Defining and interpreting the clinical relevance of intervention effects for patient-reported outcomes: the smallest...

In clinical research, statistically significant effects do not necessarily indicate that an intervention provides benefits that are meaningful to patients. This is particularly important for patient-reported outcomes, where thresholds used to interpret clinical relevance are often derived from within-person changes, such as the minimal clinically important difference, and then inappropriately applied to between-group effects in randomised trials and meta-analyses. This article clarifies the conceptual distinction between within-group change and between-group effects, and argues that the latter should be the focus when judging the comparative value of healthcare interventions. We introduce the smallest worthwhile effect (SWE) as a patient-centred, intervention-specific construct representing the smallest between-group effect of an intervention over a comparator that patients consider worthwhile when weighed against harms, costs and other inconveniences. We describe the main methods used to estimate the SWE, including benefit-harm trade-off studies and discrete choice experiments, and illustrate its application by reinterpreting a randomised trial of physiotherapy for low back pain and a meta-analysis of discectomy versus non-surgical care for sciatica. We also show how the SWE can inform judgements of imprecision within the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, offering a patient-derived threshold for distinguishing trivial from worthwhile effects. By focusing on patient-derived thresholds rather than arbitrary statistical or within-group approaches, the SWE construct can help researchers, clinicians and other stakeholders make more transparent and meaningful judgements about the worthwhileness of compared healthcare interventions from a patient perspective.