Methodological issues in negative symptom trials
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Updated: Jun 4, 2026

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Published on: July 7, 2023
Stephen R Marder1, David G Daniel, Larry Alphs
1The Semel Institute for Neuroscience at University of California, Los Angeles, CA, USA.marder@ucla.edu
Abstract:
Individuals from academia, the pharmaceutical industry, and the US Food and Drug Administration used a workshop format to discuss important methodological issues in the design of trials of pharmacological agents for improving negative symptoms in schizophrenia. The issues addressed included the need for a coprimary functional measure for registration trials; the characteristics of individuals who should enter negative symptom trials; the optimal duration for a proof-of-concept or registration trial; the optimal design of a study of a broad-spectrum agent that treats both positive and negative symptoms or a co-medication that is added to an antipsychotic; the relative strengths and weaknesses of available instruments for measuring negative symptoms; the definition of clinically meaningful improvement for these trials; and whether drugs can be approved for a subdomain of negative symptoms.
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