Health-related quality of life in patients with prominent negative symptoms: results from a multicenter randomized Phase II trial on bitopertin
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Symptoms of schizophrenia fall into three categories (positive, negative and cognitive symptoms), which probably impact differently on patient’s health-related quality of life (HRQoL). The present study aimed to explore HRQoL in patients with prominent negative symptoms.
In the 323 patients with prominent negative symptoms included in a multicenter Phase II trial investigating the safety and efficacy of bitopertin, HRQoL was assessed using the Schizophrenia Quality of Life Scale (SQLS), symptoms severity using the Positive and Negative Syndrome Scale and functioning using the Personal and Social Performance Scale. SQLS measurement properties were assessed; HRQoL was compared between treatment arms, and relationships between HRQoL, symptoms and functioning at baseline were explored.
Both SQLS scores (Vitality/Cognition and Psychosocial Feelings) demonstrated good test–retest (ICC = 0.77 and 0.74) and internal consistency reliability (Cronbach’s α = 0.86 and 0.93). Clinical validity with regard to schizophrenia severity and ability to detect change in severity of symptoms of schizophrenia were satisfactory. The SQLS structure was not formally disconfirmed. No statistically significant difference was observed between treatment arms. Negative symptoms were more strongly associated with functioning than positive symptoms. Functioning and Anxiety/Depression were strongly related to both SQLS domains.
Overall, SQLS measurement properties were supported in these patients with prominent negative symptoms of schizophrenia. The impact of negative symptoms on functioning and HRQoL suggests that improving these symptoms will be a meaningful benefit in this population of patients.
KeywordsQuality of life Schizophrenia Negative symptoms Bitopertin
The authors would like to thank Fatoumata Fofana (Mapi) for support with the statistical analysis, and Jérémy Lambert (Mapi) for medical writing assistance and editorial support in manuscript preparation. J&J agree and acknowledge that OXFORD OUTCOMES exclusively owns all intellectual and other property rights, including all worldwide copyrights to the SQLS and revisions to it for perpetuity. From 2003, OXFORD OUTCOMES is permitted to consent to the use of the SQLS or revisions of it by any person or entity subject to them signing the user’s agreement without the permission or knowledge of J&J.
Compliance with Ethical Standards
This study was funded by Hoffmann-La Roche.
Conflict of interest
DR and SS are employees of Roche Products LTD, and CGB and DU are employees of F Hoffmann-La Roche. AR, employee of Mapi, was paid consultant to Roche Products LTD. RF was paid consultant to Roche Products LTD.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 1.U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, and Center for Devices and Radiological Health. (2009). Guidance for industry. Patient-reported outcome measures: Use in medical product development to support labeling claims. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM193282.pdf
- 14.Noetzel, M. J., Jones, C. K., & Conn, P. J. (2012). Emerging approaches for treatment of schizophrenia: Modulation of glutamatergic signaling. Discovery of Medicine, 14(78), 335–343.Google Scholar
- 15.Pinard, E., Alanine, A., Alberati, D., Bender, M., Borroni, E., Bourdeaux, P., et al. (2010). Selective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia. Journal of Medicinal Chemistry, 53(12), 4603–4614.PubMedCrossRefGoogle Scholar
- 16.Umbricht, D., Alberati, D., Martin-Facklam, M., Borroni, E., Youssef, E. A., Ostland, M., et al. (2014). Effect of bitopertin, a glycine reuptake inhibitor, on negative symptoms of schizophrenia: A randomized, double-blind, proof-of-concept study. JAMA Psychiatry, 71(6), 637–646.PubMedCrossRefGoogle Scholar
- 20.Patrick, D. L., Burns, T., Morosini, P., Rothman, M., Gagnon, D. D., Wild, D., et al. (2009). Reliability, validity and ability to detect change of the clinician-rated Personal and Social Performance scale in patients with acute symptoms of schizophrenia. Current Medical Research and Opinion, 25(2), 325–338.PubMedCrossRefGoogle Scholar
- 21.Schumacker, R. E., & Lomax, R. G. (1996). A beginner’s guide to structural equation modeling. Mahwah, NJ: Lawrence Erlbaum Associates.Google Scholar
- 22.Chassany, O., Sagnier, P., Marquis, P., Fullerton, S., & Aaronson, N. (2002). Patient-reported outcomes: The example of health-related quality of life: A European guidance document for the improved integration of health-related quality of life assessment in the drug regulatory process. Drug Information Journal, 36, 209–238.CrossRefGoogle Scholar
- 23.Zumbo, B. D. (1999). A handbook on the Theory and Methods of Differential Item Functioning (DIF): Logistic Regression Modeling as a Unitary Framework for Binary and Likert-type (Ordinal) Item Scores. Ottawa, ON: Directorate of Human Resources Research and Evaluation, Department of National Defense.Google Scholar
- 26.Hays, R. D., Anderson, R. & Revicki, D. (1998). Assessing reliability and validity of measurement in clinical trials. In Quality of life assessment in clinical trials: Methods and practice (pp. 169–182). Oxford: Oxford University Press.Google Scholar
- 27.Nunnally, J. C., & Bernstein, I. H. (1994). Psychometric theory. New York: McGraw-Hill Inc.Google Scholar
- 29.Cohen, J. (1977). Statistical power analysis for the behavioral sciences. New York: Academic Press.Google Scholar
- 30.Kline, R. B. (2005). Principle and practice of structural equation modeling. New York: Guilford Press.Google Scholar
- 32.Arango, C., Nasrallah, H., Lawrie, S., Ochi Lohmann, T., Zhu, J., Garibaldi, G., et al. (2013) Efficacy and safety of adjunctive bitopertin (5 and 10 mg) versus placebo in subjects with persistent predominant negative symptoms of schizophrenia treated with antipsychotics—Results from the Phase III DayLyte study. In 4th Biennial Schizophrenia International Research Society Conference, 5–9 April 2013. Florence, Italy.Google Scholar
- 33.Blaetter, T., Bugarski-Kirola, D., Fleischhacker, W. W., Bressan, R. A., Arango, C., Abi-Saab, D., et al. (2013). Efficacy and safety of adjunctive bitopertin (10 and 20 mg) versus placebo in subjects with persistent predominant negative symptoms of schizophrenia treated with antipsychotics—Results from the Phase III FlashLyte Study. In 4th Biennial Schizophrenia International Research Society Conference, 5–9 April 2013. Florence, Italy.Google Scholar
- 35.Wilkinson, G., Clayson, D., Wild, D., Doll, H., Martin, C., & De Hert, M. (2004) The development and psychometric validation of the Schizophrenia Quality of Life Scale-revision 4 (SQLS-R4). Abstracts of the XIIth Biennal Winter Workshop on Schizophrenia. Schizophrenia Research. July 2, 2004.Google Scholar
- 37.Lipkovich, I. A., Deberdt, W., Csernansky, J. G., Sabbe, B., Keefe, R. S., & Kollack-Walker, S. (2009). Relationships among neurocognition, symptoms and functioning in patients with schizophrenia: A path-analytic approach for associations at baseline and following 24 weeks of antipsychotic drug therapy. BMC Psychiatry, 9, 44.PubMedPubMedCentralCrossRefGoogle Scholar