|Year : 2020 | Volume
| Issue : 2 | Page : 49-50
COVID vaccines; the search continues!!!
Sr Consultant, Department of Cardiology, Dean-Post Graduate Medical Education, KIMS Health, Thiruvananthapuram, Kerala, India
|Date of Submission||20-Aug-2020|
|Date of Acceptance||23-Aug-2020|
|Date of Web Publication||02-Oct-2020|
Dr. G Vijayaraghavan
KIMS Health, Thiruvananthapuram, Kerala
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Vijayaraghavan G. COVID vaccines; the search continues!!!. Ann Clin Cardiol 2020;2:49-50
COVID-19 pandemic has become the most crippling disease affecting humans since the Spanish flu in 1916.
Recently, Russian scientists announced development of the first COVID-19 vaccine for humans and named the vaccine “Sputnik V” after the first Russian satellite launched into space in 1957. The vaccine was developed by the Gamaleya Research Institute for Epidemiology and Microbiology in partnership with the Russian Defense Ministry. The head of the Institute, Alexander Gintsburg, announced that in the final stage of testing, volunteers would receive two inoculations. Industrial production would begin in September with a goal to manufacture 5 million doses per month. In response, Western scientists have been skeptical with some warning that moving too quickly on a vaccine could be dangerous.
In 1747, James Lind, a Scottish naval surgeon, conducted probably the first clinical trial among sailors to find a cure for scurvy with a diet of lime and oranges. The findings of his study prevented scurvy, especially among sailors. Over the next centuries, drug trials became a common practice. However, in 1955, the “Cutter Incident” took place: an error in the production process of Salk polio vaccine at Cutter Laboratories led to the manufacture of large quantity of vaccine with live poliovirus rather than the inactivated virus. This incident still remains as “one of the worst pharmaceutical disasters in medical history,” resulting in 40,000 cases of poliomyelitis which included permanent paralysis of 51 cases and mortality of five cases. Moreover, 113 cases of paralysis and five deaths were reported among the contacts of vaccinated people. As a result of this disaster, the US government and the medical community across the world introduced stringent monitoring measures and strict rules and regulations for the drug/vaccine industry. The Food and Drug Administration (FDA) now necessitate well-planned extensive testing to ensure the safety and efficacy of drugs/vaccines before its release, and the long-term impact of these drugs/vaccines are evaluated post-marketing as Phase IV study to identify the long-term impact of them in the community.
The Indian Council of Medical Research has divided the evaluation of a new drug into four phases similar to what the FDA has done.
| Phase 0|| |
At this phase, single subtherapeutic dose of the study drug is administered to a very small number of subjects (typically 10–15) for understanding the pharmacodynamics and pharmacokinetics in humans. It documents the absorption, distribution, metabolization, and removal (excretion) of the drug and the also the drug's interactions within the body.
| Phase 1|| |
This phase includes testing of the study drug within in a small group of healthy volunteers including patients (typically 20–80) to determine the safety, safe dosage range, side effects, and drug activity. Immunogenicity is measured in the case of vaccines.
| Phase II|| |
This phase may be divided as Phase IIa which aims at determining the dosage requirements (how much drug should be given) and Phase IIb which meant for measuring the efficacy (to understand how well the prescribed dose[s] works and to establish the therapeutic dose range). The study participants of this are selected a strict inclusion or exclusion criterion and they are strictly monitored throughout. Early studies in Phase II are aimed at estimating the dose response and later studies are meant for the confirmation of the dose response.
| Phase III|| |
Testing of the study drug among a large of group of study subjects (typically 1000–3000) for determining the efficacy, effectiveness, and side effects by comparing it with the commonly used treatments is intended at this phase. The outcomes of this phase will determine if the study drug could be used safely among the patients.
| Phase IV|| |
The study drug which successfully completes the Phase III is ready for the therapeutic usage; however, postmarketing studies are required to determine the long-term risks, benefits, and optimal use. Therefore, postmarketing studies or phase IV studies are carried out during the drug's lifetime of active medical use.
Currently, COVID-19 vaccines are going through various stages of clinical trials. None of these trials have completed the Stage III phase to be marketed with confidence, yet the Russians are going ahead without the results of Phase III trials. Here, in India, we are keeping an eye on the progress of 359 global industry sponsored trials. 19 of them have completed their initial phase. Four reported that they have met their primary endpoints, while two did not meet their endpoints. With a significant volume of trials still in various phases, we will continue to track their progress and outcomes. At this time, we do not know what time frame we can be fix for the marketing of a vaccine which has successfully completed the Phase III trial. Even after we succeed in identifying a marketable vaccine, we still have to manufacture it in very large amounts, potentially billions of doses. During this process, we must be aware of the track record of many vaccines in the current use: mumps vaccine is about 80% effective; rubella is 93%; whooping cough about 75%, while the flu vaccine is only 40%–60% effective. We are going to face problems when, despite vaccination, still large numbers of people may not be immune with the need for more than one injection. For example, the HPV vaccine for cervical cancer is a two- or three-shot vaccine, the flu vaccine is taken yearly and annually modified, and cholera is a multiple-dose vaccine. If a COVID-19 vaccine requires more than one dose, this will require a staggering manufacturing and distribution effort. The U.S. and the U.K. governments have already stated that if they are investing vaccines, they will naturally be used in their own country first. Other countries are likely to do the same. The WHO insists that vaccines ought to be available where needed most. The cost of a vaccine is still not yet known and is likely to drive a lot of problems in terms of global availability. This is a problem as it is important to avoid pockets where populations are not vaccinated where the virus can incubate and return later.
Finally, since none of the vaccines have cleared Phase III clinical trials, we can also expect the politics behind it to surface as well. At this time of acute global need, we can only hope that the pharmaceutical industry will not be trying to profit and hold the world to ransom. Everyone should understand that the whole world is watching this scenario to prevent this dreaded pandemic.
After writing this Editorial, three important vaccines have gone for Stage III clinical trial. These are the Oxford Vaccine of Asta Zenica, the Sputnic V Vaccine from Russia, and the Chinese Vaccine. Indian subjects are being enrolled for the first two vaccines. Last week, the Oxford Vaccine was temporarily put on hold due to one adverse reaction reported to the Internal Review Board. If this is resolved as “not due to vaccine,” the trial can continue. Otherwise, they have to change the formulation. These are important safeguards in the clinical trial process.
Editor in Chief