What is the FDA's stance on the offshoring of clinical trials by a number of biotech and pharma companies?
Efficient, well-designed clinical trials are a key area of focus for the FDA and a critical element of our public health mission to ensure that safe, effective medical products are available for patients. The FDA has taken steps to advance innovation (e.g., using decentralized elements) in clinical trials, to ultimately promote the reliable evidence needed to demonstrate the safety and effectiveness of medical products.
Data supporting many previous FDA product approvals have included evidence collected from clinical trial participants around the world, and the number of international sites and clinical trial participants contributing data to support U.S. marketing applications is increasing. The FDA recognizes that sponsors may choose to conduct multinational clinical studies under a variety of scenarios. Some sponsors may even seek to rely solely on foreign clinical data as support for an IND or application for marketing approval in the U.S. When an application is supported only by data from trial outside the U.S., these data must be applicable to the U.S. population and U.S. medical practice.
To meet FDA’s rigorous approval standards, clinical trials to support U.S. licensure—regardless of where they are conducted—must follow Good Clinical Practice (GCP) laws and regulations to protect the rights, safety, and welfare of trial volunteers, and help ensure that these trials produce reliable, high-quality data. The FDA engages with stakeholders globally through international venues to respond to the increasingly complex and global nature of industry operations and related regulatory oversight.
The FDA encourages enrollment of diverse populations to help further medical product development and availability. Strategic use of properly designed and executed multi-regional clinical trials can increase efficiency of product development. Such trials may enable simultaneous submission of marketing authorization applications, lessen the burden for companies, and support regulatory decision-making in multiple regions, allowing earlier access to new medical products worldwide.
Did the streamlined approval of the COVID-19 vaccine serve as a precedent for the FDA? In other words, should the FDA have a more liberal approach when it comes to new life-saving therapies that target high unmet needs?
The FDA facilitated the development and availability of COVID-19 vaccines as expeditiously as possible without cutting corners or compromising our scientific and regulatory standards. Instead, intensive interactions between the FDA and manufacturers minimized the time between different studies in the clinical development process and facilitated manufacturing scale-up at risk. This process also allowed for the timely availability of the vaccines to the public once the FDA evaluated and analyzed all of the available data and determined that the vaccines met the agency’s rigorous standards for authorization or approval.
Building on some of the lessons learned during the COVID-19 pandemic such as the benefits of enhanced communication and global regulatory collaboration, the FDA is committed to helping facilitate the development and approval of safe and effective treatments for patients with serious and rare diseases, especially when the product is the first available treatment - or if it has advantages over existing treatments.
To start, providing appropriate and balanced regulatory oversight for applications involving treatments for serious medical conditions where there is an unmet medical need, including areas where the scientific field is fast-paced and rapidly evolving, is not new or unique to the FDA. For decades, the FDA has used review pathways such as Fast Track,Breakthrough Therapy, Priority Review, and Accelerated Approval. While these expedited regulatory pathways offer some level of flexibility intended to support medical product development and innovation, every decision related to a product review made by the FDA is based on a comprehensive review of the totality of data submitted in support of the labeled indication. As such, all medical products, whether they receive an expedited designation or not, still have to meet the FDA’s gold standard for safety and effectiveness.
Applying knowledge gained during the pandemic to help further accelerate the development of novel drug and biological products for rare diseases, a limited number of sponsors will have the opportunity to participate in the Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program. The START program allows for more frequent communication with the FDA staff to provide a mechanism for addressing clinical development issues. Sponsors will be able to obtain frequent advice and regular ad-hoc communication with the FDA staff to address product-specific development issues, including, but not limited to, clinical study design, choice of control group and fine-tuning the choice of patient population. Additional information about the START pilot can be found on the FDA’s website here.
The FDA also supports work toward global regulatory convergence and, ultimately, global harmonization of regulations for these products. The agency is pursuing this goal with international partners, global regulators, and the World Health Organization by exploring the possibility of concurrent collaborative review of applications with global regulatory partners in a manner similar to that being undertaken through Project ORBIS in the FDA’s Oncology Center of Excellence. To support this goal, the Collaboration on the Gene Therapies Global Pilot (CoGenT Global) is intended to explore the possibility of concurrent collaborative review of applications with global regulatory partners.
What do you see as the biggest regulatory challenges in the approval and oversight of AI-driven medical devices and how is the FDA planning to address them?
Please see the January 2024 GAO report on selected emerging technologies – starting on page 18 of the report, the FDA notes that for AI/ML devices, it would be valuable to have explicit authority to proactively collect performance data from AI/ML-enabled medical device manufacturers after the devices have been marketed.
The FDA currently only has authority to conduct this postmarket surveillance in specific circumstances, such as in the case of an adverse event or if the device is recalled. Another challenge is inflexibility in the statutorily-defined structure of premarket reviews and the corresponding safety controls that the FDA must apply. Under the statutory framework, the FDA categorizes devices into three risk categories, and the controls necessary to ensure device safety and effectiveness depend on that categorization. FDA review of these devices could be improved if the agency had the flexibility to more specifically tailor review and safety controls to these AI/ML-enabled devices. The agency is considering approaches to solving these challenges while navigating this rapidly evolving landscape within the agency’s current authorities.
What is the FDA’s message to our readers who are constantly faced with the threat of medical misinformation?
Misinformation affects virtually every corner of our society, from the interpretation of history to politics, from advertising to education. As we consider our nation’s lower life expectancy and burden of chronic disease relative to other high-income countries, the continuing and growing challenge of medical misinformation is a serious threat to public health.
Medical misinformation is already having a significant negative impact on health outcomes, leading people to make adverse choices regarding their health because of the influence of incorrect information. We see the impact of misinformation across the spectrum -- from the foods they eat, continuing use of tobacco products and vaping, to failure to use effective medical treatments. Too many of these decisions are made in the face of scientific evidence that makes clear these actions are harmful.
Perhaps the most compelling recent example of the harm that comes from medical misinformation involves vaccines, and specifically COVID vaccines. Ongoing proliferation of misinformation and disinformation about the overall safety of vaccines while misinforming about their effectiveness contributes to vaccine hesitancy and lowers vaccine uptake. However, with over a billion doses of the mRNA vaccines administered, available scientific evidence is powerful -- the benefits of COVID-19 vaccines far outweigh their risks. It is simply a fact that millions of lives have been saved because of the COVID-19 mRNA vaccines and many more people have avoided serious illness and hospitalization.
The cumulative effect of these attacks on the integrity of science, is damaging our critical institutions and further threatening the already eroding life expectancy in the U.S.
All of this is particularly disheartening for us as scientists and clinicians, since the cornerstone of our disciplines is the understanding that science and data, while not infallible, give us the most reliable information to inform decisions. At the FDA, when we reach a decision, we have confidence that we have done our best to base this decision on all of the available evidence. While imperfect, our decisions can and should be relied on by the American public as the best decisions as a result of a time-tested systematic approach.
Unfortunately, thanks to misinformation, that basic chain of trusted communication is frayed, and in many cases, completely severed. The sharing of misleading resources, including so-called evidence that may appear to have some semblance of legitimacy, is increasingly the rule, not the exception.
As scientists, it is disappointing that the fundamental basis for the remarkable gains that have led to so much progress in health is eroded by this constant, pervasive misinformation. So this topic can’t be avoided in today’s world of public policy and public health. And the medical community has a particularly important role to play, to be a powerful force for the use of reliable evidence from good scientific methods, through the trust and respect you command and the opportunity you have to transmit reliable information to patients and consumers. Study after study shows that personal connections – connections in which the listener has trust and confidence in the speaker – makes enormous difference in acceptance and agreement with evidence in a way that leads to activation for decisions that improve health.
We need to rebuild this trust and continue our collective efforts to convey scientific, public health and regulatory work in words that can be understood and embraced by the spectrum of people so that good decisions based on good evidence can lead to good health.