Earlier this month, Russian President Vladimir Putin announced the ‘ approval’ of Russian COVID-19 vaccine, Sputnik V , dubbed after the Soviet spacecraft of the 1950s. Numerous scientists around the world, however, found the announcement ridiculous, as the approval came before phase III of the required clinical trial was even started.
Stages of a clinical trial
In its developing stage, a vaccine must go through three phases of rigorous experimental testing on human beings, referred to as clinical trials, to judge its safety and efficacy. With an average sample size of less than 100, phase I is the preliminary study of safety, where the objective is to find the acceptable dose level which will not cause serious side-effects. Phase II is a study of safety and efficacy together, with a few hundred people or even fewer. Doses appearing to be simultaneously effective and safe are forwarded for a phase III study, which is a detailed evaluation of effectiveness in comparison to some existing treatment or some similar-looking treatment having no effect (called placebo). Hundreds or even a few thousand people are given either the vaccine or a placebo. They are then tracked over months to determine whether the people receiving the vaccine get infected less than people who get the control. This stage even allows scientists to look for rare side-effects that can’t be spotted in smaller, earlier stage trials. After the three phases, if the vaccine is found to be safe and effective, the study report is forwarded to the regulatory agency, which, if convinced, permits its usage en masse. Phase IV is the postmarketing surveillance stage. Such surveillance can only be conducted after the drug is marketed.
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Note that the phase I/II of the much-hyped Oxford trial had 1,077 participants, whereas Russia has claimed to have tested its vaccine on just 76 people in the first two phases. Even as researchers worldwide are rushing to develop vaccines for COVID-19, following standard practice, they continue to publish their studies in peer-reviewed journals, which are constantly scrutinised by the relevant scientific community. The community, in effect, enhances the credibility of these studies. However, no such article is available in the public domain about the Russian vaccine.
Playing Russian roulette
The race to find a vaccine is more of a marathon than a sprint. Top scientists such as the U.K.’s chief scientific adviser, Sir Patrick Vallance, and his U.S. counterpart, Anthony Fauci, and even the World Health Organization (WHO) have repeatedly maintained that a vaccine is not expected before 12-18 months. In contrast, the Russian vaccine is dangerously rushed — it got approval in less than two months of starting the trial.
A Nature Medicine article in June stated that SARS-CoV-2 antibodies may last only 2-3 months after a person becomes infected. Another recent study of King’s College London found that levels of antibodies that can destroy the virus peaked about three weeks after the onset of symptoms and then started declining. Certainly, if antibody levels due to infection wane in 2-3 months, the vaccine might potentially do the same thing. And nobody knows the durability of the antibody created by the Russian vaccine — is it durable for a few years or a few weeks? This should be scientifically settled before the vaccine is used. Also, carefully conducted clinical trials might even show that a vaccine could be harmful for a section of the population. For example, a new type of measles vaccine in the early 1990s was found to be detrimental to baby girls, and so it was never licensed for the general population.
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In a 2018 research article published in the journal Biostatistics , a group of MIT scientists analysed data of 4,06,038 trials on drugs and vaccines in 2000-15. They observed that for vaccines of infectious diseases, the probability of success from phase II to phase III was 58.2%. And the approval rate of vaccines that passed phase III successfully was 85.4%. An approval, however, doesn’t always mean the vaccine works particularly well. For example, the seasonal flu vaccine was approved with no good alternatives being available.
Thus, the Russian vaccine at the moment seems to be a lethal game of chance, such as the Russian roulette. In this dangerous game, a bullet is loaded into one chamber of a revolver, the cylinder is spun, and then the trigger is pulled while pointing the gun at one’s own head. In fact, in a survey of 3,040 Russian doctors and health specialists, conducted by the Doctor’s Handbook app, 52% said they were not ready to be vaccinated; only 24.5% said they were. And just a fifth said they would recommend the vaccine to patients, colleagues or friends. What’s more, a leading respiratory doctor in Russia has quit the Health Ministry citing “gross violations” of medical ethics in the development of the COVID-19 vaccine.
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Also, a vaccine should come out with clear-cut guidelines. For instance, the guidelines should specify whether one or more booster doses would be required. An inadequately vetted vaccine is not only potentially dangerous for the people who receive it, it could also impede global efforts to develop quality COVID-19 immunisations. Another Russian experience might illustrate the importance of the trust factor in vaccination programmes. In the 1990s, the massive re-emergence of diphtheria in the Newly Independent States of the former Soviet Union was the result of the fall in rates of the diphtheria-tetanus-pertussis vaccination due to rapidly decreased trust in the public health system.
The driving force
Could Russia not imagine the possible worldwide outrage over its sudden premature announcement of vaccine? In early August, the WHO warned against “vaccine nationalism”, noting that unless countries cooperate, an actually successful vaccine could touch off a worldwide frenzy. While a premature Russian vaccine might have partially been triggered by Russian nationalism, weren’t there similar shades when Dr. Fauci expressed “serious doubts” about the effectiveness of the Russian vaccine? The Russian vaccine might even emerge as a very effective vaccine in future. Also, didn’t Russia want to capture the huge world market for COVID-19 vaccines? That’s a potential market of billions of dollars. Ethics, however, should be the driving force for developing a vaccine. People taking the Russian vaccine at this stage would effectively be part of a grand phase III clinical trial. And I’d not like to be a guinea pig of the trial in this way.
Atanu Biswas is Professor of Statistics at the Indian Statistical Institute Kolkata
