Covid-19: What you need to know today
The Indian Council of Medical Research (ICMR) now wants to reduce the time it takes to conduct Phase 1, Phase 2, and Phase 3 trials for a vaccine candidate of Hyderabad-based Bharat Biotech to 45 days.Updated: Jul 04, 2020 07:21 IST
In 1963, Merck scientist Maurice Hilleman cultured the mumps virus from the throat of his ill daughter and used the weakened strain to create a vaccine. The company’s Mumpsvax vaccine was introduced in 1967. It took a little less than four years from start to finish; of this, the human trials lasted two years. When it comes to vaccine development, this is a record that stands to the day. For some time, it looked like a vaccine for the Zika virus could beat the record, but that looks unlikely now.
Vaccine development can be broken into two phases — a pre-clinical study, and the clinical study. Once the pre-clinical study phase is done (and it is preferable that the results are published even if they aren’t peer-reviewed), the clinical study phase starts. This is the time-consuming part of vaccine development which, by its very nature, is a risky business.
The Zika example highlights this — even three-and-half years ago, when work on the first Zika vaccines started, there were fears that the disease wouldn’t be relevant by the time the vaccine was developed. Vaccine development is an expensive proposition costing billions, and no company wants to back research for a vaccine that will not have a market (or a viable one) when it is eventually ready.
Generally, the clinical study of a vaccine has three phases, which measure safety, immune response, efficacy, and try and figure out the correct dosage as well as the schedule of vaccination.
The first phase could last between one and two years, and involves administering the vaccine to a few people to see if it is safe and provokes an immune response in them (all vaccines work by doing this). There’s a growing opinion that the timeline for Phase 1 can be crashed to months, which is what many of the vaccine candidates for Covid-19 have done.
The second phase, which normally lasts anything between two and three years, is a so-called randomised double-blind placebo-controlled study. In such studies, test subjects are randomly assigned to a so-called control group to which placebos are given, and another group (called the intervention group) to which the candidate vaccine is administered. Neither the researchers nor the subjects know who is getting what (that’s why it is called double blind). Phase 2 usually involves testing the vaccine on hundreds of subjects who have the condition (in this case Covid-19) but do not suffer from any other conditions. The results are studied for safety and efficacy, but also to understand the correct dosage of the vaccine, and how and when it should be given. Typical Phase 2 studies do not measure clinical outcomes.
The third phase, which could last for anything between two and four years, involves another (but much larger) randomised double-blind placebo-controlled study. In this, the vaccine is administered to thousands (sometimes tens to thousands) of subjects who are representative of the larger population. The two most important parameters studied in this are safety and efficacy. Phase 3 trials measure clinical outcomes, and at the end of this trial, the researchers should have enough data to show that the “benefits outweigh the risks” as the US Food and Drug Administration puts it.
Most vaccine candidates for Covid-19 are crashing timelines by combining Phase 2 and Phase 3 trials. The opinion among experts is that the time involved can be reduced to around a year, although the researchers behind some of the candidates have more aggressive targets.
The Indian Council of Medical Research (ICMR) now wants to reduce the time it takes to conduct Phase 1, Phase 2, and Phase 3 trials for a vaccine candidate of Hyderabad-based Bharat Biotech to 45 days. This is a vaccine based on an inactive virus, but while pre-clinical studies have been carried out, they are yet to be published. ICMR wants the clinical study phase on this vaccine, called Covaxin, to start soon. Its urgency perhaps comes from news reports about other vaccine candidates in the pipeline launching combined Phase2/3 trials. Indeed, CanSino Biologicals and China’s PLA have decided that even as they proceed with Phase 3 trials for their candidate vaccine, it has shown enough success to be approved for military use.
But can ICMR’s deadline of 45 days be met without sacrificing any of the integrity of each phase of the trial?
We will know on August 15, but a fragment from a widely reported June 22 call vaccine maker Sanofi’s CEO Paul Hudson had with reporters is worth highlighting. He said his company couldn’t “move faster than the biology” of its processes. It will be interesting to see if Bharat Biotech can.