Our goal is to produce core outcome sets of patient-rated, family care giver-rated and clinician-rated Fluid Overload (FO) measures that can be applied across the FO severity continuum, fit for regulatory use. We propose to develop and validate a core set of publicly available clinical outcome assessments (COAs) of fluid overload (FO) as they relate to a range of chronic disorders that cause nephrotic syndrome (NS), fit for regulatory purpose. These COAs will assess FO and its contribution to symptom burden, as well as impact on health-related quality of life (HRQOL). We anticipate creating patient-reported outcomes (PRO), observer-reported outcomes (ObsRO) and clinician-reported outcomes (ClinRO).
UG3 Phase – Phase 1
In the 2-year UG3 planning phase, we will work with a broad range of stakeholders, experts, and the FDA, to consider NS-associated FSGS, MCD and MN as an initial list of conditions and define a final target FO-associated set of diseases that are chronic, symptomatic, and have an impact on daily function and HRQOL (e.g., activities of daily living and instrumental activities of daily living). We propose to examine the relationships between self-reported FO, symptom burden, and HRQOL among both children and adults. Following extensive literature review and analysis of qualitative and quantitative data collected as part of our prior research, in collaboration with FDA investigators, we will conduct a gap analysis to refine and expand this set of COAs covering a range of FO content (e.g., edema, mobility, pain), impairment severity, and respondent type.
UG3 Aim 1: To convene stakeholders, including patients, family care givers, clinicians, measurement experts, payers, regulators, and pharmaceutical industry representatives, around the topic of FO as it relates to approval of new drugs.
UG3 Aim 2: To confirm model conditions in which to test measures of FO with a spectrum of mild to severe FO associated impairments, and then identify gaps, if any, in our proposed FO measures.
UG3 Aim 3: To propose interim and final plans for refining and testing FO PRO, ObsRO, and ClinRO based on the FSGS-MCD PRO v1, Edema ClinRO v1, and gap analysis.
In the 3 year UH3 implementation phase, we will conduct the approved research required for validation, and in accordance with FDA recommendations. All work will draw on the input of stakeholders from the patient, family care giver, clinical, regulatory, payer, pharmaceutical industry, and researcher perspectives. Modification to the PROs and ObsROs proposed in the UG3 will derive from the FSGS-MCD PRO and PROMIS item banks. The FO measures will comprise a cross-cutting COA core set responsive to this grant mechanism.
UH3 Aim 1: To produce a full-range FO PRO and FO ObsRO derived from mixed-methods research, preliminary FSGS-MCD PRO measures and relevant PROMIS item banks.
UH3 Aim 2: To produce a FO ClinRO derived from mixed-methods research and the Edema ClinRO v1, optimized for responsiveness to conditions that affect FO.
UH3 Aim 3: To validate the FO PRO, ObsRO and ClinRO in longitudinal studies addressing children and adults with chronic health conditions associated with NS.
The impact of this work will be FDA standardized endpoints usable in future clinical trials.
Description of Grant Mechanism
The Preparing a clinical outcomes assessment set for nephrotic syndrome [Prepare-NS] is funded as part of the FDA’s Patient Focused Drug Development efforts and include patient input for the purposes of drug development in their CDER Pilot Grant Program: Standard Core Clinical Outcome Assessments (COAs) and their Related Endpoints -
Other 2021 Awardee:
Expanding the Observer-Reported Communication Ability (ORCA) Measure: Measuring the communication ability of individuals with rare, neurodevelopmental disorders (NDDs). The project team, led by Christina Zigler, Ph.D., M.S.Ed., of Duke University, will evaluate changes in communication ability among a broad range of populations with neurodevelopmental disorders (NDDs).
2019 CDER Pilot Grant Awardees:
Migraine Clinical Outcome Assessment System (MiCOAS) – This project will develop and standardize a core set of endpoints and related COAs for use across migraine clinical trials. The team of investigators, led by RJ Wirth, Ph.D., M.A., at Vector Psychometric Group and Richard Lipton M.D., at Albert Einstein College of Medicine, project website
Clinical Outcome Assessments for Acute Pain Therapeutics in Infants and Young Children (COA APTIC) – This project, led by Kanecia Zimmerman M.D., M.P.H., and Bryce Reeve Ph.D., M.A., at Duke University, will identify COAs and endpoints for use when developing acute pain therapeutics in infants and young children, primarily those 0-2 years. project website
Northwestern University Clinical Outcome Assessment Team (NUCOAT) – This project will develop and validate COAs with applicability across a range of chronic conditions that assess physical function using patient-reported and performance outcomes. The team of investigators, led by David Cella Ph.D., M.A., at Northwestern University, will research a full range of physical function severity. project website