Clinical Outcomes in Early-Phase Clinical Trials

Mission statement/aims

The overarching goal of this ECNP Thematic Working Group (TWG) is to bring together excellent researchers and experts across disciplines from throughout Europe and beyond to increase the efficiency of early trials in the context of drug development by promoting efficient strategies for clinical outcome selection that are applicable to different therapeutic areas in the CNS. This goal is to be achieved in the following ways:

• Promoting the identification, validation and standardization of Core Outcome Sets (COS) for interventional studies, including the validation of measurement methods.
• Promoting the validation of measurement methods in the regulatory context of Fit-For-Purpose (FFP) Clinical Outcomes Assessments (COAs) aimed at detecting efficacy in early trials. This task includes exploring the correlations among FFP COAs with biomarkers and neuro-imaging, defining its benchmarking in terms of clinical, functional and quality-of-life measures, and generating adequate evidence to support its content validity and patient-centricity as a core element of drug discovery.
• Conducting research to explore the use of cognitive endpoints (Performance-Reported Outcomes – PerfOs) as tools to optimize early trial designs, for example, in terms of sample size and stratifying/covariant factors.
• Establishing bridges between academia and industry to accelerate the application of available measurement methods in early trials for drug development (FFP and patient-centric approaches).
• Offering guidance to research groups regarding the application of scientific COA methods in innovative interventional contexts to accelerate innovation in this field.
• Submitting collaborative international multicentre research proposals to the EU Commission and comparable agencies that are specific to therapeutic areas or transnosological opportunities.
• Accelerating the validation of new measurement tools by overcoming the barriers that prevent the use of the existing datasets of completed clinical trials and facilitating access to cohort studies (RWE).
• Developing a shared database of the available data to facilitate collaborative research.
• Promoting a better understanding of needs and challenges related to specific indications by regulatory authorities and health agencies to support clinical outcome validation.
• Offering training and educational programs on COA Science applied in clinical trials.
• Lobbying policy-makers at the national and international levels to increase research budgets for scientific COS/COA research.

History

The ECNP Thematic Working Group in Clinical Outcomes in Early-Phase Clinical Trials has its roots in interactions among experts at the ECNP and at the International Society for CNS Clinical Trials and Methodology (ISCTM). Due to our concerns regarding the number of clinical trials with negative results in neuroscientific fields, we agreed that we had a common interest in promoting good practices in COA selection, encouraging innovation and boosting the application of the most innovative approaches in early trials for drug development.

The members of this TWG have been working together since 2018 under the auspices of the Experimental Medicines TWG at the ECNP and the mentorship of Gerry Dawson.

Since that time, we have succeeded in attracting representative of the various stakeholders involved in drug development to our working group, including experts from academia, the pharmaceutical industry, service provider companies, expert consultants and experts from medical health agencies. With a current total of more than 40 affiliated members, we have common goals and sufficient motivation to advance those goals.

During the past three years, we have conducted regular meetings and organized webinars to share information and learn from experienced researchers with respect to the methodology used in COA selection, which are known as SMART sessions. These sessions offered us the opportunity to engage in deep discussions with experts regarding scientific, methodological and strategic topics. SMART sessions additional materials are available upon demand.

As a next step, we plan to consolidate our group and interact with other existing TWGs to contribute to specific projects. Projects whose goal is to promote efficient trial outcome selection/development strategies is our focus of interest; we also intend to make joint efforts to apply for public funding.