Purpose: In this review we describe the general methodology and the results of the international projects, conducted by the Paediatric Rheumatology International Trials Organisation (PRINTO), in collaboration with the Paediatric Rheumatology Collaborative Study Group (PRCSG). The aim of these projects were to identify and validate criteria for the evaluation of response to therapy in clinical trials and in daily clinical practice in patients with the three major paediatric rheumatic diseases (PRD): juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM) and juvenile systemic lupus erythematosus (JSLE).
Methods: The methodological approach to identify and validate outcome measures can be divided into three main phases: (1) the development of a preliminary core set of measures to evaluate the outcome (e.g. response to therapy, remission criteria, disease activity or damage etc.) through literature review and consensus techniques; (2) a large-scale data collection for a prospectively evidence-based validation of the preliminary findings; (3) the final development of a validated criteria for the evaluation of the outcome.
Results: The core sets for three diseases included domains that are common to all diseases (physician's global assessment of disease activity; parent's global assessment of the overall patient's well-being; disability and/or health-related quality of life) plus additional domains that are specific for each disease. In order to be classified as a responder to a given treatment, a patient should demonstrate a different minimum level of improvement (≥30% in JIA, ≥20% in JDM, and ≥50% in JSLE) with no more than one of the remaining variables worsening by more than 30%.
Conclusions: The proposed core sets and definitions of improvement incorporate clinically meaningful change in a composite endpoint for the evaluation of global response to therapy in the major PRD. The definitions are proposed for use in PRD clinical trials and may help physicians to decide if a child has responded adequately to therapy.