basic concept of clinical study
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Basic concept of clinical study. Vuthiphan Vongmongkol Weranuch Wongwatanakul. Epidemiology. Basic science of public health. - PowerPoint PPT PresentationTRANSCRIPT
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Basic concept of clinical study
Vuthiphan Vongmongkol
Weranuch Wongwatanakul
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Epidemiology
Basic science of public health“The study of the distribution and determinants of health-related states or events in specified population and the application of this study to
control of health problems”Last JM:A dictionary of Epidemiology,ed 2. New York,
Oxford University Press,1988
Distribution (Prevalence, Incidence)Determinants (Risk factors, Causes of diseases)
*Ram Ragsin, MD MPH DrPHDepartment of Military & Community MedicinePhramongkutklao College of Medicine
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Research question in Epidemiology
• Size of the problems− Prevalence of DM in the population− How many people don’t have adequate health care?
• Association of the problems– Did the DM in this population related to education
level?– Did those Whose do not have adequate health care
relate to geographic region of residences?
*Ram Ragsin, MD MPH DrPHDepartment of Military & Community MedicinePhramongkutklao College of Medicine
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Measurements in Epidemiology
• Size of the problems (Measuring the occurrence)– Prevalence– Incidence
• Association of the Problems (Measuring the association)– Prevalence Rate Ratio ===> Cross-Sectional Study
– Odds Ratio ===> Case-Control study–Relative Risk ===> Cohort study
*Ram Ragsin, MD MPH DrPHDepartment of Military & Community MedicinePhramongkutklao College of Medicine
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Rate
• The central tool of Epidemiology is the comparison of RATES
- Mortality Rate- Prevalence- Incidence
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Prevalence
“The number of existing case of disease at a particular point in time.”
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Incidence (1)
There are two ways of measuring
1) Cumulative incidence
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Measuring the incidence (2)
2) Incidence density or Incidence rate• Adding “Time Dimension” into the denominator
“Person-time”
• person-month, person-year• 1 person-year = Following 1 person for 1 year period• 10 person-year = Following 1 person for 10 year period or Following 10 persons for 1 year period
*Ram Ragsin, MD MPH DrPHDepartment of Military & Community MedicinePhramongkutklao College of Medicine
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Measuring the incidence (3)
2) Incidence density or Incidence rate
If 100 subjects are followed for 1 year and 20 develop disease, the incidence density is
20 cases/ 100 person-years of observation= 20/100 person-years
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ประชากร 118539, คนในเวลา 8 ป!Smoking No. of stroke Person-
years Incidence rate
of observation
/100,000 person-years
Never 70 395,594
17.7
Ex-smoker 65 232,712
27.9
Smoker 139 280,141
49.6
Total 274 908,477
30.2
Cumulative incidence = 274 /
1 1 8 ,5 3 9 = 2 .3 1 /
1000
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Classification of Clinical Study Design
Observation(natural exposure)
Experiment (exposure given by researcher)
Randomized controlled trials
Cross-sectional Case control Cohort
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Ability to prove causation
Type of study Ability to “prove” causation
Randomized controlled trials
Cohort studiesCase control studiesCross-sectional studies
StrongModerateModerate
Weak
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Cohort Study !!!!
We are dealing with
“INCIDENCE”
*Ram Ragsin, MD MPH DrPHDepartment of Military & Community MedicinePhramongkutklao College of Medicine
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Cohort Study (1)
• The most powerful observational study for identifying an association between risk factors and a disease
• The most time consuming
• The most expensive
*Ram Ragsin, MD MPH DrPHDepartment of Military & Community MedicinePhramongkutklao College of Medicine
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Cohort Study (2)
• Start with a group of people without the disease
• Then divide people based on the basis of the exposure to a suspected risk factor
• Follow the “whole group” for a period of time
• Then assess the disease occurrence outcome
*Ram Ragsin, MD MPH DrPHDepartment of Military & Community MedicinePhramongkutklao College of Medicine
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Cause Effect
Cigarette•Exposure•Risk factor•Covariate
- Age- Gender- Income
Lung Cancer•Disease•Death•Intermediate outcomes
- CD4+count- Increased Creatinine
*Ram Ragsin, MD MPH DrPHDepartment of Military & Community MedicinePhramongkutklao College of Medicine
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Design of a cohort study
Time
Direction of inquiry
Exposed
Not Exposed
People without
The disease
Population
disease
no disease
disease
no disease
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Risk
“ The probability of disease incidence”
Risk = number of cases of disease number of people at risk
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Relative Risk
A B
C D
A+B
C+D
Smoke
Not Smoke
CA Lung No CA
Relative Risk = A / A+B C / C+D
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Interpretation of Relative Risk (RR)
45 445
1 499
500
500
Smoke
Not Smoke
CA Lung No CA
Incidence of smoker who develop Lung Cancer = 45/500Incidence of Non-smoker who develop Lung Cancer = 1/500Relative Risk of smoking for Lung Cancer = 45/500 = 45
1/500
“Those who smoked were 45 times more likely to develop lung cancer than those who did not smoke”
*Ram Ragsin, MD MPH DrPHDepartment of Military & Community MedicinePhramongkutklao College of Medicine
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Design of case-control study
Exposed
Not Exposed
Cases(People with
disease)
Population
Exposed
Not Exposed
Controls(People without
disease)
Time
Direction of inquiry
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Case-control VS Cohort
Cause Effect
Factors Disease
Case-Control
Factors Disease
Cohort
*Ram Ragsin, MD MPH DrPHDepartment of Military & Community MedicinePhramongkutklao College of Medicine
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Case-Control Study
• Strengths– Uniquely suited to diseases with long incubation
periods– More efficient in terms of time and money– Good for study of rare disease– Can look at multiple exposures for a single disease– Case-control studies usually require much smaller
sample sizes than do equivalent cohort studies– Case-control studies are generally able to evaluate
confounding and interaction rather more precisely for the same overall sample size than are cohort studies.
*Janit Kaewkungwal Faculty of Tropical MedicineMahidol University
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Case-Control Study
• Limitation– Inefficient for evaluation of rare exposures– Cannot directly compute incidence rates of disease– Temporal relationship between E and D may be hard to
establish. Case-control studies often do not involve a time sequence, and so are limited in their ability to demonstrate causality.
– Particularly prone to bias (selection and recall in particular)– Being identified as a case might reflect survival rather than
morbidity.– Case-control studies can investigate only one disease outcome.– May be confounded by unknown exposures– Appropriate control group often difficult to find
*Janit Kaewkungwal Faculty of Tropical MedicineMahidol University
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Odds
“The number of times the outcome occurs relative to the number of times its does not.”
Odds = number of cases of disease number of non-cases of disease
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Odds Ratio
CA lung(case)
No CA(control)
smoke
Not smoke
Exposure
Disease
Odds of exposure if case = [a/(a+c)] / [c/(a+c)] = a/cOdds of exposure if control = [b/(b+d)] / [d/(b+d)] = b/dOR = Odds of exposure if case = a/c Odds of exposure if control b/d
a b
c d c+d
a+c b+d N
a+b
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Relative risk VS Odds ratio (1)If disease is rare
relative risk Odds ratio
Cohort study
Cases Non-cases Total
Exposed 75 (a) 9,925 (b) 10,000 (a+b)
Unexposed 25 (c) 9,975 (d) 10,000 (c+d)
Total 100 19900 20,000
Relative Risk = A / A+B = 0.75%/0.25% = 3.0 C / C+D
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Relative risk VS Odds ratio (2)
Case-control study Cases Controls
Exposed 75 50
Unexposed 25 50
Odds ratio = 75X50 = 3.025x50
relative risk Odds ratio
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Cross-sectional studies
• Measure the prevalence of disease and often called prevalence studies
• The easiest step to find an association (Factor & Disease) by comparing exposed and non-exposed population
• Assess both EXPOSURE and DISEASE at the SAME TIME (simultaneously)
• Analyze results from a survey*Ram Ragsin, MD MPH DrPHDepartment of Military & Community MedicinePhramongkutklao College of Medicine
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Design of a Cross-sectional study
Defined population
Gather data onExposure and
disease(simultaneously)
+Exposure +Disease
-Exposure +Disease
+Exposure -Disease
-Exposure -Disease
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Prevalence Rate Ratio
• Estimate the “Relative Risk” from a cross-sectional study
• Prevalence Rate Ratio = 10% / 5%
= 2
• “Those who had high cholesterol were 2 times more likely to develop HT than those who did not”
*Ram Ragsin, MD MPH DrPHDepartment of Military & Community MedicinePhramongkutklao College of Medicine
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Thank you