Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA² five-stage...

Area of Science:

• Clinical Trials Methodology
• Health Research Statistics

Background:

• Randomized controlled trials (RCTs) are the gold standard for evaluating health interventions.
• Sample size calculation is critical for RCT design, ensuring adequate statistical power.
• The 'target difference' is a key component in sample size calculations, representing the minimum important difference in outcomes.

Purpose of the Study:

• To provide practical guidance on selecting the target difference for sample size calculations in RCTs.
• To assist researchers and funders in making informed decisions about trial design.
• To improve the quality and reporting of sample size justifications in clinical trials.

Main Methods:

• Development of recommendations through a five-stage process, including literature reviews and stakeholder engagement.
• Utilized a Delphi process and a workshop to refine advice.
• The Difference ELicitation in TriAls (DELTA²) project informed the recommendations.

Main Results:

• 10 recommendations are provided for choosing the target difference and conducting sample size calculations.
• Advice is tailored for definitive trials (Phase III/IV).
• Recommended reporting items for trial proposals, protocols, and results are included.

Conclusions:

• Appropriate sample size is essential for informing clinical practice and optimizing resource allocation.
• The choice of target difference is a critical element in conventional sample size calculations.
• The document aims to enhance practice and reporting for this crucial aspect of trial design.