Boosting drug development for depression with an integrated research platform

By WP4 (Stefan M. Gold, Yanina Flossbach, Witte Hoogendijk, Christian Otte, Carmine Pariante, Toni Ramos-Quiroga)

Depression, or “major depressive disorder” (MDD) as it is known by the medical community, is a serious and life-threatening condition with high rates of morbidity and a chronic disease course. It affects approximately 1 in 6 adults at some point during their lifetime and this pattern is seen – with just small variations – throughout the entire world. This makes depression one of the two most “costly” non-communicable diseases in terms of years lost to disability and burden of disease worldwide. MDD is also associated with substance abuse, suicidal behavior, and many other mental and somatic health conditions, accounting for a substantial proportion of the “mental health crisis”.

Depression one of the two most “costly” non-communicable diseases in terms of years lost to disability and burden of disease worldwide.

While considerable efforts over the past 40 years have led to the introduction of safer and better tolerated pharmacological treatments for depression, they only achieve sufficient symptom reductions in about 50% of the patients with this disabling condition. Importantly, the major drug classes in this area were discovered and developed decades ago and there have been very few successful attempts to develop novel drugs since. Moreover, there is  a paucity of potential treatments with new mechanisms of action, that could help those patients for whom the current medications fail to alleviate symptoms. Consequently, there have been very few new approvals in this area recently and the number of new regulatory approvals in psychiatry has consistently lagged behind other areas of medicine, such as oncology, infectious diseases, or neurology.

The number of new regulatory approvals in psychiatry has consistently lagged behind other areas of medicine, such as oncology, infectious diseases, or neurology.

All of the medications available today for MDD have been developed by the current paradigm of “one drug, one trial”. This is effective in the sense that it will eventually provide an answer whether a drug works and is safe. However, this approach is slow and not very efficient with regard to the resources required and the number of participants who need to volunteer in order to provide a robust estimate of treatment efficacy. In addition, exposure of a vulnerable patient population such as MDD to placebo, which is often used as a comparator especially in earlier phases of drug development, is also a concern and associated with safety risks in clinical trial settings.

New approaches to more quickly and more efficiently detect the most promising new drug candidates could therefore substantially accelerate the development of new medications and improve the clinical care for those patients who currently do not benefit from the available pharmacological treatments. At EU-PEARL, we are developing what is called an “integrated research platform”, that provides a reusable infrastructure for screening, enrolling, and assessing/treatment of participants in a flexible and highly adaptive “platform trial”.

New approaches to more quickly and more efficiently detect the most promising new drug candidates could substantially accelerate the development of new medications.

Unlike traditional “one drug, one trial” approaches, this allows new treatments to be added to the trial anytime they become available for testing and discontinued as soon as it becomes apparent that they do not work as well as expected. This approach can dramatically increase the speed by which the best treatments can be selected for further development and regulatory approval, and reduce operational costs associated with clinical trial conduct and execution. The integrated research platform also requires fewer participants overall and – importantly – fewer participants will receive placebo treatments in this setting.

Patient-centricity is key in this type of trial and all key stakeholders including patient advocacy groups and associations are already involved in the planning stages of the research platform. By establishing a patient-focused network of clinical investigators and sites, we are aiming to more seamlessly integrate this type of trial into routine clinical care, reducing the extra efforts required for participation by physicians as well as patients.

Platform trials can “host” many different types of treatments at any given time, therefore providing patients with higher variety and better treatment options.

Ultimately, platform trials can “host” many different types of treatments at any given time, therefore providing patients with higher variety and better treatment options. Indeed, such platforms will include the possibility of testing novel drugs with innovative mechanisms of action and routes of administration, such as fast-acting intravenous antidepressants, and will have the potential to respond quickly to new, unforeseen developments in the way future antidepressants will work and/or will be given to patients. Moreover, this approach offers flexibility for the sites and patients, accelerating the development of new treatments

Our approach thus has the potential to provide a significant boost to new treatments for depression, bringing them to the patients, and serving as a blueprint for similar endeavours in other areas of psychiatry.

Find out more about EU-PEARL patient-centric strategy here.

Read about our Integrated Research Platform approach here

Learn more about platform trials here

 

 

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