REPORTS of Pfizer-BioNTech’s “90% effective” Covid-19 vaccine claim has sent the world – anxiously awaiting a vaccine after the coronavirus has killed more than 1.2 million people – into a frenzy.

The source of the news is Pfizer’s press release on the interim efficacy analysis of its Phase 3 clinical trial.

What matters most is not which company or country is ahead in producing an effective vaccine, but the overall transparency in producing it. An efficacy claim has to be able to stand up to scientific scrutiny.

Although the more than “90% effective” claim reveals scant data, it has put Pfizer’s coronavirus vaccine candidate – named BNT162b2 – as a front-runners among the numerous vaccines currently under clinical evaluation.

CoronaVac, a vaccine by China’s Sinovac in Phase 3 trial and already fast-tracked for an unofficial rollout in China, is a close contender for the lead. Sinovac has not released any data of its clinical trial.

No data was provided to support the more than “90% effective” claim. The study protocol, a randomised, double-blind and placebo-controlled trial, started on July 27 and enrolled 43,538 participants allocated equally to the vaccine and placebo arms.

The primary endpoint was to evaluate the efficacy of the vaccine in preventing Covid-19 in participants who had no prior infection to SARS-CoV-2 before they received the vaccine.

Of the 43,538 participants, 94 contracted Covid-19, split between the vaccinated and placebo groups, but at what proportion is not known.

Presumably, about nine people in the vaccinated group contracted the disease while the rest fell into the placebo group, which, if the presumption is correct, may show efficacy statistically, but is not full proof in terms of Covid-19 prevention.

The 94 people make up only 0.21% of the total number of participants, and is too low an absolute figure to enable drawing conclusions of efficacy. Any claim of efficacy is premature at this stage.

The media release mentioned, “No serious safety concerns have been observed”. This does not mean mild or moderate adverse reactions have not been observed. Hopefully all data, including those of safety issues, will soon be made public.

With regard to evidence of infection, the interim report did not mention which diagnostic test was used, such as the RT-PCR (reverse transcriptase polymerase chain reaction) or the NAAT (nucleic acid amplification test).

Both antibody levels and T-cell responses over time give a profile to corroborate what is expected of a vaccine. These are important information left out.

Nor was the composition of the placebo mentioned. Answers to these questions could skew results.

The clinical trial protocol included an external Data Monitoring Committee (DMC) comprising five members reviewing endpoints and data.

According to the press release, the DMC conducted this first interim efficacy analysis, which it had no business doing. Its role was to monitor the conduct of the trial and preserve the integrity of data against fraud. Conducting the analysis calls into question its independence.

Ethics demand that the DMC be independent to safeguard against bias and data falsification.

In an environment where there is tremendous political pressure to produce fast results, integrity could be easily compromised. Thus, revealing the identities of the DMC members helps dispel questions of conflict of interest.

The anonymity of the DMC members compromises the independence and objectivity of the trial. Anonymity is rarely necessary, but if done for safety reasons, then the trial protocol must be specific in detailing data.

The proponent of the BNT162b2 vaccine candidate plans to submit safety data gathered over two months and after two shots of the vaccine to the US Food and Drug Administration for Emergency Use Authorisation.

While it can be assumed at this stage that there are no serious adverse events – meaning death, as otherwise the trial would have stopped – it cannot be assumed that there are no other adverse effects.

A serious concern of RNA-based vaccines is unintended immune reactions. Concerns that it may induce an interferon response, inflammation and autoimmune conditions that could aggravate existing diseases, are all valid. The manifestation of autoimmune conditions could surface only after several months or years have passed.

Vaccine stability is another concern, especially with an RNA vaccine, as in BNT162b2. It has to be transported and stored in ultra-cold temperatures of -70°C. Stability data has yet to be made available.

The purpose of this article is to make a case for transparency concerning the rolling out of Covid-19 vaccines, not to pour cold water over the prospects of any vaccine candidate. Public trust in vaccines is crucial. Secrecy and withholding of information will undermine such public trust.

From the little information available, Pfizer’s vaccine candidate sounds promising, both for the developing science in messenger RNA (mRNA) technology, and for overcoming the coronavirus pandemic. But it is still too early for celebration. – November 19, 2020.

Postscript

The Zhang et al (2020) study titled “Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomized, double-blind, placebo-controlled, phase 1/2 clinical trial” was published in The Lancet on November 17, 2020. Zhang and colleagues showed the vaccine candidate, CoronaVac, could effectively induce antibodies in almost 100% of the subjects vaccinated after 28 days. This study, published in a prestigious journal and the most transparent, has now put the CoronaVac in the forefront of the race for an effective vaccine for Covid-19.

* Captain Dr Wong Ang Peng is a researcher with an interest in economics, politics, and health issues. He has a burning desire to do anything within his means to promote national harmony. Captain Wong is also a member of the National Patriots Association.