Mills Mackenzie
Medical Technology Research Group, Department of Health Policy and LSE Health, London School of Economics and Political Science, Houghton Street, London, WC2A 2AE, UK.
Pharmacoeconomics. 2023 May;41(5):529-545. doi: 10.1007/s40273-023-01248-9. Epub 2023 Feb 23.
Conditional approval pathways facilitate accelerated marketing authorisation based on immature clinical evidence for drugs that address an unmet medical need in a life-threatening or chronically debilitating condition. Lowering evidence requirements for marketing authorisation results in higher clinical uncertainty, which may present challenges for the health technology assessment (HTA) of these products.
The objective of this study is to assess whether conditionally approved drugs face higher probabilities of HTA rejection or delays in HTA approval relative to drugs with standard marketing authorisation.
This paper adopts a mixed-methods approach to provide a meta-analysis of HTA outcomes across 80 drug-indication pairs in France, England, Scotland and Canada. Differences in the characteristics (i.e. disease rarity and clinical trial design) of conditionally approved drugs and drugs with standard marketing authorisation and drivers of HTA outcomes are assessed through logistics regressions. Delays in HTA approval are assessed through a survival analysis.
Relative to standard approval drugs, conditionally approved drugs are less likely to include phase III trial designs, less likely to include clinical endpoints and less likely to include an active comparator. Uncertainties in clinical and economic evidence are raised more frequently by HTA agencies for conditionally approved drugs, which have a marginally lower probability of receiving HTA approval relative to drugs with standard approval. Conditionally approved drugs face moderate delays (an average of 6 months) in receiving HTA approval relative to standard approval drugs.
Overall, conditionally approved drugs likely face increased barriers at the HTA level.
有条件批准途径有助于基于不成熟的临床证据加速对治疗危及生命或慢性衰弱病症中未满足医疗需求的药物进行上市许可。降低上市许可的证据要求会导致更高的临床不确定性，这可能给这些产品的卫生技术评估（HTA）带来挑战。
本研究的目的是评估相对于具有标准上市许可的药物，有条件批准的药物面临HTA拒绝或HTA批准延迟的可能性是否更高。
本文采用混合方法，对法国、英格兰、苏格兰和加拿大的80种药物适应症对的HTA结果进行荟萃分析。通过逻辑回归评估有条件批准的药物和具有标准上市许可的药物在特征（即疾病罕见性和临床试验设计）上的差异以及HTA结果的驱动因素。通过生存分析评估HTA批准的延迟情况。
相对于标准批准的药物，有条件批准的药物不太可能包括III期试验设计，不太可能包括临床终点，也不太可能包括活性对照。HTA机构对有条件批准的药物在临床和经济证据方面的不确定性提出得更频繁，相对于标准批准的药物，其获得HTA批准的可能性略低。相对于标准批准的药物，有条件批准的药物在获得HTA批准方面面临适度延迟（平均6个月）。
总体而言，有条件批准药物在HTA层面可能面临更多障碍。
