SCHRES-06350; No of Pages 11 Schizophrenia Research xxx (2015) xxx–xxx

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The Management of Schizophrenia in Clinical Practice (MOSAIC) Registry: A focus on patients, caregivers, illness severity, functional status, disease burden and healthcare utilization Henry A. Nasrallah a,⁎, Philip D. Harvey b, Daniel Casey c, Csilla T. Csoboth d, James I. Hudson e, Laura Julian d, Ellen Lentz d, Keith H. Nuechterlein f, Diana O. Perkins g, Nirali Kotowsky d, Tracey G. Skale h, Lonnie R. Snowden i, Rajiv Tandon j, Cenk Tek k, Dawn Velligan l, Sophia Vinogradov m, Cedric O’Gorman d,1 a

Saint Louis University, 1438 South Grand Boulevard, Saint Louis, MO 63104, USA University of Miami, 1120 NW 14th Street, Miami, FL 33136, USA c Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA d Genentech, 1 DNA Way, South San Francisco, CA 94080, USA e Harvard Medical School McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA f University of California, Los Angeles, CA 90095, USA g University of North Carolina, Chapel Hill, NC, USA h Greater Cincinnati Behavioral Health Services, 1501 Madison Road, Walnut Hills, OH 45206, USA i University of California, Berkeley, CA, USA j University of Florida, Gainesville, FL 32611, USA k Yale University/Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06519, USA l University of Texas, San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA m University of California, San Francisco, 500 Parnassus Avenue, San Francisco, CA 94143, USA b

a r t i c l e

i n f o

Article history: Received 5 January 2015 Received in revised form 9 April 2015 Accepted 22 April 2015 Available online xxxx Keywords: Schizophrenia Registry Disease characteristics Functioning Disease burden

a b s t r a c t Background: The Management of Schizophrenia in Clinical Practice (MOSAIC), a disease-based registry of schizophrenia, was initiated in December 2012 to address important gaps in our understanding of the impact and burden of schizophrenia and to provide insight into the current status of schizophrenia care in the US. Recruitment began in December 2012 with ongoing assessment continuing through May 2014. Methods: Participants were recruited from a network of 15 centralized Patient Assessment Centers supporting proximal care sites. Broad entry criteria included patients diagnosed with schizophrenia, schizophreniform or schizoaffective disorder, presenting within the normal course of care, in usual treatment settings, aged ≥18 years and able to read and speak English. Results: By May 2014, 550 participants (65.8% male, 59.8% White, 64.4% single, mean age 42.9 years), were enrolled. The majority had a diagnosis of schizophrenia (62.0%). Mean illness duration at entry was 15.0 years. Common comorbidities at entry were high lipid levels (26.9%), hypertension (23.1%) and type II diabetes (13%). Participants were categorized by baseline overall Clinical Global Impression—Schizophrenia Severity Score as minimally (9.1%), mildly (25.3%), moderately (39.9%), markedly (22.3%) and severely (3.4%) ill. Most commonly used second generation antipsychotics at entry were risperidone (17.8%), clozapine (16.5%), olanzapine (14.0%), aripiprazole (13.6%) and quetiapine (5.6%).

Abbreviations: AE, adverse event; B-CATS, Brief Cognitive Assessment Tool for Schizophrenia; BMI, body mass index; CAINS, Clinical Assessment Interview for Negative Symptoms; CGI-SCH, Clinical Global Impression—Schizophrenia; CHMC, Community Mental Health Center; COPD, chronic obstructive pulmonary disease; CRO, Contract Research Organization; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; FGA, first generation antipsychotic; GED, General Education Degree; IEQ, Involvement Evaluation Questionnaire; IRB, institutional review board; KI, key informant; MINI, Mini International Neuropsychiatric Interview; MOSAIC, Management of Schizophrenia in Clinical Practice; NSA-4, 4-Item Negative Symptom Assessment; PAC, Patient Assessment Center; PANSS, Positive and Negative Syndrome Scale; PSP, Personal and Social Performance; SD, standard deviation; SGA, second generation antipsychotic; SQLS, Schizophrenia Quality of Life Scale; TC, treatment center; WPAI, Work Productivity and Activity Impairment. ⁎ Corresponding author at: The Sydney W. Souers Endowed Chair, Department of Neurology & Psychiatry, Saint Louis University School of Medicine, 1438 South Grand Blvd., Suite 105, St. Louis, MO 63104, USA. Tel.: +1 314 977 4824; fax: +1 314 977 4876. E-mail address: [email protected] (H.A. Nasrallah). 1 Intra-Cellular Therapies, Inc. 3960 Broadway, New York City, NY 10032, USA

http://dx.doi.org/10.1016/j.schres.2015.04.031 0920-9964/© 2015 Elsevier B.V. All rights reserved.

Please cite this article as: Nasrallah, H.A., et al., The Management of Schizophrenia in Clinical Practice (MOSAIC) Registry: A focus on patients, caregivers, illness severity, functio..., Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.04.031

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Conclusions: No large-scale patient registry has been conducted in the US to longitudinally follow patients with schizophrenia and describe symptom attributes, support network, care access and disease burden. These data provide important epidemiological, clinical and outcome insights into the burden of schizophrenia in the US. © 2015 Elsevier B.V. All rights reserved.

1. Introduction Schizophrenia, a chronic and debilitating multifaceted syndrome that afflicts over 60 million individuals worldwide (Perälä et al., 2007), has a considerable adverse impact not only on the patient's health and well-being, but also on their families and wider society (Knapp et al., 2004). The economic impact of schizophrenia on healthcare budgets is substantial, typically between 1.5 and 3% of national healthcare expenditure (Knapp et al., 2004). In the United States (US), schizophrenia is associated with annual direct and indirect costs of over $60 billion covering hospitalizations, the need for long-term medical management, housing, emergency room visits, legal expenses, psychosocial support and disability payments as well as life-time lost vocational productivity (Wu et al., 2005). Notably, the economic burden extends well beyond the healthcare system to other care organizations and public sector bodies, such as social service (welfare) agencies, housing departments and the criminal justice system (Knapp et al., 2004). As a result of the shift of burden of care from hospitals, most people with schizophrenia are now being cared for in the community where caregivers often experience significant stress, depression and/or anxiety and have high levels of emotional and financial burden (Martens and Addington, 2001; Saunders, 2003). Overall, there is paucity of large scale studies in the US to assess the potential unmet need for treatment in schizophrenia. While a number of studies have utilized data from the US Schizophrenia Care and Assessment Program (US-SCAP), a 3-year, prospective, observational, noninterventional study (n = 2327) of schizophrenia treatment in usualcare settings in the US conducted between July 1997 and September 2003 (Ascher-Svanum et al., 2006, 2010; Cuyún Carter et al., 2011), many worldwide studies have not included populations from the US. For example, The Schizophrenia Outpatient Health Outcomes (SOHO) study, a 3-year, prospective, observational study designed to assess the comparative costs and outcomes of antipsychotic drug treatment in over 10,000 patients, was conducted in 10 Western European Countries (Haro et al., 2003, 2006). Likewise, the Worldwide-Schizophrenia Outpatient Health Outcomes (W-SOHO) study, which was undertaken to provide longitudinal data about the course of illness, treatment patterns and clinical and functional outcomes for more than 17,000 patients, was conducted in 37 countries in the following six regions: Southern Europe (n = 5788), North Europe (n = 4291), Central and Eastern Europe (n = 2175), Latin America (n = 2566), Northern Africa and the Middle East (n = 1341) and East Asia (n = 1223) (Karagianis et al., 2009; Haro et al., 2011). As such, there continues to be a dearth of “realworld” data to fill in the many information gaps in the US. Notably, a better understanding of clinical stages and disease progression along a continuum of illness for patients in usual care is needed to advance scientific understanding of the disease and its treatment (Tandon et al., 2009). Furthermore, there is limited quantification of the totality of the burden of schizophrenia on the patient, the family, the healthcare system and society. Disease registries have been increasingly used for medical disorders such as diabetes, asthma, congestive heart failure and depression (Casalino et al., 2003), where they have provided substantial insights about the natural history and management of these conditions (Metzger, 2004; Schmittdiel et al., 2005). While some schizophrenia registries have been established to examine certain aspects of the disease (e.g., antipsychotic use, long-term treatment and clinical and functional outcomes) (Olivares et al., 2009; Peuskens et al., 2010), few have attempted to examine the entirety of the disease in a global approach.

In 2012, the Management of Schizophrenia in Clinical Practice (MOSAIC) disease-based registry (NCT01746134) was initiated to address some of the information gaps in our understanding of the impact and burden of schizophrenia and also to provide insight into the current status of schizophrenia care in the US. Through the collection of real-world data relating to a diverse representation of patients with a diagnosis of schizophrenia, schizoaffective disorder or schizophreniform disorder, the objectives of this prospective, non-interventional, MOSAIC registry were to: (i) describe the longitudinal course of schizophrenia; (ii) document the patterns of treatment in usual mental healthcare settings at all stages in the illness trajectory; and (iii) estimate the burden of disease from the perspective of patients, caregivers and providers (clinical and societal). Recruitment to the registry began in December 2012 with ongoing assessment continuing through May 2014. At the time of study discontinuation, 550 participants and 229 caregivers had been enrolled in the registry. Here, we present various data sets for these 550 participants enrolled in the schizophrenia MOSAIC registry. Data collected include information on symptoms, cognition, functioning and treatments received. In addition, data on medical co-morbidities and the characteristics of patients across the life-span were examined. 2. Methods 2.1. Patient Assessment Centers A network of 15 centralized Patient Assessment Centers (PACs) was formed to act as foci of clinical oversight and evaluation, each with up to 10 peripheral clinical treatment centers (TCs) at a variety of practice settings (Fig. 1). The majority of study sites were located at Community Mental Health Centers (CHMC) (69%), with the remainder located in academic departments of psychiatry (38%). PACs had a mean of 2.8 TCs. Clinicians at TCs recruited and referred patients along with medical record information centrally to the respective PACs. Throughout the course of the study, participants continued to visit their treating clinician for usual care according to their clinician's treatment plan; treatment decisions were conducted at the discretion of the treating clinician for the entire time the participant was in the registry. Each PAC served as a research base for standardized data collection from participants and available caregivers/key informants (structured interviews, patient reported outcomes and medical record abstraction) (Fig. 2). For functional and disease status measures, PACs utilized independent evaluators who were not treating clinicians of the participants. Raters were trained simultaneously at a single National Investigators' Meeting by PhD level assessors using case vignettes. Competency and reliability of ratings were established by PhD level rater trainers. The primary role of the PACs was to conduct all routine and followup participant assessments and coordinate complete data collection from all data sources, including TCs' medical chart data. While treatment decisions were made at the treating clinician level, PACs were selected based on their associated experience and expertise in the area of psychiatric research. Each center was tasked with establishing and maintaining a high degree of research rigor and assessments that occurred there. The PAC assessors were required to be a PhD or MD with treating and rating experience in psychiatry. Frequent MOSAIC steering committee meetings and regular communication with the Contract Research Organization (CRO) ensured that any required protocol clarifications were dealt with promptly. All PAC principle investigators assumed responsibility for local site data quality. Central

Please cite this article as: Nasrallah, H.A., et al., The Management of Schizophrenia in Clinical Practice (MOSAIC) Registry: A focus on patients, caregivers, illness severity, functio..., Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.04.031

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Minneapolis

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NOTE: Alaska and Hawaii not to scale Fig. 1. Geographic location of the Participant Assessment Centers (PAC).

data collection and verification of all data entry ensured adherence to the assessment protocols and data validity. All PACs received approval from an approved local institutional review board (IRB). All patients, informants and treating clinicians provided signed informed consent for the aspects of the study in which they participated.

Patient /KI Patient /KI

Patient /KI

2.2. Participant and caregiver inclusion and exclusion criteria To achieve a typical cohort of patients with schizophrenia and related disorders receiving care in the US, the registry established broad inclusion and exclusion criteria for subject recruitment. Patients diagnosed with

Site 3 Site 2

Proximal Care Site • Recruit and consent ~17 pts • Refer pts to PAC

Site 4

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Participant Assessment Centers (N = 15) • Assist with recruitment of sites and participants • Conduct all patient assessments • Collect and record study data • Ensure high level of recruitment and retention • Enable high-quality, reliable data • Minimize interference with usual care, so as to maintain the noninterventional nature of the registry PAC staff may support treating clinician with baseline processes

Site 10 Site 6

Site 9

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Fig. 2. Participant Assessment Centers (PAC) — relationship to clinical treatment centers (TC). KI = key informant.

Please cite this article as: Nasrallah, H.A., et al., The Management of Schizophrenia in Clinical Practice (MOSAIC) Registry: A focus on patients, caregivers, illness severity, functio..., Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.04.031

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schizophrenia, schizoaffective disorder or schizophreniform disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition — Text Revision), presenting within the normal course of care, in usual treatment settings, aged ≥18 years, able to read and speak English and able and willing to provide informed consent and to comply with the study protocol were eligible for enrollment. Participants were excluded from the registry if they were actively participating in a clinical treatment trial at registry enrollment or if it was anticipated that they would be unable to participate in regularly scheduled assessments. However, subjects were allowed to volunteer for clinical trials after enrolment in the registry. To assess caregiver burden, caregivers acting in an informal or unpaid capacity (e.g. relatives, friends) who spent at least 4 h a week with the participant were asked to provide information regarding caregiving tasks and burden. Key informants were considered caregivers if they fulfilled caregiving responsibilities for the participant (e.g., providing emotional, financial, or instrumental support, assisting with activities of daily living) and could provide information about the participant's course of illness, treatment variables and general health status. Participants and caregivers/key informants provided separate informed consent and had the right to withdraw from the study at any time irrespective of the subject's participation. The results on caregiver burden will be presented in a separate publication. 2.3. Study assessments Participants and their available key informants/caregivers completed ongoing assessments administered by trained clinical raters at the PACs. Assessments of participants (including medical comorbidities) were made by self-report, performance-based assessments, interviews by PAC personnel, trained clinical raters and caregiver reports. Assessments of caregivers/key informants were made by self-report and interviews by PAC personnel. A wide range of measures were used to assess the course of schizophrenia (duration, symptom severity, cognitive impairment, clinical and functional outcomes), treatment (medications, adherence, satisfaction with treatment) and burden of schizophrenia (quality of life, caregiver and clinician burden, direct and indirect costs) compiled from assessments completed at the participating PACs, based on coordinated data collection from participants, treating clinicians and caregivers/key informants (Table 1). Medical histories were obtained from both participants and their informants, as well as from documented health records that were released following written authorization from participants. Participants were assessed at baseline and at 3-month intervals with data collected via an electronic data-capture system. Treating clinicians provided data at screening, baseline and semi-annually. Caregiver/key informants provided data at screening, baseline and semi-annually. Although MOSAIC did not include a pharmacologic intervention, all protocol specified adverse events (AEs) were recorded in the participant's medical records and reported as required by local IRBs and the study sponsor. 2.3.1. A brief note on particular measures The Personal and Social Performance (PSP) scale is a clinician rated 100-point single-item rating scale, subdivided into 10 equal intervals. The ratings are based mainly on the assessment of patient's functioning in four main areas: 1) socially useful activities; 2) personal and social relationships; 3) self-care; and 4) disturbing and aggressive behaviors. Each of these four domains is rated on a 6-point severity scale: absent, mild, manifest, marked, severe and very severe. The final result is a single measurement from 0 to 100% of functioning, with higher scores indicating better personal and social functioning (Morosini et al., 2000). The Clinical Assessment Interview for Negative Symptoms (CAINS) assesses the severity of five consensus-derived negative symptoms: asociality, avolition, anhedonia (consummatory and anticipatory),

Table 1 Study assessments. Objective

Measure

Course of disease

• Positive and Negative Syndrome Scale (PANSS)a - PANSS Positive, Negative, Disorganized Thought/Cognition, Uncontrolled Hostility/Excitement and Anxiety/Depression Factor Scores - PANSS Total Scores • Clinical Global Impression—Schizophrenia (CGI-SCH) Scalea - CGI-SCH Positive, Negative, Depressive and Cognitive Symptoms - CGI-SCH Overall Severity • Birchwood Insight Scalea - Birchwood Insight Awareness of Symptoms, Awareness of Illness and Need for Treatment - Birchwood Insight Total Score • Brief Cognitive Assessment Tool for Schizophrenia (B-CATS)a - B-CATS Trial making Test A and B - B-CATS WAIS III Digit Symbol Total Score - B-CATS Animal Fluency • Clinical Assessment Interview for Negative Symptoms (CAINS)a - CAINS Experiential and Expressive Subscales • 4-Item Negative Symptom Assessment (NSA-4)a - NSA-4 Restricted Speech Quantity, Reduced Emotional Range, Reduced Social Drive and Reduced Interest - NSA-4 Global Rating • Mini International Neuropsychiatric Interview (MINI)a • Personal and Social Performance (PSP)a - PSP Socially Useful Activities, Personal and Social Relationships, Self-care and Disturbing and Aggressive Behaviors Score - PSP Total Score • Schizophrenia Quality of Life Scale (SQLS)a - SQLS Psychosocial and Vitality Subscale Scores - SQLS Total Score • Schizophrenia Caregiver Questionnairea • Involvement Evaluation Questionnaire (IEQ)a • Work Productivity and Activity Impairment (WPAI)b • Healthcare service utilization (hospitalizations, emergency department visits, outpatient care, psychosocial and medication treatments) • Community resource utilization and medications

Functioning and Quality of Life

Treatment characteristics

a b

Source: participant reported outcomes. Source: participant and caregiver reported outcome.

affective flattening and alogia (Kring et al., 2013). The CAINS is comprised of two scales (the nine-item Motivation and Pleasure scale and the four-item Expression scale) that are scored separately. The Motivation and Pleasure scale rates items on a 7-point (0 to 6) scale, ranging from 0 (strong or very intense pleasure) to 6 (no pleasure), while the CAINS Expression Scale rated items on a 5-point (0 to 4) scale, ranging from symptoms being absent (0) to severe (4). The 4-item Negative Symptom Assessment (NSA-4) scale is a validated tool, derived from the NSA-16, to rapidly evaluate negative symptoms of schizophrenia (restricted speech quantity, reduced emotion, reduced social drive and reduced interests). Utilizing a 1 to 6 severity rating scale, the NSA-4 provides a rating for the four negative symptom items and overall global negative symptoms (Alphs et al., 2010). The Brief Cognitive Assessment Tool Score (B-CATS) is a cognitive screening tool that assesses orientation, verbal recall, visual recognition, visual recall, attention, abstraction, language, executive functions and visuo-spatial processing. The B-CATS provides a summary score of four existing cognitive tests, Trail Making Test A and B, Digit Symbol and Animal Fluency (Mansbach et al., 2012). The Birchwood Insight Scale is an eight-item self-report measure with three insight subscales: awareness of illness (two items), awareness of symptoms (two items) and awareness of the need for treatment (4 items). All items are statements (e.g., “I am mentally well”, “My doctor is right in prescribing medication for me”) with possible responses of “agree”, “unsure”, or “disagree” that are scored on a 3-point Likert-type scale ranging from 0 to 2. Total scores may be summed for a Birchwood

Please cite this article as: Nasrallah, H.A., et al., The Management of Schizophrenia in Clinical Practice (MOSAIC) Registry: A focus on patients, caregivers, illness severity, functio..., Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.04.031

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Insight Scale total score (range 0–12), with higher scores indicating greater insight (Birchwood et al., 1994). The Schizophrenia Quality of Life Scale (SQLS) is a self-reported 30item questionnaire for measuring quality of life specific to patients with schizophrenia, comprising three scales: psychosocial (15 items), motivation and energy (7 items) and symptoms and side effects (8 items). Each scale has a range from 0 (best possible health) to 100 (worst possible health), with lower scores indicating better functioning (Wilkinson et al., 2000).

2.4. Statistical analyses Key characteristics for PACs, treating clinician sites, participants and caregivers/key informants are summarized using descriptive statistics. Mean, median, minimum and maximum and standard deviation (SD) are provided. For some analyses, patients were grouped by duration of illness (time since diagnosis): (i) newly diagnosed (0 to b3 years following diagnosis), (ii) 3–10 years following diagnosis; and (iii) long-term (more than 10 years following diagnosis). All longitudinal data were also summarized by the scheduled interval. The Statistical Analysis System (SAS), Version 9.2, was utilized for all analyses.

3. Results 3.1. Participant disposition Between December 2012 and February 2014, 550 participants were screened and enrolled across 42 study sites represented by 15 PACS. In addition, 229 caregivers or key informants for these patients were enrolled, the results of which will be reported in a subsequent manuscript. The great majority of participants (511/550 [92.9%]) enrolled in the registry remained until the study was stopped in May 2014, approximately 13 months after study initiation. Of the 39 participants who did not remain in the registry, three had died (two myocardial infarctions and a motor vehicle accident). The remaining 36 participants either withdrew consent (n = 6), were lost to follow-up (n = 18), were unwilling or unable to comply with protocol (n = 1), withdrew due to physician decision (n = 1) or left the study for other undisclosed reasons (n = 10). Participants spent a mean (SD) duration of 7.1 (3.6) months in the registry.

3.2. Participant demographics and baseline characteristics Participant demographics and baseline characteristics are shown in Table 2. Baseline characteristics were similar among participants grouped by duration of illness (0 to b3 years, 3–10 years and ≥10 years following diagnosis) and results examining correlates of duration of illness will be reported in a subsequent manuscript. The gender and race distributions in the MOSAIC sample are similar to most published schizophrenia US clinical trials, with male gender and Caucasian race predominating (Harvey et al., 2011, 2012). The mean age of participants was 42.9 years and the mean duration of diagnosis was 15.0 years. The majority of participants were single (64.4%), living in a private home or apartment (72.0%), had an income of b$20,000 per year (60.7%) and were high school graduates, and attended or completed some college. Of the 92 participants who were students, 20 were fulltime students. Of the 501 participants for whom height and weight measurements were available at baseline, body mass index (BMI) calculations determined 50.2% to be obese (BMI N 30), 24.4% overweight (BMI 25.0–29.9) and 16.0% of normal weight (BMI 18.5–24.9). Overall, 50.8% of participants were a current smoker or had smoked within the past 6 months.

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Table 2 Participant demographic and baseline characteristics. Characteristic

Total population (N = 550)a

Gender, n (%) Male Female Age at entry, mean (SD), years

362 (65.8) 161 (29.3) 42.9 ± 12.9

Race, n (%) White African-American/Black Asian American Indian or Alaska native Unknown Other

329 (59.8) 157 (28.5) 8 (1.5) 4 (0.7) 12 (2.2) 13 (2.4)

Ethnicity, n (%) Hispanic or Latino Not Hispanic or Latino Unknown

60 (10.9) 425 (77.3) 38 (6.9)

Marital status, n (%) Single Married/partner Divorced Separated

354 (64.4) 66 (12.0) 73 (13.3) 9 (1.6)

Have children, n (%) Yes No

147 (26.7) 358 (65.1)

Education, n (%) Less than a high school education High school graduate or equivalent (GED) Some college or vocational school College degree Graduate or professional degree

78 (14.2) 135 (24.5) 184 (33.5) 83 (15.1) 27 (4.9)

Current employment, n (%)b Yes No

145 (26.4) 358 (65.1)

Income, n (%) Less than $20,000 $20,000 to less than $40,000 $40,000 to less than $60,000 $60,000 to less than $80,000 $80,000 to less than $100,000 $100,000 or more Don't know

334 (60.7) 55 (10.0) 29 (5.3) 10 (1.8) 10 (1.8) 10 (1.8) 55 (10.0)

Ongoing comorbid conditions at study entry (≥5% of participants), n (%) High lipid levels High blood pressure or hypertension Type II diabetes Emphysema, asthma or COPD Arthritis, gout or chronic Thyroid disease

148 (26.9) 127 (23.1) 71 (12.9) 56 (10.2) 40 (7.3) 37 (6.7)

Smoker Current smoker or smoker within past 6 months Former smoker (quit 6 or more months ago) Never smoked Missing

184 (33.5) 69 (12.5) 109 (19.8) 188 (34.2)

Met DSM IV criteria for alcohol abuse/dependence Yes No

74 (13.5) 442 (80.4)

Met DSM-IV criteria for substance abuse/dependence Yes 103 (18.7) No 418 (76.0) SD = standard deviation; GED = General Education Degree; COPD = chronic obstructive pulmonary disease. DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. a Due to the exclusion of missing or unknown data, some categories do not total 100%. b Assessed by the Work Productivity and Activity Impairment Questionnaire (WPAI).

Please cite this article as: Nasrallah, H.A., et al., The Management of Schizophrenia in Clinical Practice (MOSAIC) Registry: A focus on patients, caregivers, illness severity, functio..., Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.04.031

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3.3. Participant baseline disease characteristics Participant baseline disease characteristics are shown in Table 3. Initial analyses revealed that baseline disease characteristics were similar Table 3 Participant baseline disease characteristics. Characteristic

Total population (N = 550)a

Diagnosis, n (%) Schizophrenia Schizoaffective disorder Schizophreniform

341 (62.0) 175 (31.8) 7 (1.3)

Age at first antipsychotic treatment for schizophrenia/schizoaffective/schizophreniform disorder, years Mean (SD) Median (min, max)

26.3 (9.2) 23.8 (6, 56)

Time to first antipsychotic treatment for schizophrenia/schizoaffective/schizophreniform disorder, months Mean (SD) Median (min, max)

22.1 (58.0) 0.1 (−7, 420)

Number of overnight hospitalizations in 6 months before enrolment Mean (SD) Median (min, max)

0.3 (0.7) 0.0 (0.6)

Any antipsychotic treatment in 6 months prior to enrolment, n (%) Yes No

498 (91.0) 15 (2.7)

PANSS total score Mean ± SD Median (min, max)

69.5 ± 16.8 68.0 (33, 125)

PSP total score Mean (SD) Median (min, max)

55.4 ± 13.0 56.0 (21, 91)

CAINS Experiential subscale Mean (SD) Median (min, max) Expressive subscale Mean (SD) Median (min, max) NSA-4, global rating Mean (SD) Median (min, max) B-CATS Trail Making Test A Mean (SD) Median (min, max) Trail Making Test B Mean (SD) Median (min, max) WAIS III Digit Symbol Total Score Mean (SD) Median (min, max) Animal Fluency Total Score Mean (SD) Median (min, max)

16.8 (7.3) 17.0 (0, 33) 4.7 (4.0) 4.0 (0, 16)

3.6 (1.2) 4.0 (1,6)

42.8 (23.3) 38.0 (11, 207) 98.7 (54.2) 85.0 (0, 444) 51.9 (24.6) 51.0 (0, 445) 18.2 (5.5) 18.0 (2, 41)

Birchwood insight scale, total score Mean (SD) Median (min, max)

2.8 (1.2) 3.0 (0, 4)

SQLS, total score Mean (SD) Median (min, max)

44.4 (14.4) 44.7 (0, 86)

SD = standard deviation; PANSS = Positive and Negative Syndrome Scale; PSP = Personal and Social Performance; CAINS = Clinical Assessment Interview for Negative Symptoms; NSA-4 = Four-item Negative Symptom Assessment; B-CATS = Brief Cognitive Assessment Tool Score; SQLS = Schizophrenia Quality of Life Scale a Due to the exclusion of missing or unknown data, some categories do not total 100%.

among participants grouped by duration of illness (0 to b3 years, 3– 10 years and ≥10 years following diagnosis). As such, participant baseline disease characteristics are presented for the total population. Overall, 62.0% were diagnosed with schizophrenia and 32.0% with schizoaffective disorder. The majority of participants (54.7%) had a baseline PANSS score in the range of 61–90, followed by 27.8% in the score range 30–60 and 9.5% with scores N90. The most commonly used first generation antipsychotic (FGA) medication at study entry was haloperidol used by 13.2% of participants. The mean duration of use for FGA medications ranged from 8.3 months to 50.5 years. The most commonly used second generation antipsychotic (SGA) medications at study entry were risperidone (23.1%), clozapine (21.4%), olanzapine (18.4%) and aripiprazole (17.9%). The mean duration of use for SGA medications ranged from 10.4 months to 7.9 years. Not surprisingly perhaps, in patients with a longer duration of illness, there was more clozapine use and less use of other SGA agents (Fig. 3). The most commonly used concomitant medications (excluding antipsychotic therapy) at study entry were as follows: benztropine mesylate (12.9%), trazodone (8.9%), metformin (8.5%), clonazepam (8.5%), lorazepam (7.3%), acetylsalicylic acid (6.7%) and bupropion hydrochloride (6%). The concomitant medications used by N 10% of participants throughout the study were as follows: benztropine mesylate (15.8%), metformin (12.7%), trazodone (12.4%) and clonazepam (10.5%). At baseline, patients were categorized by overall Clinical Global Impression—Schizophrenia (CGI-SCH) score as minimally (9.1%), mildly (25.3%), moderately (39.9%), markedly (22.3%) and severely (3.4%) ill, indicating high levels of symptomatology even though patients were actively involved in outpatient care. No participants were rated as ‘normal’ or ‘among the most severely ill’ at baseline. The mean overall severity scores ranged from 3.6 to 3.9 through the study, with the majority of participants rated as a 3 (mildly ill) or a 4 (moderately ill). Few (≤3.4%) participants were rated as a 6 (severely ill). At baseline for the entire sample, the mean (SD) baseline total PANSS score was 69.5 (16.84), with mean (SD) scores of 17.0 (5.36), 18.3 (5.85) and 34.1 (8.86) on the positive symptom, negative symptom and general psychopathology subscales, respectively (Fig. 4). There were minimal variations of subscores by duration of illness (Fig. 4). From baseline to the 12–18 month assessment time point (n = 20), there was a slight decrease in mean [SD] PANSS total scores (69.5 [16.84] vs. 58.2 [12.99]), PANSS positive symptom subscale scores (17.0 [5.36] vs. 12.7 [4.67]), PANSS negative symptom subscale scores (18.3 [5.85] vs.16.4 [5.44]) and PANSS general psychopathology subscale scores (34.1 [8.86] vs 29.1 [6.16]. 3.3.1. Functional status At baseline, the mean (SD) total PSP score for the MOSAIC sample was 55.4 (13.02), corresponding to a patient who requires help to perform most everyday functional tasks (Morosini et al., 2010). The mean total PSP scores varied slightly throughout the study with no apparent trends. 3.3.2. Negative symptoms At baseline, the mean (SD) CAINS motivation and pleasure subscale score was 16.8 (7.30), reflecting a moderate deficit; a gradual decrease was observed over the course of the study. At baseline, the mean (SD) CAINS expression subscale score was 4.7 (3.97), which remained constant throughout the study and demonstrated a mild deficit. For the global rating of the NSA-4, the majority of participants were rated in categories 3 (mild evidence of this symptom; 28.9%) or 4 (moderate evidence of this symptom; 34.1%) at baseline, which remained constant during the course of the study. 3.3.3. Cognition The total mean (SD) scores for Trail Making Test A (42.8 s [23.27]) and B (98.7 s [54.15]) of the B-CATS were higher (worse) at study entry than at any point during the study. The total mean WAIS III Digit Symbol scores and Animal Fluency Total Score increased slightly from

Please cite this article as: Nasrallah, H.A., et al., The Management of Schizophrenia in Clinical Practice (MOSAIC) Registry: A focus on patients, caregivers, illness severity, functio..., Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.04.031

H.A. Nasrallah et al. / Schizophrenia Research xxx (2015) xxx–xxx

Clozapine (n=91)

Olanzapine (n=78)

Risperidone (n=98)

7

Aripiprazole (n=76)

Others (n=202)

60 51.8

Percentage of patients

50

47.5

45.9 43.4 39.1

40

31.1

30 24.3

23.2

21.7

23

20

23.1

21.4 18.4

17.8 17.8 14.9 14.9

17.9

14.7

8.7

10

0 n=

6

15

30

16

27

0 to < 3 years

11

11

18

23

34

3 to 10 years

44

34

34

28

54

91

>10 years

78

98

76

202

Total

Duration of diagnosis Fig. 3. Percentage of participants who used any second generation antipsychotics at study entry by duration of diagnosis. The percentage of participants = actual number divided by the total number of participants in which any antipsychotic was used. A participant may be using more than one antipsychotic medication.

baseline through the study, from a mean (SD) score of 51.9 (24.63) and 18.2 (5.47), respectively. All of these scores reflect moderate impairment compared to normative standards in healthy controls based on age. At baseline, the mean (SD) total score for the Birchwood Insight Scale was 2.8 (1.15), demonstrating that patients had poor insight; scores remained similar through the study.

3.3.4. Quality of life At baseline, the mean (SD) SQLS total score was 44.4 (14.4), indicating that patients were experiencing moderate impairment in regard to

Positive

Negative

overall quality of life; scores slightly declined over the course of the study.

3.4. Safety Overall, AEs were reported for 42 (7.6%) participants throughout the study. The most common AEs were weight gain (11.9%), suicidal ideation (11.9%) and schizophrenia (7.1%). The severity of AEs was evenly distributed among mild (18 events), moderate (19 events) and severe (22 events). The severe AEs tended to be associated with new

Psychopathology

70.0

70

Total 69.5

68.6

67.6

60

Symptom score

50

40

35.2

34.1

33.5

33.3

30

20

19.1 15.7

16.0

18.2

17.4 17.7

17.1

18.3

10

0 0 to < 3 years

3 to 10 years

>10 years

Total

Duration of illness at baseline Fig. 4. Mean total PANSS score and subscale scores for positive symptoms, negative symptoms and general psychopathology symptoms of enrolled participants at baseline (n = 550). Data for whom duration of illness is unknown has been excluded. PANSS = Positive and Negative Syndrome Scale.

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H.A. Nasrallah et al. / Schizophrenia Research xxx (2015) xxx–xxx

in-patient hospitalizations. Three participants died during the course of the study for causes that were not directly related to their diagnoses: myocardial infarction (n = 2) and motor vehicle accident (n=1). 4. Discussion The MOSAIC schizophrenia registry represents a unique research infrastructure and methodological model to observe patients receiving usual care in a variety of treatment settings. Moreover, it demonstrates the feasibility of such a registry and establishes a foundation for further much needed attempts. This US-based registry compliments the ongoing European-based multinational registry (PATTERN) which has similar objectives (Haro et al., 2014). No large-scale US registry has yet done enough to longitudinally follow patients with schizophrenia and describe symptom attributes, support networks, care access and disease burden. There are some similarities between the MOSAIC registry and the US-SCAP study (Cuyún Carter et al., 2011) in terms of objectives (both studies sought to better understand the treatment of patients with schizophrenia in usual care settings), participants (both enrolled adult patients with schizophrenia, who were geographically and ethically diverse), socio-demographic information and reported outcomes (clinician-rated and patient-reported measures). While the MOSAIC registry ultimately had fewer participants and ran for a shorter duration, it provides a number of important updates on schizophrenia care in the US. Firstly, MOSAIC provides a broader picture of schizophrenia in the US since it is a multicenter study covering important geographical areas throughout the country that utilized a network of PACS to support proximal care sites (although geographically dispersed, US-SCAP only used six participating regional sites represented by large systems of care). Secondly, unlike US-SCAP, which included infrequent assessments (annual clinician reported outcomes and six-monthly patient reported outcomes), MOSAIC was designed to collect longitudinal data every three months. Thirdly, MOSAIC utilized data from three different sources – patients, clinicians and caregivers – thereby providing a more complete perspective of the participant's course of disease. Notably, MOSAIC, with its focus on caregivers roles and burden will provide critical information about caregiver characteristics and burdens that are better understood in neuropsychiatric conditions such as Alzheimer's disease. Finally, MOSAIC assessed several domains that have been rarely analyzed in longitudinal observational studies in schizophrenia, such as a formal assessment of everyday functioning in everyday activities and social functioning (assessed with the PSP scale), negative symptoms (assessed with the CAINS) and insight (assessed with the Birchwood Insight Scale). Results from the MOSAIC registry demonstrated that patients had high levels of symptomatology. This is in line with the findings from the three-year, prospective, observational study utilizing data from the US-SCAP, which demonstrated that only a small percentage of patients (10%) achieved sustained favorable long-term outcomes (Cuyún Carter et al., 2011). Likewise, both the study populations in W-SOHO and the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) studies had relatively high levels of clinical symptomatology and pronounced functional deficits (Karagianis et al., 2009; Lieberman et al., 2005). Patients in both the W-SOHO and CATIE studies were moderately ill (mean CGI-SCH overall score of 4.4 ± 1.0 and 4.0 ± 0.9 in the W-SOHO and CATIE studies, respectively). In addition, only 16–23% of patients in the W-SOHO were in paid employment and 85% of patients in the CATIE study were unemployed (Karagianis et al., 2009; Lieberman et al., 2005). Results from these studies demonstrate that there continues to be a great need for improvement in the treatment of schizophrenia and that relatively little is known about the baseline characteristics that can be used to predict a favorable long-term outcome among patients with schizophrenia. A comparison of the baseline demographic and clinical characteristics of participants from MOSAIC, US-SCAP, W-SOHO and CATIE are shown in Table 4. There are many benefits to having implemented the MOSAIC disease-state patient registry. The resultant findings allow researchers

to describe, and society to understand, how patient care differs across regions, and to identify any disparities associated with treatment settings or patient groups. The data produced also enable us to compare real world practice with actual evidence-based treatment guidelines. Non-acute patients with schizophrenia are particularly vulnerable to finding themselves isolated from healthcare services. Although registries are not the solutions to helping these under-served patients receive better care, they can help describe the flow of patients through the healthcare system and identify how they may be further assisted. The current diversity of practice settings recruited, including CMHCs, academic departments of psychiatry, Veterans Affairs Medical Centers and hospital-based or practice-based centers was a strength of the MOSAIC registry. It facilitates the representation of a broad-based patient population and also institutional treatment practices. In recent times, particularly with continuing deinstitutionalization, daily caregiving for individuals with schizophrenia has transitioned to informal care by family members, presenting numerous challenges for the caregiver regarding management of the patient's illness and substantial negative impact on daily life (Knapp et al., 2004; Martens and Addington, 2001; Saunders, 2003). MOSAIC, with its focus on caregiver roles, will provide important information on the burden of schizophrenia on caregivers. Nevertheless, challenges exist in the execution of any large-scale patient registry and there are some unique aspects specific to a schizophrenia registry of this size. Recruitment of a sufficiently broad and diverse population of people with schizophrenia – a condition characterized by diverse clinical manifestations that are not clearly demarcated from other clinical entities – can be challenging. The better functioning patients, from one side of the illness spectrum, as well as those most afflicted by isolating negative symptoms, on the other, may be two examples of groups under-represented in this schizophrenia registry. Furthermore, MOSAIC did not recruit schizophrenia patients from correctional facilities, where a substantial proportion of patients are incarcerated and which may represent a more severe variant of schizophrenia (Uggerby et al., 2011). Another interesting finding among the patient population was the high rate of clozapine use (mostly reserved for treatment-refractory patients) and this was directly associated with longer duration of illness. There are inherent limitations to the collection of data. Identification and understanding of how information can differ across assessments that rely on self-report, medical records and observation have been underscored in previous reports (Harvey et al., 2012). Assurance of appropriate richness of data collection to address potential confounders, including differences in types of care provided (such as urban–rural differences) is important. Such confounders have the potential to cause divergent results. Understanding the strength of the correlation between demographic characteristics and outcomes in this patient population is key, for example, for exploring the relation between educational status, illness severity and work status. All these are potential areas of further exploration with the resultant data from MOSAIC. Convergence between information sources is a critical issue for outcomes assessment in schizophrenia in both naturalistic and treatment trials. Data from the MOSAIC study are well positioned to expand on previous smaller studies addressing this topic (Harvey et al., 2012; Rocca et al., 2014). Following patients for a sufficiently informative length of time is critical. In the MOSAIC registry, participant and key informant data decreased at each timepoint after baseline (i.e. 3, 6, 9 and 12 months) not so much as a result of attrition, but because duration of participation was limited for many patients due to early study termination. For example, at study entry, 507 patients were administered the PANSS and PSP scale compared to 20 participants at the 12–18 month assessment window; this significantly impacted on the interpretation of assessments over time and must be taken into consideration when evaluating the results. The earlier-than-planned termination of the MOSAIC registry by the sponsor highlights the vulnerability of such initiatives as a result of high operational costs, as well as the challenges associated

Please cite this article as: Nasrallah, H.A., et al., The Management of Schizophrenia in Clinical Practice (MOSAIC) Registry: A focus on patients, caregivers, illness severity, functio..., Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.04.031

H.A. Nasrallah et al. / Schizophrenia Research xxx (2015) xxx–xxx

9

Table 4 Baseline demographic and clinical characteristics of participants in the MOSAIC, US-SCAP, W-SOHO and CATIE studies (Ascher-Svanum et al., 2010; Karagianis et al., 2009; Lieberman et al., 2005). Baseline characteristics Gender, n (%) Male Female Age, mean (SD), years Race, n (%) Caucasian African-American/Black Black Asian American Indian or Alaska native Unknown Other Marital status, n (%) Single Married/partner Married Divorced Separated Previously married Never married Have children, n (%) Yes No Education, n (%) High school education or less Less than a high school education High school graduate or equivalent (GED) Some college or vocational school College degree Graduate or professional degree Education, mean (SD), years Current employment, n (%) Yes No Paid Unpaid Unemployed (available) Unemployed (unavailable) Retired Other Income, n (%) Less than $20,000 $20,000 to less than $40,000 $40,000 to less than $60,000 $60,000 to less than $80,000 $80,000 to less than $100,000 $100,000 or more Don't know Housing status, n (%) Living in private home/apartment Independent Dependent Supervised Hospitalized Homeless Other Smoker, n (%) Current smoker/smoker within past 6 months Former smoker (quit 6 or more months ago) Never smoked Missing Alcohol abuse or dependency, n (%) Yes No Substance abuse/dependence, n (%) Yes No Comorbid conditions, n (%) High lipid levels High blood pressure or hypertension Diabetes (Types I and II) Type II diabetes Emphysema, asthma or COPD

MOSAIC (N = 550)

US-SCAP (N = 1557)a

W-SOHO (N = 17, 384)

CATIE (N = 1460)

362 (65.8) 161 (29.3) 42.9 (12.9)

948 (60) Not reported 42.4 (11.1)

Not reported (43.3) 38.0 (12.8)

1080 (74) 380 (26) 40.6 (11.1)

329 (59.8) 157 (28.5)

762 (48) 589 (37)

Not reported

874 (60) 513 (35)

8 (1.5) 4 (0.7) 12 (2.2) 13 (2.4) 354 (64.4) 66 (12.0)

66 (4)

71 (5)

938 (60) (32.1) 167 (11)

73 (13.3) 9 (1.6)

Not reported

Not reported

1047 (67)

Not reported

Not reported

Not reported Not reported

Not reported

12.1 (2.3)

147 (26.7) 358 (65.1)

78 (14.2) 135 (24.5) 184 (33.5) 83 (15.1) 27 (4.9) Not reported

425 (29) 868 (59) Not reported

145 (26.4) 358 (65.1)

1217 (85)

Not reported

(19.0) (3.3) (19.1) (26.5) (19.9) (12.1) Not reported

334 (60.7) 55 (10.0) 29 (5.3) 10 (1.8) 10 (1.8) 10 (1.8) 55 (10.0)

Not reported

Not reported 396 (72.0)

Not reported

Not reported

(41.7) (49) (7.2) (1.1) (0.2) (0.9) Not reported

184 (33.5) 69 (12.5) 109 (19.8) 188 (34.2)

Not reported

Not reported 74 (13.5)b 442 (80.4)b 103 (18.7)b 418 (76.0)b 148 (26.9)d 127 (23.1)d

(12.6)c

358 (25)

413 (26)

(11.4)c

422 (29)

Not reported

Not reported 204 (14) 289 (20) 154 (111)

71 (12.9)d 56 (10.2)d (continued on next page)

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H.A. Nasrallah et al. / Schizophrenia Research xxx (2015) xxx–xxx

Table 4 (continued) Baseline characteristics

MOSAIC (N = 550)

US-SCAP (N = 1557)a

W-SOHO (N = 17, 384)

CATIE (N = 1460)

Arthritis, gout or chronic Thyroid disease PANSS total score, mean (SD) CGI-SCH, mean SD Overall Positive Negative Depressive Cognitive CGI-SCH, % Normal Minimally ill Mildly ill Moderately ill Markedly ill Severely ill Most severely ill PSP total score, mean (SD) CAINS, mean (SD) Experiential subscale Expressive subscale NSA-4, global rating, mean (SD) B-CATS, mean (SD) Trail Making Test A Trail Making Test B WAIS III digit symbol total score Animal Fluency total score Birchwood Insight Scale, total score, mean (SD) MADRS, mean (SD) QoL scales SQLS, total score, mean (SD) SF-12, mental composite score SF-12 physical composite score EuroQoL VAS score, median (interquartile range) Caregiver data collected, n (%)

40 (7.3)d 37 (6.7)d 69.5 (16.8) Not reported

69.1 (18.4) Not reported

Not reported

75.7 (17.6) 4.0 (0.9)

Not reported

4.4 (1.0) 3.9 (1.4) 4.0 (1.3) 3.4 (1.4) 3.7 (1.3) Not reported

Not reported Not reported

Not reported Not reported

Not reported Not reported

Not reported Not reported

Not reported Not reported

Not reported Not reported

42.8 (23.3) 98.7 (54.2) 51.9 (24.6) 18.2 (5.5) 2.8 (1.2) Not reported

Not reported 13.6 ± 10.2

Not reported Not reported

44.4 (14.4) Not reported Not reported Not reported 229 (41.6)

Not reported 42.5 (12.9) 45.3 (13.1) Not reported Not reported

Not reported Not reported Not reported 50 (30–62) Not reported

Not reported Not reported No reported Not reported Not reported Not reported Not reported Not reported

0 9.1 25.3 39.9 22.3 3.4 0 55.4 (13.0) 16.8 (7.3) 4.7 (4.0) 3.6 (1.2)

Not reported

The results presented here are not from head-to-head comparative trials. MOSAIC = The Management of Schizophrenia in Clinical Practice; US-SCAP = US Schizophrenia Care and Assessment Program; W-SOHO = Worldwide-Schizophrenia Outpatient Health Outcomes (W-SOHO); CATIE = Clinical Antipsychotic Trials of Intervention Effectiveness; SD = standard deviation; GED = General Education Degree; COPD = chronic obstructive pulmonary disease; PANSS = Positive and Negative Syndrome Scale; CGI-SCH = Clinical Global Impression—Schizophrenia; PSP = Personal and Social Performance Scale; CAINS = Clinical Assessment Interview for Negative Symptoms; NSA-4 = Four-item Negative Symptom Assessment; B-CATS = Brief Cognitive Assessment Tool Score; QoL = Quality of Life; SQLS = Schizophrenia Quality of Life Scale; MADRS = Montgomery–Asberg Rating Scale; SF-12 = Short Form 12-item Survey; EuroQoL VAS = EuroQol EQ-5D scale and Visual Analogue Scale. a Baseline data not available for the complete US-SCAP cohort (n = 2327). The data presented here is a subset of participants who completed a 1-year follow-up interview and for whom complete mental health resource utilization data were available for an entire year (n = 1557 or 85.7%). b Met DSM-IV criteria for alcohol and substance abuse/dependence. c Prior or current diagnosis of abuse or dependency. d ≥5% of participants.

with psychiatric drug development within the pharmaceutical industry. Extensive efforts by the original sponsor to find alternate sponsorship that would ensure continuation of the registry were sadly unsuccessful. However, the need for an ongoing schizophrenia registry remains. One solution might be the creation of a “consortium” composed of pharmaceutical, government, academic and patient advocacy partners willing to proportionally and appropriately fund and support the maintenance of such a registry. The richness of the data produced, the insights around unmet need gleaned, as well as the opportunities for improving patient care within schizophrenia should be compelling enough to encourage participation for interested parties. To emphasize this point, the MOSAIC registry provides important epidemiological and clinical insights into the burden of schizophrenia in the US. These analyses, and the registry itself, provide a unique opportunity to further our understanding of the depth and complexity with which schizophrenia affects the lives of patients and their caregivers and to provide insight into optimization of care.

Role of funding source This study was not a Phase III registrational study with the intent to assess efficacy of an investigational agent for schizophrenia and Genentech does not currently have a medication approved for the indication of schizophrenia.

Contributors Henry Nasrallah participated in the writing and multiple edits of the manuscript drafts and in presenting the data at national meetings. Philip Harvey contributed to the design of the study and participated in the writing and review of the manuscript drafts. Daniel Casey and Tracey Skale reviewed the manuscript drafts. Csilla Csoboth was involved in the proposed analyses. James Hudson was involved in the design of the study and the collection of data. Laura Julian was involved in the design of the study, the writing of protocol and the proposed analyses. Ellen Lentz participated in the design of the protocol and the Case Report Form, the proposed analyses and interpretation of the results. Keith Nuechterlein contributed to the design of the study. Diana Perkins and Sophia Vinogradov contributed to the design of the study and data interpretation. Nirali Kotowsky was involved in the proposed analyses and participated in the writing and review of the manuscript drafts. Lonnie Snowden and Dawn Velligan were involved in the design of the study. Rajiv Tandon and Cenk Tek participated in the conceptual development of the MOSAIC registry and study design. Cedric O'Gorman was involved in the design of the study and writing of the protocol, proposed analyses and participated in the writing and review of the manuscript drafts. All authors contributed to and approved the final manuscript.

Conflict of interest Henry Nasrallah has received research grants from Forest, Forum, Genentech and Otsuka and has been a consultant and on the speaker's bureau for Boehringer-Ingelheim, Genentech, Forum, Janssen, Lundbeck, Merck, Novartis, Otsuka, Sunovion and Teva. Philip Harvey has received consulting fees from Abbvie, Boehringer-Ingelheim, Forum Pharma, Forest labs, Genentech, Otsuka-America, Roche Pharma, Sunovion Pharma and Takeda

Please cite this article as: Nasrallah, H.A., et al., The Management of Schizophrenia in Clinical Practice (MOSAIC) Registry: A focus on patients, caregivers, illness severity, functio..., Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.04.031

H.A. Nasrallah et al. / Schizophrenia Research xxx (2015) xxx–xxx Pharma. Daniel Casey is a consultant to Genentech. James Hudson has received consulting fees from Genentech, Roche and Shire and has received research grant support from Genentech and Shire. Keith Nuechterlein is a paid consultant to Genentech and also serves as a consultant to Janssen Scientific Affairs, Otsuka and PositScience. Diana Perkins is a consultant and research grant recipient for Genentech/Roche and a consultant for Otsuka/Lundbeck, Sunovion and Janssen Pharmaceuticals. Tracey Skale is a consultant for Merck, Sunivion and Otsuka/Lundbeck. Lonnie Snowden has no conflicts of interest related to this manuscript. Rajiv Tandon was an investigator on the MOSAIC Schizophrenia registry and has no other conflicts of interest related to this manuscript. Cenk Tek is a consultant and has received grant support from Roche. Dawn Velligan is a consultant and is on the advisory board for Genentech/Roche, a consultant, and on the advisory board and speaker's bureau for Otsuka/Lundbeck, a consultant and research grant recipient for Amgen Pharmaceuticals, a consultant and on the speaker's bureau for Janssen Pharmaceuticals, a consultant for Takeda Pharmaceuticals and a consultant for AbbVie Pharmaceuticals. Sophia Vinogradov is a paid consultant of PositScience, Inc. and Forum Pharmaceuticals. Nirali Kotowsky is an employee of Genentech/Roche. Csilla Csoboth, Laura Julian and Ellen Lentz are employees and stockholders of Genentech/Roche. Cedric O'Gorman was an employee and stockholder of Genentech/Roche at the time the study was performed.

Acknowledgments The authors received medical editing support from inVentiv Medical Communications, which was funded by F. Hoffmann-La Roche Ltd. The authors would also like to thank all the investigators, their site staff, and research participants and their caregivers in collection of these data.

References Alphs, L., Morlock, R., Coon, C., Cazorla, P., Szegedi, A., Panagides, J., 2010. Validation of a 4-item Negative Symptom Assessment (NSA-4): a short, practical clinical tool for the assessment of negative symptoms in schizophrenia. Psychiatry (Edgmont) 7 (7), 26–32. Ascher-Svanum, H., Faries, D.E., Zhu, B., Ernst, F.R., Swartz, M.S., Swanson, J.W., 2006. Medication adherence and long-term functional outcomes in the treatment of schizophrenia in usual care. J. Clin. Psychiatry 67 (3), 453–460. Ascher-Svanum, H., Zhu, B., Faries, D.E., Salkever, D., Slade, E.P., Peng, X., Conley, R.R., 2010. The cost of relapse and the predictors of relapse in the treatment of schizophrenia. BMC Psychiatry 10, 2. Birchwood, M., Smith, J., Drury, V., Healy, J., Macmillan, F., Slade, M., 1994. A self-report insight scale for psychosis: reliability, validity and sensitivity to change. Acta Psychiatr. Scand. 89 (1), 62–67. Casalino, L., Gillies, R.R., Shortell, S.M., Schmittdiel, J.A., Bodenheimer, T., Robinson, J.C., Rundall, T., Oswald, N., Schauffler, H., Wang, M.C., 2003. External incentives, information technology, and organized processes to improve health care quality for patients with chronic diseases. JAMA 289 (4), 434–441. Cuyún Carter, G.B., Milton, D.R., Ascher-Svanum, H., Faries, D.E., 2011. Sustained favourable long-term outcome in the treatment of schizophrenia: A 3-year prospective observational study. BMC Psychiatry 11, 143. Haro, J.M., Edgell, E.T., Jones, P.B., Alonso, J., Gavart, S., Gregor, K.J., Wright, P., Knapp, M., SOHO Study Group, 2003. The European Schizophrenia outpatient health outcomes (SOHO) study: rationale, methods and recruitment. Acta. Psychiatr. Scand. 107 (3), 222–232. Haro, J.M., Novick, D., Suarez, D., Alonson, J., Lépine, J.P., Ratcliffe, M., 2006. SOHO Study Group. 2006. Remission and relapse in the outpatient care of schizophrenia: three-year results from the schizophrenia outpatient health outcomes study. J. Clin. Psychopharmacol. 26 (6), 571–578. Haro, J.M., Novick, D., Bertsch, J., Karagianis, J., Dossenbach, M., Jones, P.B., 2011. Crossnational clinical and functional remission rates: Worldwide Schizophrenia Outpatient Health Outcomes (W-SOHO) study. Br. J. Psychiatry 199 (3), 194–201. Haro, J., Altamura, C., Corral, R., Elkis, H., Evans, J., Malla, A., Krebs, M.O., Zink, M., Alberti, L., Bernasconi, C., Lalonde, J., Nordstroem, A.L., 2014. Understanding the impact of persistent symptoms in schizophrenia: cross-sectional findings from the Pattern study. Poster presented at European College of Neuropsychopharmacology (ECNP), October 18–21, Berlin, Germany.

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Harvey, P.D., Raykov, T., Twamley, E.W., Vella, L., Heaton, R.K., Patterson, T.L., 2011. Validating the measurement of real-world functional outcomes: phase I results of the VALERO study. Am. J. Psychiatry 168 (11), 1195–1201. Harvey, P.D., Sabbag, S., Prestia, D., Durand, D., Twamley, E.W., Patterson, T.L., 2012. Functional milestones and clinician ratings of everyday functioning in people with schizophrenia: overlap between milestones and specificity of ratings. J. Psychiatr. Res. 46 (12), 1546–1552. Karagianis, J., Novick, D., Pecenak, J., Haro, J.M., Dossenbach, M., Treuer, T., Montgomery, W., Walton, R., Lowry, A.J., 2009. Worldwide schizophrenia outpatient health outcomes (W-SOHO): baseline characteristics of pan-regional observational data from more than 17,000 patients. Int. J. Clin. Pract. 63 (11), 1578–1588. Knapp, M., Mangalore, R., Simon, J., 2004. The global costs of schizophrenia. Schizophr. Bull. 30 (2), 279–293. Kring, A.M., Gur, R.E., Blanchard, J.J., Horan, W.P., Reise, S.P., 2013. The clinical assessment interview for negative symptoms (CAINS): final development and validation. Am. J. Psychiatry 170 (2), 165–172. Lieberman, J.A., Stroup, T.S., McEvoy, J.P., Swartz, M.S., Rosenheck, R.A., Perkins, D.O., Keefe, R.S., Davis, S.M., Davis, C.E., Lebowitz, B.D., Severe, J., Hsiao, J.K., Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators, 2005. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med. 353 (12), 1209–1923. Mansbach, W.E., MacDougall, E.E., Rosenweig, A.S., 2012. The Brief Cognitive Assessment Tool (BCAT): a new test emphasizing contextual memory, executive functions, attentional capacity, and the prediction of instrumental activities of daily living. J. Clin. Exp. Neuropsychol. 34 (2), 183–194. Martens, L., Addington, J., 2001. The psychological well being of family members of individuals with schizophrenia. Soc. Psychiatry Psychiatr. Epidemiol. 36 (3), 128–133. Metzger, J., 2004. Using computerized disease registries in chronic disease care. California Healthcare Foundation, Oakland, CA (Available at: www.chcf.org/~/media/MEDIA% 20LIBRARY%20Files/PDF/C/PDF%20ComputerizedRegistriesInChronicDisease.pdf (Last accessed 12 December 2014). Morosini, P.L., Magliano, L., Brambilla, L., Ugolini, S., Pioli, R., 2000. Development, reliability and acceptability of a new version of the DSM-IV Social and Occupational Functioning Assessment Scale (SOFAS) to assess routine social functioning. Acta. Psychiatr. Scand. 101 (4), 323–329. Olivares, J.M., Rodriguez-Morales, A., Diels, J., Povey, M., Jacobs, A., Zhao, Z., Lam, A., 2009. Long-term outcomes in patients with schizophrenia treated with risperidone longacting injection or oral antipsychotics in Spain: results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR). Eur. Psychiatry 24 (5), 287–296. Perälä, J., Suvisaari, J., Saarni, S., Kuoppasalmi, K., Isometsä, E., Pirkola, S., Partonen, T., TuulioHenriksson, A., Hintikka, J., Kieseppä, T., Härkänen, T., Koskinen, S., Lönnqvist, J., 2007. Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch. Gen. Psychiatry 64 (1), 19–28. Peuskens, J., Olivares, J.M., Pecenak, J., Tuma, I., Bij de Weg, H., Eriksson, L., Resseler, S., Akhras, K., Jacobs, A., 2010. Treatment retention with risperidone long-acting injection: 24 month results from the electronic schizophrenia adherence registry (E-STAR) in six countries. Curr. Med. Res. Opin. 26 (3), 501–509. Rocca, P., Montemagni, C., Zappia, S., Piterà, R., Sigaudo, M., Bogetto, F., 2014. Negative symptoms and everyday functioning in schizophrenia: a cross-sectional study in a real world-setting. Psychiatry Res. 218 (3), 284–289. Saunders, J.C., 2003. Families living with severe mental illness: a literature review. Issues Ment. Health Nurs. 24 (2), 175–198. Schmittdiel, J., Bodenheimer, T., Solomon, N.A., Gillies, R.R., Shortell, S.M., 2005. Brief report: the prevalence and use of chronic disease registries in physician organizations. J. Gen. Intern. Med. 20 (9), 855–858. Tandon, R., Nasrallah, H.A., Keshavan, M.S., 2009. Schizophrenia, “just the facts” 4. Clinical features and conceptualization. Schizophr. Res. 110 (103), 1–23. Uggerby, P., Nielsen, R.E., Correll, C.U., Nielsen, J., 2011. Characteristics and predictors of long-term institutionalization in patients with schizophrenia. Schizophr. Res. 131 (1–3), 120–126. Wilkinson, G., Hesdon, B., Wild, D., Cookson, R., Farina, C., Sharma, V., Fitzpatrick, R., Jenkinson, C., 2000. Self-report quality of life measure for people with schizophrenia: the SQLS. Br. J. Psychiatry 177, 42–46. Wu, E.Q., Birnbaum, H.G., Shi, L., Ball, D.E., Kessler, R.C., Moulis, M., Aggarwal, J., 2005. The economic burden of schizophrenia in the United States in 2002. J. Clin. Psychiatry 66 (9), 1122–1129.

Please cite this article as: Nasrallah, H.A., et al., The Management of Schizophrenia in Clinical Practice (MOSAIC) Registry: A focus on patients, caregivers, illness severity, functio..., Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2015.04.031

The Management of Schizophrenia in Clinical Practice (MOSAIC) Registry: a focus on patients, caregivers, illness severity, functional status, disease burden and healthcare utilization.

The Management of Schizophrenia in Clinical Practice (MOSAIC), a disease-based registry of schizophrenia, was initiated in December 2012 to address im...
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