Standardization, Personalization and Real-world Practice in Pragmatic Trials for Integrative Medicine: The Methodological Design of a Semi-individualized Randomized Controlled Trial for Diabetic Kidney Disease

Abstract

Purpose: Pragmatic trials have been advocated across different specialties in the past few decades in a hope to generate real-world evidence to inform decisions in clinical practice. Although pragmatism in clinical trials has been introduced for more than 50 years, the balance between flexibility in trial design and scientific rigor remains a key challenge to the trial design. Also, the discordance in epistemology between conventional and traditional medicine warrants special attention in trial design to reflect realworld practice of different streams of medicine. Methods: We gathered the perspectives of patients and physicians of conventional and traditional medicine, evaluation of previous service program, and data from registrybased study to inform the design and evaluation of SCHEMATIC, an on-going semi-individualized pragmatic randomized controlled trial evaluating a Chinese medicine clinical protocol for diabetic kidney disease, a medical condition currently with no specific treatment (NCT02488252). Results: The methodological design including intervention, outcome measurement, flexibility of protocol, and hierarchy of analysis were based on and optimized by expert consensus, preliminary data from previous service program and qualitative stakeholder analyses. The trial design closely resembled real-world practice of integrative Chinesewestern medicine and was merged into the existing infrastructure of public out-patient clinics which can be easily translated to routine clinical service. The first half of SCHEMATIC subjects have completed the study and the attrition is well-controlled. Conclusion: Expert consensus, stakeholder analysis, realworld registry-based data, and pilot programs are key to the design and translation of pragmatic clinical trials for integrative medicine.