Special Report
Patient-Reported Outcomes in Clinical Trials of CKD-Related Therapies: Report of a Symposium Sponsored by the National Kidney Foundation and the US Food and Drug Administration

https://doi.org/10.1053/j.ajkd.2013.07.004Get rights and content

The National Kidney Foundation and the US Food and Drug Administration (FDA) convened a symposium in September 2010, bringing together more than 70 experts, including representatives from the FDA, the National Institutes of Health, the Critical Path Institute, nephrologists, patients, and the pharmaceutical industry to discuss the feasibility and process of developing patient-reported outcome (PRO) measures to access how patients feel or function to be used in clinical trials for regulatory review of treatment benefit. Three disease areas were evaluated for development of end point models in which PRO measures may be useful: anemia secondary to chronic kidney disease, autosomal dominant polycystic kidney disease (ADPKD), and nephrotic syndrome. The participants thought it valuable to use observational data to generate hypotheses regarding patient baseline characteristics that are likely to predict clinically important changes in PROs in response to anemia treatment and to design adequately powered blinded randomized controlled trials of anemia treatment using PROs as primary rather than secondary end points. Validated PRO instruments that reflect the patient experience in ADPKD and nephrotic syndrome are essential to incorporate into clinical trials of new therapeutic interventions because glomerular filtration rate decline may occur late in the disease course, at which point therapeutic benefit is less likely. Conference attendees addressed how PRO measures could be used to evaluate, monitor, provide care, and facilitate the introduction of treatments for patients with these challenging conditions.

Section snippets

Overview

The constellation of criteria that typically define nephrotic syndrome are proteinuria with protein excretion >3.5 g/d in adults or >40 mg/h/m2 in children, hypoalbuminemia with serum albumin level <3.5 g/dL, hypercholesterolemia, lipiduria, and edema.11 Nephrotic syndrome is a complex condition affecting both children and adults that may result from a variety of primary and secondary glomerular disorders. Patients with nephrotic syndrome also are at higher risk for related conditions, such as

Overview

C-Path is a private not-for-profit organization created in 2005 by the University of Arizona and the FDA with the mission of supporting the FDA's Critical Path Initiative. In late 2008, working with the FDA and the medical products industry, C-Path established the PRO Consortium to develop, test, and qualify PRO instruments as measures of primary or key secondary efficacy end points in clinical trials of new medical products.53 PRO instrument qualification through the FDA's drug development

Conclusion

The participants in the workshop agreed that while there are challenges (Box 1) to developing and using PRO instruments in this population, there would be significant value in using these end points in CKD trials. They supported that there is an opportunity for PRO end points in nephrotic syndrome to improve therapy and care and that the development of PRO instruments is feasible although complex due primarily to the heterogeneity of the condition. Fundamental research examining the experience

Acknowledgements

Support: C-Path's PRO Consortium is supported by grant U01FD003865 from the US FDA and by Science Foundation Arizona under grant SRG 0335-08. The NKF gratefully acknowledges Abbott, Affymax, AMAG Pharmaceuticals, Amgen, Boehringer Ingelheim, Centocor Ortho Biotech, FibroGen, and Takeda, which provided grants to support the conference. Kerry Willis, PhD, and Tom Manley from the NKF assisted in meeting logistics and manuscript preparation.

Financial Disclosure: Dr Perrone has received research

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