Cutting Corners on COVID-19 Treatments?

At the height of the COVID-19 pandemic, the U.S. Food and Drug Administration (FDA) scrambled to distribute resources to protect the public against the virus. FDA issued over 400 emergency use authorizations (EUA) to accelerate market access to medical products, including ventilators, antibody tests, vaccines, and more.

But did FDA bypass necessary safety standards in the process? In some circumstances, FDA did cut corners on safety, according to a recent article by professors Efthimios Parasidis, Micah L. Berman, and Patricia J. Zettler of the Ohio State University Moritz College of Law.

They say that FDA cut corners, for example, when it first approved the EUA for hydroxychloroquine—a malaria drug—in response to White House pressure. To reduce the risks of political influence on FDA’s EUA decisions, Parasidis, Berman, and Zettler suggest that Congress and FDA reform the EUA mechanism before the next pandemic.

Although they were controversial during the COVID pandemic, EUAs were no less controversial at their founding, recount Parasidis, Berman, and Zettler. In the early 2000s, the U.S. Department of Defense mandated anthrax vaccine inoculation for all active duty and reserve service members to protect against terrorist groups’ use of biological weapons. This mandate provoked controversy because the anthrax vaccine was not approved to protect against airborne anthrax. A court eventually halted the Defense Department’s program and Congress stepped in to add EUA provisions to the Federal Food, Drug, and Cosmetic Act (FDCA) enabling the Defense Department to vaccinate the military.

Despite the EUA provision’s origin as a medical countermeasure for the military, Congress drafted the measure to include civilian uses during public health emergencies, such as the COVID-19 pandemic.

The statutory standards for an EUA are low compared to what is required for traditional FDA approval, explain Parasidis, Berman, and Zettler. The U.S. Department of Health and Human Services (HHS) Secretary must determine that a “public health emergency, or a significant potential for a public health emergency” exists to permit FDA to issue an EUA. Then, FDA must find that no adequate medical alternative to the product exists. Finally, FDA must determine that “it is reasonable to believe” that the product’s known benefits outweigh the risks and that the product “may be effective” for the relevant condition.

Political influence, however, can detract from proper deployment of the EUA mechanism, according to Parasidis, Berman, and Zettler. Given the low statutory standards for issuing an EUA, FDA has more discretion than in its traditional approval pathway. Moreover, public health crises inevitably exert pressure on the government to make medical countermeasures available quickly. Although fast-tracking COVID-19 devices, drugs, and vaccines helped to prevent the spread of the virus, maintaining public trust is equally essential to a successful public health response, argue Parasidis, Berman, and Zettler.

During the COVID-19 pandemic, HHS and White House officials participated in FDA decision-making to an unprecedented degree. Seven former FDA commissioners even released a joint public statement decrying the Trump Administration’s intrusion into FDA’s activities. Parasidis, Berman, and Zettler identify the harms caused by the administration “pressuring FDA to produce regulatory ‘wins’ quickly,” including intense vaccine hesitancy.

Parasidis, Berman, and Zettler examine problematic EUAs issued for three types of regulated products: COVID-19 drugs, tests, and vaccines.

With respect to drugs, Parasidis, Berman, and Zettler explain how FDA used EUAs to fill the gap in biologic products to treat or prevent COVID-19. For instance, FDA issued EUAs for two drugs—chloroquine and hydroxychloroquine—in March 2020 based on limited data of effectiveness and in spite of several known risks. Subsequent studies found that the drugs were unlikely to treat COVID-19, however, and FDA revoked the EUAs in June 2020. Parasidis, Berman, and Zettler contend that FDA should instead require drug manufacturers to complete rigorous clinical trials prior to issuing an EUA and then condition continuation of the EUA on robust post-market studies. They also suggest that Congress should consider amending the FDCA to require post-market studies.

In addition, Parasidis, Berman, and Zettler analyze FDA’s issuance of EUAs for COVID-19 diagnostic tests. By September 2020, FDA had issued more than 250 EUAs for diagnostic tests. But some tests, such as Abbott’s ID Now rapid test, showed false negative rates of 20 percent in post-market studies. Despite these poor results, FDA did not revoke its EUA. Parasidis, Berman, and Zettler contend that FDA ignored its own accuracy guidelines and applied inconsistent data standards in evaluating COVID-19 diagnostic tests generally. They argue that FDA should identify a consistent risk-based framework for evaluating device EUAs rather than relying on third-party certification of such devices.

Parasidis, Berman, and Zettler also examine FDA’s EUAs for COVID-19 vaccines. FDA’s commitment to requiring a higher standard of evidence than the statutory mandate paved the way for vaccine EUAs’ relative success compared to other EUAs issued during the pandemic. Still, the FDA’s vaccine EUA approvals also proved controversial.

Throughout vaccine development, the White House threatened to override FDA’s position on the evidence needed to issue an EUA. For instance, the same day that President Donald J. Trump called FDA “a big, old, slow turtle,” the agency accelerated its review and issued the first vaccine EUA to Pfizer. FDA’s decisions to issue the vaccine EUAs helped to save lives, consistent with the purpose of the EUA provision, but Parasidis, Berman, and Zettler warn that a large-scale immunization program with less good fortune could cause serious harm. Parasidis, Berman, and Zettler advocate that FDA and Congress adopt more rigorous standards for vaccine EUA clinical trials and approvals.

Overall, both FDA and Congress should take steps to shield FDA from political influence and safeguard the EUA pathway for future public health crises, conclude Parasidis, Berman, and Zettler.