Developing a transdiagnostic core outcome set protocol for perception and understanding of self

Reconceptualising traditional diagnostic boundaries into broader transdiagnostic concepts grounded in biological mechanisms is a promising new avenue within precision medicine. However, validated, reliable and regulatory-approved core outcome measures are necessary to be able to apply these concepts to clinical research. Perception and understanding of self is a construct in the Research Domain Criteria framework, containing the two subconstructs self-knowledge and agency. Self-knowledge is characterised by the ability to evaluate one’s internal states, whereas agency is the capacity to perceive oneself as the responsible of our own actions and thoughts [1,2]. Disruptions to these subconstructs are seen in many psychiatric conditions, including depression, borderline personality disorder, autism, schizophrenia, eating disorders and obsessive-compulsive disorder [3,4]. This research protocol, developed within the context of the Course on Health outcomes: Standards for clinical research in Neuroscience at the European College of Neuropsychopharmacology Learning Hub, aims to present the steps necessary to create a fit-for-purpose core outcome set for the transdiagnostic constructs self-knowledge and agency.

The development of the clinical outcome set protocol will follow the seven-step method. The first step consists of a qualitative literature review based on the SPIDER search tool. This procedure will permit the identification of the relevant disorders that present alterations in the perception of self. Once the scope of use is assessed, the design of the preliminary common endpoint model will begin. The core outcome set will consist of two measurement methods, a patient-reported outcome, in the form of a transdiagnostic questionnaire, and a performance outcome, a standardised behavioural task which will be combined with neuroimaging. A Delphi panel, integrated by different stakeholders involved in the matter (e.g., clinicians, patients grouped by disorder, and/or caregivers), will participate in refining and reaching consensus on a list of concepts of interest that the core outcome set will measure. Once the dimensions of interest are agreed on, Medline and EMBASE search tools will be used to examine the available existing Outcome Measurement Instruments and to select the most suitable for measuring the core concepts. Post hoc analysis will then be conducted to address remaining gaps and limitations that may have been overlooked during the initial screening.

Adopting the Research Domain Criteria framework, this multi-level core outcome set links subjective experience with objective behavioural and neural indices of self-knowledge and agency. Although requiring validation, the objective of this core outcome set is to provide standardised, regulatory-aligned metrics for use across psychiatric conditions where the field currently lacks a standardised consensus measure. These sub-constructs are disrupted across many disorders, therefore a core outcome set such as this can improve mechanistic understanding while also practically serving as secondary or exploratory endpoint in clinical trials, refining treatment targets and increasing access to self-assessment among relevant patient populations.

References

1. Thai, M., Başgöze, Z., Schreiner, M. W., Roediger, D. J., Falke, C. A., Mueller, B. A., Fiecas, M. B., Quevedo, K., Pfeifer, J. H., Klimes-Dougan, B., & Cullen, K. R. (2024). A multi-modal assessment of self-knowledge in adolescents with non-suicidal self-injury: A research domains criteria (RDoC) study. Psychological Medicine, 54(12), 3273–3284. 2. Haggard P. Sense of agency in the human brain. Nat Rev Neurosci. 2017 Apr;18(4):196-207. doi: 10.1038/nrn.2017.14. Epub 2017 Mar 2. PMID: 28251993. 3. Palma, A. M. G., Sánchez-Sánchez, L. C., & Garcia-Montes, J. M. (2021). Is “Self-Experience” Really a Transdiagnostic Concept? Preliminary Evidence in Favor of the Transdiagnostic Conception of Functional Analytic Psychotherapy. Frontiers In Psychiatry, 12. https://doi.org/10.3389/fpsyt.2021.671223 4. Eddy, C. M. (2022). The Transdiagnostic Relevance of Self-Other Distinction to Psychiatry Spans Emotional, Cognitive and Motor Domains. Frontiers in Psychiatry, 13. https://doi.org/10.3389/fpsyt.2022.797952