Contrasting evidence to reimbursement reality for off-label use (OLU) of drug treatments in cancer care: rationale and design of the CEIT-OLU project

Abstract

BackgroundOff-label use (OLU) of a drug reflects a perceived unmet medical need, which is common in oncology. Cancer drugs are often highly expensive and their reimbursement is a challenge for many healthcare systems. OLU is frequently regulated by reimbursement restrictions. For evidence-based healthcare, treatment ought to be reimbursed if there is sufficient clinical evidence for treatment benefit independently of patient factors not related to the treatment indication. However, little is known about the reality of OLU reimbursement and its association with the underlying clinical evidence. Here, we aim to investigate the relationship of reimbursement decisions with the underlying clinical evidence.Methods/ designWe will extract patient characteristics and details on treatment and reimbursement of cancer drugs from over 3000 patients treated in three Swiss hospitals. We will systematically search for clinical trial evidence on benefits associated with OLU in the most common indications. We will describe the prevalence of OLU in Switzerland and its reimbursement in cancer care, and use multivariable logistic regression techniques to investigate the association of approval/rejection of a reimbursement requests to the evidence on treatment effects and to further factors, including type of drug, molecular predictive markers and the health insurer.DiscussionOur study will provide a systematic overview and assessment of OLU and its reimbursement reality in Switzerland. We may provide a better understanding of the access to cancer care that is regulated by health insurers and we hope to identify factors that determine the level of evidence-based cancer care in a highly diverse western healthcare system.

Characteristics and survival of patients with cancer with intended off-label use—a cohort study

“…This retrospective cohort study is part of the CEIT-OLU project (Comparative Effectiveness of Innovative Treatments in Cancer—Off Label Use) described elsewhere 13. In brief, we screened medical records of patients with a first consultation at three major Swiss oncology/haematology centres (Basel, Bern and St. Gallen) between January 2015 and July 2018.…”

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

“…This study is part of the Comparative Effectiveness of Innovative Treatments in Cancer—Off Label Use project, described elsewhere. 13 In brief, we used routinely collected health data from medical care records to investigate the prevalence of intended off-label use in patients with cancer, reimbursement of off-label use, and the association of RCT evidence with reimbursement of off-label use. The reporting follows the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline.…”

“…For each off-label use indication with at least 3 requests, we systematically determined the evidence supporting an intended off-label use at the time of request (details of the systematic search have been published elsewhere 13 ). Two reviewers (A.K.H.…”

“…In a further sensitivity analysis, we only included requests for indications for which an RCT was available (trial model). We anticipated missing data 13 for our main outcome, and we prespecified analyses based on multiple imputations.…”

Off-Label Use of Antineoplastic Drugs to Treat Malignancies: Evidence From China Based on a Nationwide Medical Insurance Data Analysis

“…In clinical practice, OL use for treatment of advanced malignancies is common (Herrero Fernandez et al, 2019). Off-label drug use is particularly common for treatment of malignancies due to the existence of numerous cancer subtypes, difficulties involved in performing clinical trials, rapid diffusion of preliminary results, and delays in approval of new drugs by regulatory bodies (Lerose et al, 2011;Herbrand et al, 2019;Mascolo et al, 2020). Therefore, OL use of antineoplastic drugs to treat malignancies is prevalent.…”