Sep 17, 2020
Clinical trials and COVID-19
It felt like the right time to get to know more about clinical trials, so here it is…all I know about clinical trials and some data about COVID-19 clinical trials.
What are clinical trials? As Wikipedia says — “Clinical trials are experiments or observations done in clinical research. Such prospective biomedical or behavioral research studies on human participants are designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietary choices, dietary supplements, and medical devices)”. These clinical trials as experiments have been prevalent since centuries ago, though looking at the modern times and the protocols that are active today, it was Ronald A. Fisher in 1920s who first introduced some of the ideas used today including the idea of randomization.
Let’s now look at when these trials are conducted. It starts with a hypothesis or proposal by a company or a research lab, they come up with an idea regarding an intervention for betterment of human health. Once they have their hypothesis verified by some computational/biophysical models or “wet lab” analysis, they go forward to testing the intervention in humans. As FDA mentions — “Potential treatments, however, must be studied in laboratory animals first to determine potential toxicity before they can be tried in people. Treatments having acceptable safety profiles and showing the most promise are then moved into clinical trials.” After testing in animal models, they move to clinical trials, which these interventions need to pass in order to get approved by the FDA. A study by MIT in 2018 mentioned how nearly 14% of drugs in clinical trials get the FDA approval.
The next step to understand is how these clinical trials are held. The figure below[1,2] shows the process which every drug goes through till it is approved by FDA. After getting approved, it goes on for phase 4 of the clinical trial where long term effects of the intervention are evaluated. As mentioned by this paper by Harrer et al.— “Probabilities of success for compounds to proceed through the clinical trial stages vary from phase to phase, and lead to a situation where only one of 10 compounds entering clinical trials advances to FDA approval. High clinical trial failure rates are one major cause for the prevailing inefficiency of the drug development cycle.”
Though clinical trials have high utility and are necessary, their is one con that I would point out here that I learnt of recently. Clinical trials are at the behest of time — time taken by the company/lab to process the start and execution of the trial, time taken by FDA to approve trial registration, time taken to find partners to perform study with. The second factor that I mention in the figure is the amount of money spent, which can again have a major contribution in how the trial is conducted, as with more money, more combination therapies can be tried out among other possibilities. [These problems can be unpleasant for many of patients relying on these trials - you can check one example here].
Covid-19 Clinical Trials
The reason I want to talk about COVID-19 trials is because of the time in which these drugs/vaccines are hoping or have been rolled out into the population. These interventions which on average take 8–15 years to get approved and pass the Phase 4 trial are now being approved within a matter of months.
In the face of the pandemic, taking extreme measures becomes mandatory to keep up with the issues being faced.Yet, there are certain future issues that get ignored when such extreme decisions are made. Take for example, the case of these treatments mentioned above. The long term impact of these are not known yet, not only that with a hurried roll out of drugs there is always a higher potential of making mistakes.
I would also want to talk about the recent issue with the University of Oxford/AstraZeneca trial for COVID-19 vaccine.
Well 1 patient shouldn’t be an issue right? It could be that the patient had some underlying condition, or one of the following reasons mentioned by Dr. Mukherjee in his latest post. Well, it matters because some of these reasons can be trial breaking, so if even 1 more patient in the trial was to suffer from such a side-effect then this trial would be buried.
There is a reason why these trials are being sped up, this pandemic needs to stop at some point. But how do we make sure they come out in time and not have any negative heath impacts to human body? It is a million dollar question and I wish I knew the answer. Unfortunately till we have an answer to that we try our best and make sure we do our best to make sure the guidelines and moral codes are followed. I was very happy to see how these companies pledged to ‘Stand with Science’. All we can do is hope that we are able to beat this pandemic soon and without any lives being sacrificed to roll these treatments out!
You can check out the list of current clinical trials on https://clinicaltrials.gov/ct2/home.
