Depression can affect anyone. It is common and in many cases serious. These days, good treatments are available, usually involving a combination of psychotherapy and medication. However, finding the right treatment can take time. Not everyone responds equally well to every medication. Researchers at six European university medical centers, led by Charité – Universitätsmedizin Berlin, have collaborated to accelerate the process of deriving solid findings about new and known treatments. Key will be a joint study design, supported over the next four years with more than €13m (£11.7m) in funding from Wellcome.
According to the World Health Organization (WHO), major depression is one of the main contributors to the global burden of disease. Although there are many drugs available to treat depression – around 30 antidepressants have been approved in Germany alone – continuous improvement remains elusive for some patients, despite multiple attempts to use different treatment approaches. Why is this, and how can clinicians discover more quickly what really helps specific patients? Researchers at six member institutions of the European University Hospital Alliance (EUHA) systematically collaborate in the PEARLDIVER project to find answers.
Research “pearls” of depression
Clinical trials are the foundation of evidence-based medicine. However, many of the studies that have been conducted are not large enough to draw sound conclusions for clinical practice. In many cases, available treatments are only effective for some patients, and approval of new drugs for mental health conditions lags behind drugs for other medical fields, such as oncology, infectious diseases, and neurology.
“For patients with depression who do not respond to first treatment, there is a huge need for evidence-based, safe and effective new treatments,” explains Professor Christian Otte, Director of the Department of Psychiatry and Neurosciences at Charité Campus Benjamin. Franklin and medical director of the great European project. He has high hopes for the structured new approach: “Our platform study will significantly speed up the development and testing of treatments for depression. At the same time, we will be able to more quickly clarify which of the treatments already available are most promising for specific person”.
One structure – many studies
To find the “pearls” of depression research and quickly make new treatments available, researchers turned to the highly effective platform study method. While new or existing therapeutic approaches have previously been evaluated in individual studies, in which patients are randomly assigned to either an intervention or a control group, a platform study relies on a common infrastructure and a common control group to evaluate many different therapeutic approaches while maintaining even the principle of random group assignment.
Clinical trials are very resource intensive. They are time consuming and require a lot of effort. The previous practice was to create the entire infrastructure and logistics for each study from scratch. You could think of it like building a new stadium for every football game. At PEARLDIVER, we take a different route. Figuratively speaking, we build a big field together as a first step, and then all partners can use this infrastructure for an almost unlimited number of games – or, in our case, studies. In addition to speeding up the process, this also makes individual studies more meaningful and comparable.”
Prof. Stefan Gold, professor of clinical neuroscience at the Charité and scientific director of the project
The aim is to create a pan-European research infrastructure over the next four years that will enable researchers to reach consistent findings aligned to the highest possible scientific standards in comparisons of treatment and control groups to study new and known therapeutic approaches. The first year will mainly focus on building the platform. The platform will then assess the safety and effectiveness of the first two new depression drugs to demonstrate the trial’s suitability and effectiveness, with plans to add more treatments over time. Enrollment of participants is expected to begin in 2026.
Patients have a voice
Platform studies are already being used successfully in other areas of medicine, such as oncology research. This approach is new to mental health. Another novel aspect is that the patients themselves played a role in the design of the study as collaborative partners. Patient advocate Fanni-Laura Mäntylä explains: “Our aim is to work together to find better solutions for how clinical trials in mental health are designed and conducted, how mental health treatment evolves, how to better help people with mental health challenges health. The European Patient Forum (EPF) supports the project.
Since many treatments can be revised simultaneously, having a reusable infrastructure is extremely efficient. It represents less burden on study participants. Regulatory and ethical approval processes also take less time. Interim analyzes allow quick conclusions about whether a treatment will be promising, and apparently ineffective study groups can also be stopped quickly.
“This innovative platform study approach is very exciting because it will make testing new treatments for depression much more efficient and streamlined. It will help researchers work together to find answers about whether treatments are effective and for whom they would work best “, says Dr. Donoghue, Senior Research Director at Wellcome. This project to study depression, the largest in Europe, can also serve as a model for other mental health issues.
