Freiman J A, Chalmers T C, Smith H, Kuebler R R
N Engl J Med. 1978 Sep 28;299(13):690-4. doi: 10.1056/NEJM197809282991304.
Seventy-one "negative" randomized control trials were re-examined to determine if the investigators had studied large enough samples to give a high probability (greater than 0.90) of detecting a 25 per cent and 50 per cent therapeutic improvement in the response. Sixty-seven of the trials had a greater than 10 per cent risk of missing a true 25 per cent therapeutic improvement, and with the same risk, 50 of the trials could have missed a 50 per cent improvement. Estimates of 90 per cent confidence intervals for the true improvement in each trial showed that in 57 of these "negative" trials, a potential 25 per cent improvement was possible, and 34 of the trials showed a potential 50 per cent improvement. Many of the therapies labeled as "no different from control" in trials using inadequate samples have not received a fair test. Concern for the probability of missing an important therapeutic improvement because of small sample sizes deserves more attention in the planning of clinical trials.
重新审视了71项“阴性”随机对照试验，以确定研究人员是否研究了足够大的样本，以便有很高的概率（大于0.90）检测到25%和50%的治疗反应改善。其中67项试验错过真正25%治疗改善的风险大于10%，同样有此风险的情况下，50项试验可能错过50%的改善。对每项试验真正改善的90%置信区间的估计表明，在这些“阴性”试验中的57项中，有可能有25%的潜在改善，34项试验显示有50%的潜在改善。在使用样本量不足的试验中，许多被标记为“与对照无差异”的疗法并未得到公平的检验。在临床试验规划中，因样本量小而错过重要治疗改善的可能性值得更多关注。
