Ethical concerns have been raised around human challenge trials after Oxford University proposed that they would conduct these trials to accelerate the process of creating a vaccine against SARS-CoV-2. In human challenge trials, an individual is deliberately exposed to the pathogen to understand if an immune response is developed.
Human challenge trials are different from the phased human trials that are being followed by all other vaccine candidates. In a symposium held by the Indian Council of Medical Research in July, many eminent scientists debated over the use of human challenge trials. While Anthony Fauci, Director of National Institute of Allergy and Infectious Diseases, USA called them unnecessary, several other scientists felt they could be given a chance. Concerns about the risk associated with these trials are raised since there is no definite cure for SARS-CoV-2 yet.
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India does not have a set legal framework in place for human challenge trials and has never conducted any for any diseases. Speaking to BOOM, Vineeta Bal, immunologist at IISER, Pune said, "Only countries that have the feasibility to carry out human challenge trials should consider conducting them for COVID-19, provided all the ethical and risk considerations are in place."
A group called 1 Day Sooner has been accepting volunteers for participating in human challenge trials for SARS-CoV-2. This group also wrote an open letter with 100 scientists including 15 Nobel Laureates to the National Institutes of Health, USA, advocating the use of human challenge trials.
Adrian Hill, Director at Jenner Institute at Oxford University that is working on the Oxford vaccine stated in the ICMR symposium that these trials will complement the Phase III trials that are already underway. Hill is one of the signatories of the letter written by 1 Day Sooner. A paper by scientists Nir Eyal from Rutgers University, Marc Lipsitch from Harvard T Chan School Of Public Health, and Peter Smith from the London School of Tropical Health and Hygiene states that these trials if conducted with all ethical regulations in place will accelerate the search for a vaccine against the pandemic that has affected over 18 million people across the world, so far.
Phase III or Human Challenge Trials?
While the paper by the three professors suggests replacing conventional Phase III testing, Hill emphasised that these will only be complementary with Phase III. The Oxford vaccine is already in Phase III trials in UK, Brazil, and South Africa. Trials for Phase III have been proposed in USA and India as well.
Vaccine development follows a protocol of pre-clinical development where the various vaccines are experimented on different animals that have a similar genetic make-up. Post this, the vaccines follow three phases of trials. Phase I with a few volunteers. If they develop an immune response after being the administered the vaccine, Phases II with 100-1,000 volunteers and Phase III with more than 1,000 volunteers are followed.
After vaccine administration, the participants are followed to see if their body has produced an immune response against the virus which will protect the person from contracting the infection even if exposed. "Participants both who received the vaccine and those that were given the placebo are tested to see if they have developed killer T cells and neutralising antibodies against the virus," explained Bal.
What are human challenge trials?
In human challenge trials, the participants are administered the vaccine and after a few weeks as per the study protocol are exposed to the pathogen. For SARS-CoV-2, the participants will be monitored in closed and controlled environments to understand their immune response.
Human challenge trials have been conducted earlier for diseases like small pox, cholera, typhoid, and malaria. In case of the other diseases, existing research and treatment were readily available while the SARS-CoV-2 is still being researched. The World Health Organisation has set eight criteria that should be met for human challenge trials. These include rigorous informed consent, selection of appropriate sites and participants, understanding risks and benefits, consultation and co-ordination with experts who will independently review the trials, and be scientifically robust.
WHO also acknowledges that challenge trials will accelerate the process and help in increasing the likelihood that the most effective (candidate) vaccines will ultimately become available, validate tests of immunity, and improve knowledge about SARS-CoV-2 infection and transmission.
Disadvantages of human challenge trials
Although useful, these studies will only include healthy and fit individuals between the age groups of 18-30. This is not the group that has faced the adverse effects of the virus. In India, over half of the deaths were reported from people in the age group of 60 and older.
"Healthy individuals with co-morbidities will be excluded. Also, these results cannot be extrapolated for the population in general. Once any vaccine is selected, the high risk group will be prioritised to receive the vaccine.This group however will not be a part of the challenge trials," Bal emphasised.
The immunologist concluded by saying that both Phase III and ethically designed human challenge trials should be pursued simultaneously for testing vaccine candidates. "The participants should be well aware about all the potential risks for these trials as the research on the current medicines such as Remdesivir are providing different results", she concluded.