Thinking about vaccine results (AstraZeneca redux)

Two weeks ago, after Pfizer announced its preliminary results, I posed a set of questions that can guide how you understand the details in COVID-19 vaccine press releases.

I’m revisiting those questions now in the wake of AstraZeneca and the University of Oxford’s news. The 70% effectiveness rate announced last Monday is promising at first glance, but details about this vaccine’s clinical trials have puzzled epidemiologists. Here’s what to consider as we await more details on AstraZeneca and Oxford’s findings, drawing on reports from STAT NewsNature, and the New York Times.

  • What is the sample size? Or, how many people were involved in the trial, and how many of them were diagnosed with COVID-19? AstraZeneca’s Monday announcement reported results from ongoing trials in the United Kingdom and Brazil, which include about 11,400 participants. 131 patients in the trial have tested positive for COVID-19. But here’s where things get tricky: out of those 11,400 participants, about 2,700 were given a lower dose of vaccine in their first shot due to an error in the U.K. trial. The other 8,900 trial participants received a standard two shots, i.e. two full doses of the vaccine. So, that 70% effectiveness rate is actually the average of results from two groups. In patients who received two full doses, the vaccine was 62% effective, while in patients who received a half dose and full dose, the vaccine was 90% effective.
  • Wait, the vaccine worked better in a lower dose? Yes—or at least, that’s what the data tell us so far. The researchers who made that dosing error may have gotten lucky by giving patients an initial dose which better stimulated their immune systems to act against the coronavirus. Nature’s Ewen Callaway quotes immunologists who say a lower dose might more effectively turn on T cells—immune cells that support antibody production—or more quickly activate the immune system’s memory of the virus. Still, the effectiveness rates we’ve seen for this vaccine so far may have been skewed by a small trial size; AstraZeneca has not reported how many patients among the 131 diagnosed with COVID-19 received a half-dose of the vaccine as compared to two full doses. AstraZeneca and Oxford will continue to study both the half-dose and full-dose regimens, and the scientific community eagerly awaits more data (and more details on how these trials are operating).
  • Who is included in the sample size? Or, has this vaccine been tested on seniors, people of color, people with preexisting medical conditions that may garner worse COVID-19 outcomes, and other marginalized groups? In addition to their U.K. and Brazil trials, AstraZeneca and Oxford are conducting trials in the U.S., Japan, Russia, South Africa, Kenya, and Latin America with planned trials in other nations, including up to 60,000 total participants. AstraZeneca’s press release states that these global trials include “participants aged 18 years or over from diverse racial and geographic groups”; no further information on participant demographics is available.
  • Does the vaccine work for severe cases? Or, can this vaccine help reduce COVID-19’s severity by boosting immune system defenses for patients who may otherwise get seriously ill? So far, it seems possible: no patients in AstraZeneca and Oxford’s initial analysis group went to the hospital or otherwise reported severe illness. But more results are needed for a conclusion to be made.
  • Does the vaccine work for mild or asymptomatic cases? Or, can this vaccine prevent people from spreading COVID-19 even if they don’t cough, sneeze, or otherwise show symptoms? AstraZeneca and Oxford are more poised to answer this question than other potential vaccine makers because participants in the U.K. trial have routinely tested themselves for the coronavirus, regardless of if they exhibited any symptoms. Results so far show that yes, this vaccine may block COVID-19 transmission—but again, more data are needed from a wider study group.
  • Does the vaccine have any adverse effects? Or, what might happen to you when you get the shot? Pfizer has reported that a small number of patients got headaches or felt fatigued after receiving their shots; Moderna has reported similar side effects as well as fever and muscle pain. AstraZeneca and Oxford have yet to report side effects from their vaccine, but their ongoing global trials will give the researchers more opportunity to see and communicate possible small hazards of the vaccination experience.
  • What are the vaccine’s logistical needs? Like Pfizer and Moderna’s vaccine candidates, AstraZeneca and Oxford’s vaccine requires two doses given weeks apart. Unlike the other two candidates, this vaccine can be stored in a normal refrigerator for up to six months, making it much easier to distribute—particularly to remote and low-income areas. It’s also easier to mass-produce, and AstraZeneca will only be charging $3 to $4 a dose, making it cheaper for governments to buy in bulk. (The U.S. government has promised that COVID-19 vaccines will be free to all Americans.) More logistical needs for all three vaccine candidates will be finalized in the coming months.

Meanwhile, in Russia, vaccine trial results have been reported after only 39 documented COVID-19 cases:

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