Amanda Katherina Herbrand1,2, Andreas M Schmitt1, Matthias Briel3,4, Hannah Ewald3,5, Marius Goldkuhle6, Stefan Diem7,8, Anouk Hoogkamer1, Markus Joerger7, Giusi Moffa9, Urban Novak10, Lars G Hemkens3,11,12, Benjamin Kasenda1,13. 1. Department of Medical Oncology, University Hospital Basel and University of Basel, Basel, Switzerland. 2. Department of Internal Medicine, St Claraspital, Basel, Switzerland. 3. Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland. 4. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada. 5. University Medical Library, University of Basel, Basel, Switzerland. 6. Department of Internal Medicine, University of Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany. 7. Department of Oncology and Hematology, Cantonal Hospital St Gallen, St Gallen, Switzerland. 8. Department of Oncology and Hematology, Spital Grabs, Grabs, Switzerland. 9. Department of Mathematics and Computer Science, University of Basel, Basel, Switzerland. 10. Department of Medical Oncology, Bern University Hospital, Bern, Switzerland. 11. Meta-Research Innovation Center Berlin (METRICS-B), Berlin Institute of Health, Berlin, Germany. 12. Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California. 13. Research and Development, iOMEDICO, Freiburg, Germany.
Abstract
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.
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.
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Authors: F Cardoso; A Costa; L Norton; E Senkus; M Aapro; F André; C H Barrios; J Bergh; L Biganzoli; K L Blackwell; M J Cardoso; T Cufer; N El Saghir; L Fallowfield; D Fenech; P Francis; K Gelmon; S H Giordano; J Gligorov; A Goldhirsch; N Harbeck; N Houssami; C Hudis; B Kaufman; I Krop; S Kyriakides; U N Lin; M Mayer; S D Merjaver; E B Nordström; O Pagani; A Partridge; F Penault-Llorca; M J Piccart; H Rugo; G Sledge; C Thomssen; L Van't Veer; D Vorobiof; C Vrieling; N West; B Xu; E Winer Journal: Ann Oncol Date: 2014-09-18 Impact factor: 32.976
Authors: Lars G Hemkens; Benjamin Kasenda; Amanda Katherina Herbrand; Andreas Michael Schmitt; Matthias Briel; Stefan Diem; Hannah Ewald; Anouk Hoogkamer; Markus Joerger; Kimberly Alba Mc Cord; Urban Novak; Sirintip Sricharoenchai Journal: ESMO Open Date: 2019-12-01
Authors: Andreas Michael Schmitt; Martin Walter; Amanda Katherina Herbrand; Markus Jörger; Giusi Moffa; Urban Novak; Lars Hemkens; Benjamin Kasenda Journal: BMJ Open Date: 2022-05-24 Impact factor: 3.006