WMIF: FDA Commissioner Discusses Revamping Accelerated Approval

Balancing Risks and Benefits of Accelerated Approval 

Califf acknowledged the role of Congress in the ongoing revamping process and emphasized the fundamental premise of accelerated approval, which is to provide fast access to life-saving drugs for patients with serious conditions. It allows the FDA to approve drugs based on intermediate outcomes instead of long-term data. This balances timely access with scientific evidence, with post-approval studies required to confirm benefits, he clarified. 

He emphasized that the American people are more willing to take risks if there's a severe life-threatening disease without an effective treatment. The accelerated approval is based on intermediate clinical outcomes or unvalidated biomarkers that reasonably predict a clinical benefit outweighing the risks. 

However, Califf also emphasized the need for the pharmaceutical industry to fulfill its responsibilities in conducting follow-up studies. “The next phase while on the market should be to get studies done to prove that the benefits outweigh the risk,” he explained. 

In response to a question about time limits for confirmatory studies after accelerated approval, Califf emphasized the importance of constant communication and judgment between the FDA and drug developers. Additionally, Congress has empowered the FDA to take action if studies are not progressing as required, granting the FDA more authority to enforce these specific requirements and ensure the withdrawal of products, if necessary. 

Monitoring Drugs and Diseases 

Baden raised a question about monitoring different drug and disease classes, specifically gene therapy and anti-infectives. Califf mentioned that the FDA relies on the expertise of its staff in various areas and seeks to establish a common view in the medical ecosystem regarding standards for each disease and patient population. He highlighted the importance of health equity and incorporating input from patients who live with the diseases being treated. 

Unique Targeted Therapies 

The conversation shifted to the approval of unique targeted therapies, particularly in gene therapy, where treatments are tailored to individual diseases. Califf expressed optimism about the future of rare and ultra-rare genetic diseases and mentioned plans to hire additional staff to navigate these uncharted territories.  

He also stressed the need to create a reliable and predictable industry for targeted therapies, ensuring patients receive consistent quality regardless of where they access the healthcare system. 

“In areas where we can, we got to make this a robust industry that's reliable and predictable in terms of what it's delivering,” he insisted, arguing the need for stability and consistency. 

Post-Approval Follow-Up and Safety Monitoring 

Addressing the issue of post-approval follow-up and safety monitoring, Baden asked if the FDA has the teeth to assess the long-term safety profile of approved therapies.  

Califf acknowledged that, although the FDA “has the teeth,” a system is still needed to effectively follow patients' progress over time. He mentioned the potential collaboration between the FDA, NIH, CMS, and CDC to leverage electronic health records (EHRs) and establish a comprehensive post-market monitoring system. 

“The FDA should be able to follow people that received gene therapy for a lifetime based on their electronic health records. So, there is a place for collaboration,” he reassured. “I have great hopes that the NIH, CMS, and CDC will work together in a public–private partnership to make this possible.” 

FDA and CMS Relationship 

The conversation touched upon the relationship between the FDA and CMS, particularly regarding reimbursement decisions for approved treatments. Califf clarified that the FDA's overall mission is to ensure safety and efficacy, while CMS focuses on reasonable and necessary standards for the population it covers.  

“To be clear, we’re not talking about CMS deciding what FDA decides or vice versa,” Califf continued. “It's really about designing a system so those who develop the best products and interventions get paid and that those therapies get to the people that need them.”  

He highlighted the importance of communication between the agencies to ensure a smooth transition and decision-making process, particularly in designing appropriate clinical trials that provide essential data for reimbursement determinations. 

“It's been a tragedy in this country that the worlds of the FDA and CMS have been almost entirely separate,” he revealed. “We're making progress, but don't confuse that with whether we ought to have one opinion about everybody in the United States getting a particular treatment." 

Conflicts of Interest in Medical Education 

Lastly, the conversation addressed the potential conflicts of interest from drug companies funding medical coursework. While acknowledging the issue's complexity, Califf expressed his reservations about pharmaceutical and device companies financing the education courses for medical professionals.  

For example, Stanford University School of Medicine has accepted a $3 million grant from Pfizer to support a new curriculum for continuing education. Although this partnership is intended to redefine the relationship between academia and industry, critics have raised concerns about potential conflicts of interest. 

"This is a very complicated set of issues: Why would there ever be a need for a pharmaceutical or a device company to fund coursework for medical students,” Califf asked. “The healthcare delivery industry is much larger than the medical products industry, and the academic medical centers are strong, lobbying for financial interests of the academic medical center.” 

Regardless, Califf stressed the need for equality and transparency in the current healthcare delivery system and for avoiding biases and conflicts of interest in medical education. 

“If you think there's no bias in health systems today in the United States in terms of what is taught and what is allowed — I'm sorry, I’ve experienced the opposite," Califf said. 

While the conversation with the current US FDA Commissioner provided valuable insights into the drug approval process, post-approval follow-up, and collaborations between the FDA and CMS, questions about achieving more significant health equity and transparency still need to be answered. 

“We don't want to be in a situation where only wealthy, highly educated people have access to a treatment,” Califf added. “So, the bigger question is ‘how do we work across professional groups and health systems and payers to optimize who gets treatment cost-effectively?’”