Sample size determination for clinical trials in patients with nonlinear disease progression.
This paper provides explicit sample size determination formulas for planning a long-term trial in patients with chronic disease by using available results from existing short-term studies that may predict long-term disease progression patterns. The sample size calculation formulas are flexible to incorporate different nonlinear disease progression patterns. Various within-patient correlation structures are considered. By using the proposed formulas, sample size sensitivity can be easily explored for possible choices of study duration, assumed nonlinear disease progression patterns, randomization ratio, and expected clinical meaningful difference in the end of study. In addition, sample size calculation formulas are provided when the primary endpoint is change from baseline. Discussions on the relationship among required sample size, study duration, randomization ratio are also included.
Yan
Xin
X
Merck Research Laboratories, 785 Jolly Road, PO Box 4, Blue Bell, PA 19422, USA. xin_yan@merck.com
Su
Xiaogang
X
D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D018450:Disease Progression; D006801:Humans; D008137:Longitudinal Studies; D015233:Models, Statistical; D017711:Nonlinear Dynamics; D018401:Sample Size; D013997:Time Factors