Our penchant for somehow "topping the class" is deeply embedded in our cultural psyche. Now, we want to be the first in the world to develop and produce a Covid-19 vaccine, even though many other potential vaccines in the fray are far ahead on the developmental trajectory. One way to win this race is to just declare that we will get there first - and even announce a deadline for the exact date on which this will happen.
The Indian Council of Medical Research (ICMR) - the nodal public agency that leads the official fight against the Covid-19 pandemic - did just that in its letter of July 2, 2020. It stated that "it is envisaged to launch the vaccine for public health use latest by the 15th August 2020 after completion of all clinical trials"! The reference was to Covaxin, a vaccine being developed by Bharat Biotech, a company in Hyderabad, in collaboration with ICMR. The unprecedented fiat that such a short deadline must be met, and the tone of the letter, was met with huge backlash. The main issue is that the numbers relating to the timeline just do not add up, apart from numerous other problems.
The clinical trial of a vaccine, involving humans, begins after a pre-clinical phase. In this phase, the vaccine is tested on animals and human trials are proposed only if the results look promising.
Phase I of human trials involve only a few candidates, a few tens. The objective is to test safety and dosage levels. Because this is the very first injection of the vaccine into humans, it is often started with just a few individuals in the first few days, who are observed 24X7 for any adverse reactions and tested for their immune system response. This phase can last up to a few months.
Phase II expands the trials to a larger group of people, ranging up to several hundreds. The groups are diverse - for instance, in terms of age and gender - so that different responses can be captured. The aim here is also to assess safety, and the kind and level of antibodies that get generated. Only if the right type of antibodies develop and persist in significant concentrations, does the trial proceed to Phase III.
Phase III is to check if the vaccine is really effective in very large groups of people (efficacy), as large as tens of thousands. The objective is to assess the prevalence, or lack of, the disease in a "real life" scenario. Placebo testing also happens in this phase. This trial can take years because it is across a large group of people.
Finally, time is also taken for manufacturing large numbers of doses for public consumption.
As of today, there are around 135 vaccines in the pre-clinical stage, and around 30 in human trials.
Where does Covaxin stand in this whole scenario? It has been approved for Phase I and II trials; volunteer recruitment was to end on July 7 but even now safety screenings of volunteers - to check for existing infections, health checks - are being conducted.
Many other vaccines are already in Phases I, II and even III. Oxford COVID-19 vaccine began Phase III trials on July 1, 2020 and exciting results are expected anyday; Moderna vaccine development group published their interim results from Phase I trials this week. For Covaxin, even the data from the pre-clinical phase, which apparently lasted around 50 days, is not available in the public domain - something which is unacceptable for a scientific endeavour. The period seems to be too short by comparison with other vaccines under trial. Phase I is proposed to last for 28 days and involve 375 subjects; phase II for about 14 months involving 750 volunteers. The submissions from Bharat Biotech themselves state a total period of 15 months for these two phases. So even these two phases will not be completed till August 15, 2020.
ICMR issued a "clarification" that the letter of July 2 was only "meant to cut unnecessary red tape, without bypassing any necessary process"; The Health Ministry too "clarified" that trials would be done "without compromising on safety and security concerns". These clarifications are peculiar "official-speak" in that they do not actually clarify the main contention - of the deadline - but instead dwell on generic assurances which are not compatible with the announced date for public use. In a somewhat aggressive swipe, the ICMR statement also said, "The best of India's medical professionals and research scientists should not be second guessed for their professionalism or adherence to the highest scientific rigour." This is a clever deflection as no one attacked medical or research staff but the ICMR leadership for the declared deadline. The statement issued by the Indian Academy of Sciences, which also has medical and research professionals, said clearly that the "announced timeline was unreasonable and without precedent".
These trials are to be conducted in 12 institutions - how some of these were chosen remains a mystery. As this article indicates, many of these institutions have not received approval from their ethics committees whose job is to ascertain whether the institution is equipped to do the trials (e.g. detailed monitoring, emergency response to adverse reaction) or not; also, in some of the institutions, the ethics committees are less than a year old!
There are many deeper issues hidden in the background of this situation. First is the issue of due diligence. A vaccine trial involves the administering of something alien into the bodies of volunteers. Despite all the prior work there always remain chances of short and long-term adverse reactions. Some of these can be unexpected and some can be severe. In some cases, there are chances that the vaccine can actually worsen the disease (vaccine-enhanced disease). Therefore, Phase II trials are absolutely necessary to determine vaccine safety. Unknown efficacy - the kind that is determined from Phase III trials - can lead to a situation where many vaccinated people may just end up being bearers of a false anti-viral shield, and actually remain at high risk of getting infected. As the Indian Academy of Science statement said, "The Academy strongly believes that any hasty solution that may compromise rigorous scientific processes and standards will likely have long-term adverse impacts of unforeseen magnitude on citizens of India."
Second, episodes of this kind raise doubts about the autonomy of professional public agencies. Specific agencies are then looked upon as politically partisan, and not professional. Their credibility assessment now passes through the prism of political orientation as well. This also has international repercussions and can create impressions that we are not serious players in science. The scientific community becomes subject to scorn and derision.
Third, there is the much larger issue of damage to the credibility of scientific agencies and science in general. Episodes like this tend to engender impressions that scientific bodies "say anything", are unreliable and therefore, it is not necessary to believe or follow what they recommend. It can be expected that when the declared deadline for public release of the vaccine is missed, many people will develop a disdain for official pronouncements. This is very dangerous in a situation where recommendations of public health agencies must be followed in order for individuals to not get infected and the chain of infection to be brought under control. So, then, why wear masks or wash hands or do social distancing, just because some agency says so? It would be the last straw on the camel's back if important agencies were to lose credibility.
Lastly, in today's world, so much "learning" happens through the nonsense that pervades social media and messaging platforms (the infodemic about Covid-19 cures, for instance). Expertise - and science - is devalued every now and then, when significant sections of the population believe that there is no one truth, it is my truth versus someone else's, so what is so special about theirs? Low-quality research papers in prestigious journals - retracted after publication, and bizarre statements made by powerful Presidents about Covid-19 cures, have muddied the waters enough. There is a need to be extremely careful about what we publish and what we say.
Science cannot be done by fiat because the laws of biology, physics, chemistry - and mathematics - are not subject to human desires.
(Anurag Mehra is a Professor of Chemical Engineering and Associate Faculty at the Center for Policy Studies, at IIT Bombay.)
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