Covishield's approval process hinges on adverse event investigation

The outcome of the in-depth investigation by the country’s drug regulator on the serious adverse event reported in a 40-year-old trial participant in Chennai will decide the future course of the approval process of the AstraZeneca-Oxford vaccine, said the country's apex health research institution. 

In October, a trial participant suffered a neurological illness (acute encephalopathy) and was hospitalised 10 days after he received the first jab of the vaccine in the Covishield trial. He sent a legal notice to the Serum Institute of India (SII), the sponsor of the trial, seeking Rs 5 crore in damages. 

SII has in response stated that the allegations made in the legal notice are ‘malicious and misconceived’, and that it will seek damages in excess of Rs 100 crore. 

At present, an in-depth investigation is being undertaken by the drug regulator, analysing the data and information submitted to it by the clinical trial site ethics committee, the principal investigator, and the sponsor.  The subject expert committee under the Central Drugs Standard Control Organisation on the Covid-19 vaccine and drug trials is reviewing the matter. 

Samiran Panda, head of epidemiology and communicable division, Indian Council of Medical Research (ICMR), the country's apex health research institute, said ICMR has no role to play in this investigation and it has to be an objective and scientific probe. Elaborating on the process followed during clinical trials, Panda said adverse events happen in any clinical trial, but the issue is whether there is a causal link between the investigational product (in this case the vaccine Covishield) and the adverse event.  

“According to good clinical practices (GCP) and even trial protocol, the sponsor or principal investigator (PI) has to report the adverse event to the institutional ethics committee within 24 hours. Thereafter, the PI and the team functioning at the site are bound by GCP to report the adverse event to the Drug Controller General of India (DCGI) within seven days," added Panda. This has been already done in this case, he added. 

Ethics committees at clinical trial sites comprise independent experts from different walks, medical experts, subject-matter experts, legal experts, and also ethicisists. The local team at the clinical trial site at Chennai's Sri Ramachandra Institute of Higher Education and Research has done an initial assessment to examine the adverse event and it has shown there was no link between the product and the event, clarified Panda. Now the DCGI is doing a detailed investigation.  The outcome of this investigation will decide the future course of approval of Covishield in India.  SII did not wish to comment on the matter, but indicated it had submitted the data to the regulator for review. 

On Saturday, SII CEO Adar Poonawalla had indicated that the firm would apply for emergency-use authorisation of the vaccine in two weeks. 

Meanwhile, experts feel trials cannot be halted for every adverse event. “The trial is halted only if the investigation warrants it. This is a decision taken by the regulator and the Data Safety and Monitoring Board,” said Dr Shahid Jameel, senior virologist and director at Ashoka University.  Sources in the know, however, claimed the participant has not yet received anything in writing from either the sponsor or the PI that his illness is not related to the vaccine trial. 

The All India Drug Action Network in a statement said, “We are shocked at this blatant attempt at intimidation of a clinical trial participant by SII.”