FDA, Sponsors Look to Expand Patient Input to Clinical Trials

Patient focused drug development (PFDD) is moving into the mainstream, promising to alter the conduct of clinical trials and FDA regulatory policies. PFDD appears increasingly useful and accepted in designing clinical studies and in assessing outcomes and treatment benefits most importance to patients with a certain condition.  Building on the experience gained from a series of FDA meetings to solicit patient perspectives for treating important chronic conditions, sponsors are querying patient groups to help define the key goals of clinical studies and to avoid research programs that yield less useful results. FDA is bringing in patients to consult with review divisions and to join FDA-sponsor meetings to help shape research studies and product labeling.

To further this trend, FDA is expanding its patient representative program beyond participation in advisory committee meetings. The agency has identified some 200 patient representatives based on their experience, FDA training, and clearance on conflicts of interest. Last year, members of this cadre were involved in 10 consultations with FDA review divisions and in additional meetings with sponsors, explained Richard Klein, head of FDA’s patient liaison program in the Office of Health and Constituent Affairs. Qualified patient representatives not only have experience with a disease or condition, but are active in patient advocacy organizations, knowledgeable about treatment options, and able to grasp basic scientific principles, Klein pointed out at the recent conference on PFDD sponsored by the University of Maryland Center of Excellence in Regulatory Science & Innovation (M-CERSI).

One FDA initiative is to develop a “roadmap” to patient-focused outcome measurement in clinical trials, reported Ashley Slagle of the Office of New Drug (OND) Study Endpoints and Labeling Development staff  in the Center for Drug Evaluation and Research (CDER). The roadmap aims to establish an orderly pathway for selecting or developing instruments to accurately measure treatment benefit, she explained. Key criteria are the natural history of the disease or condition, the affected patient population, treatment alternatives, and current care standards.  Clarifying what treatment benefit is most meaningful to patients (survival? pain relief? increased function?) can help design clinical trials with appropriate entry criteria and endpoints, as well as the optimal type of clinical outcome assessment (COA).

Biopharma companies described their efforts to establish more formal and productive patient engagement programs at the CERSI conference. Sanofi is building a strategic framework for ensuring patient-centricity, pointed out chief patient officer Anne Beal, who previously developed a “patient engagement rubric” for the Patient Centered Outcomes Research Institute (PCORI). The challenges are to ensure “patient readiness” through training, to promote “researcher readiness” of scientists and investigators; and to address legal and compliance rules that vary around the world. Pfizer is assessing what changes are made in research decisions as result of interactions with patients as part of its framework for systematic patient inclusion in development programs, commented Roslyn Schneider, head of global patient affairs. A valuable resource is an “alumni association” of patients who have participated in Pfizer clinical trials.  Novartis vice president Marjorie Gatlin described processes for identifying the right patients for a particular engagement and the need for appropriate consulting agreements and contracts for such activities.

Patients also can be helpful in promoting access to new therapies following FDA approval. Evidence that a new drug meets clear patient needs may be important in gaining coverage and reimbursement by insurers. Also useful is evidence that a new therapy is designed to drive compliance and adherence, or that it eliminates unnecessary care, noted Marc Boutin, head of the National Health Council.

Over time, this increased attention to patient perspectives will “change the way clinical trials are designed and carried out,” observed Klein of FDA, noting that patient input at pre-IND meetings can help design informed consent to encourage enrollment. The trickiest issue for including patients in sponsor meetings, he noted, is screening for conflicts of interest:  patient reps can’t be overly favorable to the test drug or have pre-conceived opinions on its value.

Theresa Mullin, director of CDER’s Office of Strategic Programs, described the dozen PFDD meetings that FDA has organized since the program was established in 2012, and that another five are on the schedule. Public participation has been strong, and the resulting reports are helpful in developing disease-specific guidance and new outcomes measurement tools. One unexpected result is that patient groups are organizing additional external meetings to continue the discussions. The program has revealed that patients with chronic serious disease are real experts on their conditions, Mullin noted, encouraging agency efforts to seek patient-identified disease impacts from the beginning of drug development and to translate them into a “vetted measurement set.”