Assessing EMA Outcomes in Xanomeline-Trospium Treatment for Schizophrenia

In this expert Q&A, first author Philip D. Harvey, PhD, University of Miami Miller School of Medicine, Miami, Florida, discusses the Ecological Momentary Assessment (EMA) sub studies that were completed as part of the EMERGENT-5 trial. Presented in a poster at the 2025 Schizophrenia International Research Society (SIRS) Annual Congress in Chicago, Illinois, the studies utilized EMA surveys to measure treatment effects of xanomeline-trospium in patients with schizophrenia. Dr Harvey unpacks the benefits of collecting momentary data reports, particularly in research focused on schizophrenia populations. He also discusses the trial’s findings on treatment-related reductions in disorganized behavior, delusions, and hallucinations, and the implications these data may have on real-world treatment planning.

For more expert insights, visit the Schizophrenia Excellence Forum. 

Editors' note: This interview has been lightly edited for clarity.

Psych Congress Network: In long-term management of schizophrenia, what specific clinical gaps or unmet needs do you think were addressed by integrating the EMA into the EMERGENT-5 trial of xanomeline-trospium? 

Philip D. Harvey, PhD: The EMA assessments offer momentary information on functioning.  Data on location, social context, activities, moods, and symptoms are collected concurrently. Thus, ratings of anxiety or sadness, as well as happiness, are completely temporally convergent with activities and changes in moods and activities can be examined for their longitudinal associations as well. 

PCN: How does the approach of using EMA to assess treatment effects in the EMERGENT-5 trial enhance our understanding of xanomeline-trospium’s impact compared to more conventional symptom rating scales? 

Harvey: Conventional rating scales collect dispersed assessment data. Thus, participants are asked to recall their experience, often over periods of time. Even healthy individuals would have a hard time providing a single report of their social activities or hedonic responses over 3 months; for participants with schizophrenia, this is clearly impossible. As a result, reports collected at assessments do not span the whole assessment period and it is not clear what they reflect: the most salient experiences, the most recent experiences, or some idiosyncratically selected sample. 

PCN: Implementing EMA in a schizophrenia population likely presented unique challenges. Could you share what obstacles were faced around patient adherence or data quality, and how those were managed throughout the study? 

Harvey: Challenges in assessments with EMA are manageable. Participants are compensated on a momentary basis for answering the surveys [receive a signal that] that their compensation has been delivered. There were participants who did not answer any surveys—these participants were also very likely (70%) to drop out before their first in-person reassessment—and were concentrated at the same research site. 

Thus, sampling adherence in a run-in to a treatment study will identify both participants and sites where poor data quality would be expected. Baseline symptom severity did not predict adherence to EMA surveys; nonadherent participants and poor sites yielded low-quality data across the board. 

PCN: The reported reductions in hallucinations, delusions, disorganized behavior, and sedentary time with xanomeline-trospium are compelling. How might these findings inform real-world treatment planning, and are there additional functional domains you hope to examine in future EMA-based research? 

Harvey: These data suggest that momentary assessments capture the important features of schizophrenia and their treatment response in real time. Monitoring for risk of relapse and detecting nonadherence early would also be important. Finally, identifying the link between change in objective behaviors and self-reported satisfaction, along with treatment and awareness of these changes, may lead to the ability to develop strategies to ensure adherence and treatment gains by ensuring that participants are aware of their level of improvement. 

PCN: Is there anything else you would like to share with our audience of practitioners? 

Harvey: The current study and previous studies have used passive digital phenotyping, including Global Positioning System (GPS) and actigraphy measures of steps and sleep to provide convergent validity data regarding self-reports of activities. Across several studies, momentary reports of the level of physical activity correlate with steps measured with actigraphy, and reports of current location correlate well with location data sampled with GPS. Thus, momentary reports may have a disarming effect, leading to reduced response bias. There is no time to think about what you “should be saying”. 

Philip D. Harvey, PhD, is a Leonard M. Miller professor of psychiatry and director of the Division of Psychology at the University of Miami Miller School of Medicine, as well as a senior research health scientist at the Department of Veterans Affairs. He started work at the University of Miami Miller School of Medicine in July of 2010. He has served on several National Academy of Medicine Panels and headed a blue-ribbon panel jointly launched by the Social Security Administration and the National Institute of Mental Health. Dr Harvey has also received a number of awards, including the Inaugural Schizophrenia International Research Society Clinical Scientist Distinguished Contributions award (2012), the 2014 Alexander Gralnick Schizophrenia Research award from the American Psychiatric Foundation, and the 2014 John Blair Barnwell award and 2021 Stanley Dean Award for Schizophrenia Research from the American College of Psychiatrists.

References
Harvey P, Chaturvedi S, Horan W, et al. Using active and passive digital phenotyping to index 12-month treatment effects of xanomeline and trospium chloride on physical activity in outpatients with schizophrenia. Schizophrenia International Research Society Annual Congress; March 29 – April 2; Chicago, Illinois.

Harvey P, Chaturvedi S, Horan W, et al. Psychosis and disorganized symptoms measured with Ecological Momentary Assessment (EMA): changes over a 12-month treatment trial of xanomeline and trospium chloride in schizophrenia. Schizophrenia International Research Society Annual Congress; March 29 – April 2; Chicago, Illinois.

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