Oxford AstraZeneca May Order Fresh Trials: What Went Wrong?
The fresh trials will examine the lower dosage combination that offered nearly 90 per cent efficacy.
After a slew of questionable practices in the way stage 3 clinical trials for a COVID-19 vaccine were carried out jointly by pharma major AstraZeneca and University of Oxford, the company CEO says they may order fresh trials.
Under question is the level of protection the vaccine offers. In preliminary data from stage 3 trials two distinct efficacies were observed, combined together the vaccine provided 70.4 per cent protection. But one dosage combination offered 62 per cent protection while the other dosage combination offered nearly 90 per cent efficacy.
The fresh trials will examine the lower dosage combination that offered nearly 90 per cent efficacy. It will be a standalone trial, and will not be combined with ongoing trials in the US and elsewhere.
Initially welcomed as good news for vaccine availability in the developing world, the company now faces a barrage of questions. What went wrong?
The company admitted to its investors that the combination that offered 90 per cent efficacy was because of an error in calculation of dosage by a contractor. This regimen, a 'low' dose followed by a 'high' dose, was offered to a smaller group of 2,800 volunteers in the UK. Nearly 8,900 volunteers received the full dose combination.
The questions being raised are whether this 'exciting' data will hold up in larger trials.
The preliminary data sharing is based on 131 symptomatic participants. But again, details of how many belonged to which group, has not been shared.
Further, the head of the US vaccine program known as Operation Warp Speed revealed that the half dosage combination was given to a population 55 years and younger. Will this efficacy hold up in older populations where vaccines traditionally don't perform too well?
Another practice under question is why AstraZeneca would pool results of two distinct trials, with distinct trial designs, one carried out in Brazil, another in the UK, and share the press release.
AstraZeneca was also questioned as to why they would share this data first with their investors and not with the public.
The company has defended public disclosures. In an interview with The New York Times, Menelas Pangalos, the AstraZeneca executive in charge of research and development, said, “I think the best way of reflecting the results is in a peer-reviewed scientific journal, not in a newspaper.”
While its not uncommon for companies to share information with their investors first, given the public health needs, more sharing is essential to maintain credibility and faith in the vaccine.
Experts have repeatedly called out data sharing via press releases, saying the data needs to be put up for scrutiny before making large splashy claims.
One critic said AstraZeneca “get a poor grade for transparency and rigor when it comes to the vaccine trial results they have reported.”
A Fluke Discovery, Hidden from Public
AstraZeneca has tried to brush off the mistake that led to researchers discovering 90 per cent efficacy, calling it 'serendipity.' But experts say this throws the whole trial under question. The trial design was not meant to study half dosage combination.
The company had not revealed this mistake in the press release, adding to the questions around '90 per cent' efficacy of the vaccine.
Implications for India?
In India, recruitments for stage 3 trials have been completed. 1600 volunteers have been selected and the trials will begin soon. India has also said that it will consider the 2 full dosage combination for its trials considering the dodgy results of the half dose regimen.
The Indian manufacturer of the vaccine, Serum Institute of India, said there is no need to panic. The Indian trials were ongoing under strict protocols.
“The AstraZeneca-Oxford vaccine is safe and effective. Even the lowest efficacy results are at 60-70%, making it a viable vaccine against the virus. That said, varied age groups with different dosage forms will result in slight variations and efficacy. We must be patient and not panic,” Pune-based Serum Institute of India said in a statement.
Meanwhile, Prime Minister Narendra Modi on Saturday visit the SII campus to review the vaccine production and its distribution.
SII is in a position to manufacture 800 million doses of the vaccine in a year. 50 per cent of this capacity is reserved for India.
The threshold for giving permission to vaccines by various health organisations is 50-60 per cent.
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