All eyes are now on India as the country has kickstarted what is being described as the world’s largest vaccination programme against the COVID-19 pandemic.
India, the world’s second-most populous country, is also officially home to the world’s second largest population of COVID-19 patients.
Prime Minister Narendra Modi said India is ready with two locally made vaccines for the protection of humanity, as he announced the mass immunisation programme.
Indian companies, which cater to more than 60% of the global requirement for vaccines, seem all set to play a pivotal role in immunising the world against the COVID-19 as well, claimed Indian foreign ministry officials, pointing to the growing queue of foreign nations waiting to procure India-made COVID-19 vaccines.
These vaccines, however, face intense scrutiny on the home turf.
As the country embarks on the massive immunisation campaign against the raging COVID-19 pandemic, experts have questioned the efficacy of the “improperly tested” desi shots, while also raising doubts about India›s preparedness to undertake the task of immunising a population of nearly 1.4 billion.
“In the near future, we will face at least two major limitations: One, availability of properly tested, emergency-approved vaccine doses on a large enough scale at an affordable price, and two, trained manpower to vaccinate the susceptible population,” says Dr Vineeta Bal MD, Former Staff Scientist, National Institute of Immunology, New Delhi.
Vaccine approvals stir a hornet’s nest
For rolling out the mass vaccination programme, India has authorised two locally-made vaccines for emergency use — Covishield and Covaxin. While the former is manufactured by Serum Institute of India through a technology transfer arrangement with innovators Oxford University and AstraZeneca, the latter is 100% native.
When the regulator announced the emergency use authorisation for the vaccines, many raised their eyebrows as they found the process too “hasty”.
Expressing shock and dismay over the restricted use authorisation granted by the Drugs Controller General of India (DCGI) to Covaxin, many pointed out that there was no data available on the vaccine’s phase 3 clinical studies.
According to DCGI, the vaccine has been approved for “restricted use in emergency situations in public interest as an abundant precaution, in clinical trial mode, especially in the context of infection by mutant strains”.
Health care activists and NGOs working in the field want to know under which provisions of the extant law has the special expert committee (SEC) set up the DCGI recommended the grant of REU approval in “clinical trial mode”.
The central government has decided to distribute 56 lakh doses of Covaxin, developed by Bharat Biotech in coordination with the Indian Council of Medical Research (ICMR), the country’s apex medical research body. 56 lakh doses means inoculation of 28 lakh persons, and such an extensive use of the vaccine “cannot be considered a “trial” by any stretch of the imagination, especially when phase-3 clinical trials for Covaxin are already underway”, said All India People’s Science Network (AIPSN), a network of over forty Peoples Science organisations in a statement.
AIPSN urged the union government to issue special protocols for Covaxin administration in “clinical trial mode,” including obtaining informed consent or refusal of recipients and ensuring compliance with all CDSCO/SEC approval conditions.
All India Drug Action Network (AIDAN), another network of several non-government organizations working to increase access and improve the rational use of essential medicines, said: “It is not clear if there is any scientific basis to claim that Covaxin will be effective in the “context of infection by mutant strains” when its efficacy has not been established and is currently unknown against any strain of the virus”.
Meanwhile, the maker of Covaxin, Bharat Biotech came out in defence of the move, saying that Indian clinical trial laws allowed “accelerated” authorisation for drugs after the second phase of trials in instances of “unmet medical needs of serious and life-threatening diseases in the country”. The Hyderabad-based firm said Covaxin, which uses inactivated SARS-CoV-2 isolated by National Institute of Virology, Pune, was safe, and the efficacy data would be submitted in February.
For Covishield, healthcare watchdogs slammed the regulator for granting the authorisation without data from a “bridge trial”. Local data from a phase 3 trial intended to demonstrate the safety and efficacy of the product in the Indian population is a mandatory requirement for approval of new medicines in the country.
At the same time, the DCGI assured the public that both the authorised vaccines are “110% safe”, while announcing the grant of approvals.
This open endorsement of the safety of the vaccines by the DCGI even before completing the mandatory trials only served to irk the experts more.
“I really don’t understand and know how he [the DCGI] arrived at that number,” quips Dr Gopal Dabade, Convenor, AIDAN, “It makes no sense at all.
“The big problem is that efficacy studies have not been done for both these vaccines in the Indian context. So, the DCGI number is just unbelievable.”
But others, including AIPSN, are more concerned about the efficacy of these vaccines rather than their safety. The early-phase trials on the candidate vaccines have found that they are safe to humans, they contend.
“Both Covaxin and Covishield have been shown to be safe in phase 1 trials. The question is of efficacy. Covishield efficacy in phase 3 trials has not been proved in the Indian population and Covaxin phase 3 trials have not been completed,” avers P Rajamanickam, General Secretary, AIPSN.
Moreover, he said, the roll-out of Covaxin is scientifically and ethically not justified prior to the public release of completed phase 3 trials data.
Over and above, immunologists and vaccinologists also find it unethical to give out an experimental vaccine for public use without adequate phase 3 data.
“While I think Covaxin is as safe as other vaccines, it is unethical to clear that for restricted use in the clinical trial mode when efficacy data are not available. There is no definition of ‘clinical trial mode’ in the 2019 New Drug and Clinical Trial Rules as far as I know. The wording of the CDSCO order leaves a lot to be defined and a lot to be desired,” comments Dr Vineeta Bal.
As the vaccinations began, reports indicated low compliance levels among healthcare workers, reflecting a vaccine scepticism among the primary beneficiaries of the nationwide programme.
A survey by National Council of Applied Economic Research found that vaccine hesitancy is 39 percent in the Delhi-NCR, with about a fifth of the respondents saying that they will not take the jab.
Another survey conducted on 17,000 people in Delhi by LocalCircles, an online platform, came out with the finding that 62% of the respondents were hesitant to take vaccines immediately due to concerns over potential side-effects.
Some resident doctors in Delhi and Bangalore also came out in the open saying they should, at least, be given an opportunity to choose between Covishield and Covaxin, despite IMA directing its 3.5 lakh members to voluntarily get COVID-19 shots after strongly endorsing the vaccines’ safety and efficacy.
IMA, in a statement, said that it has decided to actively take part in the mission of the COVID-19 vaccination programme being rolled out by the government of India after an extensive review of scientific data, indexed articles, expert panel reports and discussions with Indian Council of Medical Research (ICMR) and WHO experts.
The vaccine hesitancy signal from healthcare workers, warn experts, can go out to the general public, resulting in a further decline in acceptance levels.
“With only 50% compliance with HCW (health care workers), we cannot expect the general population to show greater acceptance,” says Dr Anil Kumar, Clinical Professor & Head, Department of Microbiology, Amrita Institute of Medical Sciences, Kochi.
As the days go by, more and more severe adverse events and even deaths may be reported, which could further reduce compliance.
Currently, the available information on the safety of the vaccine candidates is based on animal studies and phase I/II clinical trials on humans. All of these examine acute and common adverse effects, if any, of candidate vaccines. Long-term safety cannot be tested by these guidelines. Rare side effects also become apparent as the number of vaccine recipients increases, experts said.
Epidemiologists are of the view that other than fears of adverse events following vaccination, lack of information or misinformation can also be reasons for avoiding vaccine shots. SARS-CoV-2 immunisation is targeted at adults, unlike the existing vaccination for children. Therefore, proactive, timely, transparent and trustworthy communication is key.
“There are people who unquestionably accept all vaccines and then there are those who oppose every intervention,” comments Dr Chandrakant Lahariya, a medical doctor and leading public policy, vaccines and health systems expert.
The proportion of people on either of these extremes are limited but they do exist. Most of the people fall in the middle and they make the majority. This is true for all licensed vaccines and SARS-CoV-2 is not going to be an exception, elaborates Dr Lahariya who is also the lead author of the recently published book “Till We Win: India’s Fight Against The COVID-19 Pandemic”.
But low compliance is a more complex issue, opines Dr Vineeta Bal. Presently, vaccine compliance is low for different reasons. “One is problems in CoWin app, which are all over media reports saying there are glitches of all sorts and hence calling registered participants on time is difficult,” she explains.
Second, there is apprehension about vaccines in general and more so in healthcare workers because of Covaxin related publicity. It was covered extensively that Covaxin has been cleared without having efficacy data. The government authorities have not come quite clean about the rationale for their decision. Vaccine nationalism is a possible cause, but the procedure followed could possibly have bad repercussions.
Third, there is a coercion angle too. Covaxin recipients are asked to sign a consent form, the contents of which are highly confusing. If anybody refuses to sign and take Covaxin, the individuals are told, according to some media reports, that they will not be eligible for another COVID vaccine!
Ill-equipped for the challenge?
While the health ministry maintains that the entire central and state machinery is all geared up for the fierce battle against the COVID-19 pandemic via a mass immunisation strategy, critics view the task as formidable and challenging for a country of India’s size.
In line with global practice, India is also using a tiered approach to immunise its population, starting with the frontline healthcare workers and the most vulnerable sections of the community.
First to get the vaccine will be 30 million health and other frontline workers, followed by about 270 million people older than 50 or deemed to be high-risk.
The government has brought out the CoWin app to facilitate the programme, run mock trials and conducted multiple dry runs to equip the country for the task.
It aims to administer 1.3 million shots per day in a densely populated country which is perennially haunted by infrastructural issues. 900 million citizens in India still don’t have regular access to the Internet.
Nevertheless, many, like the Indian health authorities, believe that the task is doable, given the country’s past experience with immunisation programmes.
A report released in December by Fitch Solutions said India is well suited to pull off “The world’s largest vaccination programme,” as Indian Prime Minister Narendra Modi has called it, even with the weak spots in its healthcare infrastructure. The report cited India’s “good track-record” of mass vaccination drives as evidence that it can succeed.
“The country has a robust mechanism for childhood immunisation which was established for polio eradication. The same infrastructure can be utilised for COVID-19 vaccination, but on a larger scale,” points out Prof Anil Kumar of AIMS.
There will be bottlenecks as the vaccine is injected as the programme is in clinical trial mode, efficacy data is limited and new adjuvants are being used, as in Covaxin, he said.
Dr Dabade of AIDAN too points to India’s extensive experience in tackling mass vaccinations, be it polio or smallpox. “There is trained manpower at our service. I think India can do it.”
Although it is true that India is as prepared as possible given the present conditions, the experience is going to be totally different from what the Indian healthcare system is accustomed to during the vaccination of infants, pre-school and school-going children. The COVID-19 vaccination drive involves much larger numbers, warn experts.
Additional trained manpower would be needed, for which the country is not well-prepared. “India has invested poorly in the public healthcare system for many years now. The increasing privatisation of healthcare over the past 30-odd years has adversely affected the poor more than the affluent. Ten months of pandemic cannot reverse these deficits suddenly,” says Dr Vineeta Bal.
During the pandemic, the emphasis was on the diagnosis and treatment of patients, which India scrambled to put in place. Now, another challenge is in front of us, and it is unclear how much preparation was done for this over the past 8-10 months.
Despite the CoWin app, mock trials, dry runs and so on, there are bound to be many failures in the process, even if well-stored vaccine shots are available.
Failures and set-backs should not come as a surprise, she adds.
Dr Bal also reminds us that since a lot of manpower used for childhood vaccination programmes has been diverted to this effort, childhood vaccination programmes will be adversely impacted and will result in poorer vaccine coverage for BCG, polio, rotavirus, pentavalent vaccine etc.
Meanwhile, health activists are vehement in maintaining that the country is not well prepared for a task of this magnitude. India has tremendous capacity for childhood vaccination, but it is adults who are targeted for COVID vaccination. Using the child vaccination network would deprive children of their due protection from diseases. “There is no record of what additional or alternate infrastructure and personnel are going to be used,” rues Rajamanickam of AIPSN.
The government should have involved all sections of people in the discussion and won their trust before embarking on an exercise of this scale, he says.
Vague on targets
Despite the high-voltage launch of the COVID-19 mass vaccination drive across the nation, it is not yet clear how much vaccine doses India might require to effectively immunise the targeted population groups or what the timelines are to achieve these goals.
The vaccines available at present can be administered only to adults who are not pregnant, lactating, immunocompromised or allergic. Therefore, a major chunk of the population is either left out or may come up with vague excuses for not taking the vaccine. So, it is not possible ascertain the exact duration for achieving the targeted immunisation goals at this time, experts say.
According to some estimates, 60% of the adult population fall within the target as none of the vaccines are cleared yet for children and pregnant women.
If only those above 55 years of age are taken, the total comes to 20 cr, and 60% of this will be about 12 cr. If we take everyone above 25 years of age, the total will go up to 75 cr and 60% of the same will be 45 cr.
Going by the 2-dose regimen for each individual, as many as 90 cr doses will be required to cover 60% of the above 25 population.
The first and second phases of the current campaign will together cover a total of 30 cr people, which will still not be enough to cover 60% of the above-25 population.
When it comes to the availability of vaccines, Bharat Biotech (BBIL) hopes to produce 70 crore doses of Covaxin per year and Serum Institute of India (SII) is looking to manufacture 250 crore doses of Covishield per year. But SII has agreed to supply 300 crore doses to GAVI, some of which will come back to India. So BBIL and SII can, in principle, supply enough stock to cover 60% of the over-25 population over a year. But BBIL’s Covaxin should be proved to be effective in phase 3 trials, points out AIPSN.
In the meantime, epidemiologists face the challenge of determining the level of vaccination required to induce herd immunity due to the novelty of the pathogen. Providing any “single, magic figure” as the percentage to achieve herd immunity will be counterproductive in a country like India, most feel. Different parts of the country have seen their highs and lows at different times.
“We do not have reliable data for various taluks, districts etc. around case numbers over a period of time. A general rule is — the higher the number of cases in a particular area, the higher is the proportion of immune members. Hence, even a lower vaccine coverage targeting non-immune individuals will provide immunity in the current emergency-like situation. Areas with low case incidence are likely to need more widespread vaccination. Local levels of immune populations need to be taken into account, instead of proposing national or state level figures,” suggests Dr Vineeta Bal.
One option, according to her, is to not worry about whether anybody has been infected prior to vaccination but give vaccine shots to every person. This limits the availability of vaccine doses in a period of scarcity.
A significant part of the population, however, would be immune due to symptomatic or asymptomatic infection, thereby reducing the transmission of infection, concludes Prof Anil Kumar. A seroprevalence study in the general population, he opines, should be done to assess immunity against COVID-19. This will help the administration deploy the vaccine among more vulnerable populations.