You Just Have To Wait: FDA Can't Hurry PDUFA VI Guidances

In response to stakeholder concern about multi-year schedule for patient-input guidance development, FDA says it only has a few experts and has to balance their time.

FDA had to remind stakeholders that drug development guidance is not easily written and in-house expertise has many demands on its time, even when user fee funds are supporting the projects.

An exchange during the Aug. 15 public meeting on the commitment letter for the next round of the user fee agreement (PDUFA VI) illustrates the tensions that exist between FDA and many patient activists even as they work to better understand each other.

Annie Kennedy, senior VP of legislation and public policy for Parent Project Muscular Dystrophy, suggested during the hearing that spending several years working up documents on incorporating patient voices into drug development is too slow and potentially harmful to existing drug development efforts.

But Theresa Mullin, director of the Center for Drug Evaluation and Research's Office of Strategic Programs, said the agency does not want to overwork those capable of writing the guidances.

Kennedy argued that while the guidances are necessary, they also could unknowingly cause "current development of additional tools could be delayed, chilled, slowed."

The agency should issue interim guidance or best practices so that the pipeline is not slowed, Kennedy said.

"We understand that's a tedious process and there's a delicate dance in promoting a nascent field," she said. "But what we're concerned about is that there are products currently in review for which there are disease-specific [patient-focused drug development] tools with methodological rigor currently available and that those timelines will not match-up."

FDA Only Has 'Handful' Capable Staffers

Mullin also implied that sponsors likely would prefer that the process not be rushed, given that it will affect many drug development programs potentially costing billions of dollars.

"What you need to keep in mind is that when I said a handful of people, I meant five … and only three of those really are experienced enough that they could work on a guidance," Mullin said.

"And then we've got the other folks, and there's three or four over there that are experienced enough that they could write a guidance document that you would then take and stake your whole program on.

"Writing guidances that are good is not trivial … This is stuff [that] if it had been that easy we would have written it already."

The PDUFA VI commitment letter includes a multi-year schedule for the guidances to be released. They will include various approaches to help make patient-reported outcome and similar information more usable data for drug development and review.

Patient involvement was a major focus of PDUFA V and will continue under PDUFA VI.

During PDUFA V, the agency agreed to conduct a number of disease-focused meetings where patients are allowed to talk about unmet needs and risk tolerance. (Also see "Patient-Focused Drug Development At 10: Where Does It Go From Here?" - Pink Sheet, 20 Oct, 2014.)

The next phase is to take those opinions and make them quantifiable so they can augment an application and an FDA review. (Also see "FDA Needs Formal Mechanism To Integrate Patient Input, Groups Say" - Pink Sheet, 24 Feb, 2014.)

Four Guidances Mandated

There are four patient-reported outcomes guidances that FDA agreed to produce during PDUFA VI that are intended to "bridge from initial patient-focused drug development meetings … to fit-for-purpose tools to collect meaningful patient and caregiver input," according to the commitment letter. They appear to build in complexity throughout PDUFA VI.

The deadlines are for drafts with a goal to revise or finalize them within 18 months of the end of the public comment periods. The commitment letter mandates the following drafts:

• "Approaches to collecting comprehensive and representative patient and caregiver input on burden of disease and current therapy," due by the end of September 2018
• "Processes and methodological approaches to development of holistic sets of impacts that are most important to patients," by September 2019
• "Approaches to identifying and developing measures for an identified set of impacts," such as burden of disease and treatment, "which may facilitate collection of meaningful patient input in clinical trials," by September 2020
• Clinical outcome assessments, by September 2021. When final, it will revise or supplement existing guidance on patient-reported outcome measures.

FDA also is required to create a public repository for drug development tools on its website for stakeholders to use. In addition, it must conduct a public workshop on enhancing patient engagement in clinical trials by the end of FY 2019.

Splitting Time Between Guidance and Reviews

FDA plans to bring in more expertise in the patient-reported outcomes area, but even as they arrive, agency officials still must manage their time.

Forcing FDA to produce guidance on interim best practices could take those experts away from drug review altogether, Mullin said.

"There's people developing drugs right now," Mullin said. "We don't want to take them offline and let them not talk to patients so they can go work on these guidances. We want them to keep reviewing what's coming in."

And new additions who haven't yet learned FDA's business practices also should not be writing guidance, Mullin said.

"You can't just hand that to the newest person who walks in the door," she said.

Indeed, an FDA hiring surge is planned during PDUFA VI, along with enhanced retention efforts. (Also see "FDA's Breakthrough Workload Will Be Eased By Hiring Reviewers With PDUFA VI Funds" - Pink Sheet, 20 Jul, 2016.)

The PDUFA VI commitment letter, the culmination of several months of negotiations between FDA and industry officials, was released in July. It and user fee programs covering generics, biosimilars and medical devices will expire at the end of FY 2017. (Also see "Sponsors, FDA Reviewers To Get More Flexibility Under New User Fee Program" - Pink Sheet, 15 Jul, 2016.)