Seen widely as harbingers of hope against the rampaging virus, vaccines are quickly taking a controversial turn. Close after a serious adverse event, that saw a Serum Institute vaccine volunteer experiencing ‘severe adverse reaction’, the issue may be headed for an acrimonious court battle.
Raising serious concerns on the safety and transparency of ‘Covishield’ clinical trials, a 40-year-old trial participant sued the Serum Institute of India (SII) alleging that the experimental vaccine caused a ‘severe adverse reaction’. The trial participant has demanded a Rs 5 crore compensation on charges that after getting the vaccine shot, he experienced a neurological breakdown and an inability to get back to normal life.
Apart from Serum Institute, the 18-page notice has also been served to trial co-sponsor ICMR, drug regulator DCGI, trial site Ramachandra Higher Education and Research, AstraZeneca and Professor Andrew Pollard, Chief Investigator of the Oxford Vaccine Trial. Serum Institute has collaborated with Oxford University & Astrazeneca and is conducting clinical trials for Covishield, which is seen as the country’s most viable vaccine option so far.
The volunteer had participated in phase 3 clinical trials and has claimed the vaccine is “not safe” and that the testing, manufacture and distribution of the vaccine should be stopped.
Serum Institute has not taken the allegations or the legal notice lightly and has, in turn, threatened to seek damages in excess of Rs 100 crore from the volunteer.
SII says the claims are malicious and misconceived and while the company “is sympathetic with the volunteer’s medical condition, there is absolutely no correlation with the vaccine trial and the medical condition of the volunteer. The volunteer is falsely laying the blame for his medical problems on the COVID vaccine trial.”
The statement however does not mention or clarify what protocols were followed to establish if the adverse reaction was related to the COVID vaccine trial or not. The statement also does not highlight if the Data Safety Monitoring Board and the Drug Controller General of India were immediately informed of the adverse event and subsequent protocols. Besides, it is not known whether regulators and DSMB gave a clearance or sought more details.
CNBC-TV18’s detailed queries sent to Serum Institute of India still remain unanswered.
Concerns on transparency
While the merits of the allegation will take time to be established, the manner in which the adverse event has been handled has certainly raised questions on transparency.
The adverse events were reported almost a month ago and were serious in nature. The volunteer’s hospital discharge summary states that he had suffered “Acute Encephalopathy” and was discharged “in an altered mental state” and was “disoriented”. He also had Vitamin B12 and Vitamin D deficiency, and had a probable “connective tissue disorder”.
However, there have been no statements from the trial sponsors or the regulators highlighting the event.
Serum Institute in its statement says “the claim is malicious because the volunteer was specifically informed by the medical team that the complications he suffered were independent of the vaccine trial he underwent.” It is still unclear if the DSMB or the DCGI has reviewed the clinical information or not and who assessed if the event was related to the trial or not.
The eerie silence from both the DCGI and the Drug Monitoring and Safety Board has added to the concerns on adherence to protocols and the overall safety of the vaccine.
One of the most respected scientists and vaccine experts Dr Gagandeep Kang told CNBC-TV18, “I think we definitely need greater transparency in terms of who has reviewed the clinical information to make the determination of the event not being related. The newspaper says Principal Investigator, but what about the institutional ethics committee, the Data Safety and Monitoring Board and DCGI. The company has little or no role in determining the relatedness of the event.”
Experts have questioned why the trials were not paused to investigate the matter. Similar adverse events reported in Oxford trials or Johnson & Johnson’s COVID-19 vaccine trial led to the trial being paused and resumed only after the investigation from DSMB established that the adverse event was not related to the experimental vaccine.
Vaccine experts have called for more transparent communication from the drug regulator on why the trial has not been halted and from the trial sponsors on the handling of SAEs, detailed protocol of the trial and if any amendments were made for knowledge of other trial participants.
All India Drug Action Network in a statement said, “We are shocked at this blatant attempt at intimidation of a clinical trial participant by Serum Institute. Instead of explaining why they have been silent about the reports of the SAE, Serum Institute is attempting to divert public scrutiny of its trial. Bear in mind that in Serum’s Phase 2/3 trial, safety is one of the primary endpoints in addition to immunogenicity.”
What caused the adverse event?
In his notice, the trial volunteer has stated that he participated in the trial after reading categorical assertion about the safety of the vaccine in the Participant Information Sheet. The sheet explained what might happen after vaccination, “which is not even remotely close to what our client experienced”.
Dr Shahid Jameel, senior virologist and Director at Ashoka University said there must be full transparency. “Whether associated with vaccine or not is for the regulator to determine. They should seek full disclosure from the company and then decide whether trial should be halted or not.”
ICMR’s Head of Epidemiology & Communicable Diseases Division, Samiran Panda, was quoted by a daily newspaper as saying that “any hurried inquiry or inference is prone to be wrong. Both the institutional ethics committee and the DCGI are investigating the causal links, if any, between the adverse events and investigational product, which is an anti-coronavirus vaccine. A preliminary assessment has not indicated any causal link as yet.”
There has been no formal statement from the ICMR or the DCGI so far.
Some virologists have raised a question – if acute neuro encephalopathy, the neurological breakdown which the trial participant suffered, was an associated risk with the flu vaccine category. Dr Kang explained, “Adeno infections rarely cause encephalopathy but even that mainly in children. This is chimpanzee adenovirus so we should have this data reviewed by experts for possible relatedness.”
However, experts add the causality may still not be clear unless more cases emerge as trials progress. Covishield is based on an adenovirus vector that infects chimpanzees. The virus is genetically altered to insert spike proteins from Sars-Cov2 to stimulate an immune response in the body.
The volunteer’s notice claims that after his discharge from the hospital, there have been no follow-ups or investigation of the severe reaction of the test vaccine on him. “Even after a month of the severe adverse reaction to the vaccine, neither have the regulators (Drugs Controller General of India/ Data and Safety Monitoring Committee), the sponsors (ICMR and Serum Institute of India) or the collaborators of the sponsors (Astra Zeneca and Oxford University) got in touch with him to find out about the severe adverse effect after vaccination and investigate the severe reaction the test vaccine has had on him.”
Serum’s statement threatening for a countersuit is not helping matters either and is seen as a step that will erode the confidence in volunteering for vaccine trials. Dr C S Pramesh, Director of Tata Memorial Centre, in a tweet said, “Why will clinical trial volunteers participate in research if sponsors intimidate them? There are better ways of responding than counter suing.”