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Photo: Reuters
Photo: Reuters

What numbers say, or don’t, about a vaccine

The aim is not to attain ‘100% safe’ mark, but to evaluate risks and side-effects of the drug

Here’s something worth forgetting about any vaccine for the coronavirus—though really about any drug. I’m talking about the notion that the vaccine will necessarily have no side-effects; that it will therefore be “100% safe". It’s worth forgetting because, in this context, that is a meaningless number. For every drug known to mankind has some side-effects. They may not be serious, they may not affect you in particular, and even if they do, you may not notice them—but they’re there, and some who use the drug will suffer from those side-effects.

And since that’s the case, the challenge for every company that produces a new drug is not to attain a mythical “100% safe" mark. Instead, it is to evaluate the risks and side-effects of the drug and weigh those against the benefits. It is to then make this knowledge available to customers who buy and use the drug.

For just one example, a simple web search will tell you that taking one aspirin daily has at least these two possible side-effects: a stroke caused by a burst blood vessel, and gastrointestinal bleeding. If those sound serious to you, you will wonder: Why is aspirin in the market at all, and regularly prescribed by doctors? Simple. Because it acts to reduce blood’s tendency to clot. That’s why taking an aspirin a day can prevent a heart attack in people already at risk of one, or who have already had one.

We learned this when aspirin went through its clinical trials. The scientists conducting the trials concluded that the benefits generally outweigh the risks, and that’s why aspirin is widely available. Though to be sure, there are still some experts who don’t believe this; and in any case, you as a potential consumer of aspirin should weigh the risks and benefits yourself, before making a decision. Much the same analysis and reasoning apply to the vaccines against coronavirus that are now appearing. And that’s how we should examine the claims about the coronavirus vaccines against the coronavirus that are now being administered in India: Covaxin and Covishield.

As we now know, these two vaccines have been approved for public use in India. One, Covaxin, was approved without any public disclosure of data from its trials. In fact, the Phase-3 trial of the other vaccine—Covishield —doesn’t look like one either: As health expert Dr Gagandeep Kang said recently, it is “what would be called a Phase-2 study in other parts of the world, i.e. for safety and immunogenicity and not for efficacy."

Given all this, how should we react to the claims being made about these vaccines?

Remember that these various trials are essentially statistical and mathematical exercises. Thus, we should examine them in those terms and no other. ‘Efficacy’, for example, is a measure of the ability of the vaccine to generate what we are all in search of, an immunity to the virus. We determine that statistically, after a large Phase-3 trial, often on tens of thousands of people. If two-thirds of them develop immunity, for example, we say the vaccine has a 67% efficacy.

Only, we have no Phase-3 data for Covaxin. So, we have no way of knowing what its efficacy really is. What we have instead are claims. The Drugs Controller General of India, V.G. Somani, was quoted in the Indian Express on 6 January: “The Phase 3 efficacy trial [for Covaxin] was initiated in India on 25,800 volunteers, and till date, approximately 22,500 participants have been vaccinated across the country, and the vaccine has been found to be safe."

What do we make of this statement? To start, note that it does not address the issue of efficacy at all, even though Somani calls it an “efficacy trial". After an “efficacy trial", we should see language something like this: “15,000 of the 22,500 vaccinated participants—67%—have developed immunity to the virus." Instead, we get the claim that “the vaccine has been found to be safe."

No measure of efficacy there.

Even “found to be safe" is merely a claim. It should have been supported by data from Covaxin’s Phase-1 and Phase-2 trials, which were explicitly meant to test safety. We know this because of the mandatory submissions about those trials by Bharat Biotech—the creators of Covaxin—to the government’s Clinical Trial Registry-India (CTRI).

According to those submissions, Covaxin’s Phase-1 trial was registered on 1 July 2020. The drug was to be administered to 1,125 volunteers, and the trial had an “estimated duration" of 15 months; that is, it would run until 1 October 2021. But just over two months later, on 8 September 2020, its Phase-2 trial was registered, to run on 124 volunteers for eight months, or till 8 May 2021. The “primary outcome" for both these trials, again according to those CTRI submissions, was to check for “adverse events" and to evaluate immunogenicity; in other words, the drug’s safety and its ability to produce an immune response in volunteers.

Make what you will of these declared trial durations; that we are still months away from even one of the two trials being completed; that the second trial began while the first was still in progress. But note that these tests for safety ran on a sum total of 1,249 people. We have no public data on how these people reacted to the prospective vaccine, but Somani tells us “the vaccine has been found to be safe."

In fact, he even used a number in the same news report: the vaccine is “110% safe". What did he mean, you might wonder: that of 1,249 volunteers on whom Covaxin is being tested for safety, 1,375 showed no side-effects? The managing director of Bharat Biotech, Krishna Ella, was still more emphatic a few days earlier. ANI quoted him saying “our vaccine is 200% safe."

With all this safety apparently in the bag, Covaxin’s Phase-3 trial was registered at CTRI on 9 November. Phase-3 was intended primarily to “evaluate the efficacy" of the vaccine, while secondarily evaluating its safety and immunogenicity as well. This one was indeed for 25,800 volunteers and was to run for a duration of one year—till 9 November 2021.

Make what you will, again, of this declared duration; that the Phase-3 trial began long before the Phase-1 and Phase-2 trials are scheduled to end; that we are again months away from the scheduled completion of Phase-3. But less than two months later—months before any of its three trials are concluded, without any data about those who volunteered for the trials—Covaxin has been approved for public use. In theory, all 1.4 billion of us Indians can now have it injected into us.

Numbers, numbers. From 110% to 200%; from 124 to 1,125 to 25,800 to 1.4 billion; from 8 months to 12 months to 15 months. After all, remember again that these trials are essentially statistical and mathematical exercises. So, we should expect plenty of numbers.

Except ... especially for a vaccine that has been approved, these are hardly the numbers we should expect after these exercises. What fraction of those 124 developed adverse side-effects? What fraction of the 22,500 developed immunity to the virus? How did that compare to groups who got placebos as a necessary part of the trials? (The trials did use placebos, I presume.)

Numbers like that. Think of them, yearn for them, over the next weeks and months, as you prepare to be vaccinated.

Once a computer scientist, Dilip D’Souza now lives in Mumbai and writes for his dinners. His Twitter handle is @DeathEndsFun

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