Costs and benefits of early access to new cancer drugs through the US Food and Drug Administration's accelerated approval pathway: retrospective observational study and economic evaluation.

[OBJECTIVE] To evaluate the survival gains and additional Medicare spending associated with early access to new cancer drugs granted accelerated approval by the US Food and Drug Administration (FDA), compared with access to cancer drugs following completion of confirmatory trials.

[DESIGN] Retrospective observational study and economic evaluation.

[SETTING] US Medicare programme, which provides health insurance for adults aged 65 years and older.

[PARTICIPANTS] Medicare beneficiaries who received new cancer drug indications from the time of FDA accelerated approval to conversion to regular approval, withdrawal from the market, or 31 December 2020.

[INTERVENTIONS] Use of cancer drugs for indications that initially received FDA accelerated approval between 1 January 2012 and 31 December 2020.

[MAIN OUTCOMES AND MEASURES] Primary outcomes were life year gains and additional Medicare spending associated with cancer drug indications that initially received FDA accelerated approval. Each indications's overall survival benefit to patients, if present, was determined, and a partitioned survival model was developed to estimate the life year gains and incremental Medicare spending attributable to early drug access. Beneficiaries who received accelerated approval indications were followed for survival and spending outcomes until 31 December 2022.

[RESULTS] An estimated 178 708 Medicare beneficiaries received access to 90 new cancer drug indications from the time of accelerated approval to conversion to regular approval, withdrawal from the market, or 31 December 2020. Seventeen per cent of beneficiaries (n=30 374) received drugs for indications that were ultimately withdrawn, 5574 (3.1%) received drugs for indications that remained under accelerated approval, and 142 760 (79.9%) received drugs for indications that were subsequently converted to regular approval. Overall, 80 885 (45.3%) beneficiaries received drugs for indications that provided an overall survival benefit to patients. Between 2012 and 2022, use of these drug indications was associated with an estimated 76 164 life years gained. Only three accelerated approvals (nivolumab to treat melanoma, pembrolizumab to treat non-small cell lung cancer, and pemetrexed to treat non-small cell lung cancer) accounted for 68.4% (n=52 107 years) of the total life year gains. The estimated additional cost of early access to these drugs to Medicare was $20.1bn (£15.4bn; €17.4bn) corresponding to a mean spending of $263 371 (95% confidence interval $180 139 to $373 884) per life year gained. Additional mean Medicare spending per life year gained ranged from $25 947 ($18 174 to $39 829) for melanoma indications to $4.5m ($3.1m to $12.2m) for breast cancer indications.

[CONCLUSIONS] This study examined the trade-off between the benefits of earlier access to cancer drugs through the FDA's accelerated approval pathway and the uncertainty surrounding their clinical efficacy at the time of market entry. Accelerated approval yielded uneven survival returns, with a small number of drugs accounting for the majority of life year gains. Medicare incurred substantial costs for treatments that, in over half of cases, did not provide an overall survival benefit to patients.