Certainly, scientific research has become one of 2020’s protagonists. From the smallest local newspapers to the largest media companies, the studies being carried out to find answers in fighting COVID have been broadcasted and shared all over the globe. Previously, the scientific community would hit the headlines to talk about new discoveries and prizes. But today, coronavirus is leading internet searches and increasing interest in the concept of clinical trials. Vaccines and different treatments are being tested, and we want to understand how- and why is it done this way.
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This picture shows interest over time, based on Google worldwide searches of “vaccine trial”. Taking a look at the line graph, numbers on the vertical axis represent “search interest”. A value of 100 is the peak popularity for the term, 50 means that the term is half as popular, and a score of 0 means there was not enough data from this term. We can therefore see that the popularity of this search increased significantly around March 2020 and has maintained a high level during the following months.
What are clinical trials?
A ‘trial’ can be defined as the act or process of testing, putting to proof by examination or experiment [2]. What exactly is being tested? Can we try to understand how these studies are organised? Why do scientists choose to use this type of research, and what results can they give us?
Dr Hubert Lam, Associate Professor of Epidemiology at the Nuffield Department of Population Health in Oxford University, shared with us some answers to these questions.
‘Medical research comes in many shapes and forms, from experiments done in the laboratory with test-tubes and animals to surveys and trials involving human participants. Findings from these research studies help scientists and clinicians identify the best treatment and management strategies so that the society as a whole will benefit. […]’
A clinical trial is a study that compares the effect and value of an ‘intervention’, (for example a new drug, treatment or a vaccine), against a control group in human beings. [3] The ‘control’ would be a group which does not receive this intervention, or receives a placebo instead, and that shares certain characteristics with the intervention group from the start. If these studies are well designed, conducted and interpreted, they can be a powerful experimental technique, which helps us assess not only effectiveness but also safety of new treatments.[3]
‘In a nutshell, researchers recruit volunteers and divide them randomly into two groups. The new treatment (which could be anything including drug, vaccine, surgical procedure, medical device such as pace maker) or behavioural intervention (for example dietary advice) is given to one group. The existing standard therapy is given to another, such that the effectiveness of the new treatment can be worked out. All new drugs must demonstrate they work better (or at least more cost-effective) than their existing counterpart (or a dummy drug known as placebo if the use of existing drug is not appropriate) first before they are allowed in the market.’
The importance of completing different stages – and why they may be paused.
With the urgent need of a new vaccine against Covid, we are noticing that these studies may be taking longer than we expected. This has to do with the structure of the trials, as they must complete a certain set of phases before concluding: it is a series of processes we cannot speed up.
‘Because clinical trials involve testing on humans with new treatment that has not been thoroughly understood (otherwise there is no need to conduct research in the first place), scientists must first establish that the treatment, say a new drug, is at least safe in healthy volunteers first, before they are allowed by regulatory bodies to test on real patients.’
‘A new drug [or vaccine] has to go through three phases of trials before it can be approved for use. A Phase I trial involves a small group (20-80) of healthy people to find out the appropriate dosage range that is safe and to identify potential side effects. Moving on to Phase II, more people (100 to 300) are recruited to obtain preliminary data on whether the drug works as intended. During this time, safety and side effects are continuously monitored.’
‘In a Phase III trial, a much larger group of people (typically in thousands) are tested. They are often recruited from multiple sites within and across countries so that scientists can know whether the drug works in different populations. This poses major administrative and logistical challenges because each country may have its own set of regulations governing the conduct of research (especially clinical trials) and researchers have to meet all the requirements, making clinical trials time-consuming and expensive.’
It has been lately released that some clinical trials for Covid vaccines have stopped. They may or not restart later, so is it always bad if a clinical trial pauses? Again, the main objective is to prioritise that participants are as safe as possible, even when we wish we could continue with the trial as initially planned. We must take into consideration that bioethical assessment has to be part of every step of the study, as ethical issues may arise in any of the stages. A clinical trial should prioritise looking for solutions to population health problems, without compromising the wellbeing of the participants (volunteers) who collaborate in it. [3]
‘Because of the uncertainty in the effects of the new treatment, as a safety precaution the researchers may decide to pause a trial when they receive reports of patients experiencing side effects, so that they can investigate whether or not they are caused by the treatment. This can happen many times during a trial, as has been seen in the current Oxford vaccine trial. While sometimes bureaucratic red tapes could be cut, for example, due diligence check may be expedited for accredited research teams with excellent track records (for example the RECOVERY trial on COVID-19 drugs took just 9 days from conception to launch), there is no room for compromise in safety. As a result, clinical trials can take much longer than planned.’
Why clinical trials are preferred over other studies
Can we as a society trust clinical trials are the best possible way science currently has to show that interventions are effective or not, especially during the current pandemic?
‘Among all medical research studies, clinical trials are considered to produce evidence that is most reliable and trust-worthy.[…] Particularly those large-scale ones involving multiple countries, have been driving important advances in medicine in recent years. There have been critics questioning the potential conflict of interest in trials sponsored or conducted by pharmaceutical companies, as well as the ethics of subjecting human volunteers to potential harms. However, the public should be rest assured that these issues have been seriously looked at by regulatory agencies and ethics boards before a clinical trial is given green light to go ahead.’
‘Modern clinical trials have been designed to answer the most important question “does the drug [or vaccine] work” with the highest possible scientific rigour. It is therefore important, and even more so during the times of COVID-19 when we know very little about the disease and treatment, that clinicians can base their decision not on guesswork, but from robust and reliable evidence generated by well-conducted clinical trials.’
As these trials follow their respective phases, we can expect results while knowing that sometimes they may not be the ones we wish for. The design of research in this way, attempts to evaluate reality reducing bias, drawing conclusions as true as humanely possible. It is good time now to bet on strong evidence, based on this type of high-quality research, and hope for the best while we adapt to the current circumstances.
Josefina Maria Orliacq. MSc Global Health Science and Epidemiology student. Green Templeton College
[1]Google Trends https://trends.google.com/trends/explore?=q=vaccine_trial . Accessed10/10/2020
[2] The Concise Oxford Dictionary of English EtymologyEdited by T. F. Hoad, Oxford University Press, 2003.[online] Available at <https://www.oxfordreference.com/view/10.1093/acref/9780192830982.001.0001/acref-9780192830982-e-15971?rskey=4BZ2wo&result=15973>
[3] Friedman, L.M., Furberg, C.D., DeMets, D., Reboussin, D.M., Granger, C.B. Fundamentals of Clinical Trials. Springer, 2015