Body: Health policy stakeholders and former FDA officials are backing a group of bipartisan drug development reforms they say could boost domestic clinical research and expand patient access to treatments, suggesting next year’s reauthorization of the drug user fee law could be a vehicle for the changes. The proposals direct Congress and FDA to make the review process more predictable for drug developers by codifying priority review vouchers for rare pediatric diseases, introducing new requirements for complete response letters and committing to a rolling review process. Other reforms are designed to triage early-phase clinical trial issues to foster domestic innovation, and expand flexibility in trial design and evidence generation to develop new treatments for rare disease patients. Rohini Kosoglu, a senior advisor at the Stanford Mussallem Center for Biodesign, and Ryan Long, the director of congressional relations and a senior research fellow at the Paragon Health Institute, laid out the reforms in a roadmap published this month. "The same procedural burden that pushes programs offshore also keeps therapies from patients with the least ability to wait: those with rare or fast-progressing diseases for whom there will be no large trial, whose treatments often begin in an academic lab or small biotech company and stall in a process that was not built for them,” Kosoglu and Long wrote. “Many of these rules have not caught up to the science they govern, leaving regulators with fewer tools than the work requires.” Among their recommendations, which they said weren’t exhaustive, is a pilot for lower-risk Phase 1 trials modeled after Australia’s drug development process where sponsors notify FDA when an institutional review board (IRB) completes its pre-clinical safety evaluations. Sen. Bill Cassidy (R-LA), who chairs the Senate health committee and lost his reelection bid, proposed a similar pilot in a white paper his staff published in February. Rep. Jake Auchincloss (D-MA) suggested FDA similarly model third-party oversight of lower-risk Phase 1 trials after Australia’s regulatory pathway in a white paper published in May. Former acting FDA commissioner Janet Woodcock discussed the reforms with Kosoglu, Long and Andi Lipstein Fristedt, executive vice president and chief strategy and policy officer at the Parkinson’s Foundation, during a panel hosted by the Bipartisan Policy Center Wednesday (Oct. 14). But Woodcock said IRBs lack the technical expertise needed to make the pilot approach proposed in the roadmap successful, suggesting drug development in the United States is slower because of both excessive requirements from FDA and systematic issues. “A lot of the delay is with the medical centers and forming their contracts,” Woodcock said. “They think nothing of taking nine months to sign a contract to do a clinic, be a clinical site, and then they may take a long time for standing up the site ... and then they may insist on their own IRB, and so you're dealing with 50 different IRBs, so there's a systems problem here, and just focusing the FDA, I think is missing why China is being successful.” Woodcock, a former longtime leader of FDA’s drug center, instead backed efforts to expand the agency’s flexibility in accepting substantial evidence from drug sponsors developing rare disease treatments, where there are often too few patients who also demonstrate heterogenous symptoms to participate in large randomized controlled trials. Woodcock, who currently serves as a board member to the rare disease advocacy organization Haystack Project, referenced the group’s citizens petition that would allow FDA to account for disease characteristics, like small population sizes, when reviewing endpoints and clinical data. She also indicated support for directing National Institutes of Health funding toward building natural history studies ahead of rare disease trials, citing hundreds of patient groups doing the work alone. Kosoglu and Long included similar proposals in their roadmap, suggesting FDA should develop a structured process to recognize “external scientific developments that mature during a multiyear trial, such as a biomarker’s validation or an updated understanding of disease progression, so that evaluation at readout is not confined to the endpoint assumptions locked in at trial initiation.” Kosoglu and Long also proposed a non-binding bulletin for drug developers, patient advocacy organizations and academic medical centers to share early scientific and safety findings from drug trials to prevent developers working on the same drug or technology from running into the same issues. They also suggested expanding initiatives FDA is already exploring, proposing the agency develop a formal process to recognize new approach methodologies (NAMs), which would shift preclinical drug testing from using animals toward the new technology. Most recently, FDA issued a rule that replaced all references to animal studies with “nonclinical studies,” though Kosoglu and Long wrote that “this still does not tell a developer what evidence satisfies the standard, how long a decision takes, or what a partial answer provides.” Long, who previously served as chief health counsel for the House Energy & Commerce Committee, said Wednesday that incorporating the policies into user fee reauthorizations would be beneficial because the legislation by nature needs bipartisan support and must be passed by September. “This is not something that you can do on a party-line basis,” Long said, citing a need for bipartisan work in the FDA space to create durable policy changes. While legislation could be influenced by the preferences of committee chairs in the next Congress, he said, there is buy-in across the political spectrum for improving FDA processes. He added, “But we do know that there's an end in sight, and so there's a lot of work that Congress needs to do, basically starting January 15.” -- Lauren Brensel (lbrensel@iwpnews.com)