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

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.