When President Obama signed the Food and Drug Administration Safety and Innovation Act (FDASIA) into law in 2012, it expanded FDA’s authority and allowed the agency to collect user fees from industry to fund reviews of innovator drugs, devices, and biosimilar products, along with increasing stakeholder involvement in FDA processes. Section 1137 of FDASIA, Patient Participation in Medical Product Discussions, directs the HHS Secretary to develop and implement strategies to solicit the views of patients during the medical product development process and consider the perspectives of patients during regulatory discussions, including:
- Fostering participation of a patient representative who may serve as a special government employee in appropriate Agency meetings with medical product sponsors and investigators; and,
- Exploring means to provide to identification of Patient Representatives who do not have any, or have minimal, financial interest in the medical products industry.
FDA meetings
The FDA continues to hold public meetings with the expressed intent of allowing patients to offer perspectives on the impact of treatment options. In a recent case, FDA said it is interested in the patient perspective for “the types of psoriasis with primarily skin symptoms (such plaque psoriasis, nail psoriasis, guttate psoriasis, etc.), patient views on treatment approaches, and decision factors taken into account when selecting a treatment.”
This is one of many examples that the FDA highlights to underscore its interest in the patient perspective. FDA considered it a priority for the agency, noting that it is committed to holding meetings for at least 20 disease areas, and is currently planning to hold 24 different disease-focused meetings by the end of FY2017. FDA recognizes there are many more disease areas than can be addressed in the planned FDA meetings where drug development and regulatory decision making would benefit from a meeting focused on obtaining the patient’s perspective.
Previously, industry stakeholders have complained about the lack of guidance from FDA about incorporating patient perspectives. Specifically, as reported in 2015, the Biotechnology Industry Organization (BIO) decried what it described as “little formal guidance” on the content, format or use of this benefit-risk information when it is included in regulatory submissions. “In some instances, FDA has provided no feedback to sponsors about submissions that include the use of quantitative benefit-risk modeling methods, including formal studies of patient preferences.”
BIO continued: “Given that the benefit-risk assessment is complex and includes many factors, including patient input, sponsors and patients would benefit from clear guidelines on how the Agency will synthesize patient input, how the review division should use this information at the reviewer level, and how this would be systematically implemented across the Agency.”
Previous FDA notice for comment
On December 4, 2014, FDA issued a notice for public comment related to FDA’s implementation of FDASIA’s Patient Participation in Medical Product Discussions under FDASIA section 1137. The notice announced the agency’s intent to gather input from stakeholders on strategies to obtain the views of patients during the medical product development process and to identify ways to consider patients’ perspectives during regulatory discussions.
Several of the comments asked FDA to have a prominent office to advise the Commissioner on patient engagement and to systemically implement a coordinated function working across its Centers. Additionally, the comments recommended FDA establish an external advisory group to provide counsel about input and monitoring of patient participation in regulatory processes and policy development. It was noted that patient input on clinical trial design might improve patients’ participation and engagement throughout the drug development process.
Commenters also recommended FDA regularly report patients’ participation in the program since the passage of FDASIA. The report should detail the level of patient engagement, the staffing levels within FDA dedicated to facilitating patient engagement, as well as information detailing the progress or challenges identified. Comments further recommended the agency establish a systematic approach to consistently incorporate patient preferences into the regulatory decision-making process.
Communication was also stressed as an important component of a patient program. Developing a patient data collection tool was suggested as a way to organize issues by disease area and identity topics to facilitate communications between patient organizations and FDA. A comment stated that FDA should continue to develop multiple modes of communication styles and tools such as webinars, round tables, and tele-townhall meetings. Also, other comments said FDA should enhance its patient portal allowing greater two-way communication to hear from patients about their experiences with FDA-regulatory products, especially biosimilars.
Comments furthers suggested FDA provide a mechanism for interacting with a sponsor early in the product’s development process to discuss patient preferences. Multiple commenters suggested the agency develop guidance on interactions between patients and manufacturers to facilitate collaboration in the early stages of research and development and across the lifecycle of product development, clinical trial design, endpoint selection, and patient reported outcomes.
A comment also requested FDA issue guidance describing the appropriate parameters and regulatory/legal safe-harbor for sponsor engagement with patient groups during medical product development. A perceived barrier to manufacturers’ engagement with patient groups during medical product development is that the agency may interpret such dialogue as promotion of an investigational product. It was stated FDA could clarify its policies on outreach to patient groups which would help to understand FDA’s perspectives on the design and conduct of a particular clinical development program and/or its perspectives on whether outreach on benefit-risk and meaningful clinical outcomes constitutes promotion or marketing of an unapproved investigational product or indication thus potentially subject to enforcement.
In terms of clinical investigations, multiple comments recommended FDA expand the use of measures of patient-centered patient-reported outcomes (PROs) such as physician function and quality of life, like what the European Medicines Agency has done with its Patient-Reported Outcome (PRO) qualification process. A PRO is a direct response from the patient regarding his or her condition without an intermediary’s interpretation. A PRO instrument can be developed to measure a patient’s outcome such as symptom severity, sign, or state of a disease status or change from a previous measure. In clinical studies, a PRO instrument is meant to measure the effect of a medical intervention on one or more concepts. Integrating these measures into the design of a clinical dusty is one method to enhance a patient’s assessment of a medical product’s effects.
Several commenters also recommended the agency collaborate with patient organizations to determine methods for conducting shorter, hypothesis-driven, novel trials that evaluate biomarkers as surrogate endpoints to more expeditiously develop effective therapeutics. A few comments recommended FDA increase public-private partnerships and establish or collaborate via forums among patients, industry, clinicians, and the scientific community and the FDA. Existing groups were identified that complete work which FDA could leverage, such as the National Organization for rare Disorder, FasterCures, and the Patient Centered Outcomes Research Institute.
Conclusion
FDA ultimately concluded that it will continue to involve patient and caregiver perspectives into its work. The agency recognizes the significant work reflected in the concerns submitted by stakeholder comments. The FDA’s cross-Agency work group continues to meet to discuss implementation activities. FDA will develop a comprehensive plan for implementation of FDASIA section 1137, outlining the approaches to increase patient involvement across FDA regulatory discussions. FDA expects to continue to solicit the views of patients during the medical product development process and during regulatory discussions.