequence with the traditional algorithm. We employed a decision tree for pregnant women in prenatal care that included the possibility of congenital syphilis outcomes. A simulated a cohort of 10,000 people was screened over 1 year to estimate total costs and quality-adjusted life-years (QALYs) under each algorithm. We estimated incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed to identify influential parameters affecting the ICERs and to conduct scenario analyses.

Results: During prenatal care, the reverse sequence detected four more cases, overtreated 185 more individuals, and prevented 0.42 more congenital syphilis cases (ICER $463,735/QALY gained), when compared with the traditional algorithm. Sensitivity analyses revealed that syphilis prevalence had the greatest effect on the ICER. To achieve ICERs below $50,000/QALY gained, syphilis prevalence would need to exceed 6% during prenatal care.

Conclusion: Our analysis indicates that, under likely parameter values, the reverse sequence algorithm is equally effective but more costly than the traditional algorithm and therefore not cost effective. Although treponemal test automation may offer potential savings in laboratory costs, these are outweighed by overtreatment costs.

Figure 1.

Schematic Representation of Syphilis Screening Algorithms. The reverse sequence algorithm changes the order of the tests included in the traditional algorithm, such that it performs an initial screening with an immunoassay (IA) test (treponemal) which is then confirmed by the rapid plasma reagin (RPR) (nontreponemal). Further, the reverse sequence algorithm adds a second treponemal test, the Treponema pallidum particle agglutination (TP-PA; treponemal test), for samples with discordant results. Source: Based on Soreng et al, and Papp et al.

Figure 2.

Costs accrued by the reverse sequence and traditional algorithms for syphilis screening, broken down into testing and treatment for true positive and false positive cases, among pregnant women in prenatal care (PNC). Costs are expressed in l 2024 U.S. Dollars. Values are rounded to the nearest integer.

Figure 3.

Univariate sensitivity analysis for the cost-effectiveness of the reverse sequence algorithm for syphilis screening compared to the traditional algorithm among pregnant women undergoing prenatal care (PNC). Tornado plots show the parameters that modified the baseline Incremental Cost-Effectiveness Ratio (ICER) by at least 10%. The vertical, dashed line within the plot represents the baseline ICER. The width of each bar is determined by the ICER value under the lower and higher values of the parameter’s feasible range. In this analysis, the ICER is estimated by modifying one parameter at a time to better understand each parameter’s influence in the ICER, and consequently the cost-effectiveness of the reverse sequence algorithm, compared to the traditional algorithm. Negative values (ICER<0) indicate, in this analysis, that the traditional algorithm is cost-saving. I.e. it produces a higher number of quality-adjusted life-years (QALYs) at a cheaper cost than the reserve sequence algorithm.