Sample size considerations for n-of-1 trials

Area of Science:

• Biostatistics
• Clinical Trial Design
• Personalized Medicine

Background:

• N-of-1 trials involve multiple treatment periods within individual patients.
• These trials serve diverse research objectives and can be analyzed using various statistical frameworks.
• Effective sample size planning is crucial for the validity and power of N-of-1 studies.

Purpose of the Study:

• To identify key criteria for determining appropriate sample sizes in N-of-1 trials.
• To provide practical formulas and guidance for sample size calculations in N-of-1 study designs.
• To facilitate the efficient planning and execution of N-of-1 clinical trials.

Main Methods:

• Focuses on a basic design with randomization to treatment and control within paired episodes.
• Assumes a Normal-Normal mixture model with variance components for within-patient and treatment-by-patient variation.
• Presents five distinct criteria for sample size planning.

Main Results:

• Identified five distinct criteria for sample size planning in N-of-1 trials.
• Developed formulas and provided advice to address sample size determination tasks.
• Illustrated the application of these approaches using statistical software.

Conclusions:

• The study offers a structured approach to sample size planning for N-of-1 trials.
• The provided methods and formulas support researchers in designing statistically sound N-of-1 studies.
• Availability of code in GenStat®, SAS®, and R® enhances the practical utility of these findings.