Should we short-circuit trials of experimental vaccines?
Should we short-circuit trials of experimental COVID-19 vaccines?
IS IT ethical to administer an experimental COVID-19 vaccine to a healthy person and then infect him/her with the novel coronavirus to check if the vaccine has immunised the individual against the pathogen? The question is at the centre of a global debate ever since the UK allowed a study, called human challenge trial (HCT), on a COVID-19 vaccine which will be conducted in January 2021.
Normally, a vaccine goes through three phases of human trials. The first phase tests for safety, the second immunogenicity (ability to trigger immune response) and the third involves large-scale testing on tens of thousands of participants of varied populations, who are injected with the vaccine and observed over a long period, even years, for efficacy. In HCT, instead of the third phase trial, a small number of healthy participants (often less than 100) are recruited, at times for money, and administered the vaccine before being injected with a less virulent strain of the virus. HCT thus reduces the trial period by months. The danger,
however, is that the injected virus may cause severe illness or even death of the participants during the study.
HCT is not a new concept. It was used for the development of anti-malarial and cholera vaccines in the 1970s. But when HCT was undertaken to develop vaccines for these diseases, drugs to treat them were already there. If a participant became ill, there was a cure available. This is not the case with COVID-19, because there is no guaranteed cure.
In 2016, the World Health Organization (WHO) issued guidelines for conducting HCT, but it missed out the most crucial one. “Until there is an approved treatment, a challenge trial with a potentially fatal and as-yet untreatable pathogen is unacceptable,” write Nir Eyal and Perry Haltkins in a paper published in the journal AIDS and Behavior in June 2020. “I am for HCT because it tells us efficacy in very little time. But it should be undertaken only if we have a cure,” says Gagandeep Kang, virologist and former head of the Union government’s Translational Health Science and Technology Institute, Faridabad, Haryana. “Moreover, at a time when
INDIA HAS NO PLANS TO UNDERTAKE HUMAN CHALLENGE STUDIES OF EXPERIMENTAL COVID-19 VACCINES BUT IT IS CONSIDERING TO GRANT EMERGENCY USE AUTHORISATION TO CERTAIN VACCINES THAT HAVE NOT HAD LARGE-SCALE TRIALS
we do not even fully understand the virus, how would we be able to produce a milder strain of it in the lab,” Kang asks. Virologist Shahid Jameel agrees with Kang. “For a virus whose long-term impacts on organs such as the heart and the lungs are being discussed in more and more studies, I doubt if it is a risk worth taking. If a participant dies, people will develop hesitancy towards COVID-19 vaccines,” says Jameel, who teaches at the Ashoka University, Haryana. As of now, India has no plans to undertake HCT, Union health minister Harsh Vardhan said during a social media interaction on October 4. Jameel says the country's poor health infrastructure is not ready for such an experiment even in near future.
IS IT READY FOR EMERGENCY USE?
India is considering another quick route to vaccine development. As Vardhan said during another social media interaction on September 13, it is emergency use authorisation (EUA). Under this provision, a country can permit a vaccine on the basis of results of the first two phases of trials. Russia and China have already granted EUA to their own COVID-19 vaccines for use in a limited setting and have not made those available for everyone. Russia has agreed to sell 100 million doses of its COVID-19 vaccine, Sputnik V, to Dr Reddy's Laboratories, a Hyderabad-based company, which will conduct its own trials before applying for a government clearance to sell the vaccine. It should be noted that EUA is not a full licensure but permission for limited time and settings.
Experts have reservation about EUA, too. A paper published in the Journal of
the American Medical Association on August 31, 2020, analyses EUAs granted to various therapeutics during the COVID-19 outbreak and says they can be harmful. One such is the EUA granted by the US to hydroxychlorquine (HCQ) due to political considerations, but was revoked later, notes the paper. Mortality rate was higher in people who were administered HCQ.
WHO has neither approved nor disapproved EUA. On September 28 it issued a guiding document on how to grant an EUA. It is a draft and open for remarks till October 8. “Each country has a sovereign right to define its policy for vaccination or any other therapeutic intervention in its population, but it must be guided by the highest possible ethical standards... Where countries do move forward with any form of emergency use authorisation it should be linked to very intense and increased monitoring of the implementation of that product and with a very clear view that if any safety signal was picked up, that there would be an immediate change to the policy,” Michael Ryan, executive director, emergencies programme, WHO, said on September 21.
“If a patient is severely sick and is given an experimental drug whose efficacy is not proven, it might be a risk worth taking. But vaccines are given to somebody who is perfectly fine. If an unproven vaccine is administered and the participant suffers adverse events, would that be a risk worth taking,” asks Amar Jesani, editor of Indian Journal of Medical Ethics.
Jameel, on the other hand, says the healthcare workers in India should be allowed to take an emergency vaccine without a full-fledged third phase trial because they are frequently exposed to the virus. He, however, follows this with a caveat: “The vaccine, which is to be granted EUA should have enrolled good number of participants in the first two phases. The Russian vaccine does not qualify because less than 40 participants were enrolled in its phase-1 and phase-2 trials. It must not be made available for public use before full phase-3 trial.”