The Drugs Controller General of India (DCGI) has approved two Indian candidate vaccines COVAXIN developed by Pune's National Institute of Virology (NIV) along with Hyderabad-based Bharat Biotech and ZyCoV-D of Ahmedabad-based Zydus Cadila for human clinical trials, after their successful animal studies.
The Indian Council of Medical Research (ICMR) Director General Dr. Balram Bhargava, who is a cardiologist, has issued a Demi-Official (DO) letter dated July 2, 2020 laying out that India's first indigenous vaccine against COVID-19 will be available for "public health use" by 15 August 2020. As a professional, and heading the Medical Research body Dr. Bhargava would know that this is not how vaccine development works.
A multi stage process
The stages in a vaccine development are: pre-clinical trials including animal studies, clinical trials in three phases, regulatory approvals and manufacturing on mass scale. Each of these stages take their own time and ideally a successful vaccine to be used for masses takes 10 to 13 years. With fast tracking during times of a pandemic, the period can be reduced to a year, particularly the last two stages (regulatory approvals and manufacturing) can be super-hastened to shorten the total time-frame. The government regulatory agencies can issue the license in a day and commercial entities can work 24×7 and deliver the promised numbers.
India has done that in Rota-virus vaccine ROTAVAC; which was approved and went into mass production in 2014. But the development of the vaccine took several years. Today, India meets 60% of the global vaccines demand, including the Rota-virus vaccine.
Needless to say, the clinical phases require a stipulated time frame; which cannot be shortened as it deals with 'human beings' and not 'subjects' as stated by the ICMR DG. Each phase requires clearance by institutional ethics committees, elaborate recorded video consent, human rights and liability issues. Any undue haste in these phases will be viewed with suspicion and will be open for wider criticism – nationally and globally. India, certainly cannot afford this.
Many questions therefore remain unanswered regarding how we will deliver a safe and effective vaccine against COVID-19 by 15 August 2020. After successful pre-clinical trials, human clinical trials provide gold standard scientific evidence on safety, efficacy and effectiveness of any vaccine or other medical products under study. There is a scientifically validated and accepted protocol for conducting clinical trials. To ensure that the product under study is safe for humans, the phase 1 study is done among 30-50 healthy volunteers. To ensure that the vaccine is effective against a disease for the general populations, the phase 2 study is conducted among about 500 healthy volunteers.
Leveraging on the success of phase 1 and phase 2, a phase 3 study is planned to cover almost 5,000 people for both safety and efficacy. Phase 2 and phase 3 are multi-centre trials, involving several institutions in different geographic regions. To see that it does no harm to the health of volunteers, it is of utmost importance to adhere to all scientific and ethical considerations in the protocol and guidelines of the clinical trials. The ICMR cannot be an exception and in-fact has to be extra strict being a regulatory body itself. The guidelines are drawn by the ICMR and imposed on the entire machinery that becomes part of clinical trials.
Let us look at the time frame for the candidate COVAXIN here. This vaccine's study design was registered only on 1st July 2020 in the Clinical Trials Registry of India (CTRI, managed by ICMR and National Institute of Medical Sciences, Government of India). The study design shows the duration of study (for phases 1 and 2) to be 15 months. If all goes well with the clinical trials, it will not be before September 2021 that we will learn if the vaccine is safe and effective, and ready to enter the phase-3 trial.
At this stage, based on the emergent situation and given that the lives of millions are at stake, the Government may decide on a conditional roll-out, just like the anti-tuberculosis (TB) drug 'Bedaquiline' where the license was issued while the phase-3 study is still in progress. But the ICMR letter says "it is envisaged to launch the vaccine for public health use latest by 15 August 2020". We wonder how this will be possible.
Human clinical trials have had a very bad history of misuse and human rights violations in the past century. That is why scientific protocols, guidelines and processes are now well-established worldwide to ensure study participants take part with full informed consent, protection and respect for their rights. As per the CTRI online status of this study design on 4 July 2020, only six out of 12 clinical trial sites have their ethics committee approval in place. The rest of the six ethics committees are shown as "submitted/ under review". Some of these seem to be small nursing homes/hospitals raising questions about their genuineness.
Further, the ICMR letter reads like a threat: "…you are strictly advised to fast track all approvals related to initiation of the clinical trial and ensure that the subject enrolment is initiated no later than 07 July", a date which has already passed! It adds for good measure: "non-compliance will be viewed seriously". This is like a diktat. And who will take action? Under what powers? We have never seen such a tone in any scientific or official communication from the ICMR in the past.
COVAXIN has currently only finished animal studies and human clinical trials have not even begun. Declaring a date for its "public health use" is assuming the outcome of the clinical trial like 'match-fixing' in cricket – from winning the toss to an assured world-cup victory! This is seen as unethical for a scientific study. Such declarations raise undue expectations, and may back-stage behavioural prevention and let people at risk of COVID-19 become complacent. We all want a vaccine and that too at the earliest but it is equally important to ensure science is respected and all protocols and safeguards are in place so that neither the study participant nor the general population is harmed in any way. While ensuring there is no avoidable delay in scientific research, the ICMR should also be the vanguard for protecting the integrity of science and scientific rigour.
Looking at its history, the ICMR is not new to such controversies. During the late 1980s, the then ICMR DG Dr A S Paintal had fallen from grace due to his controversial views on some health problems. He had advocated a law banning Indians from having sex with foreigners in order to curtail the spread of AIDS. Rajiv Gandhi was then the Prime Minister and married to a foreigner and this writer had asked if such a law would not apply to him? The proposal was silently dropped. That was bad but now we appear to have seen a new fall in terms of following ethical standards and well-regarded scientific conventions.
(Dr. Ishwar Gilada is a Consultant in HIV and Infectious diseases, President AIDS Society of India and Governing Council Member, International AIDS Society)
(Syndicate: The Billion Press) (email: email@example.com)