US FDA Mulling Core Criteria For Patient-Reported Outcomes

Agency wants public comment on creating clinical outcome assessments that could be adaptable to multiple trials.

The US FDA is developing a core set of clinical outcome assessments (COAs) that multiple patient groups and drug developers can use as part of the agency's expanding patient-focused drug development initiative.

A standard set of measures, pre-verified as acceptable in clinical trials, likely would save the time and money associated with developing tools for each new drug tested in a disease and ensure data that can be used for regulatory purposes.

Center for Drug Evaluation and Research Director Janet Woodcock said ideally the COAs could be used "rather easily."

"We're really interested in developing a core set of measures that can be reused to tailor in different disease areas so everybody is not going down and reinventing the wheel," Woodcock said Oct. 24 during a Milken Institute Future of Health Summit session.

Woodcock said: "We just had a big meeting the other day about this" and "people are very energized." But she also indicated there was a lot of science still to be done.

FDA has been working for several years to increase the use of patient experience data in clinical trials and in its decision-making.

Many rare disease groups collect data from patients in the hopes of helping develop new treatments, and some have already been used to push for a product's approval. The Jett Foundation, a Duchenne muscular dystrophy advocacy group, presented survey data during an advisory committee meeting on Sarepta Therapeutics Inc.'s Exondys 51 (eteplirsen) in 2016. (Also see "Duchenne Group's Presentation Is Milestone For Patient Involvement" - Pink Sheet, 2 May, 2016.)

However, there have been questions about data quality, FDA noted. In a request for information on the core COA project, the agency said that independent efforts by advocacy groups and sponsors "are resulting in a diversity of measures and proprietary COA tools that create a continued 'learning curve,' a higher level of investment by these groups, and fewer opportunities for streamlining than would be best for long-term sustainability."

"Inconsistent quality in COAs both limits their value to decision-makers and can potentially undercut confidence in these data," the agency wrote in the RFI, which closed Oct. 15.

FDA has been working on ways to systematically collect patient experience data for some time (Also see "From Listening To Advising: The Maturation Of US FDA's Patient-Focused Drug Development Program" - Pink Sheet, 8 Jan, 2018.). Those efforts are starting to come to fruition with recently released guidance. (Also see "US FDA’s Patient Input Guidance Opens Door Wider To Social Media Data Collection" - Pink Sheet, 19 Jun, 2018.)

The agency has indicated it will be flexible with clinical outcome assessments and related issues, but stakeholders have urged the agency to provide clear direction. (Also see "Patient-Focused Drug Development: US FDA 'Needs To Be Brave,' Tell Sponsors What Works Best" - Pink Sheet, 29 Oct, 2018.)

Commissioner Scott Gottlieb also mentioned during the conference that the agency intends to release a new digital health tools platform that may allow an easier approval for software that could use smartphones and smart watches to collect patient data. (Also see "Drug/Software Combo Platform Coming Soon To US FDA, Gottlieb Says" - Pink Sheet, 24 Oct, 2018.)

High-Level Concepts And Disease-Specific Measures

FDA said in the information request that the core COAs would be intended to "reflect measures, tools and endpoints that assess a minimum list of impacts that matter most to patients and are likely to demonstrate change related to disease burden, treatment burden, and if applicable, physical function."

The agency is interested in "high-level concepts," such as pain and fatigue, to minimize ambiguity and uncertainty for regulators and sponsors, as well as "specific measures and tools and exact endpoints that are proposed to be used for a given disease," according to the RFI.

A key to the program may be finding a stakeholder to develop and validate the metrics. FDA asked in the notice about the time and cost of developing and testing new measures and modifying existing measures. The agency also asked for a recommended maintenance and lifecycle management plan for them.

FDA wanted comments on adapting general measures for specific impacts of a new drug, as well as how to handle situations where an available tool has not been tested in a specific population. Officials also wanted stakeholder input on approaches when a proprietary measure available for licensing is better than the publicly available tool.

Agency officials already have said that patient reported outcomes in cancer and rheumatology could be adapted for drug development in solid organ transplant. (Also see "Patient-Reported Outcomes For Organ Transplant Drugs Could Learn From Other Fields" - Pink Sheet, 4 Oct, 2018.)

FDA Wants Broad COA Acceptance

FDA also wants the new core COAs to be acceptable in multiple jurisdictions.

The agency asked in the request for information for approaches to consult other regulators, professional societies, clinicians, industry and others "to gain needed input and ultimate acceptance of the same standard core set," and minimize the overall reporting burden for patients.

FDA said RFI responses would be shared internally with staff, agency science councils and science working groups as appropriate.

The agency also continues to encourage patient groups to help develop patient experience data, including by convening patient-focused drug development meetings to describe concerns about existing treatments and unmet needs. Groups also may submit suggested drug development guidance to FDA. (Also see "There's More To Patient Experience Data Submissions Than Just Guidances, Advocates Tell US FDA" - Pink Sheet, 20 Mar, 2018.)