Evaluating Bias in the Anchor-Based Method for Finding the Minimal Clinically Important Difference

Music City Center 

The minimal clinically important difference (MCID) concept recognizes the limitations of statistical significance in determining practical relevance for patients. One popular methodology for determining the MCID is the anchor-based approach. However, the theoretical properties and robustness of the methodology are not fully understood. To address the gap, we conducted a simulation study to explore the performance of anchor-based methods across a range of values for clinical outcome assessment (COA) variance, placebo effects, anchor measurement noise, and confounding. Our findings revealed that some scenarios exhibited bias exceeding 50%. This bias can be in either direction, meaning the MCID estimate is not always conservative. We observed an increase in bias when the calculated MCID deviated significantly from the mean COA. In the COA variation scenario, the bias may also be more pronounced when the standard deviation of the COA is small relative to the calculated MCID. Finally, confounding effects are more likely when the COA represents only one of several factors influencing the anchor. We conclude by discussing strategies for identifying and mitigating these biases.

COA - clinical outcome assessment

MCID - minimal clinically important difference

Anchor-based method

Bias

Placebo effect

Confounding 

Biopharmaceutical Section