Sample size estimation for non-inferiority trials of time-to-event data

• Published in: Pharmaceutical statistics : the journal of the pharmaceutical industry Vol. 7; no. 4; pp. 236 - 244
• Main Authors: Crisp, Adam, Curtis, Paula
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.10.2008
• Subjects: Clinical Trials as Topic - methods; Clinical Trials as Topic - standards; Clinical Trials as Topic - statistics & numerical data; Follow-Up Studies; hazard ratio; Humans; non-inferiority; Research Design - standards; Sample Size; survival data; Time Factors
• ISSN: 1539-1604; 1539-1612; 1539-1612
• DOI: 10.1002/pst.292

We consider the problem of sample size calculation for non‐inferiority based on the hazard ratio in time‐to‐event trials where overall study duration is fixed and subject enrolment is staggered with variable follow‐up. An adaptation of previously developed formulae for the superiority framework is presented that specifically allows for effect reversal under the non‐inferiority setting, and its consequent effect on variance. Empirical performance is assessed through a small simulation study, and an example based on an ongoing trial is presented. The formulae are straightforward to program and may prove a useful tool in planning trials of this type. Copyright © 2007 John Wiley & Sons, Ltd.