Avoiding ambiguity with the Type I error rate in noninferiority trials

Area of Science:

• Biostatistics
• Clinical Trials Methodology

Background:

• Noninferiority trials often lack clarity regarding the specific Type I error rate evaluated.
• Inconsistent reporting of Type I error rates complicates reader comprehension and comparison across studies.

Purpose of the Study:

• To review and differentiate between within-trial and across-trial Type I error rates in noninferiority trials.
• To provide guidance on selecting the appropriate Type I error rate for regulatory approval.

Main Methods:

• Review of existing literature on Type I error rates in noninferioriority trial analysis.
• Discussion of the characteristics of within-trial, unconditional across-trial, and conditional across-trial Type I error rates.
• Analysis of paradigms for historical data treatment in noninferiority trials.

Main Results:

• The within-trial Type I error rate and the unconditional across-trial Type I error rate are commonly examined.
• The conditional across-trial Type I error rate is also relevant but less frequently discussed.
• Controlling the within-trial Type I error rate is essential for regulatory approval of new treatments in active-controlled noninferiority trials.

Conclusions:

• Understanding the distinction between different Type I error rates is vital for interpreting noninferiority trial results.
• The within-trial Type I error rate is the recommended metric for regulatory submissions in active-controlled noninferiority trials.
• This review aims to enhance clarity and consistency in reporting Type I error rates within the field of noninferiority trials.