Early-phase trials used in reimbursement submissions in Canada

Abstract

Early-phase trials on cancer drugs are frequently used in reimbursement submissions to the pan-Canadian Oncology Drug Review (pCODR) committee of the Canadian Agency for Drugs and Technologies in Health (CADTH), according to findings of a study published in PharmacoEconomics. Cancer drug submissions to pCODR and CADTH between January 2015 and October 2019 were reviewed, and data was extracted on the year of submission, tumour type, pivotal clinical trial, trial phase, primary endpoint, and the pCODR expert review committee (pERC) reimbursement recommendation. Of the 108 submissions that met the inclusion criteria, 13% had been given priority review by Health Canada. Overall, 78% of submissions were recommended for reimbursement by pERC, and 71% of these received conditional approval subject to improvement in cost effectiveness, usually via price negotiations. For the rejected submissions, negative recommendations were most frequently based on lack of strength in clinical evidence due to uncertainties in data from single-arm studies, inappropriate comparators, unvalidated surrogate outcomes or non-randomised study design. Approximately 25% of submissions were based on data from early-phase trials, and 96% of these relied on a surrogate endpoint such as progression-free survival instead of a clinical endpoint such as overall survival. Overall, 77% of early-phase trials were single-arm trials and 69% were not randomised. However, 59% of early-phase trials used in reimbursement decisions received positive reimbursement recommendations from CADTH. The uncertainty associated with evidence generated from early-phase clinical trials ultimately imposes a burden on all stakeholders in the health system: analysts, decision makers, clinicians, and patients. If reimbursement recommendations and decisions are made on the basis of early-phase trials, it is imperative that mechanisms exist to reverse these decisions should subsequent evidence not confirm the additional benefit, said the authors.