Basic concept of clinical study

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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?


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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


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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


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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”


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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


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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


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Cause Effect

Cigarette•Exposure•Risk factor•Covariate

- Age- Gender- Income

Lung Cancer•Disease•Death•Intermediate outcomes

- CD4+count- Increased Creatinine


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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”


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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


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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”


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Thank you

Basic concept of clinical study

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