Open Journal of Psychiatry, 2012, 2, 423-432 OJPsych Published Online November 2012 (
Regional disease characteristics and comorbidities of
patients with schizophrenia in the Ziprasidone
Observational Study of Cardiac Outcomes (ZODIAC):
Findings from an international large simple trial*
John M. Kane1#, Wolfgang Fleischhacker2, Francesca Kolitsopoulos3, Onur N. Karayal3, Jamie Geier3,
Cynthia Siu4, Robert Reynolds3, Gerald Faich5, Brian L. Strom6
1Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, USA
2Department of Biological Psychiatry, Medical University Innsbruck, Innsbruck, Austria
3Pfizer Inc., New York, USA
4Data Power (DP), Inc., Ringoes, USA
5Department of Epidemiology, United BioSource Corporation, Blue Bell, USA
6Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Center for Pharmacoepidemiol-
ogy Research and Training, University of Pennsylvania School of Medicine, Philadelphia, USA
Received 28 September 2012; revised 29 October 2012; accepted 8 November 2012
Background: Using baseline data from the Ziprasi-
done Observational Study of Cardiac Outcomes
(ZODIAC), we assessed disease characteristics and
prevalence of select comorbidities among subjects
with schizophrenia in different clinical settings across
18 countries. ZODIAC was a randomized, open-label,
one-year, large simple trial (LST) that enrolled 18,239
individuals with schizophrenia. Methods: Subjects
were randomized to open-label treatment with zipra-
sidone (n = 9120) or olanzapine (n = 9119) in natural-
istic (usual care) settings and followed for one year.
Study sites (n = 749) applied minimal selection crite-
ria in an attempt to make the study population as
representative as possible of those receiving treat-
ment in “real world” circumstances across the coun-
tries. Results: Mean patient age was 41 years, 55%
were male, 34% were markedly ill or presented with
more severe disease, and 66% of subjects had one or
more select comorbid conditions [i.e. heart attack,
stroke, hypertension, CAD/angina, high choles-
terol/triglycerides, diabetes, or overweight (BMI 25)]
at baseline. History of suicide attempt was greatest in
the US (38%), compared with Sweden (34%), Bra-
zil/South America (26%), Asia (23%), and Eastern
Europe (20%). Overweight or obesity was the most
prevalent comorbid risk factor, representing 60% of
enrolled subjects, 70% of US subjects compared with
30% in Asia and 52% - 64% in the other regions
studied. High cholesterol/triglycerides levels were
found in 23% of US subjects compared with a rela-
tively low prevalence in other countries (3% - 11%).
History of cardiovascular or diabetes-related comor-
bidities was found in 31% of subjects. Current
smoking (46.5%) and past smoking (11.8%) were
common with men dominating the proportion of cur-
rent smokers: US (61%); Asia (60%); Sweden (50%);
Eastern Europe (49%); and Latin America (44%).
Conclusions: Our findings indicate substantial base-
line variations across countries in demographics, co-
morbid conditions, and psychiatric disease history.
These data provide an international epidemiologic
picture of schizophrenia and may help guide future
research and treatment initiatives.
Keywords: Large Simple Trial; Schizophrenia;
ZODIAC; Comorbidities
*This study was supported by funding from Pfizer, Inc., New York,
ew York. These results have previously been presented in poste
format at the NCDEU 2010 50th Anniversary Meeting, June 14-17,
2010; Boca Raton Hotel, Boca Raton, FL. Cynthia Siu, Ph.D. at Data
Power (DP), Inc. was a paid consultant for Pfizer, Inc. in connection
with the development of this manuscript. She provided editorial assis-
tance and analysis. We thank Mr. Vito Calamia at Pfizer Inc. for pro-
gramming support and data quality review in this study.
#Corresponding author.
Large simple trials (LSTs), with minimal selection re-
quirements, are designed to assess the reliability, gener-
alizability, and overall relevance of treatments in real
world environments. As such, they verify and supple-
ment findings from classical randomized controlled trials
J. M. Kane et al. / Open Journal of Psychiatry 2 (2012) 423-432
(RCTs) by providing robust, real-life safety and effec-
tiveness based on observed patterns in naturalistic set-
tings [1-3]. This is especially relevant for persons with
psychotic disorders when baseline ethnic, health, and
other risk factors are known to be potential moderators or
mediators of psychiatric treatment outcomes [1,4].
The majority of clinical and observational data on
schizophrenia published to date are derived from North
American and West European populations. However,
these data do not capture the full scope of disability
given the high percentage of persons with psychiatric
disorders residing in middle- or low-income countries [5].
This has prompted criticisms [6,7] and calls to address
this imbalance [8,9].
The Ziprasidone Observational Study of Cardiac Out-
comes (ZODIAC) was a global, randomized, LST in
schizophrenia that enrolled 18,239 subjects from 18
countries in North America, South America, Europe, and
Asia [10]. It provided real-world data on outcomes for
persons with schizophrenia from practice settings in di-
verse healthcare systems and cultures [10,11].
The aim of this paper is to highlight key demographic
characteristics and assess the prevalence of psychiatric
comorbidities among this large cohort. Data from inter-
national studies like ZODIAC offer the advantage of
comparisons that could add important insight on diversi-
ties and challenges in treating this debilitating illness.
2.1. Study Design
A total of 18,239 persons diagnosed with schizophrenia,
schizophreniform, and schizoaffective disorder were
enrolled in the ZODIAC LST between February 2002
and February 2006 (last patient last visit: April 2007). As
described in detail elsewhere [11], participants were ran-
domized to ziprasidone or olanzapine, after which no
further protocol-mandated interventions were made. The
primary study goal was to determine whether there was a
statistical difference between ziprasidone and olanzapine
for non-suicide mortality in typical clinical situations.
Inclusion criteria were broad and exclusion criteria were
minimal. While initial assignment of drug was done in a
random fashion, neither the physician nor the subject was
blinded to treatment allocation, consistent with routine
medical care. Physicians and subjects were free to
change regimens and dosing based on subjects’ response
to the assigned medication, and use of concomitant
medications, including other antipsychotics, was permit-
ted. Patients were followed for up to 1 year, regardless of
duration on randomized treatment, to evaluate study
outcomes. No laboratory testing or clinical monitoring
was required by the protocol; rather, visits and tests were
performed at the discretion of the treating physician.
2.2. Study Assessments
Baseline questionnaires were completed by the treating
clinicians or other study team members. Data on patient
characteristics included age, height, weight, race (e.g.
Caucasian/white, African-American/black, Asian/Pacific
islander, Hispanic/Latino, other), smoking status (e.g.
current smoker, past smoker, never smoked, unknown),
age of onset and severity of schizophrenia (assessed us-
ing the Clinical Impression Scale [CIS], which is
equivalent to the Clinical Global Impression [CGI] scale),
number of previous psychiatric hospitalizations, history
of suicide attempts, prior antipsychotic use (including
ziprasidone or olanzapine), family and personal history
of cardiovascular disease (CVD) and metabolic risks (e.g.
heart attack, stroke, hypertension, coronary artery dis-
ease/angina, arrhythmia, high cholesterol/triglycerides),
history of diabetes diagnoses and prior use of insulin or
oral hypoglycemics, and other concomitant medication
use and smoking status as reported by subject or care-
The study follow-up form included questions on an-
tipsychotic medication use, incidence of diabetes since
last study visit, current diabetic therapy, height, weight,
emergency room visit or hospitalization, and patient vital
status since the last visit.
2.3. Statistical Methods
Pearson chi-square for categorical variables and F-test
for continuous variables were used to compare patient
characteristics and prevalence rates of comorbidities
among subjects in different regions. Multivariate logistic
regression models and ANCOVA were applied to evalu-
ate cross-sectional associations of patient characteristics
with comorbidities and polypharmacy (number of antip-
sychotic medications currently used >1). Patient charac-
teristics collected included age, gender, race, duration of
illness, smoking status, CIS score, psychiatric inpatient
hospitalization experience, and history of suicide at-
tempts. Duration of illness was derived as the time from
date of diagnosis (self-reported) to the randomization
date, or as “age-age of onset + 1”. All reported p-values
were 2-sided, and p < 0.05 was considered statistically
significant. Multiplicity adjustment was not performed in
this post-hoc, exploratory analysis. All analyses were
performed with SAS/STAT, version 4.3 of the SAS sys-
3. Results
3.1. Patient Characteristics
Subject demographics and baseline prevalence of co-
morbid conditions are presented in Table 1. Mean age
was 41 years (range 18 - 96) and 55% of subjects were
Copyright © 2012 SciRes. OPEN ACCESS
J. M. Kane et al. / Open Journal of Psychiatry 2 (2012) 423-432
Copyright © 2012 SciRes.
Table 1. Prevalence of comorbid risk factors at baseline (ZODIAC).
J. M. Kane et al. / Open Journal of Psychiatry 2 (2012) 423-432
*Data included for subjects with completed gender information (n = 17,818); Combining South America and Brazil; +Body Mass Index (BMI) calculated using ZODIAC subject weight and height.
Copyright © 2012 SciRes. OPEN ACCESS
J. M. Kane et al. / Open Journal of Psychiatry 2 (2012) 423-432
Copyright © 2012 SciRes.
male. US subjects were older (mean age: 43 years), com-
pared with other regions (mean ages 34 - 40 years). Age
(age deciles < 20, 20 - 29 through 60 - 69, 70), and gen-
der distributions varied significantly across regions (p <
0.001 for age by region; p < 0.001 for gender by region;
p < 0.001 for age by gender by region).
Enrolled subjects were diagnosed with schizophrenia
on average for 13 years; only 10% (1814 of 17,904 sub-
jects) had duration of illness less than 6 months (from the
date of diagnosis). Average duration of illness was long
in the US (14.0 years, 95% CI: 13.8 to 14.3 years) and
the shortest was in Asia (8.8 years, 95% CI: 8.2 to 9.4
Current smoking (46.5%) and past smoking (11.8%)
were common among this study population (Table 1)
with men dominating the proportion of current smokers:
US (61%); Asia (60%); Eastern Europe (49%); and Latin
America (44%) (p < 0.001, smoking status by region; p <
0.001 smoking status by gender; smoking status by gen-
der by region, p < 0.001).
Mental illness severity as assessed by CIS score dif-
fered among regions after adjusting for age, gender, and
race (p < 0.001, ANCOVA). The percentages of mark-
edly ill or more severe subjects varied by country as fol-
lows: Brazil (45%), the US (32%), Asia (24%), and the
other regions studied (31% - 35%). History of psychiatric
inpatient hospitalization was highest in Eastern Europe
(92%), compared with the US (78%) and the other re-
gions studied (69% - 72%). The majority of subjects took
one antipsychotic medication regardless of geographic
region (Table 2). Subjects in the US had the highest
prevalence of concomitant medication use (81%), com-
pared with Eastern Europe (52%) and the other countries
(72% - 75%).
3.2. Comorbidities and Family Medical History
The majority of subjects (66%, 11,989/18,239) entered
the study with one or more select comorbid conditions
[i.e. heart attack, stroke, hypertension, CAD/angina, high
cholesterol/triglycerides, diabetes, or overweight (BMI
25)] as shown in Table 1. Overweight or obesity (defined
as BMI 25) was the most prevalent comorbid risk fac-
tor, representing 60% of enrolled subjects. ZODIAC
subjects had a mean weight of 81.5 kg (95% CI: 81.1 to
81.9) for men, and 74.4 kg (73.9 to 74.8) for women.
Overweight or obesity (BMI 25) was seen in 69% of
US subjects compared with 30% in Asia and other re-
gions (51% - 63%) (Table 1).
History of cardiovascular or diabetes-related comor-
bidities was found in 31% of subjects. Simultaneous
presence of multiple CVDs were present in 12% of sub-
jects, 14% (1143/8007) of women and 11% (1035/9787)
of men. Hypertension was the most common cardiovas-
cular comorbidity (16% men vs. 20% women) and
prevalence was highest in the US, followed by Sweden,
Eastern Europe, Latin America, and Asia. Prevalence of
high cholesterol/triglycerides was also reported in 15%
of subjects, ranging from 8.8% in Latin American men to
24% in US women. History of Coronary Artery Disease
(CAD)/angina and arrhythmia was approximately 3.0%,
and was comparable between the US and Eastern Europe;
estimates were lower in remaining regions. History of
heart attack or stroke was about 3% in the US but less
than 1% in other regions.
Family medical history of select comorbidities were
collected with US subjects reporting a higher prevalence
of a family history of heart attack (41%), high choles-
terol/triglycerides (37%), CAD/angina (34%), stroke
(30%), and arrhythmia (15%) compared with other re-
gions (Table 1).
3.3. Correlations between Comorbid Conditions,
and Polypharmacy
Table 3 shows selected comorbidities by duration of ill-
ness (<5 years vs. 5 years). The likelihood of having at
least one of these comorbid factors increased with dura-
tion of illness (or age) (t = 4.14, p < 0.001), number of
antipsychotic medications currently used (t = 4.12, p <
0.001), and smoking (t = 6.36, p < 0.001), independent of
gender, race, regions, and severity of illness (multivariate
logistic regression analysis). There was a positive asso-
ciation between the duration of mental illness and likeli-
hood of being overweight/obese (t = 2.64, p < 0.008),
after adjusting for region, race, gender, severity of mental
illness, and other cardiovascular/diabetes comorbidities.
Table 2. Antipsychotic Medication Use History.
All subjects US Eastern EuropeLatin America Asia
Number of subjects 18,229 9735 1022 6504 921
Current antipsychotic medication use, n (%) 14,404 (79%) 7207 (74%) 797 (78%) 5543 (85%) 823 (89%)
Number of antipsychotic medications currently used
None 3825 (21%) 2528 (26%) 225 (22%) 961 (15%) 98 (11%)
1 10,679 (59%) 5724 (59%) 638 (62%) 3770 (58%) 519 (56%)
2 3725 (20%) 1483 (15%) 159 (16%) 1773 (27%) 304 (33%)
J. M. Kane et al. / Open Journal of Psychiatry 2 (2012) 423-432
Table 3. Comorbidities in ZODIAC by illness duration.
<5 Years 5 Years p-value
Number of subjects 5897 12,016
Number of comorbid factors
1 Comorbid factor 2316 (40%) 4869 (41%) <0.001
2 Comorbid factors 687 (12%) 2037 (17%)
3 Comorbid factors 269 (5.4%) 909 (9.1%)
None 2378 (41%) 3515 (30%)
Psychiatric inpatient hospitalizations 3430 (58%) 10,065 (84%) <0.001
History of suicide attempts 1660 (29%) 3724 (32%) <0.001
Number of antipsychotic medications currently used
None 1702 (29%) 2017 (17%) <0.001
1 3339 (57%) 7191 (60%)
2 851 (14%) 2803 (23%)
Smoking status
Never smoked 2723 (46%) 4524 (38%) <0.001
Comorbid factors: cardiovascular (heart attack, stroke, hypertension, CAD/angina, high cholesterol/triglycerides), diabetes, or overweight (BMI > 25).
Polypharmacy was more frequent in men (23%) than
in women (18%) (t = 6.50, p < 0.001), in overweight
subjects (t = 6.13, p < 0.001), persons with more severe
mental illness as assessed by CIS score (t = 18.20, p <
0.001), and longer duration of illness (or age) (t = 14.05,
p < 0.001). No association was found between antipsy-
chotic polypharmacy and the prevalence of other cardio-
vascular or diabetes comorbidities (t = 0.84, p = 0.401)
after adjusting for race and regions (logistic regression
3.4. Early Phase Patient Subgroup Analysis
Only 1814 subjects reported duration of illness less than
6 months. Among this subgroup, the prevalence of co-
morbid conditions was: 51% for overweight/obesity,
22% for obesity, 23% for one or more cardiovascular
morbidities, and 8.1% for the presence of multiple (2)
cardiovascular comorbidities. Estimates were all signifi-
cantly lower than those observed in subjects with 6
months or longer duration of illness (all p < 0.001), in-
dependent of region and gender.
ZODIAC is the largest prospective, randomized study of
subjects with schizophrenia conducted to date [10]. Since
procedures and data collection were greatly simplified
compared with RCTs, this study elucidates the demo-
graphic profile of persons with schizophrenia in natural-
istic clinical settings. There are, however, similarities/
differences in patient demographics and characteristics
across regions and countries.
There are few, but notable examples of cross-national
observational studies of comparable scale including the
W-SOHO (Worldwide-Schizophrenia Outpatient Health
Outcome) study, which pooled data from the SOHO
(Schizophrenia Outpatient Health Outcome) observa-
tional study in 10 Western European countries and the
IC-SOHO (Inter-Continental SOHO) study in 27 other
countries [1,12,13]; the METEOR study in 16 European
countries [14]; and the randomized SCoP safety trial on
schizophrenia subjects across Europe and Asia [15].
However, due to the paucity of published data summa-
rizing cross-national information on comorbidities and
risk factors prevalent in schizophrenia subjects, we high-
light key country and region-specific comparisons from
other schizophrenia trial populations whenever available.
In ZODIAC, most subjects were diagnosed with
schizophrenia for over ten years and 10% were diag-
nosed within 6 months of study enrollment. Longer dura-
Copyright © 2012 SciRes. OPEN ACCESS
J. M. Kane et al. / Open Journal of Psychiatry 2 (2012) 423-432 429
tion of illness appeared to be associated with poorer
clinical outcomes evidenced by more reported comorbid-
ities, e.g. heart attack, stroke, and heavy antipsychotic
medication use (i.e. more reliance on polypharmacy) in
those with five or more years of illness compared with
less than five years (Table 3). A subgroup analysis of
subjects with duration of illness less than 6 months also
confirmed these findings.
History of psychiatric inpatient hospitalization was
higher (92%) in Eastern Europe, compared with the US
(79%) and the other regions studied (69% - 72%). This
finding is consistent with use of long-term institutionali-
zation as an acceptable local practice in psychiatric
treatment and management in this region [16-20].
It is known that persons with schizophrenia also have
a high burden of comorbidities that may be manifesta-
tions of the illness itself, poor diet and lifestyle, poor
access to healthcare, or the propensity to develop CVD
and other health problems [21-23]. As a result, mortality
rates are two to three times higher among persons with
schizophrenia than that of the general population [24-27]
and corresponding elevated risks of dying from a wide
range of somatic conditions and risk factors three to ten
times higher [26]. Excess CVD mortality may be attrib-
uted to prevalence of risk factors commonly referred to
as metabolic syndrome [28,29], a problem that is com-
pounded by increased use of second-generation antipsy-
chotics, as several agents are associated with excess,
undesirable weight, and metabolic side-effects [30-33].
Metabolic and related risks, e.g. hypertriglyceridemia,
overweight/obesity, were common among ZODIAC sub-
jects. Sixty percent of subjects were considered over-
weight or obese (with a BMI 25) compared with 29.4%
of European subjects with schizophrenia (obesity = BMI
> 30) in the METEOR study [14], 32.8% in a physi-
cian-based survey in Europe [34], 76% of Brazilian sub-
jects (overweight or obese = BMI > 25) [35], and 33.3 to
39.8% in Taiwanese subjects (obese = BMI 26.4 or 27)
[36,37]. Overall, Asian subjects reported better cardio-
vascular and metabolic profiles compared with the other
cohorts, possibly owing to Asian culture, lifestyle, and
diet [38,39]. Rates of hypertension and diabetes in ZO-
DIAC, at 16% and 6.4% respectively, are corroborated
by other trials in this patient population [34,37,40-41].
Metabolic and associated risks were highly prevalent
among ZODIAC subjects, underscoring the severe public
health challenge they pose to this at-risk population.
Although anti-smoking campaigns have made health
risks associated with tobacco use clear to the general
public, high rates of smoking are reported among indi-
viduals with schizophrenia [42,43] compared with the
worldwide current smoker prevalence rate of 26% [27].
Evidence suggests that some persons with schizophrenia
might smoke as a form of self-medication, to ameliorate
the positive and negative symptoms, cognitive (mem-
ory/attention) deficits, mood changes and stress associ-
ated with the disease, or the side-effects produced by
antipsychotic medications [44-48]. Regardless, the pre-
valence of smoking among persons with schizophrenia is
two to three times higher than in the general population
and approximately 50% higher than similar, elevated
rates of smoking in people with other psychiatric diag-
noses [49-54]. ZODIAC rates were consistent with these
findings (>40% of subjects were reportedly current
smokers) with prevalence highest among US (61%) and
Asian (60%) men. Male smokers outnumbered female
smokers in each region perhaps due, in part, to cultural
norms regarding smoking behaviors [55-57]. Further,
patients with schizophrenia who smoke have a multi-fold
increase in risk of dying from CVD even when compared
to those who are nonsmokers [58], and also shown in
ZODIAC, heavy addiction to cigarettes is clearly an im-
portant factor contributing to elevated mortality and
morbidities in schizophrenia [44,59-60].
Given the high prevalence of health risks and family
history of CVD observed in ZODIAC, personal history
was expected to corroborate these data. Instead, investi-
gators reported relatively low prevalence in personal
history of heart attack, diabetes, and other cardiovascular
ailments across all regions. This, however, might reflect
the common phenomenon of under diagnosis of these
comorbidities among psychiatric subjects. The awareness
of, and hence diagnosis and monitoring of these comor-
bidities have been low among mental healthcare provid-
ers [61], and psychiatrists were the source of these data
in this study. Despite repeated calls for attention, the un-
der diagnosis and under monitoring of medical comor-
bidities, either as baseline conditions or as treatment
emergent side-effects, persist among mental health pro-
fessionals [62,63]. A related but more ominous possibil-
ity is the possibility of a “weeding-out” process; given
the elevated risks from comorbidities mentioned above,
under treatment and diagnosis, few schizophrenia pa-
tients survived to leave a history [64,65].
This study also has some inherent limitations that de-
serve attention. Despite its large-scale and global design,
ZODIAC findings may be skewed by its imbalanced
country and regional samples. Of course, it is prudent to
always exercise caution when extrapolating from re-
gional findings to specific countries, especially those in
large, diverse regions such as Asia [66,67]. Moreover,
Sweden’s study sample, the only participating country
from Western Europe, was too small to serve as an ade-
quate surrogate for the entire region. In addition, system-
atic training was not done in order to achieve inter-rater
reliability on clinically subjective measure like illness
severity across countries and regions. Finally, the ZO-
DIAC study was not designed to test regional differences
Copyright © 2012 SciRes. OPEN ACCESS
J. M. Kane et al. / Open Journal of Psychiatry 2 (2012) 423-432
in study outcomes. Of particular importance to this paper,
the methods used to enroll patients were not the same in
all countries [10,11].
ZODIAC provides valuable cross-country and regional
information on schizophrenia disease history and mani-
festations, related risks, and comorbidities, which have
important implications for clinical research, patient
management, and mental healthcare policy in the 18
countries studied. Further, it provides important insights
on conduct and interpretation of international trials, as
well as, adaptation of clinical practice and customization
of guidelines for mental healthcare management to spe-
cific regions.
Dr. Siu wrote the first draft of the paper. Statistical analysis was per-
formed by Dr. Siu. Drs Reynolds, Geier, Karayal, and Mrs Kolitsopou-
los are full-time employees and shareholders of Pfizer.
Dr. Kane served as a consultant to Pfizer in connection with the scien-
tific oversight of the study and served as a consultant or advisory board
or speakers bureau for Alkermes, Amgen, AstraZeneca, Bristol-Myers
Squibb, Cephalon, Eli Lilly, Intracellular Therapeutics, Janssen, John-
son & Johnson, Lundbeck, Merck, Novartis, Otsuka, Pierre Fabre,
Proteus Biomedical, Roche, and Sunovion, and is a MedAvante share-
holder. Dr. Fleischhacker receives research grants from Otsuka, Pfizer,
Janssen, Alkermes, Eli Lilly; consulting honoraria from Lundbeck,
Roche, BMS, Otsuka, Janssen, Pfizer, Unitedbiosource, MedAvante,
Sunovion, Merck; speaker honoraria from Lundbeck, Sunovion,
Janssen, Eli Lilly, Otsuka, Astra Zeneca; and owns MedAvante stocks.
Dr. Strom is an employee of the University of Pennsylvania, which
received financial support from Pfizer in connection with the scientific
oversight of the study and the development of this manuscript. He also
served as consultant to Pfizer on topics not related to this study and has
consulted for Abbott Laboratories, American College of Neuropsy-
chopharmacology, American Medical Association, Astra-Zeneca, Ber-
lex, Biogen, Blue Cross Blue Shield, Bristol-Myers Squibb, Boehringer
Ingelheim, Centocor, Cephalon, CV Therapeutics, Cygnus Corporation,
Daichii, Eli Lilly, Forest, GlaxoSmithKline, Hoyle Consulting, Johnson
& Johnson, Medco, Mediwound, Novartis, NPS Pharma, NUVO Re-
search, Ocient, Pfizer, Pharm Research, PhRMA Foundation, San-
ofi-Aventis, Shire, TAP Pharmaceuticals, Teva Neuroscience, and
Wyeth. Dr. Ruskin served as a consultant to Pfizer in connection with
the scientific oversight of the study and has served as a consultant or
scientific advisory board member for Astellas, AstraZeneca, Bristol-
Myers Squibb, Cardiome, Epix, Forest Labs, Genzyme, Javelin, Lund-
beck, Millennium, Myriad, Novartis, NovoNordisk, Portola, Purdue,
Sanofi-Aventis, Sequel, Sunesis, and Theravance. Dr. Faich is an em-
ployee of United BioSource Corporation, which received financial
support from Pfizer in connection with the scientific oversight of the
study and the development of this manuscript. Dr. Siu is a paid con-
sultant to Pfizer Inc. and Sunovion. Drs. Reynolds, Geier, Karayal, and
Mrs Kolitsopoulos are full-time employees and shareholder of Pfizer.
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