Department of Medical Oncology, University Hospital Basel and University of Basel, Basel, Switzerland.
Department of Internal Medicine, St Claraspital, Basel, Switzerland.
JAMA Netw Open. 2021 Mar 1;4(3):e210380. doi: 10.1001/jamanetworkopen.2021.0380.
In many health systems, access to off-label drug use is controlled through reimbursement restrictions by health insurers, especially for expensive cancer drugs.
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.
Available randomized clinical trial evidence on benefits for OS or PFS for requested off-label use indications.
The main outcome was the association between evidence for treatment benefit (expressed as improved OS or PFS) and reimbursement in multivariable regression models.
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).
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.
在许多医疗体系中，通过健康保险公司的报销限制来控制药物的超说明书使用，尤其是昂贵的癌症药物。
确定瑞士医疗体系中，随机临床试验证据是否与抗癌药物的超说明书使用报销决策有关。
设计、地点和参与者：本横断面研究使用了 2015 年 1 月至 2018 年 7 月期间 3 家主要癌症中心 5809 名癌症患者常规收集的药物治疗记录中的报销申请，涵盖了瑞士约 5%的癌症患者的癌症治疗情况，以确定超说明书用药。对于每 3 个或更多申请的超说明书用药适应证，均系统地为总生存（OS）或无进展生存（PFS）寻找治疗获益的随机临床试验证据。数据分析于 2018 年 8 月至 2020 年 12 月进行。
针对申请的超说明书适应证，用于 OS 或 PFS 获益的现有随机临床试验证据。
主要结局是治疗获益证据（表现为 OS 或 PFS 改善）与多变量回归模型中报销之间的关联。
在 3046 名癌症患者中，598 名患者（中位[四分位距]年龄 64[53-73]岁；420[60%]为男性）共提出了 695 个超说明书用药报销申请，涉及 303 种适应证。311 个（45%）的超说明书用药申请旨在作为一线治疗。446 个（64%）的申请得到了报销。在 71 种适应证中，包括 431 个针对 376 名患者的申请，有 3 个或更多的申请。其中，246 个（57%）没有 OS 或 PFS 获益的支持证据。在没有支持证据的 246 个申请中，有 162 个（66%）获得了报销。在 117 个 OS 获益得到支持的申请中，有 79 个（67%）获得了报销，在 68 个单独的 PFS 获益得到支持的申请中，有 54 个（79%）获得了报销。随机临床试验 OS 获益的证据与更高的报销机会无关（比值比，0.76；95%CI，0.45-1.27）。
这些发现表明，在允许超说明书使用的医疗保健体系中，它通常被用作癌症治疗的一线治疗。在瑞士，有随机临床试验证据表明生存获益的情况下，并没有与抗癌药物的超说明书治疗报销决策相关。为了确保公平获得癌症治疗，需要有一个基于临床证据的透明流程和考虑临床证据的标准，以做出基于证据的报销决策。
