Impact of Different Thresholds on Recommendations Made Through Cost-Effectiveness Studies: An Example From Chronic Lymphocytic Leukemia

OBJECTIVES: This study aims to demonstrate the impact of different cost-effectiveness thresholds (λ) on the recommendation of technologies in cost-effectiveness analyses worldwide.

METHODS: Structured electronic searches of Medline, Lilacs, Center for Reviews and Dissemination, Cochrane Library, and Embase were conducted to identify pharmacoeconomic analyses that compared chemotherapy+rituximab (CT+R) with chemotherapy alone (CT). The Incremental Cost-Effectiveness Ratios (ICERs) were extracted from the publications, converted to PPP-USD for the analysis year, and compared to various values of λ. The values of λ were chosen to represent a variety of approaches from around the world: (i) λ in the country of the analysis, if available; (ii) 50,000 USD/QALY; (iii) the opportunity costs threshold (κ); (iv) 3, 2, and 1 GDP per capita/QALY.

RESULTS: CT+R was dominated in the comparison between ibrutinib+rituximab (IR) and ibrutinib (I) and not cost-effective in the comparison between bendamustine+rituximab (BR) and bendamustine (B). Excluding these, only two other comparisons were found in 17 studies: fludarabine+cyclophosphamide+rituximab (FCR) vs. fludarabine+cyclophosphamide (FC) and clorambucil+rituximab (ClbR) vs. clorambucil (Clb). Two studies did not measure the outcomes in QALYs. All other studies (N=15) considered the technology cost-effective at 3 GPD per capita/QALY. At 2 GDP per capita/QALY, 1/15 studies did not recommend CT+R. At 1 GPD per capita/QALY, 7/15 studies did not suggest CT+R. In countries where an explicit threshold exists, CT+R was considered cost-effective. At the 50,000 USD/QALY threshold, only 1/15 studies did not find the technology to be cost-effective. Only two studies recommended listing rituximab at κ.

CONCLUSIONS: Regarding FCR vs. FC and ClbR vs. Clb, the combination of rituximab is considered cost-effective under most typically accepted thresholds. Nevertheless, the approach taken by regulators on the threshold might change the recommendation’s direction.