6 Crucial Unanswered Questions About Oxford Vaccine Results

AstraZeneca said Monday that the experimental coronavirus vaccine it developed with the University of Oxford was highly effective, based on preliminary results from multiple late-stage studies, marking the third consecutive week of positive vaccine news.

While this latest development appears to be good, the results are sketchy and there are potentially more caveats than previous announcements from Pfizer and Moderna.

Over the past two weeks, Pfizer and Moderna announced that their coronavirus vaccines were successful in large-scale studies that enrolled more than 40,000 and 30,000 participants respectively. Both companies said their vaccines were 95% effective in preventing COVID-19, and studies also show promising signs that they also prevent serious diseases.

The three pioneering vaccines are still experimental. Neither program has published late-stage results in a medical journal, and US regulators have yet to authorize any of the injections for emergency use, much less full approval.

To further complicate the AstraZeneca results, depending on which groups of participants were included in this initial analysis, the vaccine was 90%, 70%, or 62% effective in preventing COVID-19.

And while there are some details available to clarify why that’s the case, unanswered questions quickly start to pile up without further details.

Here are six burning questions that AstraZeneca’s vaccine program still faces.

1. So how effective is it really?

Let’s start with what we learned Monday about injecting AstraZeneca.

AstraZeneca is running multiple late stage trials around the world. Monday’s results come from a combination of results from trials in the UK, South Africa and Brazil, which include some 23,000 volunteers.

On average, receiving two doses of the vaccine was 70% effective in preventing COVID-19, the company said. That’s based on 131 COVID-19 cases among the trial participants, but AstraZeneca didn’t provide the exact breakdown of how many in the control group got sick compared to those who received the experimental injections.

Having that information is more important when you consider the following detail that the company included: The trials ended up testing different doses of the vaccine.

This was not on purpose, but rather due to a dosage error that the researchers generally decided to stick with. Instead of having an active group that received two injections of the full dose, a subgroup of participants received a half dose followed by the full dose.

The subgroup of 2,741 people showed an effectiveness of 90%. But suddenly, a massive test relies on fewer than 3,000 volunteers. Could the additional data change this figure, for better or for worse?

Professor Andrew Pollard is the Principal Investigator of the Oxford Global Clinical Trials, he was confident that the sample size is large enough and more data is being added. “It’s a reasonable amount of the trial population, about a third of [trial participants] in the UK, “he told a news conference Monday.

“We have accumulated much more data since [data collection] and we will continue to do so, “added Pollard.” So I think we will have more information in the coming weeks that will improve confidence in that result. “

Among the 8,895 participants who received both full doses, the vaccine appeared to be only 62% effective in preventing COVID-19.

62% can still be positive, especially when regulators were looking for a vaccine greater than 50% effective, but it is notably lower than the 95% results from Moderna and Pfizer.

2. What about the US-based test?

AstraZeneca says that the vaccine is most effective if you receive a dose of half the concentration initially followed by the full injection. But only about 2,700 people in clinical trials received that regimen.

Will AstraZeneca be able to spin the ongoing research to further test that dosing plan and generate more evidence? The company has a great opportunity to do so with an ongoing trial in the United States that seeks to recruit some 40,000 participants.

The trial has recruited about 11,000 people so far in the US and is currently only testing two full doses of the AstraZeneca vaccine, which appear to be 62% effective based on these preliminary findings.

“They may well decide to look at the low dose, the standard dose, or they may decide to look at the low dose, the low dose,” Associate Professor Katie Ewer, a senior immunologist involved in the Oxford research, told Business Insider. “I think they will take this information into account and think about what they want to study in the future.”

Could this American trial be adapted to begin testing a new dosing regimen, or is it too late to make such a drastic change in protocol?

That will be a discussion to follow between AstraZeneca and the US regulators.

3. Does the vaccine reduce severe disease?

An ideal coronavirus vaccine would not only prevent symptomatic illness, it would specifically help reduce the chances of getting seriously ill.

Pfizer and Moderna have presented preliminary data from their late-stage trials that show a promising trend for their vaccines.

Both vaccines appeared to significantly reduce the chances of getting seriously ill from COVID-19. The Pfizer study had 10 cases of severe illness, nine in the placebo group and one in the vaccinated arm. In Moderna’s trial, 11 people became seriously ill, and all 11 were in the placebo group.

At first glance, the AstraZeneca result appears to be similar good news. The press release touted that no participant who received the experimental injections had severe COVID-19.

In particular, rather than using a placebo to compare their results, some of the trials used a meningitis vaccine as a control group.

That control group also had zero cases of severe COVID-19. It remains to be seen if injection can actually outperform control in preventing the worst outcomes of the disease.

“It may be a coincidence that we do not have any cases in the 20,000 people that we have vaccinated, or it could be that we are detecting people before the general population when they become infected,” Ewer said.

4. Could the vaccine prevent transmission and asymptomatic infection?

It is not clear whether receiving the AstraZeneca vaccine reduced the chances of people becoming infected and spreading the virus, particularly as asymptomatic carriers.

This is a question mark faced by all the major vaccination programs. In general, clinical trials are most powerful when they are designed to answer a question. In this case, that was preventing the disease.

Oxford scientists said Monday that the group that received the AstraZeneca vaccine had fewer asymptomatic infections. The researchers sent weekly test kits to all UK participants during the course of the study to test a potential benefit in reducing infections.

But the company has not provided detailed data to back that up. It is not yet clear if that finding was statistically significant, or if the trials will be rigorous and large enough to produce a definitive answer to that question.

5. How safe is the vaccine?

On Monday, AstraZeneca said “no serious vaccine-related safety events have been confirmed.”

SVB Leerink’s biotech analyst Geoffrey Porges called that description “not very reassuring” in a note to investors.

“They did not reveal any information about any actual security events,” Porges added.

The AstraZeneca program has been under great concern for its safety profile.

All of their global trials were suspended after an ‘unexplained illness’ in a British trial participant. Studies were eventually resumed, and it took nearly 50 days for US regulators to agree that it was safe to do so.

It is not yet clear what exactly happened to that participant, and what AstraZeneca shared Monday did not clarify. However, that safety information should be sent to regulators and the company should be able to persuade regulators that there is no reason for alarm.

Ewer, who was involved in the research, said they had “published all the data that we have on safety thus far” and was not aware of other important safety concerns among trial participants.

“There was one that was reported a while ago that was investigated and that is now resolved,” Ewer said. “As far as I know, there is nothing else.”

Ewer added that there are several magazine articles on vaccine safety that will be published “probably this week.”

6. How long will the vaccine protect against COVID-19?

As effective as the AstraZeneca vaccine is, a critical question is how long people will enjoy that protection.

When attacking a new virus, scientists simply do not know when, or if, the protection of a vaccine will decrease enough to leave people vulnerable to the coronavirus.

This unknown holds true for all pioneers of the coronavirus vaccine, including injections from Moderna and Pfizer.

The only way to know for sure will be the long-term follow-up data that these studies continue to collect.

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