A day after serious concerns were raised, ICMR has reversed its stand. It says its decision to fast-track the trial process was only to cut the red-tape and not to hurry-up the trial by bypassing the trial protocol. But it has made a snide remark about the scientific community that raised concerns about the threatening letter.

A day after serious concerns were raised over Indian Council of Medical Research’s (ICMR) decision to complete before August 15 both Phase-1 and Phase-2 trials of Bharat Biotech’s vaccine for COVID-19 and make the vaccine available for public use, the nodal agency has reversed its stand.

In a press release sent out today, the nodal agency has clarified that its decision to fast-track the trial process was only to cut the red-tape and not to hurry-up the trial by bypassing the trial protocol.

“The letter by DG-ICMR to investigators of the clinical trial sites was meant to cut unnecessary red tape, without bypassing any necessary process, and speed up recruitment of participants,” the release reads.

The release says that in light of the pandemic, “all other vaccine candidates across the globe have been similarly fast-tracked,” and ICMR’s process of fast-tracking is “exactly in accordance with the globally accepted norms”.

Not second-guessing

The release also says that “ICMR is committed to treat the safety and interest of people of India as a topmost priority”. But it makes a snide comment about the adverse comments made by the scientific community. It says: “While issues raised in public domain from time-to-time by commentators are welcome, as they form an important part of feedback loop, 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.”

“We have not second-guessed the professionalism or scientific rigour of ICMR. The scientific community has only aired concerns about rushing the trial without following the well laid out norms of a human clinical trials and vaccine research. ICMR should be well aware of the repercussions of not following the trial norms in the case of the HPV vaccine trial,” says Dr. Anant Bhan, a researcher in global health and bioethics. “It helps none by criticising or raising aspersions on the intent of those who have raised valid concerns about not following standard protocols for clinical trials.”

And Dr. Bhan has tweeted asking in what “capacity exactly is ICMR expecting to expedite the clinical trials for the vaccine? They are not the sponsor, not the trial coordinator/principal investigator (ICMR staff), not a trial site. They are not the regulator (CDSCO/DCGI is)”. And in another tweet he says: “… They are a co-creator of the vaccine. Should they be writing to sites directly?”

Through thoughtless action, ICMR has soiled its reputation. Blaming the scientific community for its own failures will not stick.

Worry not about deadlines

In a conference call today with all the 12 principal investigators, Bharat Biotech had made it explicitly clear that the investigators need to follow the trial protocol to the tee without worrying about deadlines.

This message from the company underscores that ICMR has come on board and will allow the trial to be conducted as per protocol without rushing through the trials.

August 15 deadline impossible to meet

According to details posted on the clinical trial registry, which has been updated today (July 4), only six of the 12 sites where the trial is to be carried out have already obtained ethical clearance from their respective institutional ethics committee. Enrolment of trial participants can begin only after the ethics committee approves the trial.

In the July 2 letter to all the investigators, ICMR had mentioned that recruitment of trial participants should be initiated no later than July 7.

The Phase-1 trial will enrol 370 participants, and the remaining 755 will be enrolled for Phase-2 trial. The Phase-2 trial will begin only if the vaccine has been found to be safe and immunogenic in the Phase-1 trial.

Each participant will receive two doses of the vaccine on day 0 and day 14. In the case of Phase-1 trial, the follow-up will continue for 28 days after the second dose has been administered. The safety and immunogenicity will be tested on day 14 and day 28 after the second dose has been administered.

This would mean that all participants will be followed up for 42 days from the day the first dose is administered. While interim analysis will be carried out on day 28 (14 days after the second dose is administered), complete data analysis can begin only when the Phase-1 trial ends on day 42.

Thus the completion of Phase-1 trial after participants get their first dose will take nearly seven weeks. The seven-week period does not include obtaining ethics committee clearance, enrolment of trial participants, obtaining informed consent, and analysis of data. If these are also factored in, the time taken to have the results of Phase-1 trial alone will take two-three months.

How long will Phase-2 trial take

The Phase-2 trial can begin only when the results of Phase-1 trial are available and are encouraging. Like in the case of Phase-1 trial, participants in the Phase-2 trial too will receive two doses of the vaccine on day 0 and day 14.

But unlike in the case of Phase-1, the follow of participants of the Phase-2 trial will continue for six months from the day the second dose is administered. While safety will be continuously monitored, immunogenicity will be tested on days 14, 28, 104 and 194 from the time the first dose is administered.

What data may be available by August 15

If the remaining six sites get their clearances from their respective institutional ethics committee and complete the enrolment of trial participants in less than a week, the interim analysis data of Phase-1 may probably be available before August 15. But under no circumstances can the results of both Phase-1 and Phase-2 become available before August 15 and it will be impossible to launch it for public use by mid-August.

Incidentally, ICMR seems to be oblivious of the need to undertake a Phase-3 trial that studies for amount of immune responses and the duration of protection when it said the vaccine would be made available for public use latest by August 15.