What were the OR and 95 CI of variable place of recidence? Explain, what does
                                                                                26- 30
20 50
3 19
92 21
86 3
49 159
31- 35
7 12
1 3
23 4
21 1
26 Tota
l 66
181 59
209 515
55 257
17 412
741
Learning Tasks 2: After you examined the above table, please calculate the following:
1. What is the CRUDE OR? Please provide an interpretation 2. Calculate 95 CI confidence interval of the CRUDE OR using below formula:
3. After   it   is   controlled   for   age   variable,   what   is   its   SPECIFIC   OR?   What   is   the interpretation?
4. What is the SPECIFIC OR after being controlled for obstetric history variable? What is the interpretation?
Case 3: Carefully read the article entitles: “Risk factors for psoriasis: a case control study”
Learning Tasks 3: Based on the above case, please answer the following questions:
1. What is the dependent or response variable of this study? 2. What are the objectives of this study?
3. What are risk factors investigated or what are independent variables of this study? 4. Was this study hospital based or population based?
5. How long the cases were collected? 6. Who was the control group?
7. Regarding   which   variables   cases   and   control   was   comparable?
a Regarding which variables cases and control was not comparable? bWhat must be done to control these confounding variables?
8. See Table-3. How do you determine the most dominant risk factors? 9. See Table-3. Which risk factor had the highest OR? What was the 95 CI for this
risk factor?
10.  What were the OR and 95 CI of variable place of recidence? Explain, what does
it mean?
Self Assessments:
1. What are the advantages and disadvantages of case-control study in determining risk factors of diseases?
2. Explain what is mean by control by design and control by analysis in a case-control study
Udayana University Faculty of Medicine, DME
95 CI = OR exp [+ 1.96 1a+1b+1c+1d]
93
M O D U L E ~ 16
Reference Greenberg, p.91-113  Gordis, 131-163
Epidemiology Study Design: Clinical Trial
dr. Anak Agung Sagung Sawitri, MPH  Dr. dr. Gd Indraguna Pinatih, MSc., Sp.GK
AIMS:
To be able to describe the application of clinical trials to determine the effectiveness of intervention, prevention, and treatment of diseases.
LEARNING OUTCOMES:
1. To describe and to draw clinical  communitytrial design 2. To explain  the advantages and disadvantages  of clinical   community trial to
determine   the   effectiveness   of   intervention,   prevention,   and   treatment   of diseases
3. To   explain   the   definition,   aims,   subject   determination   enrolment, inclusionexclusion criteria, and randomization of intervention and control group
4. To explain statistical calculation and consideration in clinical trial 5. To explain outcome evaluation strategy blinding and how to calculate outcome
6. To explain the interpretation of study outcome 7. To explain ethical consideration in certain clinical trial
8. To explain the differentiation between clinical and community trial
CURRICULUM CONTENTS:
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1. The clinical trial design and its attributes 2. Definition of intervention and control group
3. Enrolment, Inclusion and exclusion criteria and randomization strategy 4. Blinding strategy in clinical trial
5. Statistical calculation and its parameters 6. Data analysis in clinical trial and its interpretation
7. Ethical consideration 8. Differentiation of clinical and community trial
ABSTRACTS
Evidence-based medicine can be defined as the integration of current best evidence with clinical expertise, pathophysiological knowledge and patient preferences to make health
care decisions. Although there are barriers to the practice of evidence-based medicine, such   as   the   skills   and   time   required   in   appraising   the   literature,   this   approach
encourages effective management of diseases. It can serve to optimize health outcomes and promote cost-effective management.
Fundamental   practice   of   evidence-based   medicine   is   the   ability   to   critically assess the design, conduct and analysis of clinical studies. For the purpose of assessing
the comparative benefits of alternative treatment, the randomized controlled clinical trial is the “gold standard” approach. The evidence-based practitioner,  therefore, must be
thoroughly familiar with this research method.
The   principal   strength   of   this   approach   derives   from   assigning   treatment   to
patients by randomization, thereby tending to balance the study groups with respect to both known and unknown prognostic factors.
Before   enrolling   patient   in   a   clinical   trial,   the   investigation   can   determine   the baseline and follow-up information that will be required to all subjects. Procedures can
then be put in place to enable the researches to collect data in a fairly complete and accurate manner. The investigator can also allocate subjects to desire dose level rather
than relying on physicians or patients preference. When  blinding  of the evaluation or patients is feasible, the assessment of clinical outcomes is less likely to be influenced by
knowing which treatment was used.
Randomized   controlled   clinical   trial   is   subject   to   certain   constraints,   however. Restrictive   criteria   for   inclusion   of   subjects   may   produce   a   very   homogenous   study
population,  which  may restrict  the ability to extrapolate  results to patients with  other characteristics.   Clinical   trial—particularly   those   involving   chronic   processes—may
require   years   of   follow-up   to   determine   the   outcome   of   the   treatment.  A  prolonged observation period leads to higher costs, increases the likelihood that patient will be lost
to follow-up, and delays the time at which a treatment recommendation can be made. The   use   of   intermediate   end   points,   such   as   measurement   blood   glucose   levels
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glycosylated   hemoglobin   in   the   diabetes   therapy   trial,   can   help   limit   the   length   of required follow-up. Nevertheless, a definitive conclusion about treatment benefit often
requires years of observation.
Large sample sizes typically are required in clinical trial when the magnitude of differences in responses between study groups is small. Furthermore, large numbers of
subjects are likely to be required to demonstrate differences between study groups when there   is   wide   variability   in   responses   to   treatment.   Increasing   the   size   of   the   study
population not only raises the cost of a trial but may also lead to pragmatic difficulties in locating a sufficiently large pool of eligible patients.
Ethical concern may arise in clinical trial if one or more of the treatment options has   serious   potential   effects   or   if   early   suggest-but   do   not   establish-   a   therapeutic
advantage for one of the treatments. In this situation, a decision must be made about whether the trial should be continued until a definitive conclusion is reached or should be
terminated   early   so   that   all   patients   have   the   opportunity   to   receive   the   apparently superior treatment. To minimize the possible influence of real or perceive conflicts of
interests, and external advisory group should review these ethical questions.
An investigator cannot control the behaviour of subjects enrolled in clinical trial. Even after initial informed consent has been given to participate in clinical trial, a subject
has the right withdraw at any time. Some subject may elect to remain in the trial but not comply with the assigned regimen. Noncompliance can reduce the statistical power of
clinical trial and thereby lead to a false-negative conclusion.  Accordingly,  every effort must be made to achieve maximal compliance with assigned treatment without infringing
on the patients’ right to refuse therapy. Ultimately, treatment decisions should be best on the best evidence available concerning therapeutic benefit. The standard approach to
gathering this evidence is the randomized controlled clinical trial. Although this type of investigation labour intensive, time consuming, and expensive it can provide the most
convincing evidence of the superiority of one treatment over another. Through the use of randomized control clinical trial such as the diabetes therapy study, decisions concerning
patient treatment and care can be based on rigorous scientific information.
SELF DIRECTING LEARNING:
Basic knowledge and its application that students must know include: 1.
Clinical trial design and its attributes 2. The procedures of a clinical trial
3. The concept of subject selection, restriction and randomization 4. Statistical calculation and its parameters
5. Findings and its interpretation
SCENARIO  LEARNING TASKS
Case 1.
Please carefully study the article entitles “Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3,
randomised, observer-masked, placebo-controlled trial”
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Learning Tasks 1: After   you   carefully   read   through   the   article   above,   please   discuss   the
following questions:
1.
What is the study intervention?
2.
What is the expected outcome its dependent variable?
3.
Why did the researcher consider to do this study,  or in other words,  what  is the problem in the community?
4.
Based on clinical trials definition, describe the purpose of this trial.
5.
Describe how researchers design the study, the period, and selected the sites for study. What considerations were put in place when selected the sites?
6.
Describe   how   the   researcher   selected   the   subjects   of   this   study.   What   are   the inclusion and exclusion criteria? What are the purposes of defining these criteria?
7.
Which type of randomization has been done? What is the purpose in doing this?
8.
See the Figure 1. Trial Profile. What is the purpose to describe this figure?
9.
Describe how the method of intervention was performed?
10.
What are the outcomes dependent variables? Describe the operational definitions.
11.
Based on measurement scale, that dependent variable is part of which type?
12.
Is this study using a blind design? What is the purpose to use blind design?
13.
What is one limitation for this longitudinal study with regard to study subjects?
14.
Look   at   Table   1.   Baseline   Characteristics   of   the   Participants.  What   is   the purpose of researchers for showing the table?
15.
What is the main result of this study? Which intervention was more effective?
16.
What other outcomes were also resulting from this study?
17.
How you interpret the vaccine efficacy of primary analysis per protocol?
18. How you compare the vaccine efficacy for the dengue serotype?
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19. What are ethical aspects you see from the study? Case 2.