The Oxford / AstraZeneca COVID-19 vaccine has already been considered the pioneer in US regulatory approval. No longer. For safety reasons and questions about conducting one of its Phase III tests, it has been approved by the tandem and Modern sponsored Pfizer / BioNTech mRNA candidates. It is now possible for the Food and Drug Administration (FDA) to refuse an emergency use request for the vaccine, despite its prominent use in the UK and elsewhere. With millions of Americans desperate to be vaccinated this spring, the question arises: is America’s caution justified?
There is no doubt that adding the candidate Oxford / AstraZeneca to the US arsenal, if it were as effective as advertised, would hasten protection for the American public. Currently, the United States is expected to receive only 200 million combined doses from Pfizer-BioNTech and Moderna by March 31, which is sufficient to protect 100 million people. Another 200 million doses will be delivered by the end of July. So, in total, the two vaccines that have been approved for emergency use by the FDA can protect 200 million people before the end of the summer, but that is not enough to guarantee the immunity of the herd, which is likely to require vaccination of at least 250 million Americans, or 70 percent of the total population.
There is also a certain urgency in relation to the increase in supply due to the decrease in American patience with the restrictions to the pandemic. With each passing month, more and more people are finding it difficult to put aspects of their lives on hold pending the vaccination number.
There is hope that a third candidate – from Johnson & Johnson – will ease some of the supply pressure. He is being tested as a single inoculation, and the results of his Phase III test may arrive before the end of the month. If so, and if the safety and efficacy data is positive (as many vaccine experts hope), introducing it to the US market would improve the outlook, but not quickly. J&J said it could deliver only several million doses in February and perhaps a slightly larger number in March. Even with three vaccines approved, there would still be room for another competitor this spring and summer.
The Oxford / AstraZeneca vaccine has advantages that make it an attractive possibility. It can be stored at normal refrigeration temperatures and its price is low compared to competitors. Public health experts have long considered it ideal for use in low and moderate income countries because of these characteristics.
The problem is that his US Phase III study was postponed because of an adverse event investigation in the fall, and the international test data used by the UK government is difficult to interpret due to unplanned changes in levels of dosage. The sponsoring organizations explained that the clinical trial sites accidentally administered half a dose as a first injection to a portion of the trial participants, followed by a full dose over a larger than planned interval. All other study participants in the vaccine arm received two full doses of the vaccine. Unexpectedly, trial data showed that the half-dose / full-dose combination was more effective (90 percent) than giving two full doses at a one-month interval (62 percent). The combined effectiveness of the two dosing regimens was 70.4 percent – well below the documented effectiveness of mRNA vaccines.
In addition, the number of participants who received the half-dose / full-dose regimen was only about 1,400 people. The FDA is asking vaccine sponsors who request regulatory approval to conduct tests with at least 15,000 participants in the vaccine arm and want to discard vaccines with a 2.5 percent or more chance of being less than 30 percent effective. The Oxford-AstraZeneca vaccine is unlikely to perform as poorly, but the small sample receiving the most effective dosing regimen means that there is a 2.5% chance that its effectiveness will be below 67%. In addition, the half-dose / full-dose regimen excluded participants over 55, who are among those who face the greatest risk of contracting the disease.
Adding to the confusion is the UK regulator’s decision not to grant approval for a half-dose / full-dose regimen, but rather to administer two full doses per person, indicating that neither the sponsors nor the UK government Kingdom are confident in the reported phase III test results. It also allowed the second dose to occur up to 12 weeks after the initial dose, although there are limited data showing acceptable efficacy of such spacing. The vaccine’s real effectiveness is likely to become clear soon, as the UK is aggressively implanting it, including in nursing homes. The bet may be worth it, and the government may have felt it had no choice, given the seriousness of the pandemic this winter. Still, there is a risk that, as the administration of the Phase III trial has failed, UK citizens may obtain inferior protection from the vaccine due to wrong signals around the ideal dosage and spacing of the two injections.
US regulators are unlikely to fall behind what the UK has approved without further clarification on the important issues still hanging over the Oxford / AstraZeneca candidate. The United Kingdom approved a dosage regimen with reported efficacy of only 62%, well below the 95% efficacy rates of mRNA vaccines. In addition, there is a 1 in 10 chance that the effectiveness of the Oxford-AstraZeneca vaccine is below 50 percent for the full dose / full dose regimen. In comparison, there is only a 1 in 10 chance that the Pfizer-BioNTech vaccine is less than 92% effective. (We explained the statistical methods behind evaluations of vaccine effectiveness in an earlier article in The Dispatch.)
It would be difficult to introduce such a vaccine to the US market without causing confusion and concern in the public about some people being forced to accept an inferior candidate vaccine, while others receive more guaranteed protection against the virus.
This does not mean that the candidate Oxford / AstraZeneca does not start in the United States. With the proper dosage and a large trial, it is entirely possible that the trial in the United States will reveal that the vaccine is closer to the 90% effectiveness rate reported for some UK trial participants. If that is the case, then, by all means, the vaccine must be introduced quickly into the United States’ arsenal.
Unfortunately, it appears that the test results in the USA may take a few weeks. Waiting is difficult, but in this case, hasty approval is almost certain to create more concerns about the US vaccination strategy.
Vaccines do not have to be as good as mRNA vaccines to be useful in combating this pandemic. A usable vaccine with 80 percent effectiveness would be most welcome, especially if it is easier to store or requires only a single dose to provide protection. But until the FDA has definitive proof that a vaccine works as demonstrated in a rigorous test, waiting for more clarity on the best option.
James C. Capretta is a resident member and holds the Milton Friedman chair at the American Enterprise Institute. Scott Ganz is a researcher in economic policy studies at AEI and an assistant professor at the Georgia Tech School of Public Policy.