The US Food and Drug Administration (FDA) has called for proposals (RFA-FD-19-028) to advance existing Clinical Outcome Assessment (COA) applications forward by supporting one-year proposals to advance them toward Qualification Plans or Final Qualification Packages, as specified in the 21st Century Cures legislation. FDA recognizes the importance of measures that tap a single, well-defined domain, reflecting what is important to patients. Physical function (PF) is a significant and highly-relevant outcome in advanced cancer. Inclusion of patient-reported PF will provide the critical patient perspective on a ?common-pathway? COA that will help adjudicate whether symptom changes (worsening or improvement) have a meaningful effect on daily functioning. In 2015, the FDA sought submission of a well-defined PF measure, leading to the development of a customized short form from the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function Item Bank (COA DDT #000079). The PROMIS PF item bank was developed with significant patient input and cutting-edge psychometric approaches, and has demonstrated excellent measurement properties across multiple chronic conditions, including oncology. Our November, 2015, letter of intent was approved and we followed in 2016 with a well-received Initial Briefing Package. Interactions with FDA and two research collaborations (one qualitative and one quantitative) addressed FDA concerns about international relevance of some item content, and about the need (or lack of need) for a recall period to accompany the questions. This research activity led to the submission of a preliminary Qualification Plan in 2018, with a revised Qualification Plan submitted July 30, 2019. Several discussions and meetings with the FDA give us confidence that we can now prepare a Final Qualification Package, drawing support from this award. Under this one year U01 mechanism, we propose to finish the analytic work required to submit a Final Package for Qualification of PROMIS Short Form v2.0-Physical Function 8c as a COA approved for limited context of use in advanced oncology. We also propose to submit the Final Qualification Package itself. We therefore propose three Specific Aims:
Aim 1 : Analyze available cross-sectional data on PROMIS Short Form v2.0 - Physical Function 8c 7-Day and PROMIS Short Form v2.0 - Physical Function 8c (?no recall?) in accordance with the submitted (July 30, 2019) Qualification Plan;
Aim 2 : Submit a mixed-methods study report in collaboration with FDA, detailing the results from analyses conducted on the cross-sectional data as detailed in the submitted (July 30, 2019) Qualification Plan;
and Aim 3 : Submit cross-sectional dataset and Clinical Outcome Assessment (COA) Final Qualification Package to support Limited Context of Use qualification of PROMIS Short Form v2.0 - Physical Function 8c (7 Day and ?no recall?). The package will integrate all evidence regarding appropriateness of the PROMIS Short Form v2.0 - Physical Function 8c. We anticipate that by the end of this one-year project, we will have produced an approvable PF COA for use as an endpoint in industry-sponsored oncology clinical trials.
The overall objective is to conduct final psychometric analyses and then prepare the Final Qualification Package for Limited Context of Use of the PROMIS Short Form v2.0 - Physical Function 8c as a clinical outcome assessment (COA) in advanced cancer (COA DDT#000079). The impact of this work will be to enhance the availability of qualified COAs for physical function that can be used in future oncology clinical trials to better understand the impact of new treatments on oncology patients? lives. The long-term contribution of this research is the potential to reduce or remove the adverse impact of cancer and cancer treatment on physical function.
