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

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).