Assessments of Chinese-developed Covid-19 vaccines posted by the World Health Organization give a fuller picture of their safety and efficacy. But they also expose limits of the data for older and at-risk groups.
The WHO released the information about Covid-19 vaccines by Sinopharm and Sinovac Biotech as it continues to evaluate the candidates for emergency-use licensing. A decision on whether they will receive the internationally recognised stamp of approval is expected this week.
The new release of data and assessments about the vaccines come from an April 29 meeting of a strategic advisory group that issues recommendations about how to use WHO-listed vaccines. The group is not responsible for deciding whether they are licensed.
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Experts who were not in the group say the information shows the vaccines appear to pass the WHO’s bar for efficacy but leaves questions, including about safety and efficacy for high-risk groups and older adults.
“The problem is not that there is a concern that the [Sinopharm] vaccine has an extremely high rate of adverse effects [in the elderly] … the issue is the lack of data to show it does not,” said Jin Dong-yan, a professor at the University of Hong Kong’s medical school.
In its evaluation, the Strategic Advisory Group of Experts on Immunisation (SAGE) found a “high level of confidence” that the two-dose Sinopharm vaccine was efficacious in preventing Covid-19 in adults aged 18 to 59, and was “moderately confident” that the risk of severe adverse events was low. The efficacy was listed overall as 78 per cent.
However, when this information was evaluated for older adults, the confidence levels sank. The group judged a “low level” of confidence in the quality of evidence that the vaccine was effective in people over 60, and had a “very low level of confidence” about data on the risk of severe adverse events in this group.
Evidence was similarly limited for people with comorbidities and conditions that put them at risk of severe Covid-19.
The concern is not that the vaccines are necessarily unsafe or do not work in these groups, but that not enough data from people in these groups was collected in clinical trials data to give statistically robust assessments.
“On the one hand you can say that it’s not formally proven [in older adults], but on the other hand, if it’s protective in younger individuals and it’s the only thing you’ve got, it would be silly not to use it,” said John Donnelly, a principal with Vaccinology Consulting in the US, citing the disproportionately high death rates from Covid-19 in this group.
Donnelly said that even after vaccines were authorised, “large cohort studies” in the real world could confirm how well vaccines that were lacking data on older adults worked in this group.
A similar assessment for a Covid-19 vaccine by AstraZeneca, which gained WHO licensing in February, also reported “low” confidence levels for the data on efficacy and severe safety events for older adults. Since then, more data has been added, bolstering national regulators’ confidence in giving that vaccine for the elderly.
For Sinopharm, the WHO advisory group looked at three clinical trials for the vaccine, which was made by the Beijing Institute of Biological Products. Two were small-scale studies in China, and the third was a final-phase study including healthy adults in the United Arab Emirates, Bahrain, Egypt and Jordan.
Only an interim assessment was available for the large-scale study which, in addition to including just around 400 people over 60, only included around 4,200 women out of the nearly 28,000 people evaluated in total.
Understanding how well the vaccine works in the elderly and those with other diseases or risk factors is important because Covid-19 disproportionately affects these groups.
The advisory group’s assessment found Sinovac’s vaccine, CoronaVac, to have more robust data, but some similar limitations. The experts found a high level of confidence that the two-dose vaccine was efficacious, and moderately confident about the low risk of serious adverse events.
When it came to older adults, the group found there was a “moderate level of confidence” in the efficacy, while there was a “low level of confidence” in the quality of safety data for this group over 60. There were similar findings of moderate and low respectively for efficacy and safety for people with comorbidities.
Evaluations included clinical trials from Brazil, Turkey and Indonesia, with clinical trial efficacy rates in the 51-84 per cent range.
Another drawback is that there was still “no good explanation for the different efficacy in different countries”, according to Nikolai Petrovsky, a vaccinologist and professor at Australia’s Flinders University, after viewing the WHO documents.
“Was this due to different population groups under study, different virus variants, different trial design or even different vaccine batches? In such a situation, how can we know which estimate we should rely on, the higher ones or the lower ones?” he said.
Such differences mattered as clinical trials often showed higher efficacy than the real world, according to Petrovsky, and the figures could drop in certain groups or against variants of the virus.
He said low reporting rates for adverse events in vaccine roll-outs could show gaps in the quality of data collected.
The strategic advisory group also pointed to an “evidence gap” in evaluation of rare adverse events in post-authorisation safety monitoring for both vaccines.
No “unexpected signals” were detected from the roll-out of Sinovac in China, Indonesia, Chile and Brazil, according to the document.
Of some 35.8 million doses delivered in China, 49 serious adverse effects were reported, including six or fewer instances of cerebral haemorrhage, although it was not clear if any were linked to the vaccine after investigation.
Sinopharm’s real-world safety monitoring was limited to China, where reporting overall rates for any adverse events were comparatively low. Eleven cases of facial nerve symptoms were deemed unrelated to the vaccine.
The vaccines have been approved for emergency or other use in dozens of countries as China becomes a leading global vaccine exporter and experts call for more real-world studies to fill in gaps in information, even after the WHO makes its decision.
It is not clear if additional information has already been submitted to the WHO since the documents were written.
The WHO evaluation is the first time the vaccines – which have not published final-phase trial results in peer-reviewed journals – are being evaluated by a global regulatory body. To be approved by the WHO, the vaccine must be proven over 50 per cent effective, safe, and meet manufacturing quality standards.
On Monday, a WHO official said they were waiting for more documentation from Sinopharm to make the licensing decision.
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