Mulward S, Gotzsche P C
The Nordic Cochrane Center.
Dan Med Bull. 1996 Feb;43(1):96-8.
To study whether sample size of randomized trials has increased over recent years.
A systematic review of randomized trials published in 1976, 1981, 1986, or 1991 which were double-blind, had active treatments in both arms, were not of a crossover design, were published in English as full articles, and which had clinical outcomes.
We included 386 references. The median total sample size increased from 46 in 1976 to 71 in 1991 (p<0.0001). Sample size was not related to journal impact factor (p = 0.40). The median sample size and impact factor for 106 trials in gastroenterology, cardiology or oncology were larger than for other specialties, 83 vs 60 (p = 0.01) and 1.5 vs 1.2 (p = 0.04), respectively. The use of binary outcomes increased with time (p = 0.00001) as did the proportion of trials with significant results (p = 0.001).
Although increased, most sample sizes are still too small since several hundred patients are needed to be reasonably sure not to overlook a 25% improvement over standard therapy. A more profound change in sample size could be obtained if the bodies responsible for approving trials rejected small trials, apart from exceptional circumstances, such as very rare diseases.
研究近年来随机试验的样本量是否有所增加。
对1976年、1981年、1986年或1991年发表的随机试验进行系统评价，这些试验为双盲试验，双臂均有积极治疗措施，非交叉设计，以英文全文发表且有临床结局。
我们纳入了386篇参考文献。总样本量中位数从1976年的46增加至1991年的71（p<0.0001）。样本量与期刊影响因子无关（p = 0.40）。胃肠病学、心脏病学或肿瘤学领域106项试验的样本量中位数和影响因子分别高于其他专科，分别为83对60（p = 0.01）和1.5对1.2（p = 0.04）。二元结局的使用随时间增加（p = 0.00001），有显著结果的试验比例也随时间增加（p = 0.001）。
尽管样本量有所增加，但大多数样本量仍然过小，因为需要几百名患者才能合理确保不会忽视比标准治疗提高25%的效果。如果负责审批试验的机构除特殊情况（如非常罕见的疾病）外拒绝小型试验，样本量可能会发生更深刻的变化。
