Boissel Jean-Pierre, Cogny Frédéric, Marko Nicholas, Boissel François-Henri
Novadiscovery, Lyon, France.
Department of Neurosurgery, MD Anderson Cancer Center, Houston, TX, USA.
Drugs Real World Outcomes. 2019 Sep;6(3):125-132. doi: 10.1007/s40801-019-0159-z.
Randomised, double-blind, clinical trial methodology minimises bias in the measurement of treatment efficacy. However, most phase III trials in non-orphan diseases do not include individuals from the population to whom efficacy findings will be applied in the real world. Thus, a translation process must be used to infer effectiveness for these populations. Current conventional translation processes are not formalised and do not have a clear theoretical or practical base. There is a growing need for accurate translation, both for public health considerations and for supporting the shift towards personalised medicine.
Our objective was to assess the results of translation of efficacy data to population efficacy from two simulated clinical trials for two drugs in three populations, using conventional methods.
We simulated three populations, two drugs with different efficacies and two trials with different sampling protocols.
With few exceptions, current translation methods do not result in accurate population effectiveness predictions. The reason for this failure is the non-linearity of the translation method. One of the consequences of this inaccuracy is that pharmacoeconomic and postmarketing surveillance studies based on direct use of clinical trial efficacy metrics are flawed.
There is a clear need to develop and validate functional and relevant translation approaches for the translation of clinical trial efficacy to the real-world setting.
随机双盲临床试验方法可最大程度减少治疗效果测量中的偏差。然而，大多数非罕见病的III期试验并未纳入那些在现实世界中将应用疗效研究结果的人群。因此，必须采用一种转化过程来推断这些人群的有效性。当前的传统转化过程未被形式化，也没有明确的理论或实践基础。出于公共卫生考虑以及支持向个性化医疗的转变，对准确转化的需求日益增长。
我们的目的是使用传统方法评估在三种人群中针对两种药物的两项模拟临床试验将疗效数据转化为人群疗效的结果。
我们模拟了三种人群、两种疗效不同的药物以及两项采用不同抽样方案的试验。
除少数例外情况外，当前的转化方法无法得出准确的人群有效性预测结果。这种失败的原因在于转化方法的非线性。这种不准确性的后果之一是，基于直接使用临床试验疗效指标的药物经济学和上市后监测研究存在缺陷。
显然需要开发并验证将临床试验疗效转化至现实环境的实用且相关的转化方法。
