Last Monday’s editorial (“FDA must get it right, and fast with vaccines,” Nov. 30) injects a note of caution into the news that two companies are applying to Food and Drug Administration for Emergency Use Authorizations (EUAs) so they can make their vaccines available to the public. As the editorial states, an EUA bypasses “some of the requirements with which drug companies must comply in normal times.” From the past use of EUAs in the COVID-19 pandemic and from inadequate post-market surveillance in FDA’s proposed EUAs for COVID-19 vaccines, a note of caution is indeed needed.

Almost 200 EUAs issued by FDA tests detecting the SARS-CoV-2 virus have enabled clinical laboratories and manufacturers to market tests in abundance. The EUAs have not been sufficiently stringent, however, to assure their validity and appropriate use: Tests from different laboratories and manufacturers vary in the frequency of false negative and false positive results. Despite their abundance, tests are still not available to all those at risk. Delays in reporting results reduce the effectiveness of contact tracing, which could contain the pandemic. As a result, the United States still has the highest rate of COVID-19 infections among the world’s nations.

The FDA has taken a more cautious approach before issuing EUAs for vaccine development and distribution. The federal government first initiated Operation Warp Speed, specifying requirements in order for pharmaceutical companies, usually in collaboration with public or private research laboratories, to conduct randomized controlled trials of their respective vaccines. In return, the companies were offered subsidies of over $1 billion for development and a similar amount for distribution. (One company, Pfizer, refused the subsidy for development but accepted one for distribution.)

Under Operation Warp Speed, two companies, Pfizer and Moderna, have established that their respective vaccines prevent 95% of COVID-19 infections. Still, there are questions about effectiveness: Are the vaccines equally effective in subgroups of the population? Do they prevent or reduce the frequency of serious disease and death? How long does immunity last? Are the vaccines as effective under field conditions as they are under the controlled trials? We already know they differ in the degree of freezing and refrigeration needed to preserve their stability.

The Enterprise editorial urges “FDA officials and scientists not to bow to pressure over the vaccines by sidestepping safety considerations.” The occurrence of serious side effects, like the neurological disorder Guillain-Barre syndrome in about 1 person in 1.5 million vaccinated for the H1N1 influenza virus in 2009, could take hundreds of thousands of COVID-19 vaccinations before it would even be suspected and surveillance of millions of vaccinated people before it could be associated with the vaccine. Although the enrollment of almost 50,000 people in each of the trials under Operation Warp Speed was sufficient to establish efficacy of the vaccines, it is insufficient to detect such serious, rare complications, which could affect over 200 people population-wide. The editorial points out, “A few cases of serious side effects once the vaccines are distributed could wreck public confidence in the process.”

Before issuing EUAs to Pfizer and Moderna, FDA will convene its vaccine advisory committee, all of whose 15 voting members are experts without commercial affiliations, to assess the safety and effectiveness data of each vaccine in the next two weeks. The committee is unlikely to decide that the unanswered questions regarding vaccine effectiveness are of sufficient concern to delay approval. They will not, however, have sufficient data to assess the likelihood of rare, serious complications. If such complications exist, they are unlikely to be detected promptly under current FDA guidance, which calls for companies applying for an EUA to “include a plan for active follow-up for safety … in order to inform ongoing benefit-risk determinations to support continuation of the EUA.” 

The plan for post-market surveillance should not be left up to individual companies manufacturing vaccines under their respective EUAs, but should be devised and enforced by the FDA and encompass all SARS-CoV-2 vaccines that are issued EUAs. Only then can the public be assured that side effects, especially rare ones, will be promptly detected. That will give little comfort to those who have already received the vaccine except for knowing that the government is doing everything possible to protect the public.

 —

Dr. Neil A. “Tony” Holtzman, M.D., M.P.H., is emeritus professor of pediatrics at the Johns Hopkins University School of Medicine in Baltimore, Maryland. When he was on the active faculty, he had joint appointments at the Johns Hopkins Bloomberg School of Public Health in epidemiology and health policy. He lives in Menlo Park, California, has a second home in the Upper Saranac Lake area and is the author of the Adirondack Trilogy of novels: “Axton Landing,” “The Railroad” and “Forever Wild.”