Size is everything -: large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects
Size is everything -: large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects
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DOI：
10.1016/s0304-3959(98)00140-7
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发表时间：
1998-12-01
期刊：
影响因子：
7.4
通讯作者：
McQuay, HJ
中科院分区：
文献类型：
--
作者：
Moore, RA;Gavaghan, D;McQuay, HJ
在疼痛和其他临床环境中，患者对干预措施的反应差异很大。已经提出了许多解释，如试验方法、环境或文化，但本文试图表明，变化的主要原因可能是随机机会，如果试验规模较小，他们对效果大小的估计可能不正确，仅仅是因为机会的随机发挥。这与‘为了统计准确性而必须进行多大规模的试验’的问题高度相关。以及“需要多大规模的试验才能使其结果在临床上有效？”从5000多名患者的单剂量急性疼痛止痛试验中确定了真实的潜在控制事件率(CER)和实验事件率(EER)。使用这些值计算获得具有统计学意义和临床相关性(需要治疗的人数在真实值的+/-0.5范围内的概率为0.95)结果所需的试验组大小。使用这些CER和EER值的一万个试验使用不同的组大小进行模拟，以调查仅因随机机会而产生的差异。大多数常见止痛药的EER在0.4-0.6范围内，CER约为0.19，具有这样的疗效，要有90%的机会在正确的方向上获得统计上显著的结果需要小组规模在30-60范围内，为了临床相关性，每组需要近500名患者。只有用一种非常有效的药物(EER>；0.8)，我们才能合理地确定获得临床上相关的NNT，通常使用的小组规模约为每个治疗臂40名患者。模拟试验显示，CER和EER有很大的差异，获得正确值的概率随着群体规模的增加而提高。我们认为，控制和实验事件发生率的大部分可变性仅仅是随机机会造成的。单一的小规模试验不太可能是正确的。如果我们想确保在临床试验中获得正确的(临床相关的)结果，我们必须研究更多的患者，临床疗效的可信估计只可能来自大型试验或汇集常规(小型)规模的多个试验。(C)1998年国际疼痛研究协会。爱思唯尔科学公司出版。
Variability in patients' response to interventions in pain and other clinical settings is large. Many explanations such as trial methods, environment or culture have been proposed, but this paper sets out to show that the main cause of the variability may be random chance, and that if trials are small their estimate of magnitude of effect may be incorrect, simply because of the random play of chance. This is highly relevant to the questions of 'How large do trials have to be for statistical accuracy?' and 'How large do trials have to be for their results to be clinically valid?' The true underlying control event rate (CER) and experimental event rate (EER) were determined from single-dose acute pain analgesic trials in over 5000 patients. Trial group size required to obtain statistically significant and clinically relevant (0.95 probability of number-needed-to-treat within +/- 0.5 of its true value) results were computed using these values. Ten thousand trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to random chance alone. Most common analgesics have EERs in the range 0.4-0.6 and CER of about 0.19, With such efficacy, to have a 90% chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30-60, For clinical relevance nearly 500 patients are required in each group. Only with an extremely effective drug (EER > 0.8) will we be reasonably sure of obtaining a clinically relevant NNT with commonly used group sizes of around 40 patients per treatment arm. The simulated trials showed substantial variation in CER and EER, with the probability of obtaining the correct values improving as group size increased. We contend that much of the variability in control and experimental event rates is due to random chance alone. Single small trials are unlikely to be correct. If we want to be sure of getting correct (clinically relevant) results in clinical trials we must study more patients, Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional (small) size. (C) 1998 International Association for the Study of Pain. Published by Elsevier Science B.V.