Epidemiology Research Report: Analysis of Clozapine and Diet Study

This report provides a comprehensive analysis of a research study by Wu et al. (2007) investigating the outcomes of obese schizophrenic in-patients treated with clozapine who participated in a 6-month diet and physical exercise program. The report critically examines the study's title, abstract, introduction, research formulation (including the PICOT framework), sampling and sample size, research design (randomized controlled trial), ethical considerations, and bias control. The analysis delves into the validity of variables, statistical analysis, and the study's strengths and limitations. The study's methodology, including the use of anthropometric, metabolic, and enzyme assays, is evaluated, along with the statistical techniques employed to analyze the data. The report also considers the ethical aspects of the study, including informed consent and adherence to the Helsinki Declaration. Furthermore, the analysis assesses the internal and external validity of the study's findings, the control of confounding variables, and the potential for bias. The report concludes with an evaluation of the study's implications for clinical practice and future research directions. The study's findings suggest the effectiveness of a diet and exercise program for obese schizophrenic patients treated with clozapine.

Epidemiology
Epidemiology and Research Methods
Wu, M et al. (2007). Outcomes of obese (overweight) with schizophrenic in-patients being
treated with Clozapine placed in 6 months dieting as well as physical- exercise program:
Psychiatric services. 58(4):544

Epidemiology
Title and abstract
Wu et al (2007) has given a highly clear and concise title that is congruent with the study.
According to Polit & Beck (2016), title of the study should stimulate an accurate perception
about the study’s nature which is evident in this study. At this point, the abstract has to be
analyzed to clarify the focus of the study. The abstract of the current study presents their study
focus of evaluating the effect of 6-month dietary with physical activity regimen on obese
schizophrenic in-patients who is treated with Clozapine. The abstract condenses the main points
as the problem, study-hypothesis, study-objectives, research methodology, findings, conclusions
as well as recommendations (Boswell, n. d.). Though the recommendations for future studies
were not given in abstract, they have included other aspects of it.
Introduction
The researchers have given an elaborate literature review to demonstrate their study
motivation. A review of literature in a research study involves a critical summary of the studies
that are related to the topic of interest, often developed to conceptualize a research study (Polit,
2016). They have begun by quoting studies to show the relationship between intake of anti-
psychotic drugs and weight gain as well as obesity-induced conditions as heart diseases, which is
adequate. They have clearly and concisely described about various studies to demonstrate the
relationship between Clozapine and its effect on weight and obesity-caused disorders among
schizophrenia patients. They have concentrated more on the association of Clozapine intake with
cardio-vascular risks, which could be understood that the authors wanted to concentrate more on
weight gain that is associated with cardiac disorders. The literatures included were relevant,
recent and appropriate with correct in-text citations. Most of the studies are current yet few
studies are very old to consider. Though the older studies are highly helpful to understand the

Epidemiology
underlying concepts as well as the effect of clopiazine in that period, it could increase the chance
of bias in understanding the fundamental concepts, as science advances day by day (Tappen,
2010).
They have mentioned a couple of studies to show the effect of diet control programs on
the clozapine-treated schizophrenic patients, which showed contradictory results. This has
motivated the researchers to conduct a randomized- controlled trial to determine the effect of
regular physical-activities with dietary-control programs (6-month) on obese, schizophrenic in-
patients those treated with clozapine. They have measured anthropometric with bio-chemical
indices (triglycerides, cholesterol, serum-glucose, insulin levels, cortisol levels, prolactin levels,
growth-hormone as well as IGF-1 & IGFBP-3) at 3rd and 6th months. This shows that the
researchers have described their views systematically, logically as well as sequentially in an
unbiased way (Greenhalgh, 2010). They have demonstrated their insight into the problem by
involving more suitable and comprehensive studies.
Research Formulation
The researchers have identified the study problem appropriately and have given the study
statements as per PICOT framework (Population, Exposure/Intervention, Comparison/ Control &
Outcome). A study problem is defined as a perplexing condition that requires investigation by a
disciplined inquiry (THS, 2015). The research text suggests that the researchers are interested in
evaluating the effect of weight control program on cloziapine- treated schizophrenic patients; at
risk for weight gain of at-least 4.45 kg as well as obesity- related risks. The authors have stated a
clear and appropriate research- purpose to evaluate the effect of diet control plus exercise
program on the outcomes of obese schizophrenic patients taking clozapine. The purpose of a
study should agree with its problem and title (Fink, 2013) which is evident in this study. They

Epidemiology
have given a clear and an achievable objective as ‘to evaluate the effect of diet control as well as
physical activity regimen that is given for six- month period on the obese schizophrenic in-
patients under clozapine’. Hypothesis is an expected or predicted relationship between two
variables (Polit, 2016). The researchers have not clearly stated their hypothesis yet it could be
understood from the objectives.
Sampling and sample size
According to Greenhalgh (2010), the process of selecting the target population and the
samples is highly critical in a research study. The target population involves a population group
in which the authors are interested in collecting data and generalizing the results (Houser, 2011).
Their selection of target population of 753 hospitalized schizophrenia patients admitted from
2003 September to 2004 February is appropriate. They have selected the patients who were
diagnosed as schizophrenia based on DSM-IV criteria particularly between 18 to 65 years of age.
Sample is a subset of the population who are selected to represent the entire population
(LoBiondo-Wood, 2014).
According to Moule (2013), a sampling plan involves selecting samples appropriately
with sampling technique. They have selected 56 samples based on inclusion and exclusion
criteria. They have randomly assigned 25 samples to control group and 28 samples to study
(interventional) group (with 3 samples withdrawn from control group as they have discharged)
which is adequate for a RCT trial. Yet, power analysis was not done to select an appropriate
sample size. As given by Polit (2016), random sampling is a technique by which samples are
selected in such a way of providing equal opportunity to all the members of target population
being studied which could reduce bias and hence is highly appropriate. The researcher has given

Epidemiology
intervention of dietary control with physical activity regimen continuously for six- months to
study group while no intervention to control group.
Research design
Research design is an overall plan that is framed to address the study hypothesis (Polit,
2016). In this study, the researcher has selected the most appropriate randomized controlled trial
(RCT) design to address their research question. RCT also called as true- experimental research-
design is a quantitative research that involves manipulating the experimental group with
intervention (diet control plus physical activity); a control group (without intervention) as well as
randomization by allocating samples to both the groups (control & experimental group) in a
random basis (Fink, 2013) and hence it is of higher value as compared to that of other
quantitative studies. According to Yartsev (2017), this RCT design will help to draw
comparison between two groups. As the researchers have adopted this design, they can
appropriately compare the study group (with intervention) and control group (without
intervention). Thus, the research design they have adapted is adequate and can provide the
strongest evidence to practice in a psychiatric setting.
Ethical issues
Ethics are the system of standards that is concerned with the extent to which the study
follows the professional, legal, ethical as well as societal aspects to the study participants (Polit,
2016). A researcher has to get ethical approval from an Ethical Committee before commencing
(Tappen, 2010). In this study, the researchers have carried- out the study in-accordance with the
Helsinki’s Declaration. Further, they got ethical approval from the Ethical Reviewing Committee
of the Yu-Li Veteran’s Hospital. It is understood from the text that they have informed all the
patients about the study and obtained written (informed) consent before proceeding. The ethical

Epidemiology
principles as beneficence, maleficience, autonomy, justice and respect (Houser, 2011) including
right to withdrawal at any time without penalty is followed.
Bias control
Bias is any influence that affects the study results and undermines validity (Polit, 2016).
Controlling bias plays a significant role in obtaining high evidenced data so as to be utilized
undoubtedly in patient practice. The researchers should try to avoid the maximum possible bias
to ensure the quality of finding (Houser, 2011). Similarly, the researchers of this study have tried
to avoid bias by following few methods. The participants in this study have distorted behavior
(lack of condor) which could affect the researchers from obtaining information. Hence, the
researchers have intelligently measured only anthropometric, metabolic and enzyme assays to
avoid bias.
Researcher subjectivity that involves pre-judging the expected finding and
communicating to participants, but it could not be possible as the patients had distorted behavior.
In regard to sample imbalances (sample bias/ faulty samples), the researchers have meticulously
avoided bias by adapting random sampling technique to give equal chance to every participants.
Sometimes, faulty methods of data collection could create bias. In this study, they have collected
anthropometric data by a single investigator and have followed the directions in labels of
chemicals for tests done to avoid bias. But, they have mentioned about the validity of the
chemicals they have used for various tests anywhere which may increase the chance of bias.
There could be possible measurement bias during anthropometric measurements due to
inappropriate measurement tapes and improper observation. They have used RCT trial to avoid
bias by manipulation, keeping controls and randomizing.

Epidemiology
Validity of variables
Confounding variables are the extraneous variables that affect the relationship between
study variables and hence should be controlled (Polit, 2016). The use of biological measurements
in this study requires controlling these variables to avoid bias. Blinding that involves masking
the individuals those involved in the study from getting information about the samples, the
intervention modalities and/or the study-investigators to reduce bias which is not done here
(LoBiondo-Wood & Haber, 2014). They could have blinded at-least the investigators to control
confounding variables. They have not controlled confounding variables by blocking/stratifying,
crossover or homogeneity but have controlled by adapting variance with covariance (ANCOVA)
analysis.
The scientific merit of a quantitative study is measured by assessing the reliability and
validity of the study instruments. But, validity and reliability was not shown for the instruments
in this study which questions the scientific merit of the study. In regard to internal validity, they
have supported their findings with other studies to show that there is a causal association
between exposure (diet control plus physical activity regimen) and outcome (reduced BMI, body
weight, waist & hip- circumference, level of triglyceride, insulin level, with IGFBP-3 levels).
This proves causality (i.e. cause and effect) relationship between variables. The researchers have
also proved the internal validity of findings by drawing statistical difference between control and
study group and hence could be practiced in psychiatric settings. In case of external validity, the
validity that inferences about the relationships observed over the variations in settings,
individuals, and study-time or measure outcomes has to be accounted (Houser, 2011). In this
study, they have proved their external validity by conducting the study in the same hospital,
individuals with same diagnosis and measure outcomes. Only the duration of study is lengthy by

Epidemiology
is unavoidable to get sufficient number of patients. Hence, the study is of externally valid and
could be applied in similar settings. Yet, future studies are needed to prove the effectiveness of
intervention/exposure in other settings.
Statistical analysis
According to LoBiondo-Wood (2014), statistical analysis is the process of organization
as well as analysis of collected data using statistical methods such as descriptive and/or
inferential analysis. Descriptive statistics that involves describing and summarizing data and
inferential statistics that involves drawing inferences between variables were employed in this
study which is highly appropriate (NewCombe, 2012). The researchers have performed a
detailed analysis of the data collected based on their objectives by testing hypothesis. They have
used tables to show the difference between control (N=25) and study group (N=28) regarding
anthropometric measurements, metabolic & hormonal and growth factor data at baseline, 3rd and
6th months for schizophrenia in-patients treated with clozapine which is adequate (Tappen, 2010).
They have collected and analyzed only the clinical data but not the demographic data.
Demographic data is highly important to understand the physical characteristics of the patient. It
could be better if they could have included demographic data in calculation and could have
associated it with the comparative findings. The anthropometric measurements such as weight,
BMI, waist- & hip-circumference with waist- to -hip ratio, as well as fat percentage related to
weight of both the study and control groups doesn’t differ significantly and hence the
demographic characteristics of both the groups are similar, thus reducing participant bias.
Moreover, the mean fat% among men in study group was 30.9±4.8 and in control group was
30.0±5.1 whereas among women of study group, it was 43.6±10.7 and in controls of 41.4±5.7,
which shows that the fat% is similar in both groups, thus minimizing participant bias. But, if the

Epidemiology
overweight classification of WHO is considered (0.85 for women and 1.0 for men), only the
female participants in this study could be considered to have central obesity which may alter the
comparison of data between both groups.
The comparative analysis of anthropometric, blood samples, metabolic and enzyme
analysis at baseline, 3rd and 6th months between groups is highly adequate; though difficult
particularly using variance with covariance analysis (ANCOVA) along with SPSS (statistical-
software’s 10.0 version); based on general linear-type model. They have not given any statement
about the acceptance or rejection of research/null hypothesis except mentioning about statistical
significance. They could have included hypothesis statement in introduction as well as analysis,
which is crucial for a quantitative study. Overall, their selection of appropriate samples by
considering their anthropometrics and their method of calculation and comparisons at varied
levels (baseline, 3rd & 6th-month) and method of discussion is adequate except few issues.
Findings, study-discussions, conclusions with recommendations
Discussion of results and recommendations are an integral part of a research study
(Moule, 2013). They have discussed each and every finding to show the usefulness of their
intervention/exposure based on their objectives. They have showed a signification reduction in
anthropometric measures and metabolic parameters except growth factor as a benefit of their
intervention in study group. They could have included cardiovascular components in their study
as they are much concerned about cardiac risks. They have discussed their strengths and
weaknesses but they have not mentioned anywhere about validity and reliability of study
measurements particularly blood and metabolic parameters.
The conclusion of a study should clearly summarize and derive the study-findings as well
as establish the importance of the findings (Pilot, 2016). They have followed all the principles of

Epidemiology
conclusion by stating about their findings with its importance. Their mention about the
applicability of their intervention/exposure in reducing the metabolic and anthropometric
parameters, normalizing some metabolic abnormalities, reducing hormonal disorders and
attenuation of few neuroleptic adverse effects that includes sedation with reduced day-to-day
activities is adequate. They recommend walking to all clozapine-treated schizophrenic patients to
avoid obesity and in-turn cardiac complications; which are inexpensive. It could also be done
alone or with no/less instructions from others.
Pilot study which is small- trail run could have been conducted to rule out any alterations
or additions to be done with entire research process. They have not given any recommendations
for conducting similar studies in other psychiatric settings or with alterations in
interventions/exposure.
Overall, though there are certain demerits in this study, the study-results will definitely
serve as a guide to the health professionals caring schizophrenic patients. It could be difficult for
them to motivate schizophrenic patients to follow instructions, yet it could help them
significantly to reduce weight and weight-related complications. Hence, continuous
exposure/intervention of diet control along with physical activity regimen for six- months to
clozapine-treated obese schizophrenic inpatients reduces the body-weight, BMI, waist-& hip-
circumference, triglyceride level, insulin, as well as IGFBP-3 levels.
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Epidemiology
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