- Challenge Trials are ideally done where a virus causes mild disease: Expert
- Some researchers believe challenge trials can help develop vaccine fast
- Challenge trials are risky as much is still unknown about COVID-19: Experts
New Delhi: As the COVID-19 pandemic continues to rage, pharmaceutical firms and scientists all over the world have been working relentlessly and racing against time to develop a safe vaccine against coronavirus. According to the Centres for Disease Control and Prevention (CDC), the major stages of vaccine development include initial research followed by a series of pre-clinical trials which are mostly done on animals and clinical or human trials consisting of three phases and each of the steps can take two or more years to complete. Vaccine development takes years because the process involves studying and determining for how long the vaccine will provide protection and also observing volunteers for any side-effects, says Dr. KK Agarwal, President, Confederation of Medical Associations in Asia and Oceania (CMAAO). The fastest ever vaccine to be developed is the one for mumps – and even that took four years, he said. However, for countering the COVID-19 pandemic and provide a vaccine at the earliest, the steps involved in vaccine development are being rapidly accelerated. Experts say that ‘Human Challenge Trial’ or deliberately exposing volunteers to the virus during the Phase-3 clinical trials is also a way of accelerating vaccine trials. According to Dr. Chandrakant Lahariya, epidemiologist, vaccinologist, and public health and policy expert based in Delhi, the researchers across the globe are currently divided on the matter of considering this method of studying the performance of a vaccine candidate for COVID-19.
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On July 15, 153 academics, doctors, epidemiologists, and scientists wrote an open letter to health regulatory bodies in the U.S. like CDC, National Institutes of Health, the Coronavirus Task Force, the Department of Health and Human Services, the Food and Drug Administration and international bodies like the World Health Organisation (WHO) asking for human challenge trials to address the urgent need for a vaccine to curb the pandemic. They wrote in the letter,
If challenge trials can safely and effectively speed the vaccine the development process, there is a formidable presumption in favour of their use, which would require a very compelling ethical justification to overcome.
What Are Human Challenge Trials?
According to Satyajit Rath, an immunologist and specialist in infections and diseases with the Indian Institute of Science Education and Research (IISER), Pune, in human challenge trials, volunteers are deliberately infected with the virus causing disease to test whether a vaccine provides enough protection. Human challenge trials or Human infectious microbial challenge studies, also referred to as the ‘Controlled Human Infection Model” or CHIM studies, are different from the standard late-stage vaccine trials where the developers have to wait for people to be exposed to an illness naturally, he said. Mr. Rath further added,
Mostly, the challenge trials are intended to provide well-controlled human infection situations for analysis, where the type, dose, route of intake, and time of infection are well known which is not likely to be the case in actual, naturally occurring infections. So, typically, researchers will deliberately give infections to healthy people, and follow various study parameters like the course of the infection and immune responses, and/or the effects of various drugs/medications, or vaccine.
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Could Human Challenge Trials Be Used To Speed Up The Process Of COVID-19 Vaccine Development?
According to Dr. Aggarwal, challenge trials have improved vaccine development for seasonal flu, cholera, among other diseases and there is now an increasing discussion that preparations should begin for COVID-19 challenge trials in case needed. He added that in July, the team behind the Oxford COVID-19 proposed to start human challenge trials by the end of the year and Professor Adrian Hill of Oxford University, that is developing a vaccine candidate with pharmaceutical company AstraZeneca, has said that challenge trials may be done in parallel with Phase-3 trials or after these trials are completed.
During an online discussion organised by Indian Council of Medical Research (ICMR) on July 30, Professor Adrian Hill of Oxford University, reiterated,
There are multiple therapies in use now to consider both challenge trials as well as randomised control trials to get quicker results, and that these had been conducted for other viruses like malaria and cholera without any issues.
During the same discussion, other experts like Dr Anthony S Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID), US, expressed concerns over conducting ‘human challenge trials’ to accelerate vaccine development for COVID-19. He said,
Purposely exposing someone to the coronavirus is unnecessary and unethical in the case of a disease for which we have no proven cure yet.
The WHO has also acknowledged 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. In its guidance document on criteria for conducting challenge clinical trials and providing clinical care for the participants, WHO says,
Well designed human challenge studies provide one of the most efficient and scientifically powerful means for testing vaccines, especially because animal models are not adequately generalizable to humans. SARS-CoV-2 challenge studies could add value to other types of vaccine research by enabling (a) accurate assessment of asymptomatic infection, (b) more rapid and standardized testing of multiple vaccine candidates, and (c) testing vaccines in contexts where there is little continuing transmission (for example, due to public health measures or during inter-epidemic periods).
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WHO further says that SARS-CoV-2 challenge studies should be conducted in specialized facilities, with especially close monitoring and ready access to early supportive treatment for participants, including critical care if required.
Dr. Paul Offit, an American Pediatrician and specialist in infectious diseases, vaccine, immunology and virology, however, said that challenge trials are not needed in case of COVID-19 as the natural infection is already widely present across the globe. He further added,
Human challenge trials don’t exactly mimic the real infection because when you are out there in the real world, you may get exposed to different quantities of virus. Sometimes you may get exposed to a large quantity of virus that may make you sicker as compared to a smaller quantity of virus.
Ethical Concerns Regarding The Use Of Human Challenge Trials For COVID-19 Vaccine Development
According to Mr. Rath, there are major ethical difficulties in any SARS-CoV-2 human challenge trial study. This is because challenge studies are ideally done in situations where the disease caused is expected to be mild and where the infection can be quickly treated and eliminated if the need arises. However, in the case of COVID-19, there is no definitive cure which means that even the young and healthy people who are considered low-risk can become very ill and some could even die. Along with this, as much is still unknown about the SARS-CoV-2, there is not much clarity about the long-term effect of the infection on humans and so deliberately infecting anyone would pose an ethical difficulty, said Mr. Rath.
Dr. Lahariya said that it will be upto the countries to decide whether they would take this route and device regulations regarding it.
WHO’s guidance document says that an important principle in human challenge studies is that subjects must give their informed consent in order to take part. This means they should be provided with all the relevant information about the risk they are considering. However, Mr. Rath says,
As of now, informed consent is not possible because there is a lot to be learnt about the disease like potential long-term implications of it since it is such a new disease. This means that no volunteer is able to give true informed consent.
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According to an official of the Ministry of Health and Family Welfare human challenge trials are not being considered for any of the vaccine candidate being developed in the country. He said,
Sure, there are scientists debating the usefulness and the risks involved in challenge trials but India is not considering it as of now. All of our vaccine candidates are currently undergoing Phase 1 or Phase 2 of clinical trials while human challenge trials take place in Phase 3. Also, there is already enough infection out there and many volunteers who are ready to participate. It is highly unlikely that we take the challenge trial route.
Talking about if there is any risk of using monetary rewards as motivation to bring in participation for trials, the official said,
We have highly elaborate regulations for vaccines trials. While volunteers can be given a little compensation for the time that they divert from their daily work/routine to the trials and thus helping in vaccine development but it is never given as a way for earning money.
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NDTV – Dettol Banega Swasth India campaign is an extension of the five-year-old Banega Swachh India initiative helmed by Campaign Ambassador Amitabh Bachchan. It aims to spread awareness about critical health issues facing the country. In wake of the current COVID-19 pandemic, the need for WASH (Water, Sanitation and Hygiene) is reaffirmed as handwashing is one of the ways to prevent Coronavirus infection and other diseases. The campaign highlights the importance of nutrition and healthcare for women and children to prevent maternal and child mortality, fight malnutrition, stunting, wasting, anaemia and disease prevention through vaccines. Importance of programmes like Public Distribution System (PDS), Mid-day Meal Scheme, POSHAN Abhiyan and the role of Aganwadis and ASHA workers are also covered. Only a Swachh or clean India where toilets are used and open defecation free (ODF) status achieved as part of the Swachh Bharat Abhiyan launched by Prime Minister Narendra Modi in 2014, can eradicate diseases like diahorrea and become a Swasth or healthy India. The campaign will continue to cover issues like air pollution, waste management, plastic ban, manual scavenging and sanitation workers and menstrual hygiene.