Applied Clinical Trials
The "Cures" bill and PDUFA IV are the latest measures pushing for more systematic inclusion of patient views into drug development.
Regulators and sponsors increasingly are looking at the experiences and recommendations of individuals suffering from a disease or condition in developing and testing new therapies, and new legislation and user fee initiatives are poised to further this approach. A more formal patient-focused drug development (PFDD) framework was established by the 2012 FDA Safety & Innovation Act (FDASIA), and the Prescription Drug User Fee Act (PDUFA V) has provided support for incorporating patient viewpoints into a clearly articulated benefit-risk assessment of emerging treatments. Sponsors applaud this model, in that clear patient acceptance of greater risks of adverse events or limited efficacy in a new therapy can support greater leniency in FDA approval decisions.
The role of patients in shaping clinical research may be strengthened further by the “21st Century Cures” legislation, which gained House approval last month due to strong support from some 250 patient groups, as well as hundreds of research organizations, medical societies, and biopharma companies. The bill establishes a “structured framework” to more fully incorporate patient experiences in considering a drug’s benefits and risks, while also aiming to expedite new drug approvals through biomarker qualification, incentives for developing antibiotics and treatments for rare diseases, and speedy designation of breakthrough drugs. The Association of Clinical Research Organizations (ACRO) also cites specific provisions in the bill to modernize clinical trials, namely, enhancements in the clinicaltrials.gov website, streamlined institutional review board processes, and support for data sharing.
More fee support
The House measure now will be debated and revised in the Senate, a process that could extend to next year and become enmeshed in efforts to renew FDA user fees in 2017. FDA launched the PDUFA VI negotiating process with a public meeting in July; regular discussions with industry begin this fall, along with monthly meetings with patient, consumer, and health professional groups to hear their views on relevant issues.
A main topic on the PDUFA VI agenda is to more systematically incorporate patient views into drug development from early discovery through clinical testing and regulatory approval. FDA expects to discuss strategies for advancing the science of patient input and methodologically sound approaches for shifting from PFDD meetings to a more systematic collection of the experiences of people living with a disease, said Theresa Mullin, director of the Office of Strategic Programs (OSI) in the Center for Drug Evaluation and Research (CDER), at the June annual meeting of the Drug Information Association (DIA). Mullin noted interest from sponsors and disease groups in devising new approaches for capturing and communicating patients’ experiences on disease burden over time.
More disease meetings
Meanwhile, FDA is continuing to hold PFDD meetings with patient groups to discuss disease burden and treatment options for specific conditions. The agency has held 14 PFDD meetings since 2013, addressing conditions ranging from lung and breast cancer to hemophilia and Chagas disease; three more sessions are scheduled for this fall, and seven more in 2016-2017. FDA announced last month that those final meetings will consider autism, alopecia areata, hereditary angioedema, organ transplant patients, psoriasis, neuropathic pain, and sarcopenia.
FDA looks to these sessions to ask patients about which symptoms have the greatest impact on daily life, how well current therapies treat significant symptoms, what an ideal treatment would look like, and what most spurs individuals to use a treatment or to participate in a clinical trial. PFDD meetings have been relatively small, Mullins commented, but have led to revisions in CDER policies and to new FDA guidance on developing treatments for certain diseases and to new patient-reported outcomes (PRO) tools. A compendium of PROs is scheduled for publication by FDA in September; it will list PROs that have been identified as important to patients and whether these have been used to support labeling claims.
Sponsors find that the PFDD program have encouraged earlier interactions with patient groups, which can facilitate subject enrollment in clinical trials and help identify relevant clinical endpoints, noted Mary O’Donovan, executive director of BioMarin Pharmaceuticals, at the DIA conference. Pre-FDASIA, sponsors often did not hear patient viewpoints until advisory committee meetings; now such engagement occurs well before those sessions.
Looking ahead, O’Donovan expects PDUFA VI to further industry engagement with patients and to provide more resources to support PFDD meetings and better systems for identifying suitable patient representatives for advisory committees and other FDA programs. A white paper from the Biotechnology Industry Organization (which is changing its middle name to “Innovation”) describes the value of PFDD meetings. It (see https://www.bio.org/fdawhitepaper) advises sponsors to start a dialogue with patient representatives early in development in order to establish a complete benefit/risk framework by the end-of-Phase II meeting with FDA that can help shape Phase III studies.