Pharmaceutical Regulatory Science, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Drug Metab Pharmacokinet. 2013;28(3):187-95. doi: 10.2133/dmpk.dmpk-12-rg-044. Epub 2012 Sep 11.
Microdose (MD) clinical trials have been introduced to obtain human pharmacokinetic data early in drug development. Here we assessed the cost-effectiveness of microdose integrated drug development in a hypothetical model, as there was no such quantitative research that weighed the additional effectiveness against the additional time and/or cost. First, we calculated the cost and effectiveness (i.e., success rate) of 3 types of MD integrated drug development strategies: liquid chromatography-tandem mass spectrometry, accelerator mass spectrometry, and positron emission tomography. Then, we analyzed the cost-effectiveness of 9 hypothetical scenarios where 100 drug candidates entering into a non-clinical toxicity study were selected by different methods as the conventional scenario without MD. In the base-case, where 70 drug candidates were selected without MD and 30 selected evenly by one of the three MD methods, incremental cost-effectiveness ratio per one additional drug approved was JPY 12.7 billion (US$ 0.159 billion), whereas the average cost-effectiveness ratio of the conventional strategy was JPY 24.4 billion, which we set as a threshold. Integrating MD in the conventional drug development was cost-effective in this model. This quantitative analytical model which allows various modifications according to each company's conditions, would be helpful for guiding decisions early in clinical development.
微剂量 (MD) 临床试验已被引入药物开发早期以获得人体药代动力学数据。在这里，我们在一个假设模型中评估了微剂量综合药物开发的成本效益，因为没有这样的定量研究来权衡额外的有效性与额外的时间和/或成本。首先，我们计算了 3 种 MD 综合药物开发策略的成本和效果（即成功率）：液相色谱-串联质谱法、加速器质谱法和正电子发射断层扫描。然后，我们分析了 9 种假设情况的成本效益，其中 100 种进入非临床毒性研究的药物候选物通过不同的方法被选择，作为没有 MD 的常规方案。在基础情况下，有 70 种药物候选物没有 MD 被选择，30 种药物候选物平均通过 3 种 MD 方法中的一种被选择，每批准一种额外药物的增量成本效益比为 127 亿日元（1.59 亿美元），而常规策略的平均成本效益比为 244 亿日元，我们将其设定为阈值。在这个模型中，在常规药物开发中整合 MD 是具有成本效益的。这个定量分析模型可以根据每家公司的条件进行各种修改，将有助于在临床开发早期做出决策。
