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

Abstract

AimsTo review clinical and cost‐effectiveness evidence underlying reimbursement decisions relating to drugs whose authorization mainly is based on evidence from prospective case series.MethodsA 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.ResultsSix 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.ConclusionFor 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.

Associations between uncertainties identified by the European Medicines Agency and national decision making on reimbursement by HTA agencies

“… 3 These may cause a medium level of composite uncertainty to be weighed differently and considered acceptable, whereas a high level of uncertainty is not. The importance of unmet medical need in HTA decision making has been highlighted by others that studied uncertainty associated with medicines that had been approved based on data from uncontrolled trials 11 , 24 or through early access pathways. 12 Both uncontrolled trials and approval through early access pathways are typical characteristics of medicines that address an unmet medical need, 25 , 26 , 27 and may also have played a role in our study.…”

Personalised medicine and the decision to withhold chemotherapy in early breast cancer with intermediate risk of recurrence – a systematic review and meta-analysis

“…Therefore, this may call for a more solid evidence base. Conversely, new cancer drugs are sometimes approved based on limited evidence regarding patient-relevant effects [ 52 ], and not all meet the threshold for a clinically meaningful effect [ 53 ].…”

Promoting innovation while controlling cost: The UK's approach to health technology assessment

“…Moreover, it was found that expedited drugs were based on early studies which relied on surrogate outcomes [ 107 , 108 ], which do not necessarily translate to long-term clinical benefits [109] . Irrespective of this, analyses to data has indicated that both NICE and SMC are willing to grant positive recommendations to novel medicines based on uncertain evidence such as prospective case studies [110] . Therefore, it is important that any move towards accelerated access to medicines is combined with thorough monitoring of real-world efficacy, and if necessary renegotiation of prices.…”