Depression affects approximately 1 in 6 adults worldwide at some point during their lifetime. Finding the right treatment for depression is challenging, because although there are a lot of different therapies to choose from, not everyone responds equally well to the medications available. About half of all patients show either only a partial response or a total lack of response to antidepressants.
Traditionally, to test the effects of different treatments a series of clinical trials would have to be run. But clinical trials are notoriously resource- and time-intensive and require a lot of infrastructure to be established for each individual trial. Recruitment of participants can also be challenging.
The EU-PEARL project developed a new type of platform trial where several treatments can be tested at the same time, using a shared infrastructure and participant pool. The design is based on a single master protocol to which new treatment groups can be added at any time and treatments that prove ineffective can quickly be dropped.
EU-PEARL successfully developed a master protocol specifically for depression studies, and this will now be used in the first Europe-wide platform study on the safety and efficacy of treatments for depression.
With funding from the Wellcome Trust, the platform trial will be rolled out in six European countries – Germany Spain, the Netherlands, Italy, Denmark and the UK. Two drugs plus a shared placebo arm will be investigated initially, with plans to add more treatments over time.
“The initial EU-PEARL funding really paved the way for our successful application because it allowed us to carefully think about all different aspects that need to be taken into account when planning and conducting a platform trial in mental health,” says Christian Otte, director of the clinic for psychiatry and psychotherapy at the Charité Universitätsmedizin Berlin.
“It was important that we developed the required tools such as statistical simulation software, master protocol templates and so forth during EU-PEARL,” says Stefan Gold, head of the research group on neuropsychiatry at Charité Universitätsmedizin. Both were involved in the development of the master trial protocol in EU-PEARL and are now part of the new trial.
“What was maybe even more influential was that we were also able to build a broad coalition of stakeholders including experts by experience, regulators, clinicians, industry and ethics commissions. Because of EU-PEARL, we had a track record of successful collaboration and all the pieces were in place to demonstrate that this will actually work in practice.”
The advantages of using platform trials are that robust results can be delivered more quickly, there is less of a burden on study participants, and both regulatory and ethical approval processes take less time. In addition, treatment pathways that are clearly not working can be cut off without losing the investment of too many resources. Patients benefit from an increased likelihood of receiving a promising treatment instead of a placebo and this method also makes it easier to recruit participants.
As a first step, the platform will be fine-tuned for the specific needs of the study, and in 2026 the enrolment of patients will begin.
EU-PEARL was supported by the Innovative Medicines Initiative, a partnership between the European Union and the European pharmaceutical industry.