Association of Supporting Trial Evidence and Reimbursement for Off-Label Use of Cancer Drugs

Key Points Question Is evidence from randomized clinical trials associated with the reimbursement decisions that determine access to off-label use of cancer drugs in Switzerland? Findings In this cross-sectional study including 3046 patients with cancer, there were a total of 695 off-label use requests for 598 patients (20%). A total of 67% of requests were reimbursed when supporting trials showed overall survival benefit, but 65% of requests were reimbursed without evidence for overall survival or progression-free survival benefit. Meaning These findings suggest that reimbursement for off-label cancer treatment in Switzerland was not evidence-based and that a transparent process considering clinical evidence is urgently needed for reimbursement decisions to guarantee fair access to off-label cancer drugs.
This cross-sectional study examines the association of evidence for benefit from randomized clinical trials with off-label cancer drug reimbursement decisions in Switzerland.
Importance In many health systems, access to off-label drug use is controlled through reimbursement restrictions by health insurers, especially for expensive cancer drugs. Objective To determine whether evidence from randomized clinical trials is associated with reimbursement decisions for requested off-label use of anticancer drugs in the Swiss health system. Design, Setting, and Participants This cross-sectional study used reimbursement requests from routinely collected health records of 5809 patients with drug treatment for cancer between January 2015 and July 2018 in 3 major cancer centers, covering cancer care of approximately 5% of the Swiss population, to identify off-label drug use. For each off-label use indication with 3 or more requests, randomized clinical trial evidence on treatment benefits was systematically identified for overall survival (OS) or progression-free survival (PFS). Data were analyzed from August 2018 to December 2020. Exposures Available randomized clinical trial evidence on benefits for OS or PFS for requested off-label use indications. Main Outcomes and Measures The main outcome was the association between evidence for treatment benefit (expressed as improved OS or PFS) and reimbursement in multivariable regression models. Results Among 3046 patients with cancer, 695 off-label use reimbursement requests in 303 different indications were made for 598 patients (median [interquartile range] age, 64 [53-73] years; 420 [60%] men). Off-label use was intended as first-line treatment in 311 requests (45%). Reimbursement was accepted in 446 requests (64%). For 71 indications, including 431 requests for 376 patients, there were 3 or more requests. Of these, 246 requests (57%) had no supporting evidence for OS or PFS benefit. Reimbursement was granted in 162 of 246 requests without supporting evidence (66%). Of 117 requests supported by OS benefit, 79 (67%) were reimbursed, and of 68 requests supported by PFS benefit alone, 54 (79%) were reimbursed. Evidence of OS benefit from randomized clinical trials was not associated with a higher chance of reimbursement (odds ratio, 0.76, 95% CI, 0.45-1.27). Conclusions and Relevance These findings suggest that in a health care system enabling access to off-label use, it was frequently intended as a first-line treatment in cancer care. Availability of randomized clinical trial evidence showing survival benefit was not associated with reimbursement decisions for off-label anticancer drug treatment in Switzerland. A transparent process with criteria considering clinical evidence is needed for evidence-based reimbursement decisions to ensure fair access to cancer treatments.