Winterer G, Herrmann W M
Department of Psychiatry, Frele Universität Berlin, Germany.
Pharmacopsychiatry. 1996 Jul;29(4):135-41; discussion 142-3. doi: 10.1055/s-2007-979559.
While the "effect" of a drug can be observed or deduced from observational data, the concept of "therapeutic efficacy" represents mainly a theoretical construction of a high degree of abstraction which is inconceivable without reciprocal combination with other theoretical constructs. The "therapeutic efficacy" of drugs can be investigated only via clinical-pharmacological or clinical "models". Several examples are given and discussed against the background of the actual considerations for shortening phase III studies and extending pharmacoepidemiological phase IV studies for scientific, practical and economic reasons. Of special relevance is the question whether study data of phase III allow an extrapolation to the wider patient population which it is intended to treat. Thus, it is well known that the criteria for representativeness in the investigated population are rarely achieved in phase III studies. Furthermore, observations have shown that various intervening moderator variables, such as the investigated subgroup or the trial setting (e.g. Inpatient or respectively out-patient treatment), might influence therapeutic efficacy and the possibility of generalizing the results. This again raises the crucial question of clinical relevance of significant effects. Possible ways of overcoming this unsatisfactory situation are suggested.
虽然药物的“效应”可以从观察数据中观察到或推导出来，但“治疗效果”的概念主要是一种高度抽象的理论构建，如果不与其他理论构建相互结合，是难以想象的。药物的“治疗效果”只能通过临床药理学或临床“模型”来研究。出于科学、实际和经济原因，文中给出了几个例子，并在缩短III期研究和扩展药物流行病学IV期研究的实际考量背景下进行了讨论。特别相关的问题是，III期研究数据是否能够外推至其旨在治疗的更广泛患者群体。众所周知，III期研究很少能达到所研究人群代表性的标准。此外，观察表明，各种干预调节变量，如所研究的亚组或试验设置（如住院治疗或门诊治疗），可能会影响治疗效果以及结果推广的可能性。这再次引发了显著效应临床相关性的关键问题。文中提出了克服这种不尽人意情况的可能方法。
