Oh, how much has changed in 1 week. I received my final semester results and I got a B+ in my pharmacology course so maybe I am not qualified to talk about this. (Yes, I am very salty about my grade and instead of coping and accepting it as an adult I have decided to go for a low blow because I am not “better than that”.) But, COVID-19 still ravages on. Worldwide the cases are spiking with record deaths in many countries. All this while, scientists and researchers are still working day and night to discover a vaccine to end this nightmare.
In the last post, we talked about the pre-development process and the challenges of finding a drug target for a novel virus. But even after a major breakthrough in that stage, the release of the vaccine to the general public takes a longer time due to CLINICAL TRIALS.
Drugs and vaccines are very strictly regulated, for all the right reasons. Drugs should be efficient in low doses, non-toxic even in higher doses and must elicit enough positive response to make the drug marketable and profitable. The efficacy and toxicity of the drug are parameters strictly evaluated by regulatory bodies like the Food and Drug Administration (FDA) in the USA or the Central Drugs Standard Control Organisation (CDSCO) and the Drugs Controller General of India (DCGI) in India. They are responsible for the safety and well being of the country’s citizens and act as a watchdog to the multi-billion pharmaceutical industry. They monitor the drug's effect even after it’s release and any clinician or citizen can write to them about any potentially harmful trend among users of a certain drug.
The marketability and profitability of a drug is the concern of the pharmaceutical company producing it. After investing millions or billions of dollars on a drug, they would hate to see it fail in the market or be too costly to produce such that the profit range is significantly reduced. However, I am not a huge fan of the pharmaceutical industry. I agree there are a lot of people working in the industry with the best intentions in mind- to help people and solve major health crises. But, the top tier management has been known to make questionable decisions when it comes to ignoring potential side effects and pricing life-saving drugs very high. I guess, as usual capitalism is bad, we need to eat the rich and redistribute the wealth. We take Jeff Bezos first :)
Coming back to clinical trials after a little communism detour, there are 4 stages to it. The figure below represents it perfectly.
The first row represents the number of subjects at each phase of the trial. As the drug progresses through the phases, more and more volunteers are administered with the drug. As the number of required volunteers increases, so does the diversity of test subjects. Volunteers from around the world participate to make sure that the drug acts similarly without any side effects among all racial and geographical population.
The second row describes the health status of the volunteers. The volunteers are rigorously vetted and monitored over a long period of time to assure the safety of the vaccine/drug. In the first phase, the volunteers are typically healthy and are not suffering from the target disease. In subsequent phases, patient volunteers are recruited. The third row explains the randomisation of the trials to remove any bias and prevent any possible data manipulation and stop potential malpractice.
The fourth row explains what factor of the drug is tested at each phase. Initially, safety and tolerability are tested to check for side effects and decide on a safe range of dosage for the drug. Subsequently, the efficacy of the drug against the disease is tested in patient volunteers and the dose range is refined. Finally, any dataset can only be viable if it is a large number. So, the efficacy and safety are tested in thousands of patients to confirm the results and ensure it is statistically relevant.
The time range given in the figure is for a typical clinical trial. However, due to the pandemic, the entire process has been fastened. The Oxford vaccine was in Phase I and Phase II simultaneously. Many drugs that were used in the previous coronavirus outbreaks have been allowed to enter the clinical trials easily due to previous data and results. The budget and success rate, however, varies from vaccine to vaccine.
Phase IV of the clinical trial is post-marketing surveillance. This is after the drug has passed the first 3 stages of clinical trial and been approved for release into the market by competent authorities. In this stage, companies and clinicians alike look out for any patterns of side effects among patients consuming the drug.
Currently, the Oxford vaccine is in the third phase of the clinical trial along with the vaccine from Moderna, a US-based pharma company. Even by March 6th, the WHO confirmed that more than 200 clinical trials for a potential COVID vaccine had been registered. Currently, many of them have advanced to later phases and our best hope, the Oxford vaccine is in the final stages. Despite the challenges explained in the previous post, scientists, with the help of regulatory bodies and brave volunteers stepping forward for humanity, have come a long way in terms of developing the vaccine.
One of the major roadblocks for the process is a lack of funding. Over the past years, government budget cuts have left many research institutes and scientists helpless. Increased defence spending and tax cuts to the rich come at a cost of lower financial aid for education, science and research. Private non-profits like the Bill and Melinda Gates Foundation have pledged money for the development of anti-viral vaccines, not just against COVID but also other life-threatening infections like malaria and AIDS. Unless we invest in the human resource and infrastructure required to support and sustain the research community, real progress will be hindered due to easily avoidable causes. The least we can do as a society is to be aware of our country’s budget allocation for science and RND and try to collect and share reliable information that could start a discussion regarding funding for research.
Until next time.
Stay safe. Wear a Mask.