Clinical trials involving controlled substances significantly increase complexity in trial design, execution, and more. However, given the promising potential of these treatments, does not deter the investigation of these substances in central nervous system (CNS) indications.
Running these trials successfully requires a true understanding of the laws and regulations surrounding this category of drugs across Europe. In this article, we will outline key considerations sponsors looking to run controlled substances clinical trials in the European Union (EU).
The number of these trials has been rising steadily with a notable increase in new trials over the past two years, according to data pulled from Citeline’s Trialtrove® (AUG 2023).
Note: This is a paid platform that requires a subscription and the data displayed is dynamic, changing in real time.
The rapid growth is fueled by rising research interest in CNS and Europe’s openness to studying controlled substances.
The development of drugs that interact with receptors in the brain and alter consciousness offer the potential for promising therapeutic benefits across a range of psychiatric, neurological, pain disorders.
Europe is an attractive destination for these studies due to diverse patients, expertise, and infrastructure that can support in the investigation of the safety and efficacy of these substance for therapeutic application.
Each European country categorizes controlled substances differently based on international drug conventions. The level of control depends on the substance’s potential for harm or abuse—high-risk drugs face stricter regulations than lower-risk ones.
While the EU Clinical Trials Regulation (EU-CTR) harmonizes processes for clinical trials across Europe, controlled substance protocols still require individual country approvals. Extra steps are still needed for handling, administration, and oversight compared to other investigational drugs.
These measures aim to prevent diversion and ensure proper use, but they also create logistical complexities versus standard clinical trials. Companies must budget more time and resources when working with controlled substances.
Under the EU-CTR, some differences in definitions and procedures for controlled substances have been unified across Europe. For example, rules for importing, storing, and transporting these drugs are now standardized. However, some country-specific nuances remain around aspects like license applications, dose preparation, documentation, and destruction requirements.
While the changes resulting from the EU-CTR have helped to streamline certain requirements, there still exists the need to navigate individual country variations and nuances. Sponsors should look to verify the current laws in each target country when planning a study.
5 Considerations for Managing DEA-Controlled Substances in CNS Clinical
Due to the added oversight and restrictions around controlled substances, the start-up phase requires extra attention compared to standard clinical trials. Sponsors must identify and mitigate risks early to prevent delays.
Key start-up tasks include:
Robust planning and strong oversight foundations during start-up are essential to comply with laws and run studies smoothly.
To avoid issues with controlled substance trials, sponsors should look to incorporate these best practice strategies into the planning:
Following these steps will help to minimize risk and avoid delays when working with this class of drugs.
Preventing controlled drug diversion or misconduct is critical from a liability standpoint. Our recommended risk mitigation strategies include:
Proper vigilance and protocols are the pillars of risk management in studies with scheduled drugs.
As the field of CNS research using controlled substances expands, the EU Clinical Trials Regulation will continue unifying processes, though some country-specific nuances are likely to remain. By staying current on evolving regulations and partnering with an experienced CRO, sponsors can navigate these requirements confidently.
Challenges will always exist, but the right expertise and preparation can allow controlled substance trials to realize the potential for good these treatments can offer patients impacted by CNS.
Olya Demireva is a Senior CTM bringing over 15 years of experience. She is a certified psychiatrist and clinical immunologist with 15 years of clinical research in CNS diseases and solid medical scientific background in biological psychiatry with focus on Major Depression and Bipolar Disorders, and neuro-psycho-immunology. Her experience in clinical research spans over almost all therapeutic areas with emphasis on Oncology, Pulmonology, Cardiovascular Diseases, Sleep Disorders, Hematology, Endocrinology and Rare Diseases across phases I-IV.
Saoussen Brun is a Senior Director of Project Management at Precision for Medicine. She brings more than 18 years of Clinical and Project Management experience to the Precision team. Saoussen’s expertise covers a wide variety of therapeutic areas, with strong experience in oncology and neurology indication. She leads and motivates high-performing teams under tough deadlines to meet both project goals and company targets.
Precision for Medicine is part of the Precision Medicine Group, an integrated team of experts that extends Precision for Medicine’s therapeutic development capabilities beyond approval and into launch strategies, marketing communication, and payer insights. As one company, the Precision Medicine Group helps pharmaceutical and life-sciences clients conquer product development and commercialization challenges in a rapidly evolving environment.
