With the Covid-19 pandemic now resurgent across the globe, it’s a comfort to know that there are several promising vaccine candidates in speedy development. Their success is crucial in fighting the virus and charting a path back to normal. It’s important, though, that we are able to see rigorous, clean and transparent trial data, to help gain trust in any vaccine and know that proper protocols are in place. Unfortunately, one of the leading vaccine candidates – from AstraZeneca Plc, working with the University of Oxford — is having a problem in this area.
Astra and Oxford released interim data last week from their Covid-19 vaccine trials in the U.K. and Brazil, becoming the third developers after Moderna Inc. and the Pfizer Inc.-BioNTech SE partnership to provide such early results. Moderna and Pfizer-BioNTech had set a high bar, reporting clear and easy-to-assess, though limited, data for their vaccine candidates that showed about 95% efficacy at protecting against Covid-19. While the Astra-Oxford partnership trials faced a risk of coming up short, they did not need to show the same degree of efficacy to still be considered a success. The expectation, though, was that the data would at least be presented in a transparent, straightforward manner with a clear understanding of the trial process. Instead, it was messy and confusing.
The partnership was expected to disclose data for a regimen of either two full vaccine doses, or a full one followed by a lower dose, given 28 days apart as per its predefined trial protocol. Instead, it released two sets of data: one based on two full vaccine doses and another based on a half dose followed by a full dose, the opposite of what the trial had called for. Two full doses showed 62% efficacy in reducing Covid-19 symptoms, while a half-dose/full-dose regimen resulted in 90% efficacy. The researchers then stated a 70% efficacy level for the combined group. Why the two data sets? It turns out, the lower first dosage was given by accident — a fact that wasn’t initially disclosed — and the group that received it was much smaller than the one showing the lower efficacy, and younger too.
Taken together, the results and how they were presented created enough confusion to raise doubts about just how well this vaccine works. I, for one, was an early critic and still have questions. Astra-Oxford has responded to the growing controversy by saying it may launch a second global trial to test the half-dose/full-dose regimen. The good news is that even without a new trial, it can regain confidence in its research and vaccine – which, despite the confusion, still seems to show great promise. Here are two key things it needs to do:
Present results of the U.K. and Brazil trials separately: The interim analysis was done after 131 cases of Covid-19 in 11,636 subjects across both the U.K. and Brazil trials. When the trials are fully recruited, the U.K. study should have more than 12,000 subjects, while the Brazil trial should be at just more than 10,000, each sufficient for independent analysis. Within the next few weeks, there will unfortunately be more cases of Covid-19 in these trials given the pandemic’s resurgence. From a research standpoint, this would increase the statistical rigor of both trials. Positive results from each separate trial would go a long way toward building confidence in the vaccine’s efficacy.
Release more granular trial data: The dataset of each of the two trials should be big enough to provide detailed analysis on subjects, grouped by age and pre-existing health issues, to decipher if one group did better or worse than another. It is possible that the vaccine will have better efficacy in younger people, as is often seen with other vaccines. To win approval for use by this subset, the Astra-Oxford vaccine would need to show at least 50% efficacy in the group – though it’s likely to be higher, given the 62% already seen in the trial in a broader population. Add in the fact that there were no hospitalizations or severe Covid-19 cases in the vaccinated group so far, and there’s a strong case for the shot to win approval for use by the 30 million or so people younger than 55 in the U.K., and the almost 40% of the European Union’s 381 million. That, in turn, would help provide protection for those regions as a whole.
While Astra may not need to do additional tests to win some form of U.K. or EU approval, the fact that the company is considering another global trial or further tests to investigate the low dose/high-dose regimen suggests that it still believes that there is a sound scientific rationale for why the efficacy was different in the small group of subjects who got the wrong dose schedule in its U.K. trial. A thorough examination is needed to prove this, and could lead to even more good vaccine news.
Astra’s stumble should not be misunderstood as meaning that its vaccine doesn’t work. But it shows the importance of trial protocols and thorough disclosure. We need vaccines we can believe in. Thankfully, a good result is still possible.-Bloomberg
Also read: BMC to give ‘free’ masks, impose Rs 200 fine on rule violators in Mumbai