Getting Clinical Outcome Assessments into Endpoints Guide Coming
FDA is planning to release in the coming months a draft guidance on “Incorporating Clinical Outcome Assessments into Endpoints for Regulatory Decision Making.” Speaking during an online 9/16 Alliance for a Stronger FDA program, CDER associate director for strategic initiatives Theresa Mullin said this was the last in a series of guidances mandated by the current user fee agreement and 21st Century Cures Act to discuss the approaches and methods external stakeholders can use to bridge an initial patient focused drug development-like (PFDD) meeting into fit-for-purpose tools to collect meaningful patient and caregiver input that could be used in regulatory decision making.
The upcoming guidance is intended to address methodologies, standards, and technologies that may be used for collecting, capturing, storing and analyzing clinical outcome assessment (COA) data, according to the agency’s Web site. “The guidance will also address methods to better incorporate COAs into endpoints that are considered significantly robust for regulatory decision-making,” it says. “This includes methods to define meaningful change in a COA-based endpoint and interpretation of results.” Additionally, it will include information on the format and content required for regulatory submissions that contain patient experience COA data.
The other three guidances have already been released — two are in final form and the other is in draft form. They are:
- Collecting Comprehensive and Representative Input: The document discusses sampling methods that could be used when planning to collect patient input.
- Methods to Identify What is Important to Patients: The document discusses methods for eliciting information from individuals, such as gathering information about what aspects of symptoms, impacts of their disease, and other issues that are important to patients. It also discusses best practices in how to do qualitative research including conducting interviews, development of interview guides, selection of types of survey questions, and considerations for collecting demographics and survey information.
- Selecting, Developing or Modifying Fit-for-Purpose Clinical Outcomes Assessments: The guidance discusses approaches to selecting, modifying, developing, and validating clinical outcome assessments to measure outcomes that are important to patients.
Looking ahead to the next 10 years of PFDD, Mullen said it is important to see a “sustained integration of patient perspectives and making it standard practice. Showing confidence in the reliability and accuracy of patient experience data will be necessary for that. We need to improve the quality and reliability of the submitted data and the guidance series should be helpful with that. We also need to ensure that our review staff, industry, patients and researchers are aware of these new guidances and processes, and we’re going to be pursuing that with Webinars and workshops and other types of training opportunities.”
Sustaining the progress made under PFDD is also important to FDA, according to Mullen, and in 2019 it began a grant program to support development of publicly available standard core clinical outcome assessment measures and tools. The agency began this because there is generally little coordination in the development of clinical outcome assessments, including within a given disease area, she said. “So reviewers are currently seeing multiple independent efforts and the duplication of effort and the diversity of the measures and the proprietary tools really can limit the affordability and sustainability of integrating the patient’s perspective, and the variable quality of these tools can really result in them being of limited use, and the data that they would produce is of limited use to regulatory decision making.”
The grant program is meant to help develop some standard core sets of measures that would be made publicly available. FDA’s focus is on specific disease areas, or impact within a disease, that could apply to multiple other disease areas, according to Mullen. “And we’re looking at diseases that are chronic, symptomatic or affect functioning and activities of daily living, and disease areas that represent a broad range in terms of the size of the affected population,” she explained. Five grant programs are underway — One in the area of migraine, another in acute pain therapeutics for infants and young children, another to assess physical functioning or chronic conditions, another looking at nephrotic syndrome, and another looking at communication ability with individuals who have rare developmental disorders.
Mullen said it is possible down the road to envision a national, publicly available catalog of standard core clinical outcomes and endpoints and assessments that could apply to every disease area. “This national catalog could have reliable measures of clinical outcomes that are meaningful to patients, but at the same time they would be measuring disease specific impacts, and they could be agnostic to the type of medical intervention…” It could also have measures that could be implemented through standardized data collection tools using digital health technologies and captured/included in medical records, but also “robust enough to provide evidence sufficient for regulatory decision making,” she said.