Establishing core outcomes and minimal clinically important differences for childhood steroid sensitive nephrotic syndrome clinical trials: results from a Delphi consensus process.

Abstract

Background: Few randomized controlled trials are conducted in childhood nephrotic syndrome, and substantial global practice variation exists. Trials have not reported consistent outcomes, patient-reported outcomes, or justified minimal clinically important differences (MCID). Our aim was to establish consensus on core outcomes, assessment timepoints, MCIDs, and desirability of outcome ranking (DOOR) endpoints for future childhood steroid-sensitive nephrotic syndrome research.

Methods: We conducted a two-stage Delphi consensus survey of international healthcare providers and Canadian patients and caregivers with experience in childhood nephrotic syndrome. Respondents rated potential outcomes using Likert scales and assigned MCID values for relapse and remission endpoints. Following the surveys, we held workshops for healthcare providers and patients/caregivers in Toronto, Canada, with facilitated discussions. Qualitative data was analyzed thematically to explore perspectives on childhood nephrotic syndrome clinical trial outcomes and MCIDs.

Results: Eighty-one participants (45 providers, 36 patients/caregivers, 63% Canadian) responded to the surveys. Three disease outcomes (relapse rate, relapse-free survival, and relapse occurrence) met consensus criteria as core outcomes. Median MCID values were a 25% absolute difference between two treatments in relapse risk by 1-year (for relapse prevention) choices and 10% absolute difference in remission by 2 weeks (for relapse treatment). Consensus was achieved for five core patient-reported outcomes (pain, physical symptoms, physical function and mobility, life participation, and social function) and DOOR endpoints for nephrotic syndrome relapse and remission.

Conclusions: Consensus exists among surveyed participants on core disease and patient-reported outcomes for childhood nephrotic syndrome research. Findings can improve the quality and reporting of future trials in this population.