Sleep Methodology in CNS Trials Working Group

Chairs: Margaret Moline, PhD; Georg Dorffner, PhD

Upcoming Activity: Working Group Meeting, 2025 Autumn Conference includes joint day with ECNP, 9-11 October 2025, Amsterdam, The Netherlands

This working group aims at contributing to a better understanding of the use of sleep-related measurement methodology in CNS trials, as well as promoting their use. Since its initiation in 2024 the WG has made progress toward two deliverables:
• A review paper on sleep and vigilance-related endpoints that have been proven to be potential biomarkers for predicting or monitoring different psychiatric and neurological disorders. At the latest meeting the decision was to split the exercise by disorder, each covered by one or two volunteers.
• A consensus paper on validation methods for novel instruments (such as portable EEG devices, photo-plethysmography, actigraphy, etc.) deriving such trial endpoints. Here the proposal is to define a rigorous framework of statistical equivalence testing exploiting the well-known inter-rater variability of the gold standard as a basis for setting tolerance intervals. Also, a call for references and potential further statistical frameworks was issued.
This session will be mainly devoted to finalizing the first deliverable after presenting a first draft merging all individual contributions. Furthermore, the methodology for statistical equivalence testing as a cornerstone for the second deliverable will be discussed and refined.

Most Recent Activity: Working Group Meeting, 21st Annual Scientific Meeting, 19-21 February 2025, Washington DC – View summary – view slides

Working Group Meeting, 2024 Autumn Conference, 12-13 September 2024, San Diego, CA – View summary – view slides

INAUGURAL MEETING: 20th Annual Scientific Meeting, view summary, 21-23 February 2024, Washington DC – view slides

Sleep is a naturally occurring state of mind and body accompanied by recurrent state of reduced responsiveness to external stimulation that is accompanied by complex and predictable changes in physiology The main idea behind this working group is the fact that both nocturnal sleep and its diurnal counterparts (vigilance, wakefulness, fatigue, somnolence, etc.) are such central physiological states that they are affected by most neurological and psychiatric disorders and thus deserve attention in a large number of CNS trials. Current methodologies of objectively measuring sleep and wakefulness, such as polysomnography or multiple sleep latency tests (considered “gold standard” in many respects), all have advantages as well as major disadvantages preventing them from being more widely used in trials. In this context, possible foci of the working group are:
• A critical assessment of various modalities for characterizing sleep, wakefulness and related states and for assessing the impact of clinical trial interventions on these states. The analysis of alternative methods of measuring sleep and wakefulness and their potential applicability in CNS trials.
• Criteria for proper validation of such methods against the gold standard
• The relationship of such objective methods of measurement with subjective assessments of sleep and wakefulness and the exploitation thereof
• Key issues in the development of novel modalities of assessing sleep, wakefulness and related states that would contribute to our understanding of the impact of such interventions while being acceptable to regulatory and competent authorities.

Consequently, possible products as the outcome of the working group are:
• Systematic reviews on the evidence of the reliability and validity of different instruments for measuring sleep and wakefulness
• A consensus paper on criteria and validation strategies for measurement instruments
• The initiation of a pre-competitive study with industry participation aimed at benchmarking certain instruments for their use in CNS trials