Analytic studies
1- Observational studies. The investigator simply observe the nature al course of the events, noting who is exposed & non exposed and who has & has not developed the outcome of interest(passive investigator). We have;a- Case-control study.
b- Cohort study.
2- Interventional studies (clinical trial). The investigator him self will allocate the exposure (active investigator).
*Cohort study.
The group(s) is defined on the basis of presence or absence of the exposure to a suspected risk factor for a disease\outcome. All subjects then followed over a period of time to assess the occurrence of that outcome.Design of cohort studies
((Starting point)) Out-come Total +ve -ve Exposure+ve a b Exposed -ve c d Not-exposed TotalPresent Free N
#Strength;
Establish the temporal relation ship between exposure and outcome.
Allow direct measurement of incidence.
Examine multiple effects of single exposure.
Suitable for rare exposure.
Provide information on confounders.
*Limitations;
1- Expensive and time consuming.
2- Validity of the results can be seriously affected by losses to follow up (bias).
3- Insufficient for the evaluation of rare disease.
Selection of exposed population
For Rare exposure (e.g. radiation), we need specially exposed people (as individual in certain occupation, or exposed to special event or treatment).
For common exposure (e.g. smoking), we need specially chosen people (can obtain complete information e.g. members in certain profession as doctor, teacheretc., or student in particular college or school).
The source of exposure data can be obtained from:
Pre-existing data.
From the study subject.
Direct physical examination.
Direct investigation.
Direct measurement of environment.
Selection of comparison population
Internal comparison group, used when a single cohort entered the study.External comparison group, when specially exposed cohort enters the study.
Multiple comparison groups. Very valid.
Estimation of risk ((is there an association?))
In cohort study, we can measure the incidence (absolute risk) directly. The incidence among exposed (Ie) and incidence among non-exposed (I0).Relative risk (RR) is the measurement of association in cohort study and can be calculated as follow: (RR) = (Ie)/ (I0).
If RR=1 →No association, If RR>1 → Positive association
If RR<1 →Negative (inverse association, possibly protective).
Attributable risk (AR) provides information about absolute effect of the exposure: (AR) = (Ie) - (I0). AR indicate the number of cases among the exposed that can be attributed to the exposure it self.
Attributable risk percent (AR%): (AR)/ (Ie) x 100% , estimate the proportion of the disease among the exposed that can be attributed to the exposure it self.
Ex: To determine the relationship between cigarette smoking and CHD, 8000 healthy individual with age > 45 years were enrolled in a study. 3000 of them were smoker. Within 10 years, 84 of the smoker and 87 0f non-smokers develop CHD.
1- What is the design of the study? (Cohort study).
2- Draw 2x2 table.
Out-come (CHD)
Total +ve -ve Exposure
(smoking)+ve 84 2916 3000 -ve 87 4913 5000 Total 171 7829 8000
3- Is there any relation between smoking and CHD?
We measure the association by estimating the RR = (Ie)/ (I0). Ie(CHD in smokers)=(84/3000)x 0.1 = 0.0028 per year
I0(CHD in non- smokers)=(87/5000)x 0.1 = 0.0017 per year
RR=0.0028/0.0017 = 1.6
*Case control study.
Subject are selected on the basis of whether they do (cases) or don't (control) have a particular disease / outcome under study, the groups are then compared with respect to the proportion having a history of an exposure or characteristic of interest.
Design of case control studies.
((Starting point))Out-come Total +ve -ve Exposure
+ve a b Exposed -ve c dNot-exposed TotalPresent Free N#Strength;
Quick & inexpensive regarding other analytic studies.
Depend on already available data.
Suitable for rare diseases &diseases of long latency period.
Can examine multiple etiological factors for a single disease e.g. CHD with smoking, diet, physical exercise..etc.
*Limitations;
1- Not establish the temporal relation ship between exposure and out come (both exposure and outcome have already occurred.
2- Can't compute the incidence.
3- More prone for bias compared with other analytic studies.
4- In efficient for the evaluation of rare exposure.
Definition of cases
Homogenous disease entity (clear definition of the disease).Depend on strict diagnostic criteria (e.g. MI diagnosed by chest pain more than 30 min. ECG changes and enzyme changes).
Sources of selection of cases
Hospital-based case control study.
Advantages: common, easy and inexpensive.
Limitations: only sever cases of the disease enter the hospital (selection bias).
Population based case control.
Advantages: avoid selection bias and describe the picture of the disease in the population.
Limitations: difficult, costly and not routinely done.
Selection of control
It is important to select appropriate control group. The control group should be selected to be comparable to the cases and there is no control group fit for all situations. We have the following types of control:1- Hospital control;
Advantages: common, easy, more willing to cooperate and inexpensive.
Limitations: They are diseased.
2- General population control.
Advantages: represent healthy population.
Limitations: difficult, costly and not routinely done as it is difficult to contact with healthy individuals.
Estimation of risk ((is there an association?)).
In case control study we can't calculate the incidence (absolute risk) because we start already disease population (cases) and non disease (control) people. Hence, we use the" Odd's Ratio" (OR) which is measure using the following formula: OR= ad/bcEx: To determine the relationship between smoking and CHD, patients with CHD had been compared to patients from orthopedic department; the two groups were matched for age and sex, and were asked about smoking history, the following had been found:
Out-come (CHD)
Total +ve -ve Exposure
(smoking)+ve 112 176 288 -ve 88224 312 Total 200 400 600
1- What is the design of the study? (Case control).
2- Is there any relation between smoking and CHD?
We measure the association by estimating the OR= ad/bc
OR= (112 x224) /(176 x 88) = 1.62 (those who have CHD were 1.62 time more exposed to smoking than those free of disease).