Adverse Event Costs and Cost-Effectiveness Analyses of Anticancer Drugs: A Systematic Review.

Importance: Accurately quantifying adverse event (AE) costs is essential for cost-effectiveness analyses (CEAs) of anticancer drugs. Misestimates in AE costs may significantly affect cost-effectiveness conclusions. Objective: To assess whether AE cost quantification in anticancer drug CEAs accurately reflects the true cost of AEs and to evaluate whether replacing AE costs with actual values affects cost-effectiveness conclusions. Evidence Review: A systematic search of PubMed, Web of Science, and Tufts CEA databases was conducted from October 24 to December 1, 2023, with an additional search from November 4 to 10, 2024, for English-language CEAs and claims-based studies examining AE costs for anticancer drugs published between January 2003 and December 2023. Claims-based AE costs were considered to represent actual values. AE costs were compared in absolute terms and as a proportion of total medical costs. Impact of replacing CEA AE cost estimates with actual values for incremental cost-effectiveness ratios (ICERs) was examined at thresholds of $100 000 and $150 000 per quality-adjusted life year (QALY). AE cost differences between CEA estimates and actual values and their impact on ICERs were the main outcomes. Findings: The sample included 11 claims-based US studies with 34 022 patients and 102 US payer-perspective CEAs. AE cost estimates in CEAs were consistently lower than actual values, with a median difference of 9.73% (IQR, 5.15%-27.22%; P = .002) in proportion of total medical costs and of $17 201 (IQR, $13 365-$48 970; P = .03) in absolute costs. Adjusting AE costs led to an ICER change of $42 656 per QALY, altering cost-effectiveness conclusions in 8 of 17 cases (47.1%). Among the 102 CEAs, 41 (40.2%) did not report AE types; of the remaining 61 (59.8%), 48 (78.7%) focused on treatment-related AEs instead of all-cause AEs. Of all CEAs, 79 (77.5%) considered grade 3 or higher AEs, ignoring grades 1 and 2. Only 13 studies (12.7%) accounted for AE-related dose reductions or interruptions, 87 (85.3%) did not consider postprogression AE costs, and 77 (82.8%) assumed AEs occurred only in the first treatment cycle. Substantial variability was observed in both drug AE and unit AE costs across studies. Conclusions and Relevance: In this systematic review of AE costs in oncology CEAs, AE costs were frequently underestimated, potentially altering cost-effectiveness conclusions. Key problems included incomplete AE inclusion, inaccurate AE cost estimates, overlooked long-term AEs, and unaccounted dose modifications. Best practices and standardized guidelines should be established to improve AE cost quantification in oncology CEAs.