When we go to our GPs and are prescribed medication for the virus we’ve been suffering with, the stomach pains that have been stopping us for a bit too long, or those feelings of sadness and hopelessness that just won’t fade, we don’t tend to think about the process which made this medication available to us.
But the truth is, for each antibiotic, pain killer or antidepressant we have access to, there is a lengthy and complex process which gets it there.
Even after these drugs have been developed, they have to go through rigorous testing to ensure that they are absolutely safe for use and that they do what they intend to, before they can even be licensed and rolled out into everyday medical care. Here you can read more about how medicines become available in the UK specifically. The rigorous testing process mentioned is what we call a Clinical Trial.
This field is particularly important to me as the essence of my work revolves around clinical trials.
Back in 2015 during a bachelors degree in Psychology, I elected to complete an optional placement year where I successfully applied to join the Stress, Psychiatry and Immunology (SPI) Lab at King’s College London — this happens to be the team that brings you InSPIre the Mind! After working with them for a year as an honorary research assistant, one bachelors degree and a masters degree later, I have found myself back in the same team… instead now as a Trial Manager of a clinical trial in depression!
From my days as a placement student to now, clinical trials have become a major part of my career and I have now taken it a step further and alongside my work I am now studying for a Post Graduate Certificate in… you guessed it… clinical trials.
So, what is a clinical trial?
A clinical trial is a planned experiment typically assessing the effectiveness of a treatment or medical intervention. Such trials usually involve both patients and healthy people (who, in research, we refer to as healthy controls).
The purpose of such trials is to better understand how to treat a particular illness and, when well-designed and run correctly, they are the best way of doing so. They provide invaluable information on both the safety and efficacy of the medical product in focus. They can change standard care and offer new hope.
While, historically, this evaluation process has not been fail-proof, this is partly due to its reliance on the transparency of pharmaceutical companies when it comes to providing data regarding the safety and effectiveness of the drugs.
In 2013, for example, there was a big scandal surrounding ‘Tamiflu’, which led to the unravelling of a far bigger issue. Press was flooded with the news that drug companies only seemed to be publishing 50% of their clinical trial results, holding back important information.
In the case of Tamiflu, this had huge ramifications when the UK’s Department of Health spent £424 million stockpiling the drug but then had to write off a huge £74 million of that due to missing data as later findings concluded an inefficiency in preventing serious cases of flu.
However, nowadays strict measures and mandatory registrations have been implemented, such as ClinicalTrials.gov, which mean that trials have to be registered as soon as they start, making it more difficult for results to be hidden.
And Daniel (from the bible) and James (from the Royal Navy) were the first “trialists”
The concept behind this research can be traced back hundreds of years.
The typical protocol, consisting of both baseline (before intervention) and follow-up (after-intervention) observations compared between two groups of people, has been tracked all the way back to a 2nd Century biblical text, ‘The Book of Daniel’.
In the ‘Book of Daniel’, Daniel of Judah compared two diets over a 10-day period and measured the outcome — something comparable to a clinical trial. So as we can see, the premise is nothing new.
But as I recently learnt, the first actual clinical trial was performed in 1747 by James Lind, English Military Surgeon, and the ‘father of clinical trials.’
When at sea, Lind conducted an experiment that compared 6 different diets and the affect they had on scurvy in 12 sailors. But what was most significant about his experiment is that Lind was the first to use an actual control group — a group with which the treatment can be compared to assess the effect.
In doing so, Lind found that patients eating citrus fruits, including oranges and lemons, recovered much faster than those eating other kinds of foods.
Since Lind’s era things have only started to progress significantly in the last few decades. More recent advancements have led to the development of the most commonly-used format today — randomised controlled trials.
Typically, a randomised controlled trial is where you have two arms: treatments vs control. Each participant (volunteer taking part) is randomly (that is, being by chance alone) allocated to treatment with the investigational medicine or a placebo. A placebo is like a ‘sugar pill’ with no active ingredients but is identical to the treatment, and is commonly used as a control in clinical trials.
Today, there are an estimated 21 thousand recruiting clinical trials currently registered on ClinicalTrials.gov, investigating more that 2500 different conditions — each of these using the current model of clinical trials to investigate new treatments.
Randomised controlled trials have been coined the ‘gold standard’ of clinical research and there is no doubt about their efficacy when it comes to testing a new treatment or intervention, but this does not mean that these study designs are perfect… There are many aspects which could, and should, be improved.
So, what can we improve?
The current model of clinical trials means that we are typically evaluating one treatment or drug at a time.
When we consider the lengthy process it takes to develop the treatment, get ethical approval to run a trial, analyse the results and get the treatment licensed, this is a significant downfall. From the point of developing the drug to it being integrated into medical care, a considerable amount of time (and money) are spent, delaying making the most effective treatments available to patients. While timespan’s vary, going from initial drug development to licensing can take up to 10 to 15 years.
Furthermore, with individual trials all typically evaluating one intervention each, you have a number of competing trials trying to recruit patients. As mentioned above, there are around 21 thousands trials currently ongoing — all of these studies are recruiting patients and/or healthy controls, and most of the time patients are not able to be enrolled in more than one trial at one time, meaning that it becomes a real competition to recruit patients to a trial within the desired time frame.
It is also often reported that patients can find it difficult to navigate the complex clinical trial landscape.
Where do we go from here? A new platform trial!
On the 18th December 2019 a new project was announced — EU-PEARL (Patient-cEntric clinicAl tRial pLatforms).
EU-PEARL is a unique partnership bringing together 36 world-leading institutions for the first time, with the purpose of creating a new and adaptive clinical trial platform. The partners include European hospitals, research centres, patient groups, non-profit product developers and pharmaceutical companies.
This new project has the aim of shaping the future of drug development by changing the approach that we currently take to perform clinical trials with the creation of a platform trial.
EU-PEARL is funded by and backed by the Innovative Medicines Initiative (IMI).
I am delighted to be one of many researchers participating to this project, since my University, King’s College London, is an active partner and has a leadership role for depression. We are co-leading the Depression sector along with pharmaceutical company Janssen, global healthcare company NOVARTIS and coordinators, Vall d’Hebron Research Institute.
But what is a platform trial?
A platform trial is a clinical trial with a single master protocol (a guide that all studies have to strictly adhere to).
All clinical trials have separate protocols, however, the difference here is one overarching one, meaning that multiple treatments can be investigated at the same time, and, if a drug is not working, it can be removed from the trial, making way for a new drug to be tested. Master protocols have been described as being a way of efficiently answering multiple questions in less time.
In a typical clinical trial today, there are strict criteria which have to be met for including a patient, limitations on participating in further trials and restrictions on access to the drug following successful treatment in the trial. However, under this new approach, patients have the opportunity to try different drugs and access to the treatment will be made faster in the case of successful treatment.
As you can see, this addresses the limitations and areas of improvement mentioned when discussing the current model of clinical trials. EU-PEARL aims to transform the current approach and will focus on the patient's interests while also addressing medical needs to more quickly and effectively develop novel treatment compounds and with fewer participants.
The aim is to define a novel and enabling infrastructure where pharmaceutical companies and healthcare providers can work together to develop integrated research platforms as an achievable and realistic novel method to achieve better results in clinical studies.
In addition, modern-day research is also changing in light of a rise in technological advancements. Technological innovation and big data are opening a whole new window of opportunity in clinical research — One that EU-PEARL is also embracing with the development of digital phenotyping tools to identify patients who may be eligible to be included in the platform trial!
And all this will be done across four different diseases…
EU-PEARL, with its intent on shaping the future of clinical trials to become more patient-friendly in both design and outcome, will do so focussing on four very different disorders: Major Depressive Disorder, Tuberculosis, Non-Alcoholic Steatohepatitis and Neurofibromatosis.
These four disorders are very different in nature but are all currently facing a similar issue: getting new treatments made available to patients.
EU-PEARL, with these four disorders, is just the beginning: it will provide a valuable framework with which we can design and execute integrated research platforms in other disease areas.
With this new and unique collaboration between world-leading participants with different areas of expertise to bring together, we are hopeful that EU-PEARL can transform the future of clinical trial designs. With the new methods, tools and frameworks, it is our hope that trials will be better for patients and promote quicker access to new and novel medications.
And maybe one day students attending my course on Clinical Trials will study EU-PEARL as the first platform trial, as I am today studying James Lind!
DISCLAIMER: This article reflects the author’s view. Neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained therein. The EU-Pearl Project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 853966. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and CHILDREN’S TUMOR FOUNDATION, GLOBAL ALLIANCE FOR TB DRUG DEVELOPMENT NON PROFIT ORGANISATION, SPRINGWORKS THERAPEUTICS INC.
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