Many kidney diseases progress slowly, and trials to evaluate treatments for kidney disease require extensive durations of follow-up to determine if the treatment has been effective, increasing expense and complexity, and are usually infeasible for early stage disease. In order to obtain sufficient endpoints, randomized controlled trials in CKD often require substantial follow-up periods or are restricted to patients with rapidly progressive or late stage disease, yet some interventions may have a greater effect when applied earlier versus later in the disease course. This has likely contributed to the small number of RCTs in nephrology compared to other fields, and the paucity of therapies to slow kidney disease progression.
One of the original aims of CKD-EPI was to evaluate change in urine protein as a surrogate endpoint using past randomized controlled trials of CKD progression. The CKD-EPI has continued this work on changes in proteinuria (albuminuria) and has expanded the investigation to GFR decline. These investigations have been presented at a series of workshops (May 2008, December 2012, March 2018) sponsored by the National Kidney Foundation in collaboration with the Food and Drug Administration and European Medicines Agency.
The consensus during the most recent NKF-FDA-EMA Workshop held March 2018 was that continuing efforts are necessary to achieve the ultimate goal of developing effective therapies for CKD. Thus, CKD-EPI Clinical Trials Consortium (CKD-EPI CT) is gathering support for their consortium for a new set of analyses, with the long term goal to facilitate the design and conduct of RCTs for CKD by developing evidence-based tools to rigorously evaluate tradeoffs between alternative design strategies, including requirements for sample size and study duration. Such tools could facilitate drug development even at the earlier stages as it enables sponsors to make calculations as to the optimal path from early phase investigations to regulatory approval. More efficient trials should spur an increased number of RCTs, speeding development of effective therapies for CKD.