With recent talk about potential Coronavirus vaccines going into Phase I and II Clinical Trials, I thought it might be quite timely to discuss what this means, i.e. what the clinical trial process is, and why it often take so long for a new therapeutic agent to come to market.
For those of you with a medical or science background you may already have some idea of what I’m referring to here, though even then, it may not always be clear for you what the various steps are, or how they’re carried out. And for those with no relevant training in this area, then talk of clinical trials at any level is probably gobbledygook! Whichever the case, read on and I’ll do my best to explain it all for you. Buckle-up though – it can be a bit complicated at times!
All over the world, government agencies are incredibly strict in their regulation of new therapeutic agents that come to market, including pharmaceutical drugs, biological agents (such as vaccines), over-the-counter drugs purchased in pharmacies, and even those hotly debated colourings, preservatives and other food or drink enhancement compounds, to say the least. In simple terms, the companies offering (or using) these products, must seek approval to do so from their own local, and at the same time, international, regulatory bodies. The idea is to make sure that whatever comes to market has been shown to be useful, safe and effective and, beyond that, to monitor the long-term use of those agents and report back any significant side-effects or related problems. Governments have dedicated personnel and departments to carry out such assessments so, for example, the USA have the Food & Drug Administration (FDA), the UK have the Medicines & Healthcare Products Regulatory Agency (MHRA) and in Australia our Therapeutic Goods Administration (TGA), fill that role. Almost all countries around the globe have their own similar version.
When a company want to market a new drug or biological agent then they must first satisfy the appropriate government body and, in order to gain that all important stamp of approval, they need to provide substantial ‘evidence’ in the form of ‘Clinical Trial’ results. Essentially this means that the product must go through a very lengthy and rigorous process of being tested - first in the lab, then in animal models, and finally in humans. Once again, the human trial component is split between various stages in order to make sure that it is useful, safe and effective. Nothing can be rushed, because each stage must be successful in order to proceed to the next.
The process is complex, but goes something like this …
(1) Pre-clinical trials:
Pure research phase: Researchers begin with a new compound or biological agent and test it for potential therapeutic use; sometimes they begin with the end in mind, and sometimes not. Throughout this stage of the research, no testing is performed on human beings. Usually the testing begins in the lab and, if useful, progresses to testing in animal models (usually mice), helping the researchers to evaluate the product’s potential effects, and safety.
Animal studies only
Toxicology (is it poisonous?)
(2) Clinical trials - human testing:
Phase I Clinical Trials: If the product looks useful in the lab then testing will progress to Phase I, where a very small number of healthy human volunteers are given the product. Essentially, these are the first human guinea-pigs and the results at this stage will determine whether, or not, the testing goes any further.
Healthy patients only
Safe dosage testing
Phase II Clinical Trials: Moving on, this is where larger numbers of patients (usually suffering with the disease that the product will treat), try various dosing regimens. These trials are strictly controlled in order to obtain useful information often from hundreds of volunteers and once again with the focus predominantly on efficacy, and safety.
Human target patients
Small-scale clinical trials
Phase III Clinical Trials: When a product passes all the above and is deemed to be both safe and effective, then it moves into its final pre-approval stages known as Phase III clinical trials. This is the serious stage because literally thousands of target patients will be treated with the product, usually at many different clinics or hospitals, and by a larger number of doctors. The results provide high-level clinical evidence, and, at this stage, a submission is usually made to get approval to market the new product. The timeline from start to finish can often be many, many years.
Human target patients
Large-scale clinical trials
Efficacy (how effective is it?)
(3) Legalities & marketing approval:
Phase IV trials: Following a successful application and subsequent approval to market the product, it will be launched and put into use, however the research doesn’t stop there. In fact, clinical trials may continue for many years after the launch of a product so that the company can obtain long-term data about its usefulness, safety and effectiveness.
Human target patients
Therapeutic dose ranges
Okay, now that you understand the process let’s take a breath, process what you’ve just learnt, and get back to where we started this discussion, with the submission of various potential Covid-19 vaccines into Phase II clinical trials. I did warn you to buckle up!
At the time of writing there are biological agents from Australia (1), China (2), the USA (3) and the UK (4), all being vetted in stage I and II clinical trials, for their potential to be used as a vaccine. There are also a further 60 candidate vaccines being investigated at the pre-clinical stage according to the World Health Organisation (5). Naturally the race is on, mainly because of the devastating impact that this viral pandemic has caused worldwide, and the many lives that have sadly been lost, or are yet to be lost, in the months ahead.
The virus itself (SARS-CoV-2), is not completely new but shares its roots with several other ‘Coronaviruses’ that have been seen previously, so this has given researchers a bit of an edge in bringing a potential vaccine up to the Phase II stage fairly quickly. In general terms, vaccines are often targeted towards making your body generate a natural immune response by exposing you to a part of the virus that can stimulate such a response. Some vaccines use a ‘dead’ virus for this (your immune system doesn’t know if the virus is dead or alive, so it generates attack cells regardless, in order to protect you). Other times, vaccines rely on a small part of the actual virus, e.g. a protein spike from its outer shell, or perhaps even a slice of the viral genetic material (mRNA) that codes for that protein spike, to achieve the same effect. Whichever approach, the vaccine sort of ‘teaches’ your own immune system how to recognise, and then kill, the real thing – all of which means that if, in the future, you are exposed to the actual virus, then your body can launch an immediate and highly effective attack!
Given the urgency it’s likely that researchers will be working around the clock to find a reliable vaccine and, since there are several different candidates in the running, we may even end up with more than one that we could choose from. However, it still takes time. Rushing the vaccine at this early stage could prove fatal and cost us even more time if we suffer any setbacks, so the steps are still being followed meticulously, just as they would for any other product, and rightly so.
Most researchers agree that a realistic timeframe will be 12-18 months from now for the launch of a specific, safe and effective Covid-19 vaccine, so until then, our social distancing measures will be more important than ever to manage the spread. Until then, stay at home if you can and stay safe.
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