End points in clinical trials: are they moving the goalposts?

Area of Science:

• Clinical Trials Methodology
• Biostatistics
• Evidence-Based Medicine

Background:

• Composite end points combine multiple individual outcomes into a single measure for clinical trials.
• The use of composite end points is prevalent in various therapeutic areas, including cardiovascular disease and oncology.
• Defining and selecting appropriate composite end points is critical for trial interpretation.

Discussion:

• This analysis questions whether the drive for statistical significance in composite end points compromises their clinical significance.
• The potential for a disconnect between statistically significant findings and meaningful clinical impact is explored.
• Consideration of the trade-offs inherent in composite end point selection is essential for rigorous trial design.

Key Insights:

• Composite end points can achieve statistical significance more readily than individual components.
• There is a risk that statistically significant composite end points may not reflect a clinically meaningful improvement for patients.
• The interpretation of composite end points requires careful consideration of both statistical power and clinical relevance.

Outlook:

• Future research should focus on developing composite end point methodologies that better balance statistical and clinical significance.
• Promoting transparency in the reporting and interpretation of composite end points is crucial.
• Emphasizing patient-centered outcomes in the design of composite end points is recommended.