An Optimized Version of the Positive and Negative Symptoms Scale (PANSS) for Pediatric Trials

Background: Multiple clinical trials of modern antipsychotics have failed in pediatric samples. One possibility for these failures is the use of a primary outcome measure that was developed for adults. Surprisingly, the psychometric properties of primary outcome measures have never been reported for a pediatric sample using modern methods. The present study’s aim is to use a pediatric sample to evaluate the psychometrics of the most used primary outcome measure in pediatric schizophrenia trials, the Positive and Negative Syndrome Scale (PANSS). Methods: To evaluate the factor structure, item characteristics, and treatment sensitivity of the PANSS in a pediatric sample, secondary analyses of PANSS data at baseline and weekly throughout an 8-week randomized double-blind study of three antipsychotic agents (registered and previously published) were conducted. Subjects were 118 youths receiving outpatient psychiatric treatment for schizophrenia spectrum disorders (Mage=14.26(2.41) years). Outcomes: A 10-item short form, keeping two strongest items for each factor, had r=.89 with the full-length scale. Each of the 5 2-item subscales has alphas ranging from .66 to .84. Item Response Theory (IRT) found that the 10-item scale and 2-item subscores had high reliability across the severity range typical of clinical trials. Criterion validity was high, with equal sensitivity to treatment effects. Interpretation: The short version eliminates weaker items in the pediatric population without loss of sensitivity to treatment effects and thus may be more appropriate for subsequent pediatric trials. Funding: NIMH funded the original protocol; NDA archived the data; Signant paid for secondary statistical analyses. Declaration of Interest: Dr. Findling receives or has received research support, acted as a consultant and/or has received honoraria from Acadia, Adamas, Aevi, Afecta, Akili, Alkermes, Allergan, American Academy of Child & Adolescent Psychiatry, American Psychiatric Press, Arbor, Axsome, Daiichi-Sankyo, Emelex, Gedeon Richter, Genentech, Idorsia, Intra-Cellular Therapies, Kempharm, Luminopia, Lundbeck, MedAvante-ProPhase, Merck, MJH Life Sciences,NIH, Neurim, Otsuka, PaxMedica, PCORI, Pfizer, Physicians Postgraduate Press, Q BioMed, Receptor Life Sciences, Roche, Sage, Signant Health, Sunovion, Supernus Pharmaceuticals, Syneos, Syneurx, Takeda, Teva, Tris, and Validus. Dr. Youngstrom has received royalties from the American Psychological Association and Guilford Press, consulted with Signant Health about psychological assessment, and received funding from NIMH. He is the founder and Executive Director of Helping Give Away Psychological Science (HGAPS.org). Dr. Sikich receives or has received research support from NIMH, NICHD, and Roche. She has received partial salary support from Tris. She has a patent submission through Duke University for a new formulation of intranasal oxytocin. Dr. Frazier receives or has received funding from NIMH, NICHD, Autism Speaks, Roche pharmaceuticals, and Fulcrum. Dr. McClellan receives or has received funding from NIMH. Dr. Daniel is an employee and equity holder in Signant Health. Dr. Busner is an employee and equity holder in Signant Health. Ethical Approval: The secondary analyses were reviewed and approved by the UNC Chapel Hill IRB.