A typical vaccine development process involves 4 stages of human trials.
Experts have proposed a plan to accelerate the rollout of a potential COVID-19 vaccine in India by combining multiple phases of the vaccine development process. The proposal has been published as a commentary in the latest issue of the Indian Journal of Medical Research, the peer-reviewed in-house journal of the Indian Council of Medical Research.
A typical vaccine development process involves 4 stages of human trials: Phase 1, Phase 2, Phase 3 and Post Market Surveillance, a process that can take several years. The first two phases involve testing a vaccine in tens and hundreds of healthy volunteers to check for safety and efficacy as well as the number of doses required and side effects. The results must be evaluated by the drug regulator and only if promising, is the vaccine allowed to progress to larger phase 3 trials, that usually involve tests in thousands of volunteers at multiple hospitals across the country.
In such trials, a group of volunteers get the vaccine and another a placebo and neither researcher nor doctor, in the ideal trial, know who got what. Vaccines that prove their mettle are licensed and allowed to be manufactured and distributed and once widely available, are surveilled by marketing companies for evidence of adverse events or whether it protected against the infection.
The pandemic nature of the COVID-19 has meant that several vaccines are in early stages of tests and trials with about nine in Phase 3 trials.
The Serum Institute which is testing the UK-based AstraZeneca vaccine candidate had begun Phase 3 studies in India but has now paused them due to a reported adverse event in the United Kingdom. Two indigenous vaccines by Bharat Biotech and Zydus Cadilla are in Phase 2 trials.
Regulators, given the nature of emergency the world over, are authorising drugs for emergency use. These are drugs or repurposed medicines that haven’t been indubitably proved as effective for treating COVID-19.
The authors, in their article propose a similar scheme for the vaccines. While potential vaccines must still be tested for safety at each stage, the crucial Phase 3 and Phase 4 stages could be combined, they propose.
“This phase will telescope the conventional Phases 3 and 4, with clustered randomisation of control populations built into the rollout design, instead of having a separate control arm. From those receiving the emergency use authorized vaccine, defined end point measures of neutralizing antibody titres will be monitored among selected individuals, as also among those in the cluster control groups to continuously provide efficacy data,” say the authors Amit Dinda, of the All India Institute of Medical Sciences (AIIMS), Delhi; Santanu Tripathi, of the Calcutta School of Tropical Medicine, West Bengal and Bobby John, of Aequitas Consulting Pvt Ltd.
Currently India doesn’t have a provision for emergency use authorisation for vaccines though this is reportedly being discussed. Globally there have been concerns, especially in the context of Russia getting an approval for its vaccine even before it was tested in Phase 3 trials and U.S. President Donald Trump reportedly pushing regulators to approve a vaccine before the election.
“This rollout design, with short efficacy data feedback loop, along with safety reporting to the regulator and adverse event following immunisation monitoring by statutory bodies set up at appropriate jurisdictional levels in India, will generate real-world evidence for the vaccine, its safety and efficacy,” the proposal says.