The Clinical Trial Registry - India (CTRI) website is the principal source of getting to know about various clinical trials
Two potential COVID-19 vaccines, Bharat Biotech’s Covaxin and Zydus Cadila’s ZyCov-D, are now being tested on humans in phase-1 and phase-2 clinical trials. Another vaccine maker, Serum Institute of India (SII), is expected to begin Phase 2/3 trials shortly.
With the plethora of vaccine candidates being tested all around the world, there has been a lot of curiosity over how the trials are conducted and particularly about how volunteers are enrolled. The fact is, participating in such trials comes with risks and responsibilities. Let’s take a look at what is involved.
What are the various phases of a drug or vaccine trial and how do they differ?
In phase-1 and phase-2 of a trial, only healthy volunteers are recruited. Phase-3 accepts people with pre-existing medical conditions, including those with such conditions who are stable, those who are elderly, and children. Typically phase-3 begins following the submission of phase-1 and -2 data.
Frequently Asked Questions
A vaccine works by mimicking a natural infection. A vaccine not only induces immune response to protect people from any future COVID-19 infection, but also helps quickly build herd immunity to put an end to the pandemic. Herd immunity occurs when a sufficient percentage of a population becomes immune to a disease, making the spread of disease from person to person unlikely. The good news is that SARS-CoV-2 virus has been fairly stable, which increases the viability of a vaccine.
There are broadly four types of vaccine — one, a vaccine based on the whole virus (this could be either inactivated, or an attenuated [weakened] virus vaccine); two, a non-replicating viral vector vaccine that uses a benign virus as vector that carries the antigen of SARS-CoV; three, nucleic-acid vaccines that have genetic material like DNA and RNA of antigens like spike protein given to a person, helping human cells decode genetic material and produce the vaccine; and four, protein subunit vaccine wherein the recombinant proteins of SARS-COV-2 along with an adjuvant (booster) is given as a vaccine.
Vaccine development is a long, complex process. Unlike drugs that are given to people with a diseased, vaccines are given to healthy people and also vulnerable sections such as children, pregnant women and the elderly. So rigorous tests are compulsory. History says that the fastest time it took to develop a vaccine is five years, but it usually takes double or sometimes triple that time.
How is a vaccine trial different from a drug trial?
When it comes to testing a drug, healthy volunteers are recruited in phase-1 to check for safety, while patients are recruited in phase-2 and phase-3 to assess efficacy and safety. However, a vaccine, which is used to prevent a disease, is tested on a broad group of people.
How can people access information about clinical trials being conducted in India?
Unlike, the US and Europe, where companies or sponsors of clinical trials run awareness campaigns and advertisements to enrol volunteers, in India clinical trials are generally low-profile affairs. The Clinical Trial Registry – India (CTRI) website is the principal source of information on various clinical trials, their recruitment status, the centres that are participating, and details of the Principal Investigators at those sites.
You can find the clinical trial site (hospital) in your city or district, directly call or email the Principal Investigator, and express interest to volunteer for the trial. But searching information on the CTRI website is a little cumbersome.
Some clinical trial sites, such as the Institute of Medical Sciences and SUM Hospital, Bhubaneswar, Odisha, among the 12 sites where Bharat Biotech’s Covaxin is being tested in Phase 1/2 trials, have made things convenient for potential volunteers by creating a dedicated webpage.
What does registration involve?
The initial screening and registration of volunteers is done online by collecting details such as name, age, gender, body mass index, allergic reactions to drugs, vaccines and food, current symptoms (cough, fever, breathlessness etc), existing medical conditions such as pregnancy, diabetes, hypertension, cancer, asthma and so on. Those who meet the eligibility criteria are enrolled for the trial.
What happens once a volunteer is enrolled?
Enrolment is just the first step. The enrolled volunteers will have to go through a medical examination, and are also tested for COVID-19 using an RT-PCR and antibody test.
People who have tested positive for COVID-19, or those who have antibodies against SARS-CoV-2, are rejected from participation in the vaccine trial.
Dr E. Venkat Rao, Principal Investigator for Covaxin at the Institute of Medical Sciences and SUM Hospital, Bhubaneswar, told Moneycontrol that the hospital has had to reject several volunteers, as they already have antibodies against COVID-19. This also points to the challenges in finding volunteers for trials should the disease spread widely.
In its phase-2 trial, Covaxin is enrolling those aged 12-65, while ZyCov-D is enrolling subjects aged 12 and above (no upper limit has been specified). Covaxin will be tested on a sample size of 1,125 participants in Phase 1/2 and ZyCov-D on a sample size of 1,048.
How long does it take to assess a volunteer and does consent have to be formalised?
Rao says it takes about three days to complete the process of medical examination before recruiting eligible volunteers. The investigator, too, has discretion in accepting or rejecting a subject. The volunteer has to provide written and informed consent, after reading through the risks and responsibilities of participating in the trial.
What conditions do volunteers need to adhere to in order to participate in the trial and ensure it is conducted correctly?
Volunteers will have to ensure they are available to fulfil the study’s requirements whenever needed. For instance, in the Covaxin phase-2 trial, volunteers will have to cooperate to get tested for an immunogenicity evaluation (measuring antibody levels) seven times over a period of 194 days.
Males have to use condoms to ensure effective contraception with their female partner from the first vaccination until three months after the last vaccination.
Females need to avoid becoming pregnant from the time of study enrolment until at least four weeks after the last vaccine dose.
Also, volunteers should not participate in another clinical trial at any time during the study period and should allow storage and use of biological samples for future research.
Are there any incentives for volunteers who participate in a trial?
Volunteers will not be paid for participating in the trial. However, they are paid for food and travel to the clinical trial site. This will be fixed.
The company that is sponsoring the trial will insure the volunteer against any unforeseen medical event or death related to the clinical trial.
How are the trials carried out? Is there a guarantee that a volunteer will get the vaccine?
The clinical trials for COVID-19 vaccines are generally double-blind, randomised, controlled trials. Double-blind means that neither the researchers nor the patients know what they are getting. There is no guarantee that a volunteer will get the vaccine.
Typically, the clinical trial subjects are divided into two groups. One group will get the vaccine shot and the other group gets a placebo or a dummy injection.“Once the trial is over, we will get to know who got the placebo and who got the vaccine. Generally, we don’t disappoint the volunteer who took part in the trial and got a placebo — we will ensure he gets the vaccine on a priority basis, once it is approved,” Rao said.