The benefits of platform trials
This is the second article of a brand-new series inspired by EU-PEARL (EUropean-Patient-cEntric clinicAl tRial pLatforms). The EU-PEARL project aims to shape the future of clinical trials, creating a framework for platform trials.
Before a new treatment can enter the market, it must undergo rigorous testing. This is usually done through a randomised controlled trial (RCT): a study considered to be the gold standard at comparing the therapeutic effect of a new intervention against a control such as treatment-as-usual (TAU) (a currently accepted treatment for a condition). Check out this blog to find out more about this topic.
A standard RCT is suitable when investigating a single question focusing on the safety and effectiveness of a single intervention. However, this approach can be costly, take a long time to complete, and has resulted in many drugs failing to progress to the final stages of development.
So, what if we want to identify new effective medications for serious conditions more rapidly while recruiting the minimal number of patients to do so?
This is where platform trials come in.
I am Nare, a research assistant working at the Stress, Psychiatry and Immunology (SPI) lab at King’s College London. As part of my work with the EU Patient-CEntric ClinicAl TRial PLatform (EU-PEARL) project, I am writing this blog to inform others about some of the benefits of adopting a platform trial design. The main goal of the project is to improve patient outcomes by developing the framework and infrastructure to conduct platform trials for major depressive disorder (MDD), as well as other diseases, with patient involvement.
Platform trials are like the new kid on the block. The main defining features of their design include:
Testing several treatments that show promise in treating a particular disease at the same time, with the potential to swap treatments in or out.
Having a single common control group for comparing against different treatments being tested, instead of having a control for each treatment.
The use of a single ‘master protocol’, as opposed to preparing a protocol or guide of key trial design elements, for each separate treatment trial.
Examples of previous platform trials
Platform trials are most commonly conducted in the field of cancer.
STAMPEDE, an early and greatly successful platform trial for prostate cancer, adopted the platform design as a way to efficiently test several available potential treatments at the same time, thus overcoming the limitation of conducting a randomised trial for each treatment separately.
Furthermore, the platform design allowed researchers to change the TAU, which was deemed more ethical than continuing with the previous TAU when new evidence indicated otherwise.
More recently, the COVID-19 pandemic was the perfect example which demonstrated that it is possible to work collaboratively on a never-before-seen scale and get funding sooner in order to start testing multiple promising treatments in platform trials to meet the urgent need for reducing deaths and hospitalisations.
One trial in particular has received much positive attention worldwide. With its large-scale design, the RECOVERY trialvery quickly began recruiting patients and obtaining findings that would inform key decision-making. This had a major beneficial impact for patient outcomes. The trial team managed to show that a particular anti-malarial drug did not work, and so it was discontinued, while also showing the therapeutic benefit of a seperate anti-inflammatory steroid drug at minimising deaths by a third among hospitalised patients requiring ventilators.
This demonstrated the potential of applying this clinical design to other diseases.
The field of mental health, however, has not seen substantial progress in drug development. It could, therefore, benefit from some of the advantages of platform trials. This includes having a single common control group, which reduces the differences that can arise between individual psychology trials based on the type of control group used, and so allows for comparisons to be made more easily between the treatment vs control groups.
Positive aspects of platform trials
Instead of focusing on testing a particular intervention, platform trials tend to be more disease-focused than standard clinical trials as they want to investigate which interventions would work for treating a particular disease. This allows for more patient involvement and will likely provide more information about the condition.
Furthermore, with platform trials you are getting the best of both worlds.
Similarly to basket and umbrella trials, which investigate either a single intervention for multiple diseases or vice versa, platform trials utilise a ‘master protocol’. This is essentially a single overarching manual describing how the trial is to be conducted that uses a single shared infrastructure under which all treatments are tested, to make sure that the same trial procedures are followed.
But what differentiates platform trials from basket and umbrella trials is the ‘adaptive’ design used in, surprise surprise, adaptive trials which don’t have a master protocol.
This design allows for flexibility and means that, if during the middle of the trial the results show that a particular treatment is not working very well, it can be dropped or a new treatment can be added. This can go on continually, instead of waiting until the end of the trial to find out the outcome for a particular intervention like for standard RCTs. Especially when lives can be saved.
Moreover, in circumstances where a particular intervention is found to be successful at treating a disease and it receives approval to be the new TAU for that condition, then the control group can be updated halfway through — like in the STAMPEDE trial I mentioned earlier.
Since a common control group is used, fewer participants will need to be recruited overall in order to test the therapeutic effect of a given treatment, thus saving time and resources. This also means that participants are more likely to be randomly allocated to one of the treatment groups than the control group. Furthermore, the probability of being allocated to the more effective treatments can be adjusted based on results that are obtained during the trial, which is a method called response-adaptive randomisation.
These aspects of the trial design make platform trials more ethical than standard RCTs, since less participants will receive treatments that perform badly or the control intervention. This may encourage more recruitment and is beneficial in psychology trials where participants assigned to the control group may have to wait until after the trial to receive the therapy.
Well, what about the cost?
It is no secret that RCTs are very expensive to carry out.
One study aimed to understand whether platform trials presented any economic benefit over conventional trials. They found that even though the initial cost and time of setting up a platform trial was generally higher, in the long-term this design was shown to be more efficient and incurred a lower total cost compared to conducting several separate trials; due to some of the benefits discussed already.
Despite all these benefits, platform trials are no easy feat. They require a lot of careful planning and consideration of some of the challenges relating to the management and running of this type of trial, and whether it can realistically be done.
The EU-PEARL project is aiming to address these difficulties by bringing together experts from various fields in order to successfully design platform trials for 4 diseases, with the hope of delivering much-needed effective treatments to patients more quickly.
DISCLAIMER: This article reflects the author’s view. Neither Innovative Medicines Initiative (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 IMI 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.