Severe lapses in Covaxin trials in Bhopal; consent forms not given, participants who fell ill not treated

Jitendra Narwariya was administered Bharat Biotech’s vaccine candidate Covaxin on December 10 at the privately-run People’s College of Medical Sciences and Research Centre (PCMSRC) in Bhopal as a part of the company’s Phase 3 trials.

Four days later, he had fever, lack of appetite, discolouration of urine, cough and general weakness. He went back to the hospital, where he was directed to the vaccine centre on the hospital premises. As he was asked to pay for his treatment, he returned home.

On Tuesday, Narwariya was finally admitted at the hospital. On Wednesday, he was diagnosed with pus in his liver.

Like several others, Narwariya too had heard about Covaxin through announcements from a vehicle that went around in Shankar Nagar area of Bhopal. “The announcements informed us that all those who reach the hospital would get an injection, which would protect us from Coronavirus. The hospital authorities took care of our transportation. Additionally, we were paid Rs 750 for it,” said Narwariya from his hospital bed.

He thought there was no harm in going and the money was too good to be turned down. The 36-year-old is the primary care giver of his two young children.

Since December 14, Narwariya has been unable to go to work due to severe ill-health. But he couldn’t afford the treatment either. “We heard about him three days ago and then we raised the issue on social media. The People’s Hospital admitted Narwariya for treatment only after that,” said Rachna Dingra, a rights activist who works with the survivors of the Union Carbide disaster in Bhopal.

Being a participant in the the Covaxin double-blind trial, it is not immediately known if Narwariya had been administered a vaccine shot or a placebo. Only once the trial is unmasked later for analysis will it be known who received the vaccine and who was administered the placebo.

Bharat Biotech’s Phase 3 trial aims to enroll 25,800 people, according to the Clinical Trial Registry of India.

On January 3, the Drug Controller General of India (DGCI) gave restricted emergency permission for manufacture of Covaxin, which is still recruiting volunteers for Phase 3 trials across the country.

At least 600 others from marginalised communities and poor neighbourhoods in Bhopal such as Gareeb Nagar, Shankar Nagar, Oriya Basti and JP Nagar, which are in the vicinity of the Union Carbide factory, had enrolled for vaccination. Many of them are survivors of the 1984 Union Carbide gas leakage.

“Several of us registered for the injection. They assured that the injection would help us. I did not understand that they were testing the vaccine on us. They did a few more tests on us there. They gave us a few papers to fill, but I did not know how to fill it,” Narwariya said.

All the participants had to undergo a nasal and throat swab test. The results of these tests were not given to any of the poorer participants. They were made to sign several papers but were not allowed to take it back with them.

“There are many others who have had adverse reactions to the injection. People’s Hospital had recruited many poor people as a part of their vaccine trials and none of them knew they were being administered under-trial vaccine candidates. They were not informed about the effects of the injection and neither were they given the informed consent form which must be given to all those who participate in vaccine trials,” pointed out Dhingra.

According to the participant informed consent sheet, in the event of an injury or death that is related to the clinical trial, Bharat Biotech International Limited, Hyderabad, would provide financial compensation as per applicable guidelines of the national regulatory authority.

The New Drugs and Clinical Trials Rules, 2018, which were notified in March 2019, state that in all trials, a freely given, informed, written consent is required to be obtained from each study subject. The investigator must provide information about the study verbally as well as using a patient information sheet, in a language that is non-technical and understandable by the study subject.

The rules point out that if the trial subject, or his or her legally acceptable representative is unable to read or write, an impartial witness should be present during the entire informed consent process who must then sign the consent form.

The hospital is required to obtain the subject's consent in writing using an “Informed Consent Form”. Both the patient information sheet as well as the informed consent form should have been approved by the ethics committee and furnished to the Central Licensing Authority. Any changes in the informed consent documents should be approved by the ethics committee and submitted to the Central Licensing Authority before such changes are implemented.

The hospital is required to maintain an audio-video recording of the informed consent process in case of vulnerable subjects in clinical trials of a new chemical entity including procedure of providing information to the subject and the person’s understanding of such consent.

As Covid-19 falls under clinical trials of a new chemical entity, there should have been an audio-video recording of the informed consent process. None of the participants National Herald spoke to mentioned about them being recorded or the presence of an impartial witness in case of them being illiterate.

The PCMSRC Dean Dr Anil Kumar Dixit maintained that all the participants were counselled and informed about the trial. “This is not correct. Every individual was counselled for more than half-an-hour. After that they were examined and if they were not found fit, they were not administered the injection. Before they were injected, their RT-PCR swab and blood test were taken. They were explained in languages they knew- Hindi, English and the local language,” said Dixit.

When asked if the consent forms were given to the participants, Dixit said consent forms were given to those who asked for it. “We have the consent forms of all the participants. The participants were convinced about the injection. After the injection, as per the protocol, we followed up with all of them. All participants were called every day for the next seven days. If any participant reported adverse reaction, they were advised over the phone. If that was not enough, they were asked to come to the hospital. Several of them were treated here too. We have not turned away any of the vaccine participants,” claimed Dixit.

“There are a few things which are problematic,” said Dr Anant Bhan, a researcher in global health, bioethics and health policy. He said if the participants were not given their informed consent forms, it is problematic. “Some of them have not understood that they are part of a trial. They have not been given adequate documentation. Now, a few of them have been given the same, but they should have been given the documentation at the time of counselling.”

Next is the issue of medical care, especially if it is linked to vaccination. “If there have been side-effects or adverse events, the hospital should treat them,” added Bhan.

Sixty-year-old Manju Bai of Shankar Nagar went for her second shot on Wednesday. When she reached the vaccination site, she was diagnosed with hypertension or high blood pressure. “I was not given the second injection. They took away the papers that I had with me. They said that I do not need to keep the papers with me. I was told I do not need to come back for any more injections. When I asked the doctor to treat me for hypertension, he said it would be paid treatment,” said Manju. The doctor then gave her Rs 20 to buy one dose of hypertension medicine.

Ramesh was administered the injection on December 8 and then he was made to sign several papers. “When I went for the first injection, we were told that it was a trial for Corona. But, I don’t know what a trial meant. They told us that it was an injection for Corona. I went back for the second injection on Wednesday, January 6, and they made me sign a consent form today. I was allowed to take the papers back,” said Ramesh.

Chhota Das Biragi had been administered the shot of January 3. After that he began to fall ill regularly. “When the hospital authorities called for check-up in between, they asked me to go to the hospital. They gave me a prescription, but I was told to buy medicines for myself. When I went back on January 3, they did not give me the second shot as promised. They said I was ill,” said Biragi.

No one was told about the risks and benefits of the study.

“Nobody has gotten a copy of their informed consent form. This is a huge violation of the DCGI rules. Ideally, people with reduced immunity like gas victims should not be part of the trial and if they are being enrolled, then a thorough job of obtaining an informed consent should be taken. This was never done,” asserted Dhingra.

Bhan pointed out that he had seen and heard several social media, radio and newspaper ads recruiting participants for Covaxin trials. The ads are misleading, Bhan explained, because they state that people would benefit if they participate. In any chemical trial, one doesn’t know if the person will benefit or not as no one knows what is being administered as it is a blinded trial. “Should they have been using such language? All of these are violations and oversights.”

“The administration of this vaccine is intended to be scaled across the country. If this is happening at one site, we should be worried and look at other vaccine sites. Not just Covaxin trial sites, but also those of Serum Institute of India’s vaccine candidate Covishield,” said Bhan.

The Bhopal-based researcher was concerned about the way the recruitment was done. “They have gone to low-income areas and mass-canvassed for vaccination. We must ask if the ethics committee permitted them to do so. They should be an audit. If it is not happening, then it is worrisome. The sponsors of Covaxin are Bharat Biotech and Indian Council of Medical Research. ICMR is the Indian organisation which is setting standards for ethics,” contended Bhan.

In Bhopal, Gandhi Medical College (GMC) and PCMSRC participated in the Bharat Biotech vaccine trial. GMC was unable to recruit more than 250 volunteers, while PCMSRC, through their advertising, was able to recruit 1,700 participants.

However, Bharat Biotech insisted that protocols were being followed at all the clinical trial sites including at Bhopal. “We have not done anything different in Bhopal. The protocols being followed are same at all the 25 vaccine trial sites. As far as our company’s knowledge, the People’s Hospital had followed protocols. Maybe the volunteers are being misled. If you have heard otherwise, I will inform the company,” said Sheela Panicker, public relations officer at Bharat Biotech.

Panicker added that the hospital had tweeted about it too. “I need to check when the trials began at Bhopal. We have seen a lot of misreporting from the media,” added Panicker. She requested that all the remaining question be sent on a messaging app. But the company did not respond to the follow-up questions.