he declaration of a Public Health Emergency on January 31, 2020, by the US Department of Health and Human Services turned out to be only the first small ripple in what would become a global COVID-19 tsunami over the next 18 months. Since then, the US Food and Drug Administration (FDA) has played a central role in the US government’s frontline defense against SARS-CoV-2 and its variants. It has also been challenged in ways never anticipated throughout what Acting Commissioner Janet Woodcock called “a year like no other.”

Key Takeaways

• Through challenges of the pandemic, several new approaches emerged that likely should be sustained when the current public health crisis finally abates.
• FDA’s final guidance released in May 2021 on the design and implementation of COVID-19 master protocols can help get clinical research “out of the ivory tower and into communities,” making clinical trial participation a regular part of medical care.
• As the complexity and amount of data increase, the Technology Modernization Action Plan (TMAP) set out in late 2019 will help ensure that the FDA has proper and secure tools for data storage, access, and interoperability, as well as a central organization and platform structure to support them.

COVID’s Immediate Impact

Even a cursory look reveals the impact COVID had on the FDA’s usual business processes. It forced its leaders and scientists to navigate and build solutions that address potential and real drug and device shortages, such as propofol for ventilation patients in New York, and respond rapidly to the need for new protocols for both repurposed and new drugs, including generics and a growing number of biologics. Keeping pace with the rapid development and authorizations, through multiple parties and efforts, of the effective vaccines we have today posed additional challenges. In one of its responses to COVID-19’s immediate effects, the FDA instituted remote inspections and helped repurpose some industries outside of the healthcare sector to focus on basic needs and stave off the circulation of ineffective or dangerous products (e.g., distilleries and breweries making hand sanitizers).

The pandemic’s impact at FDA went well beyond COVID’s needs. Many ongoing and planned clinical trials of therapies for other diseases, including new CAR-T indications and types, had to go on but couldn’t be done in usual ways. And the FDA’s mandated work on food safety, tobacco regulation, veterinary products, and maternal and child nutrition had to continue as best as possible, while trying to bring its best firepower to the COVID front lines. The silver lining to the crisis is that, through all the challenges, new approaches emerged that everyone agreed could and maybe even should be sustained when the current public health crisis finally abates.

Master Protocols and Clinical Trial Outcomes

In May 2021, FDA released a final guidance on the design and implementation of COVID-19 master protocols (i.e., protocols “designed with multiple substudies, which may have different objectives and [involve] coordinated efforts to evaluate one or more investigational drugs in one or more disease subtypes within the overall trial structure.”).

Master protocol studies are difficult to set up but, if done well, provide significant improvements in reliable data that can ultimately lead to better medical practice, especially when conducted in decentralized trials. Ultimately, FDA leadership agreed that it is past time to get clinical research “out of the ivory tower and into communities,” making clinical trials a regular part of medical care. Even where this is most practiced today, such as in oncology, only a small percentage of those who could be helped are finding access.

COVID-19 vaccine trials are a prime example of how powerful this approach can be. We are seeing real-world vaccine effectiveness that almost mirrors the efficacy seen in clinical trials. This alignment is likely because the trials were highly dispersed (i.e., not just in clinical research institutions in large cities) and thus included a more diverse population than usual. Although this approach may not work in every situation, there is likely a large number for which it would, including in rare diseases, when minimizing placebo exposure, or when building adaptive designs for phase 2/3 studies in areas other than oncology. Indeed, there are challenges to wider implementation that must be overcome by all stakeholders (not only FDA) working together, but there is also a growing infrastructure in place that can be redirected to surmount these challenges.

Modernizing Massive Data Management

Beyond the extra funding Congress granted to FDA for the COVID battle, the Administration’s proposed budget for the upcoming 2022 fiscal year would give FDA a substantial 10% increase. A large part of that, if approved, will go toward realizing the Technology Modernization Action Plan (TMAP) it set out in late 2019. According to the FDA, with competing demands on its resources (and the limitations on those), it has been difficult to keep up with modern data technologies. But as the complexity and amount of data increase, particularly in this “post-genomic” world, it is even more critical that the FDA—as an “information agency”—has proper tools for data storage, access, and interoperability, as well as a central organization and platform structure to support them. We are ensured that data security is already good, but everything else digital would need to catch up. Apparently, some significant progress was made during the pandemic, but a more far-reaching, central solution is promised as a top priority going forward.

It Isn’t Over Yet

As these FDA leaders pointed out, we are nowhere near a post-pandemic reality. Indeed, at the time of the panel discussion, the alarmingly low vaccination rate in several specific regions of the US and the emergence of variants of uncertain infectivity foretold the surge we are seeing today. Even so, it is hard to imagine just how much worse off we would be without the concerted effort and leadership of stakeholders across the globe, including researchers, industry, regulatory agencies, and healthcare workers. The successful rethink of traditional approaches during a crisis provides a degree of optimism for meeting future challenges that are sure to come.