Freston J W
Am J Gastroenterol. 1986 May;81(5):307-11.
Drugs are currently released for general use without substantial knowledge of their minimum and maximum effective dose and their dose-related side effects. There are several plausible explanations for this situation, but in some cases this has resulted in patients receiving larger than necessary or smaller than effective doses and experiencing adverse reactions. A concurrent problem with drug evaluation is the rising concern with the use of placebo controls and the growing pressure to utilize positive-control studies. Such studies have many problems, however, some of which are subtle but nonetheless counterproductive in terms of proving efficacy through rigorous scientific investigation. The use of dose-ranging in clinical trials provides more information regarding a drug's TI and can circumvent some of the problems of placebo- and positive-controlled studies. Thus, such dose-ranging studies should be a feature of the development of most new drugs.
目前，药物在未充分了解其最小和最大有效剂量以及剂量相关副作用的情况下就被普遍放行使用。对于这种情况有几种合理的解释，但在某些情况下，这导致患者接受的剂量大于所需剂量或小于有效剂量，并出现不良反应。药物评估同时存在的一个问题是，人们越来越关注安慰剂对照的使用，以及采用阳性对照研究的压力不断增大。然而，这类研究存在许多问题，其中一些问题很微妙，但在通过严格的科学调查证明疗效方面却适得其反。在临床试验中使用剂量范围研究可以提供更多关于药物治疗指数的信息，并能规避一些安慰剂对照和阳性对照研究的问题。因此，这类剂量范围研究应该成为大多数新药研发的一个特点。
