Orphan drugs: predictors of coverage, time-to-coverage and indication-based pricing

摘要（不超过500字）本研究的目的有三个。首先，它试图从经验上评估哪些是孤儿药与非孤儿药覆盖率的预测因素。特别是，本研究将集中于了解覆盖决策在多大程度上由监管因素和临床和经济不确定性预测。其次，本研究将试图分析哪些因素减少或加速了孤儿药与非孤儿药的覆盖时间，即从上市许可到HTA资助决策的时间。孤儿药受益于专门的审批途径，通常针对可能加速进入市场的严重疾病，但另一方面，由于与之相关的临床高度不确定性，它们也可能在满足HTA要求方面面临困难。进一步的分析将调查缺乏正式的孤儿政策是否会影响选定国家个案研究的覆盖时间。最后，将探讨拥有多种孤儿适应症是否为基于适应症的定价提供了机会。有证据表明，制造商为其产品寻求并获得多种孤儿适应症，并利用孤儿法规，即使这被认为不是确保产品可行性所必需的，也可能以支付人的费用为代价。在支付者挣扎于医疗保健支出的时候，由于ODs的成本效益门槛明显高于非孤儿药，区分低价值和高价值孤儿药的价格可以减轻国家预算的压力。

Summary (no more than 500 words) The objectives of this research are threefold.First, it seeks to empirically assess which are the predictors of coverage for orphan versus non-orphan drugs. In particular, this research will focus on understanding to what extent coverage decisions are predicted by regulatory factors and clinical and economic uncertainties. Secondly, this research will attempt to analyse which factors reduce or accelerate the time-to-coverage, indicated as the time from marketing authorisation to HTA funding decision, for orphan versus non-orphan drugs. Orphan drugs benefit from dedicated approval pathways and usually target severe conditions which might accelerate access to market but, on the other hand, they are also likely to face difficulties in meeting the HTA requirements due to the high clinical uncertainty associated with them. Further analyses will investigate whether the lack of a formal orphan policy impacts the time-to-coverage in selected country case-studies. Finally, it will be explored whether having multiple orphan indications provides opportunities for indication-based pricing. Evidence suggests that manufacturers seek and receive multiple orphan indications for their products and take advantage of orphan regulations, also if this is not deemed as necessary for ensuring product viability, potentially at the expenses of payers. In a time when payers struggle with healthcare expenditure, with ODs cost-effectiveness threshold being sensibly higher than non-orphan drugs, differentiating prices among low and high-value orphan drugs could reduce the pressure on national budgets.