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

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.

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.

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.

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.

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.