From challenge to innovation: a narrative review on innovation in nephrology and hemodialysis randomized trials

Area of Science:

• Nephrology
• Clinical Trials
• Evidence-Based Medicine

Background:

• Randomized controlled trials (RCTs) are crucial for evidence-based medicine but are unevenly distributed across medical disciplines.
• Nephrology and kidney failure face a significant deficit in high-quality RCTs, despite high disease burden and costs.
• Barriers include patient/clinician non-participation, ethical issues, logistical complexity, financial constraints, and exclusion of vulnerable populations.

Purpose of the Study:

• To examine the scarcity of RCTs in nephrology and kidney failure.
• To propose innovative methodological solutions to overcome these limitations.
• To outline a path for more inclusive and efficient evidence generation in underserved fields.

Main Methods:

• Narrative review of existing literature on RCTs in nephrology.
• Exploration of target trial emulation using real-world data for causal inference.
• Discussion of digital twins for conducting virtual randomized trials.

Main Results:

• Identified systemic and practical barriers contributing to the dearth of RCTs in nephrology.
• Proposed target trial emulation as a method to approximate RCT-level causal inference.
• Highlighted digital twins as a novel approach for virtual RCTs.

Conclusions:

• Innovative methods like target trial emulation and digital twins can address the scarcity of RCTs in nephrology.
• These approaches can lead to more inclusive, efficient, and timely evidence generation.
• A new framework is needed for disciplines historically underserved by traditional trial infrastructure.