By James E. Valentine* –
The enactment of FDASIA, including the fifth reauthorization of PDUFA, really put patient engagement on the radar beyond some of the traditionally active disease communities (e.g., HIV/AIDS, cancer, neurological diseases). FDASIA’s section 1137, the provision on Patient Participation in Medical Product Discussions, led FDA to seek input on “strategies to solicit the views of patients during the . . . development process and consider the perspectives of patients during regulatory discussions” (see our prior coverage here). Meanwhile, CDER and CBER have been busy fulfilling their commitment to host at least 20 Patient-Focused Drug Development (PFDD) meetings on specific disease areas during fiscal years 2013-2017.
On July 2, 2015, CDER/CBER will announce the selection of the final set of disease areas to cover as part of the PFDD initiative under PDUFA V:
- Alopecia areata
- Hereditary angioedema
- Non-tuberculous mycobacterial infections
- Patients who have received an organ transplant
- Neuropathic pain associated with peripheral neuropathy
With the addition of these eight meetings, FDA is on target to have held 24 in total—four more than the minimum of 20 that the Agency committed to under PDUFA V.
The PFDD meetings have helped advance a systematic approach to gather patients’ input on their condition and treatment options, and provide what FDA has deemed “the therapeutic context” for weighing benefits and risks of investigational products for the given disease. This is accomplished through the inclusion of information synthesized from the PFDD meetings in the first two rows of the structured benefit-risk framework (sB/R) (see below). The framework was rolled out in March 2015 in CDER’s review of NME NDAs and Original BLAs.
However, it appears one industry trade group sees this sB/R framework as a platform with greater utility. In a white paper released in June 2015 by the Biotechnology Industry Organization (BIO) (soon to be renamed the Biotechnology Innovation Organization), the industry group recommends that the perspectives of patients be a standard component of decisions that are made during discussions behind closed doors between sponsors and FDA. As BIO sees it, the sB/R framework holds the potential to serve as the bridge between patient input and regulatory decisions. But in order for this to work, patient input should begin when initiating a development program, and the sB/R framework needs to be used early and often in considerations by both sponsors and FDA.
The BIO white paper provides a comprehensive set of recommendations for incorporating patient feedback into the sB/R framework and using the framework during key points of a product’s lifecycle to ensure transparency on the key areas of judgement for regulatory decision-making. Here are a few recommendations this blogger found noteworthy that bring the patient perspective earlier in the development lifecycle:
Early Stage Development (Pre-IND to Phase 1)
In the early stages of development, a sponsor has the ability to describe the development rationale for a new medicine in the context of the benefit-risk framework and use this information to screen compounds. To obtain input from patients, BIO recommends that sponsors consider organizing meetings with a representative group of patients and caregivers, including patient advocacy groups (PAGs), to engage in a dialogue around the burden of the condition and the current armamentarium of treatment options. This information would be summarized in the first to lines of the sB/R framework. This early stage, qualitative activity appears similar in scope to the discussions at FDA-hosted PFDD meetings.
In addition, BIO recommends that sponsors employ methods to gather robust and representative data that could be used in regulatory decision-making, such as patient surveys and stated choice studies, to assess patient preferences and perspectives on benefit-risk considerations and integrate this information into the framework summary.
To date, this quantitative approach to incorporating the patient perspective has been endorsed by FDA only for the review of medical devices (see our coverage on Patient Preference Information draft guidance here). However, patient advocacy groups have taken their own initiative to collect patient preference information for use in drug review (e.g., Parent Project Muscular Dystrophy’s risk tolerance survey) and CDER officials have suggested that “more systematic collection of patients’ experience” would be considered in future iterations of PFDD.
BIO postulates that, in sum, incorporating these patient perspectives in submissions to FDA (e.g., briefing materials for milestone meetings) will assist the sponsor and FDA in developing an aligned sense of the status quo. It may also provide an opportunity to identify and discuss potential differences in opinion between the two parties early in development.
Mid-to-Late Stage Clinical Development (Phase 2 to Pre-NDA/BLA)
Here, the targeted benefit-risk profile of an investigational drug continues to be investigated and refined so the focus shifts to designing registration trials that ideally reflect an alignment between the sponsor’s and FDA’s perspectives on the clinical context. BIO sees a role for the sB/R framework to facilitate this evolving dialogue.
In preparation for the end-of-phase 2 meeting, BIO recommends that sponsors obtain further patient preference input from patient organizations in the context of data emerging over the course of development. This would allow sponsors to gain insight into evolving views of the drug candidate. BIO suggests measures such as non-disclosure agreements to protect any confidential commercial information. This qualitative and quantitative patient feedback would be summarized in the bottom three rows of the sB/R framework, as well as the summary assessment. This recommendation is novel in that it expands the inclusion of patient input beyond the contextual information contained in the first two rows of the framework, now including product-specific input.
BIO suggests including the updated sB/R framework in the end-of-phase 2 meeting document to serve as an early opportunity for FDA to hear the voice of the patient as it relates to the specific drug candidate benefit and risk attributes, as well as Phase 3 clinical trial development considerations (e.g., size and complexity, recruitment and enrollment strategies, use of endpoints, the clinical outcome measure).
Other opportunities to share the patient perspective, as well as to concisely summarize available data and other factors considered by the sponsor, through the sB/R framework include at pre-NDA/BLA and other late stage meetings and at advisory committee meetings. BIO also requests that FDA integrate the sB/R framework in the decision memo at the time of approval to communicate the reasoning behind the Agency’s decisions, such as which benefits, risks, or other factors were considered and how they were weighed. In the event of a Complete Response Letter, BIO requests that FDA provide the sponsor with the framework as documentation of those same factors, but not to release that information to the public.
Shifting to PDUFA VI
While BIO’s recommendations could be implemented at any time, to establish buy-in by FDA, there is an opportunity to present and discuss such proposals during the negotiations for the next reauthorization of PDUFA. FDA is hosting a public meeting on July 15 to initiate the reauthorization process. Once under way, there will be opportunities for industry and other stakeholders, including patient advocacy groups, to participate in the process. A second iteration of PFDD is bound to be a hot topic.
*Admitted only in Maryland. Work supervised by the Firm while D.C. application pending.