Economic evaluation of factorial randomised controlled trials: challenges, methods and recommendations

Area of Science:

• Health Economics
• Biostatistics
• Clinical Trials

Background:

• Economic evaluations are increasingly integrated with randomized controlled trials.
• Factorial trials evaluate multiple treatments alone and in combination, offering statistical power and interaction assessment.
• These trials present unique challenges for economic evaluations, particularly concerning costs and quality-adjusted life-years (QALYs).

Purpose of the Study:

• To examine issues in economic evaluations of factorial trials.
• To describe analytical methods for cost and cost-effectiveness data in factorial trials.
• To provide recommendations for health economists, statisticians, and trialists.

Main Methods:

• Utilizing a hypothetical worked example to illustrate challenges.
• Describing regression analysis and transformation methods for economic endpoints.
• Simultaneously considering all factors to assess optimal treatment combinations for value for money.

Main Results:

• Ignoring interactions in economic evaluations introduces bias, potentially leading to inefficient healthcare resource use.
• Considering all interactions avoids bias but may reduce statistical power.
• The concept of 'opportunity cost of ignoring interactions' quantifies bias.

Conclusions:

• Simultaneous analysis of all factors is crucial for accurate economic evaluations in factorial trials.
• Recommendations are provided for planning, analysis, and reporting of these complex studies.
• The cost of comprehensive analysis should be considered in trial planning.