Defining and interpreting between-group differences in clinical trials of patients with osteoarthritis: Challenges and potential solutions.

OBJECTIVE

Clinical relevance is an umbrella term that encompasses methods used to determine thresholds of relevant effects from the perspectives of patients, clinicians, and/or researchers. However, what represents a clinically relevant effect remains contentious. We provide an overview of current challenges and potential solutions for defining and interpreting the clinical relevance of between-group differences in osteoarthritis (OA) trials.

DESIGN

Narrative review.

RESULTS

We review common methods used to determine thresholds of clinical relevance and outline their limitations in interpreting between-group differences in OA trials. As a conceptually more appropriate method, we suggest considering the "smallest worthwhile effect" (SWE): the smallest beneficial effect of a treatment in comparison to another that justifies its costs, risks, and inconveniences. It incorporates all proposed necessary features of clinical relevance: the patients' perspectives, consideration of intervention-specific characteristics, and a focus on outcome-specific between-group differences. We summarize the results of existing studies estimating the SWE, illustrate its potential for re-interpreting trials and meta-analyses in the field, and outline directions for future research and application of the SWE concept.

CONCLUSION

Commonly used methods to determine clinical relevance are conceptually and methodologically limited to interpret between-group differences in trials of patients with OA. To advance the field, we propose greater development and consideration of the SWE, given its conceptual advantages. While promising, the SWE is a multi-domain construct that can be challenging to apply and interpret. Therefore, further methodological work, empirical research in OA populations, and careful application are needed to ensure its proper implementation in OA trials.