Search

Background: Improved patient life engagement is a meaningful treatment goal in schizophrenia that cannot be satisfactorily measured using existing tools. This research aimed to determine whether certain items from the Positive and Negative Syndrome Scale (PANSS) can assess patient life engagement in schizophrenia., Methods: Three approaches were used to identify PANSS items that reflect patient life engagement: (1) a panel discussion with expert psychiatrists (n = 4); (2) interviews with patients with schizophrenia (n = 20); and (3) a principal component analysis to explore clustering of items (n = 954 from three randomized controlled trials). Internal consistency was assessed by Cronbach's alpha and item-total correlations. A minimal clinically important difference (MCID) was determined by anchor- and distribution-based methods., Results: Expert psychiatrists identified 11 relevant items, and patients rated 13 items as "very relevant" to patient life engagement, most of which clustered in the principal component analysis. Considering all results, a composite set of 14 PANSS items that may be relevant to patient life engagement in schizophrenia was devised: P2, N1, N2, N3, N4, N5, N6, N7, G6, G7, G11, G13, G15, G16 (Cronbach's alpha, 0.84; item-total correlations, 0.35-0.56, indicating acceptable correlation with the underlying concept; exception: G6 [depression], 0.19). An MCID of 5 points (small/moderate improvement) or 10 points (large improvement) may be appropriate., Conclusions: A subset of 14 PANSS items may be used to reflect patient life engagement in clinical practice/trials in schizophrenia, complementing the results of traditional psychiatric symptom scales with a patient-centered outcome that is relevant to real-world treatment goals., Competing Interests: Declaration of competing interest Zahinoor Ismail has received grant support from CIHR, NIH, Brain Canada, and Weston Foundation, and has served as a consultant for Eisai, Eli Lilly, Lundbeck, Novo Nordisk, Otsuka and Roche. Zahinoor Ismail is also supported by the UK National Institute for Health and Care Research Exeter Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Stine R. Meehan, Anja Farovik, and Stephane Alexandre Regnier are full-time employees of H. Lundbeck A/S. Maia Miguelez was a full-time employee of Otsuka Pharmaceutical Development & Commercialization Inc. at the time of this work. Shivani Kapadia and Zhen Zhang are full-time employees of Otsuka Pharmaceutical Development & Commercialization Inc. T. Michelle Brown and Mirline Milien are full-time employees of RTI Health Solutions, contracted to conduct this research on behalf of the sponsor. Roger S. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; and speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. He is a CEO of Braxia Scientific Corp., (Copyright © 2024. Published by Elsevier B.V.)

Background: Familial chylomicronemia syndrome (FCS) is a rare metabolic disorder that impacts physical, emotional, social, and cognitive functioning. The FCS-Symptom and Impact Scale (FCS-SIS) patient-reported outcome (PRO) measure assesses common symptoms and impacts of FCS. This study was conducted to evaluate cross-sectional psychometric properties of the FCS-SIS and its scoring method., Methods: This multisite, cross-sectional, observational study of individuals with FCS was conducted in the United States and Canada. Participants completed a survey composed of 7 PRO measures, including the FCS-SIS, and questions about clinical characteristics and demographics. The structure of the FCS-SIS was evaluated using inter-item and item-scale correlations and internal consistency reliability. Construct, known-groups, and criterion validity were evaluated by examining associations between FCS-SIS item and composite scores and other measures included within the survey., Results: Most of the 33 participants were female (63.6%) and White (78.1%). On average, participants reported first noticing FCS symptoms at ~16 years, with abdominal pain the most frequently reported initial symptom (n=20). Participants reported 2.5 acute pancreatitis attacks on average over the past year. Average FCS-SIS symptom item scores ranged from 1.8 to 3.9 (on a 0-to-10 scale [none-to-worst-possible]) within the 24-hour recall period, with an average Symptom composite score of 2.7. The average impact item scores on the FCS-SIS ranged from 1.6 to 3.0 (on a 0-to-4 scale), with an average Impact composite score of 2.1. Inter-item correlations between the FCS-SIS Symptom items ranged from 0.32 to 0.78. Corrected item-total correlations were highly satisfactory for Impact items, ranging from 0.62 to 0.85. All a priori validity hypotheses were supported by observed correlations and score differences between known groups., Conclusion: The results of this study support the structure, reliability, and validity of the FCS-SIS, laying the psychometric groundwork for longitudinal evaluation of its utility in assessing treatment benefit in FCS clinical studies., Competing Interests: TMB and SF are full-time employees of RTI Health Solutions, an independent nonprofit research organization, which was retained by Ionis Pharmaceuticals to conduct the research which is the subject of this manuscript. Their compensation is unconnected to the studies on which they work. CK was an employee of RTI Health Solutions at the time the research was conducted. MVL, ASK, and AY are employees of Ionis Pharmaceuticals and hold shares and/or stock options in the company. The authors report no other conflicts of interest in this work., (© 2024 Brown et al.)