Stakeholders seek clarity, case studies on patient experience data in applications

Stakeholders want more clarity from the US Food and Drug Administration (FDA) on how and when the agency uses patient experience data (PED) in its regulatory decision-making. They wrote to the agency with suggested topics and the direction they want the agency to take when hosting future patient-focused drug development (PFDD) workshops.

After holding a virtual public workshop on 13 December 2024 on enhancing PFDD, several stakeholders wrote to FDA with suggestions on steps the agency should consider taking to improve clarity and predictability surrounding the issue. The agency plans to take the feedback and hold another meeting on patient-focused drug development later this year.

EMD Serono, a subsidiary of Merck KGaA, asked FDA to provide more transparency and consistency in what role and impact PED plays in the agency's regulatory decision-making process.

"This could be operationalized through the FDA acknowledging in writing which data informed the FDA decision-making in review decision letters to the sponsor as well as publication of successful case studies and best practice sharing," said the company. "In addition, we recommend that the FDA incorporates PED into product labeling to improve transparency for providers, caregivers, and patients, thereby supporting informed decision-making."

The pharmaceutical lobby group PhRMA similarly encouraged FDA to take steps to provide more consistency and details to how PED is evaluated in Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) review documents. The groups encouraged the agency to provide clear descriptions of and rationale for the use of PED in regulatory decision-making.

"FDA’s inclusion of this information in review documents is critical for allowing sponsors to better understand FDA’s expectations regarding the quality and relevance of PED submitted," said PhRMA. "We encourage FDA to include in the PED section of review documents, in addition to the PED table, a summary that includes a brief description of the PED submitted, information on whether FDA considered the PED, what aspects of the review and decision it informed (e.g., FDA’s benefit-risk assessment), and rationale for not considering PED, if applicable."

"We also encourage FDA to consider including in the benefit-risk framework section of a review document a statement about the PED considered in FDA’s evaluation of the submission, when applicable," the group added.

PhRMA asked CDER and CBER to clarify its expectations for reviewers when evaluating PED during regulatory review and decision-making to mitigate potential inconsistencies.

EMD Serono asked the FDA to provide guidelines on the types of PED or PFDD data the agency wants from sponsors to be used in its regulatory decision-making. The company said it should provide guidelines on qualitative and quantitative data that can be used to determine clinical outcomes, benefit-risk assessments, and clinical outcome assessment (COA) measurement strategies.

"We propose that the FDA recognizes the value of qualitative methods, especially in cases involving small patient populations or ultra-rare diseases," said EMD Serono. "It is crucial that the FDA acknowledges the relevance of data obtained through qualitative methods or from smaller patient groups for FDA regulatory decision-making."

EMD Serono also asked FDA to expand the scope of its next workshop to include more case studies from CDER to ensure alignment across all product types. Similarly, PhRMA said it appreciated the case studies FDA presented at its December workshop to help stakeholders understand how the agency may use similar methodologies to evaluate similar cases.

PhRMA asked FDA to include case studies on repurposing COAs, methodologies to generate and use non-COA PED, case studies on understanding meaningful score differences and meaningful score ranges, and the impact of different types of PED on regulatory decision-making at the next meeting.

The biotechnology lobby group BIO also said it wants FDA to provide more examples, lessons learned, and COA best practices for industry in future workshops.

"We appreciated the CBER examples during the December workshop and encourage FDA to provide additional examples from both CDER and CBER," the group said. "While BIO agrees that early and often engagement with the FDA is critical, there remain instances where sponsors were asked to make significant changes to the COA instrument after completing the phase 2 study or before beginning the phase 3 study, which causes challenges as program delays and resource constraints as typically investigators would need to be trained on how to use a modified instrument.

“BIO also suggests composite endpoints be a topic for future discussion," the group added.

EMD Serono asked FDA to require sponsors to submit PED and PFDD data in an organized manner, preferably as part of the patient experience dossiers. These dossiers would serve as a comprehensive folder that includes details on the purpose and relevance of the data for regulatory submissions. The company also asked for guidance from the FDA on when the best time would be to submit PED and PFDD data.

"This data should be integrated early in the clinical development process, such as during Phase 2 protocols, to inform subsequent phases and sponsors regulatory interactions with the FDA," said EMD Serono. "We recommend that the FDA include discussions on the relevance of prospective PED data collection during early interactions, as this would facilitate resource allocation decisions for sponsors."

"Flexibility in the requirements for confirmation of diagnosis, particularly in rare diseases, should also be considered, allowing for self-reported diagnoses where formal confirmation is not feasible," the company added.

BIO wrote to FDA asking the agency to figure out the appropriate mechanisms and approaches to continue communicating its views on and expectations on collecting and presenting PED data in premarket applications. The group said this could include a repository of PFDD case studies that detail the best practices for PED data submissions.

"This could summarize instances on how the data was considered and provide insights and best practices on which key information FDA reviewers find useful in documents, how such data can be presented, and how the FDA uses the data," said BIO. “This information can be beneficial for sponsors to show how to best collect PED and present this data in a meaningful and impactful way without overwhelming the reviewers with large data repositories."

A key area of concern for BIO is what it said was a lack of consistency and transparency in the use of PED tables. The group noted that during the December meeting, FDA said that less than 20% of applications included PED tables in the reviewer guide.

"BIO suggests that the agency develop dedicated guidance regarding their expectations for sponsors' documentation of PED in the application," said BIO. "This guidance should especially describe instructions for pre-populating the PED table, provide additional clarity on how the table can be completed, and cross-reference the PED table with the modules."

"Another alternative BIO suggests is the FDA revise the PED data section in the summary basis of approval (including the PED table) to include a summary of how PED was considered and provide which aspects of the review and regulatory decision were informed by PED," the group added.

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Stakeholders seek clarity, case studies on patient experience data in applications

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