Leber P D
Food and Drug Administration, Rockville, Maryland.
Epilepsia. 1989;30 Suppl 1:S57-63; discussion S64-8. doi: 10.1111/j.1528-1157.1989.tb05816.x.
A finding of no significant difference in seizure incidence and/or severity among groups of epileptic patients prospectively randomized to treatment with either a standard or experimental antiepileptic drug is often advanced as compelling proof of the latter's anticonvulsant efficacy. Regrettably, the finding of no difference does not, on its own at least, support such a conclusion. A finding of no difference between treatments has numerous explanations that have nothing whatsoever to do with the pharmacological actions of the experimental drug. To be clear, it is possible to argue that a pharmacological effect is the most plausible explanation for a finding of no difference in an active control study, but this argument is only supportable if it is based on additional information gathered from sources external to the study. In most circumstances, the essential external evidence is not available, and the interpretation of the null difference as a positive result turns entirely upon the truth or falsity of the sanguine assumptions made. There is a risk in inferring efficacy from the seemingly consistent results of a series of active control studies that fail to find differences. Despite the long-recognized deficiencies in the active control study design, it remains popular.
在将癫痫患者前瞻性随机分组，分别接受标准抗癫痫药物或实验性抗癫痫药物治疗的各组中，若发现癫痫发作发生率和/或严重程度无显著差异，这一结果常被视为该实验性药物抗惊厥疗效的确凿证据。遗憾的是，至少就其本身而言，未发现差异这一结果并不能支持这样的结论。治疗之间未发现差异有多种解释，这些解释与实验药物的药理作用毫无关系。需要明确的是，在活性对照研究中，可以认为药理效应是未发现差异这一结果最合理的解释，但只有基于从研究外部来源收集的额外信息，这一论点才站得住脚。在大多数情况下，关键的外部证据并不存在，将无差异解释为阳性结果完全取决于所做乐观假设的真假。从一系列未能发现差异的活性对照研究的看似一致的结果中推断疗效存在风险。尽管活性对照研究设计中存在长期公认的缺陷，但它仍然很受欢迎。
