Tag: clinical trials

The biopolitics of Covaxin

In a new investigation, STAT has reported fresh problems with Covaxin’s approval process in India, including the phase 2 trial dropping its placebo arm in favour of one preordained to make Covaxin look good and Bharat Biotech – the maker – commencing phase 3 trials based on results from animal studies. I’m also filing the report under “yet another instance of a pro-government Indian entity responding to the foreign press but not the local press” (following this). Krishna Mohan, one of the company’s directors, responded to STAT by admitting to a wrongdoing, massaging other similar actions, and pointing a finger at the Indian government.

Is this spine? In response to similar evidence-based allegations of wrongdoing, Bharat Biotech met The Wire Science and The Wire with a defamation suit, a demand of Rs 100 crore and that the two sites not publish articles with “defamatory content” vis-à-vis the company, and obtained an ex parte injunction against 14 articles. This was in addition to the seemingly blanket refusal to respond to our questions for reports we were filing. Other senior Bharat Biotech officials also refused to communicate to anyone else asking probing questions about Covaxin’s clinical trials. No: his quote sounds more like Mohan trying to save Bharat Biotech’s face in front of a western audience (the one our government wants us to believe is inferior) while spinning India’s Bharat’s own take on the vaccine approval process.

Mohan told STAT that they didn’t take any shortcuts – at least not those that weren’t first “vetted” by the Central Drug Standards Control Organisation (CDSCO), a.k.a. the drug regulator. That is to say, the shortcuts were CDSCO-approved, so they weren’t shortcuts. I’m inclined to agree: the rules are after all not based on principles of natural justice but on what the government deems acceptable. /s

Of all the allegations, the one that irks me most is the modification to the phase 2 trial. It compromises our ability to learn anything useful about Covaxin, replacing that knowledge with knowledge of how much better one formulation of Covaxin is from another. The drug regulator should have known this is what the trial would have ended up checking, and if it approved this design anyway, it has engaged in wilful neglect – neglect of science, neglect of integrity, neglect of its mandate to look out for the people. But if we’re to believe Mohan, it’s just “product development” for an unprecedented time, not public health:

“In a classic sense of product development, we would do everything the right way — play by the book and all the rules of the game would be followed. But here was a situation the world didn’t foresee. … Please don’t think there was any issue with the veracity of the data. Yes, it was an unusual approach, but it was dictated by the nature of the pandemic.”

Ah, a classic tactic: Why did you burn down the forest? “It’s the climate crisis, which is unprecedented, and we needed land to erect smog towers.”

Later in the article, in the face of a similar allegation – changing the phase 2 trial protocol – Mohan defends the regulator and blames discrepancies in trial numbers on a company struggling to coordinate multiple teams working separately from each other while being guided by the rule of “let’s get the data out”. I’d buy what he was saying if he was talking about his company HQ installing new air-conditioners and conducting tests of indoor air quality. But he’s talking about a clinical trial for a vaccine, placing misleading data in the public domain and – crucially – implicating a national drug regulator that he claims was in the know but didn’t act.

To STAT, he’s saying they were distracted by the “safety of individuals”, the “ethics of handling subjects” and “manufacturing”, but to Indian journalists, he as well as the regulator have been mum on questions raised by the WHO and ANVISA on manufacturing practices and by almost everyone else about the People’s Hospital death and data.

A (somehow) bigger problem arises soon after when Mohan says:

“Whatever we did was with the clear intention of doing it right. There was no question of reducing sample sizes. … There were not off the cuff or random thoughts. … It was extensively debated with keeping the final objective in mind of getting a vaccine in time and not cutting any corners.”

Getting a vaccine in time and not cutting any corners? It’s baffling that the last sentence is intended as clarification rather than as a potentially tacit admission of wrongdoing. I’m sure you remember when ICMR chief Balram Bhargava called on hospitals around India to complete Covaxin’s phase 3 trials in less than two months, in time for Prime Minister Narendra Modi to avail the vaccine for public use on Independence Day 2020. One independent scientist asked me what I thought Bhargava might have been smoking at the time; it was hard to say.

But what’s tempting to speculate now is that the government realised, based on the backlash to Bhargava’s announcement, that a) a phase 3 trial in six weeks was a bigger problem than it believed, b) it wouldn’t work to have its vaccine development plan in public, c) it could accelerate Covaxin’s clinical trials by forcing Bharat Biotech to do so, and d) approve Covaxin without phase 3 trials by assimilating the drug regulator – all to achieve a similar outcome. Or at least I speculate in the absence of evidence. And until there is, we remain needles in veins.

Pandemic: A world-building exercise

First, there was light news of a vaccine against COVID-19 nearing the end of its phase 3 clinical trials with very promising results, accompanied with breezy speculations (often tied to the stock prices of a certain drug-maker) about how it’s going to end the pandemic in six months.

An Indian disease-transmission modeller – of the sort who often purport to be value-free ‘quants’ interested in solving mathematical puzzles that don’t impinge on the real world – reads about the vaccine and begins to tweak his models accordingly. Soon, he has a projection that shines bright in the dense gloom of bad news.

One day, as the world is surely hurtling towards a functional vaccine, it becomes known that some of the world’s richest countries – representing an eighth of the planet’s human population – have secreted more than half of the world’s supply of the vaccine.

Then, a poll finds that over half of all Americans wouldn’t trust a COVID-19 vaccine when it becomes available. The poll hasn’t been conducted in other countries.

A glut of companies around the world have invested heavily in various COVID-19 vaccine candidates, even as the latter are yet to complete phase 3 clinical trials. Should a candidate not clear its trial, a corresponding company could lose its investment without insurance or some form of underwriting by the corresponding government.

Taken together, these scenarios portend a significant delay between a vaccine successfully completing its clinical trials and becoming available to the population, and another delay between general availability and adoption.

The press glosses over these offsets, developing among its readers a distorted impression of the pandemic’s progression – an awkward blend of two images, really: one in which the richer countries are rapidly approaching herd immunity while, in the other, there is a shortage of vaccines.

Sooner or later, a right-wing commentator notices there is a commensurately increasing risk of these poorer countries ‘re-exporting’ the virus around the world. Politicians hear him and further stigmatise these countries, and build support for xenophobic and/or supremacist policies.

Meanwhile, the modeller notices the delays as well. When he revises his model, he finds that as governments relax lockdowns and reopen airports for international travel, differences in screening procedures in different countries could allow the case load to rise and fall around the world in waves – in effect ensuring the pandemic will take longer to end.

His new paper isn’t taken very seriously. It’s near the end of the pandemic, everyone has been told, and he’s being a buzzkill. (It’s also a preprint, and that, a senior scientist in government nearing his retirement remarks, “is all you need to know”.) Distrust of his results morphs slowly into a distrust towards scientists’ predictions, and becomes ground to dismiss most discomfiting findings.

The vaccine is finally available in middle- and low-income countries. But in India, this bigger picture plays out at smaller scales, like a fractal. Neither the modeller nor the head of state included the social realities of Indian society in their plans – but no one noticed because both had conducted science by press release.

As they scratch their heads, they also swat away at people at the outer limits of the country’s caste and class groups clutching at them in desperation. A migrant worker walks past unnoticed. One of them wonders if he needs to privatise healthcare more. The other is examining his paper for arithmetic mistakes.