CDER Conversation with Robyn Bent, Director of Patient-Focused Drug Development and Program Officer for the FDA Standard Core Clinical Outcome Assessments (COAs) and Endpoints Pilot Grant Program
FDA considers the use of patient input an important part of medical product development that can foster innovation and the availability of safe and effective drugs. Patient input can help inform the therapeutic context for regulatory review. Patient input can also inform the selection of clinical endpoints, ensure the appropriateness of instruments used to collect trial data, and help ensure that the treatment effects being assessed are treatment effects that matter to patients. If methodologically-sound data collection instruments are developed and used within clinical trials of an investigational therapy, patient input can provide a direct source of evidence that informs assessment of the benefits and risks of a drug.
It is ultimately FDA’s responsibility to ensure that the expected benefits of a medical product outweigh the risks. This benefit-risk assessment is an integral part of our decision process.
What is the Standard Core COAs and Endpoints Grant Program?
The Standard Core COAs and Endpoints Grant Program is a program created to support the development of a publicly available core set(s) of clinical outcome assessments (COAs) and their related endpoints for specific disease indications or for disease impacts that span multiple rare diseases of similar phenotypes. COAs are often endpoints in clinical trials. An endpoint is a precisely defined variable intended to reflect an outcome of interest that is statistically analyzed to address a particular research question1 . COAs can be used to support drug approval and labeling claims or other communications regarding clinical benefit. And clinical benefit is a positive, clinically-meaningful effect of an intervention on how an individual feels, functions, or survives2 . COAs can also measure the severity of side effects or the burden of a treatment.
A standard core set of COAs can include different types of COAs such as patient-reported outcome (PRO), clinician-reported outcome (ClinRO), observer-reported outcome (ObsRO), and performance outcome (PerfO) instruments, and their related endpoints. These sets should assess a minimum list of impacts that matter most to patients, are likely to demonstrate change (including differences in trial arms related to disease burden, treatment burden, and if applicable, physical function), and should be assessed during a clinical trial. A standard core set might be relevant across several disease populations or subgroups or be focused on attributes of a specific disease.
We are funding the development of these standard core COA and endpoint sets, using a collaborative, multi-stakeholder approach that incorporates input-- from patients and care partners, drug developers, researchers, regulators, payers, and other stakeholders-- into the development, modification and/or selection of COAs. By taking this approach we expect that the sets will reflect treatment effects that matter to patients. By making these sets available to the public free of charge, or for a nominal fee, we anticipate that they will be used as the endpoints of clinical trials, thus sustaining the incorporation of the patient voice in the drug development process.
Tell us about this new funding opportunity from the grant program. What should interested parties know?
On July 9, 2020 we issued our second Funding Opportunity Announcement or FOA as part of the FDA Standard Core COAs and Endpoints Pilot Grant Program.
The purpose of this second FOA is to solicit applications to support the development of a publicly available core set(s) of COAs and their related endpoints for the following four areas: fluid overload in nephrotic syndrome, age appropriate domains of pediatric daily functioning, the mechanics of swallowing and speech from infancy to adulthood, and treatment effects in systemic sclerosis. The deadline to submit an application to this FOA, RFA-FD-21-004, is October 14, 2020.
We encourage applicants to apply early. Applying early allows adequate time to make any corrections to errors found in the application during the submission process by the due date.
Last year as part of the Grant Program, FDA began funding the development of standard core sets of COAs for pain in infants and young children, for migraine, and for physical function. These awards, like those that will be funded through the current FOA, will provide avenues to advance the use of patient input as an important part of drug development. More information on previously awarded grants can be found on our webpage.
This funding opportunity uses the UG3/UH3 Cooperative Agreement funding mechanism, can you tell us more about that funding mechanism?
Yes, this grant is being funded through a cooperative agreement. A cooperative agreement is a support mechanism that is used when FDA anticipates that the grant will require substantial involvement from FDA program or scientific staff. This substantial involvement often takes the form of participating in steering committees and sub-committees central to the activity, participating in protocol design or development, and approving one portion of a collaborative project before the next portion starts.
This cooperative agreement has two phases: a planning phase (UG3) and an implementation phase (UH3). Awards made under this FOA will initially support a milestone-driven planning phase (UG3) for up to two years, with possible transition to an implementation phase of up to four years (UH3).
Applicants should know that only UG3 projects that have met the scientific milestones and feasibility requirements may transition to the UH3 implementation phase. An administrative review will determine whether the milestones and requirements have been met. It could be the case that not all funded UG3 projects will transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application, and applicants should note specific instructions for each phase in this FOA. The total award project period will not exceed five years. The number of awards is contingent upon FDA appropriations and the submission of a sufficient number of meritorious applications
Can you help us understand what Patient-Focused Drug Development is and how this funding opportunity aligns with it?
Yes. PFDD is a systematic approach to help ensure that patients’ experiences, perspectives, needs, and priorities are not only captured but meaningfully incorporated into drug development and evaluation. Patients are experts in what it is like to live with their condition. Patients and their care partners are best positioned to help FDA understand the burden of the disease, the burden of treatments or side effects, and the level of uncertainty or risk they are willing to accept.
Through our PFDD meetings we have heard from patients that the endpoints of clinical trials do not always reflect the patients’ goals for treatment. Building upon that, we started to look for ways to ensure that the chief complaints of patients are factored explicitly into drug development programs, particularly in the outcome measures and endpoints used in a clinical trial to establish safety and efficacy of a medical product.
One way we can contribute to sustaining the collection and use of patient experience data is through the development of these standard core sets. Patients will be involved throughout the development process. They will be part of focus groups and they will be part of the expert advisory groups that the grant Principle Investigator puts together in order to get project-specific feedback. When we hold public workshops, patients and other stakeholders will be invited to provide feedback on the development process and on the grant deliverables, either by attending the meeting, or by providing comments to the federal docket.
Are there other ways that patients can participate in the drug development process?
Yes, there are many ways that patient perspective can benefit the drug development process.
Patient preference studies can provide developers with valuable information about preferred routes of administration (for example, injection, infusion, tablet) and dosing frequency. Hearing from patients during the pre-clinical and translational phases of drug design can provide drug developers with valuable information about the outcomes that matter to patients. Having patients provide feedback during the design of clinical trials can help investigators to design clinical trials that answer the questions that matter to patients, and to identify factors in the trial design that may keep trial participants from enrolling or remaining enrolled in a trial.