Beware of Kinked Frontiers: A Systematic Review of the Choice of Comparator Strategies in Cost-Effectiveness Analyses of Human Papillomavirus Testing in Cervical Screening

Objectives: To systematically review the choice of comparator strategies in cost-effectiveness analyses (CEAs) of human papillomavirus testing in cervical screening. Methods: The PubMed, Web of Knowledge, and Scopus databases were searched to identify eligible model based CEAs of cervical screening programs using human papillomavirus testing. The eligible CEAs were reviewed to investigate what screening strategies were chosen for analysis and how this choice might have influenced estimates of the incremental cost-effectiveness ratio (ICER). Selected examples from the reviewed studies are presented to illustrate how the omission of relevant comparators might influence estimates of screening cost-effectiveness. Results: The search identified 30 eligible CEAs. The omission of relevant comparator strategies appears likely in 21 studies. The ICER estimates in these cases are probably lower than would be estimated had more comparators been included. Five of the 30 studies restricted relevant comparator strategies to sensitivity analyses or other subanalyses not part of the principal base-case analysis. Such exclusion of relevant strategies from the base-case analysis can result in cost-ineffective strategies being identified as cost-effective. Conclusions: Many of the CEAs reviewed appear to include insufficient comparator strategies. In particular, they omit strategies with relatively long screening intervals. Omitting relevant comparators matters particularly if it leads to the underestimation of ICERs for strategies around the cost-effectiveness threshold because these strategies are the most policy relevant from the CEA perspective. Consequently, such CEAs may not be providing the best possible policy guidance and lead to the mistaken adoption of cost-ineffective screening strategies.