Balancing early access with uncertainties in evidence for drugs authorized by prospective case series – systematic review of reimbursement decisions

AIMS: To review clinical and cost‐effectiveness evidence underlying reimbursement decisions relating to drugs whose authorization mainly is based on evidence from prospective case series. METHODS: A systematic review of all new drugs evaluated in 2011–2016 within a health care profession‐driven resource prioritization process, with a market approval based on prospective case series, and a reimbursement decision by the Swedish Dental and Pharmaceutical Benefits Agency (TLV). Public assessment reports from the European Medicines Agency, published pivotal studies, and TLV, Scottish Medicines Consortium and National Institute of Health and Care Excellence decisions and guidance documents were reviewed. RESULTS: Six drug cases were assessed (brentuximab vedotin, bosutinib, ponatinib, idelalisib, vismodegib, ceritinib). The validity of the pivotal studies was hampered by the use of surrogate primary outcomes and the absence of recruitment information. To quantify drug treatment effect sizes, the reimbursement agencies primarily used data from another source in indirect comparisons. TLV granted reimbursement in five cases, compared with five in five cases for Scottish Medicines Consortium and four in five cases for National Institute of Health and Care Excellence. Decision modifiers, contributing to granted reimbursement despite hugely uncertain cost‐effectiveness ratios, were, for example, small population size, occasionally linked to budget impact, severity of disease, end of life and improved life expectancy. CONCLUSION: For drugs whose authorization is based on prospective case series, most applications for reimbursement within public health care are granted. The underlying evidence has limitations over and above the design per se, and decision modifiers are frequently referred to in the value‐based pricing decision making.