Sample size of randomized double-blind trials 1976-1991.

OBJECTIVE

To study whether sample size of randomized trials has increased over recent years.

DESIGN

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.

RESULTS

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).

CONCLUSION

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.