|By Tré LaRosa
The origins of the FDA’s Patient-Focused Drug Development Program
Around ten years ago, the Food and Drug Administration (FDA) acknowledged the unmet need — and urgency — of including patient perspective in drug and device development in a systematic way. To address this, as part of the 2012 reauthorization of the Prescription Drug User Fee Act (PDUFA), the FDA began holding “patient-focused drug development” meetings. After a series of these meetings, it became clear to the FDA that not only are patients the experts on the conditions they live with but patient concerns are not always considered in clinical trial design and regulatory approval. These meetings and their findings led to a more advanced FDA Patient-Focused Drug Development (PFDD) Program, which as part of the 21st Century Cures Act, would produce a series of guidances meant to provide drug and device developers with a systematic methodology to collect and measure patients’ experiences in a reliable manner. The 21st Century Cures Act also defined patient experience data as data “intended to provide information about patients’ experiences with a disease or” including how the condition and necessary treatment affect the patient, including a patient’s preference on treatments.
As part of the FDA’s process for issuing each Guidance Document, they first conduct workshops and listening sessions to inform the initial draft of the guidance, followed by a period where the community can offer comments on the draft guidance. Once that period ends, the FDA then reviews the comments and makes the necessary modifications before finally releasing the Final Guidance Document.
The FDA’s Patient-Focused Drug Development Guidance Documents
The first Guidance Document to be issued as part of the FDA’s PFDD Program was issued in June 2020. This Guidance Document would set the stage for the rest of the PFDD system: Guidance 1 provides methods and approaches for how developers can collect relevant, objective, reliable, accurate, and representative patient experience data. It seems obvious, but patient experience data is not homogeneous. For patient experience data to be leveraged effectively, it must be representative and accurate. Guidance 1 is framed by a few main questions: From whom do you get input, and why? and how do you collect the information?
Guidance 1 is extensive: It covers the types of patient experience data and different parts of the patient experience that can be studied; sampling methods to be used when planning a study that includes patient input; approaches, such as defining the target population, for determining from whom to get input for specific research questions.
Also included in Guidance 1 is an understanding that patient-focused drug development does not always mean collecting patient experience data for a single or specific study; collecting patient experience data can be more general, instead focusing on collecting data on where patients would like to see more treatments developed, where there are unmet needs in care, how different symptoms affect patients’ quality of life, or just their perspective on the natural progression of the condition.
While Guidance 1 advises on types of patient experience data, defining the target population, and other questions related to the planning of the collection of patient experience data, Guidance 2 is more directly focused on collecting the information outlined in Guidance 1, specifically the information that is most important to patients. Guidance 2 was issued in February 2022.
Again, patient experiences are not homogenous, neither in their individual experiences, nor in the types of information that might be relevant to one disease state compared to another, or even across varying subpopulations within a single community. The FDA does not take this matter lightly: They advise background research, including performing a literature review and consulting with subject matter experts, as the first step for any sponsor interested in collecting patient experience data. This background research, along with using the recommendations issued in Guidance 1, should provide a foundation by which the study design can be developed.
There are two main methods for collecting patient experience data: Qualitative, where patients are given open forums in the form of interviews, focus groups, and open-ended surveys to provide their perspective; and quantitative, where patients complete closed-ended surveys which can be statistically analyzed to discern and capture population-level trends and perspectives. Both methods can of course produce insights about individual and population-level perspectives, but the drawbacks of one are often the strength of the other. In interviews, patients can provide perspectives that the researchers might not have expected — and therefore likely would not have captured in a closed survey — while surveys can require patients to put a number on certain parts of their condition like pain — which, while difficult, does allow for comparison across patients and even over time in a single patient. There’s also a third method, which is less a novel method and more a mixed model, where both qualitative and quantitative collection approaches are included.
The surveys included in quantitative research are not pulled together without any logic. These surveys are patient-reported outcome measures (PROMs; discussed in recent blogs): They are validated, reliable, and demonstrated to measure what they aim to measure.
Guidance 3 is not yet final, its draft form was issued in June 2022 and currently remains open to the public for comment. Guidance 3 converges the direction given in the first two documents and gives further advice on how sponsors should measure impacts on patients through the use of Clinical Outcome Assessments (COAs).
Guidance 3 is intended to help sponsors hone in on high-quality measures that matter to patients, evaluate the effectiveness and safety of treatments, and avoid misleading claims. Importantly, the FDA emphasizes that COAs, when used appropriately, may help support regulatory decision-making.
COAs, which include patient-reported outcomes (PROs), must outline a “concept of interest” and a “context of use.” The concept of interest is the aspect of the individual’s experience that the COA is measuring, and the context of use describes the details of the population the COA is measuring and how the assessment will be performed.
COAs, while they are similar to endpoints, are viewed as separate entities by the FDA. COAs include the full scope of what went into their development: instructions, administration materials, content, and scoring rules are all included as part of a COA, while endpoint is much more specific and precise. COAs are measured by scores through a standardized process; a single clinical outcome assessment could produce multiple COA scores if the COA is intended to measure multiple concepts.
Much like there are incorrect use cases for PROMs, there are incorrect use cases for COAs (after all, PROs are a form of COAs!). Therefore, to be included in a clinical trial, COAs must be fit-for-purpose; that is, the sponsor must clearly describe the concept of interest, the context of use, and provide sufficient evidence that the COA will be used and interpreted in the correct manner.
Much like Guidance 1 described how sponsors should approach collecting patient experience data while Guidance 2 directed sponsors on the methods to actually collect patient experience data, Guidance 4 will direct sponsors on how to collect and analyze the COAs outlined in Guidance 3 for the purpose of regulatory decision making. Guidance 4, not yet issued in even a draft format, will also include how to incorporate COAs into clinical trial endpoints.
The FDA’s Patient-Focused Drug Development Program has produced two final and one draft Guidance Documents advising drug and device developers on how to measure, analyze, and incorporate the patient perspective into their programs from start to finish. These Guidance Documents are extensive and provide drug developers with everything they need to know about how the FDA itself views patient experience data. Once the final two documents are finalized, they will fulfill their obligation as outlined by the 21st Century Cures Act. This program offers promise and should profoundly affect patient communities and drug developers in the future.