Analytical study designs ABDIRISAK MOHAMED

Analytical studies

Analytical studies are the second major type of epidemiological studies. Focus on individual within population unlike descriptive study which look for the whole

population Objective not to formulate hypothesis but to test hypothesis. To evaluate an association between exposure and disease. Analytical studies focuses on the magnitude of the association between the exposure

and the health problem under the study.

Types of analytical studies

Main types of analytical studies are; Case control study Cohort study Randomized controlled trials Non-randomized controlled study e.g. Field trials, community trials

Analytic study designs used in epidemiologyDesign Sampling Best to use when: Association

measure

Cross-sectional

Entire study group

Exposure and outcome are common

The relationship is not well understood

Prevalence

Case-controlRecruit cases of disease and a control group

without disease

Outcome/disease is rare (roughly <10% of the population has the disease)

Odds ratio

Cohort

Recruit people who are exposed to a factor and those who are

not

Exposure is rareDisease does not have a long

latency period

Closed Cohort -- Relative risk

Open Cohort -- Incidence

Experimental

Randomly assign people to be exposed (treatment group) or unexposed (control or placibo group)

You want to see if an intervention or drug is more

effective than another alternative

There is not a long latency period for the outcome

Incidence

Epidemic Investigation People exposed Outbreak situation

Attack rate ratio (RR or

OR)

1. Case control study

Case control study Case control study definitions:

A study that compares two groups of people: those with the disease or condition under study (cases) and a very similar group of people who do not have the disease or condition (controls). (National Institute of Health, USA)

The observational epidemiologic study of persons with the disease (or other outcome variable) of interest and a suitable control (comparison/ reference) group of persons without the disease(Dictionary of Epidemiology: 3rd ed; John M Last. 2000)

Definition of key terms Case : A person in the population or study group identified as having

the particular disease, health disorder or condition under investigation. (Dictionary of Epidemiology: 3rd ed; John M Last. 2000)

Control: Person or persons in a comparison group that differs, in disease experience (or other health related outcome) in not having the outcome being studied. (Dictionary of Epidemiology: 3rd ed; John M Last. 2000)

Bias: Any systematic error in the design, conduct, or analysis of a study that results in mistaken estimates of the effect of the exposure on disease.

Confounding: When a measure of the effect of an exposure on risk is distorted because of the association of exposure with other factors that influence the outcome. It creates data where it is not possible to separate the contribution that any single causal factor has made an effect.

Confounder

Exposure outcome

(i)Associated with the exposure of interest.(ii) Related to the outcome of the interest.(iii) It should not be in the direct chain or link between the exposure and outcome

Features of case control study

A case control study involves two populations – cases and controls and has three distinct features :

1. Both exposure and outcome have occurred before the start of the study.

2. The study proceeds backwards from effect to cause.

3. It uses a control or comparison group to support or refute an inference.

• Six essential elements which developed separately over time in medical history

• Idea of the case• Interest in disease aetiology and prevention

• Focus on individual, as opposed to group aetiologies

• Anamnesis or history taking from patients

• Grouping individual cases together into series

• Making comparisons of the differences between groups, in order to elicit average risk at the level of individual

History of case control studies

Examples of case control studies

1. Selection of cases and controls : The investigator selects cases with the disease and appropriate controls without the disease

2. Matching is the selection of controls so that they are similar to the cases in specified characteristics. 3. Measurement of exposure : obtains data regarding past exposure to possible etiologic factors in both groups. 4. Analysis and interpretation: The investigator then compares the frequency of exposure of the two groups.

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BASIC STEPS OF CASE CONTROL STUDY

Selection of cases Selection of CASES: Case-control studies are prone to bias and confounding therefore Care

must be taken when choosing cases for the study. By ensuring following:- 1. Representativeness: Ideally, cases are a random sample of all cases of interest in the source population

(e.g. from vital data, registry data). More commonly they are a selection of available cases from a medical care facility. (e.g. from hospitals, clinics). Information: can be collected from cases themselves, or from a respondent by proxy (relative/ friend), from records or a combination of the above.

2. Method of Selection: Selection may be from incidence or prevalence case:

Incident cases are those derived from ongoing-ascertainment of cases over time . Selection of incident cases is optimal. These should be all newly diagnosed cases over a given period of time in a defined population.

Prevalent cases are derived from a cross-sectional survey. Prevalent cases do not include patients with a short course of disease. So patients who recovered early and those who died will not be included.

Contd. Selection of cases

3.Diagnostic criteria for case studies : Diagnostic criteria regarding diagnosis of cases, types of cases and stage of disease to be included should be predefined. Ideally, all subjects who have the disease should be classified as “having

the disease” and vice versa Practically, the ability to classify individuals into the correct disease status depends on the

accuracy of the tests, among other things a. Validity is the ability of a test to indicate which individuals have the disease and which do not-Sensitivity The ability of the test to identify correctly those who have the disease

-Specificity The ability of the test to identify correctly those who do not have the disease b. Diagnostic bias: to avoid diagnostic bias only true positives cases should be selected.

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Figure 1 : the relationship between a diagnostic test result and occurrence of disease

Disease present (+)

Disease absent (-)

Test (+) True positives False positives

Test (-) False negatives

True negatives

Selection of controls i. COMPARABLE : the controls should be similar to the cases in all

respects other than having the disease . ii. REPRESENTATIVE : the controls should be representative of all non-

diseased people in the population from which the cases are selected.iii. Sources of controls

General populationRelatives/Friends/NeighboursHospital controls

iv. Number

o Large study: Cases: Control : 1:1o Small study: Cases: Control : 1:2, 1:3, 1:4.

• Sources of controls Source Advantage Disadvantage

Hospital based Easily identified.Available for interview.More willing to cooperate.Tend to give complete and accurate information (recall bias).

Not typical of general population.Possess more risk factors for disease.Some diseases may share risk factors with disease under study. (whom to exclude???)Berkesonian bias

Population based(registry cases)

Most representative of the general population.Generally healthy.

Time, money, energy.Opportunity of exposure may not be same as that of cases. (locn, occu,)

Neighbourhood controls/ Telephone exchange random dialing

Controls and cases similar in residence.Easier than sampling the population.

Non cooperation.Security issues.Not representative of general population.

Best friend control/ Sibling control

Accessible, Cooperative.Similar to cases in most aspects.

Overmatching.

Matching Matching: It is the selection of controls so that they are similar to

the cases in specified characteristics. (Epidemiology: An Introductory Text; Mausner & Bahn, 1985)

Matching is defined as the process of selecting controls so that they are similar to cases in certain characteristics such as age, sex, race, socioeconomic status and occupation. (Epidemiology; Leon Gordis, 2004)

Matching variables (e.g. age), and matching criteria (e.g. within the same 5 year age group) must be set up in advance.

Types of matching Controls can be individually matched (most common)

or Frequency matched.1.Individual matching (Matched pairs): search for one (or more) controls who have the required matching criteria, paired (triplet) matching is when there is one (two) control (s) individually matched to each cases.

2. Group matching (Frequency matching): select a population of controls such that the overall characteristics of the case, e.g. if 15% cases are under age 20, 15% of the controls must be also under age 20. another example If 30% of cases are males of Hindu religion in 60-65 years then we take 30% of similar controls

Bias in Case control Study

Bias is any systematic error in the design, conduct, or analysis of a study that results in mistaken estimates of the effect of the exposure on disease.

Types of bias in case control studies:Selection bias Information biasConfounding bias

Types of bias in case control studies

1. Ascertainment and selection bias arise due to

a. Selective loss to follow-up b. Incomplete ascertainment of cases (Detection or Diagnostic bias)

c. Inappropriate control group 2. Information Bias (estimation of exposure) Occurs due to -

a. Imperfect definitions of study variables b. Flawed data collection procedures. information bias leads to Misclassification of disease and exposure. Some of the cases

or controls who were actually exposed will be erroneously classified as unexposed, and some who were actually not exposed will be erroneously classified as exposed.—this generally results in an underestimate of the true risk of the disease associated with the exposure.

Types of Information bias – Recall bias (usually in case-control studies): Cases who are aware of their disease status

may be more likely to recall exposures than controls Interviewer bias : When interviewer is not blinded (knows) case status of subjects there

is potential for interviewer bias

Contd. Types of bias in case control studies 3. Confounding: When a measure of the effect of an exposure on risk is

distorted because of the association of exposure with other factors that influence the outcome.

It is not possible to separate the contribution that any single causal factor has made

Confounding Factor: is one which is associated with both exposure & disease , and is distributed unequally in study & control groups. E.g.: Alcohol & Esophageal Cancer ; confounding factor- smoking

Analyses and interpretation of case control study On analysis of case control study we find out :-

Exposure rates: the frequency of exposure to suspected risk factor in cases and in controls

Odds ratio : Estimation of disease risk associated with exposure. The only valid measure of association for the Case control study is

the Odds Ratio (OR) OR = Odds of exposure among cases (disease)

Odds of exposure among controls (non-dis)

Odds of exposure among cases = a / c Odds of exposure among controls = b / d

Odds ratio: = (a/c)/ (b/d) = ad / bc Odds ratio (OR )= 1.0 (implies equal odds of exposure - no effect)

Exposure rates:A case control study provides a direct estimation of

the exposure rates (frequency of exposure) to the suspected factor in disease and non-disease groups.

Exposure rates Cases = a/ (a + c) = 33/ 35 = 94.2% Controls = b/ (b + d) = 55/82 = 67.0% Odds ratio: = (a/c)/ (b/d) = ad / bc

Outcomes of Case Control Study

Cases (lung cancer)

Controls (without lung

cancer)Smokers 33 (a) 55 (b)

Non Smokers 2 (c) 27 (d)

TOTAL 35 (a + c) 82 (b+d)

How to interpret the Odds ratio?

People who smoke have an 8.1 times higher risk of developing lung cancer compared to those who do not smoke.

Exercise An investigator selected 40 cases of gastric carcinoma and an

equal number of controls matched for age, sex and socioeconomic status. It was found that among cases 30 had an evidence of H pylori infection and among controls 15 had an evidence of H pylori infection. Is there an evidence of association between H pylori infection and gastric carcinoma?

1. Draw the two by two table 2. Find exposure rate in cases3.Find exposure rate in controls4. Calculate “Odds Ratio”5. Interprets the results.

Application of case control studies

1. Vaccine effectiveness2. Evaluation of treatment and program efficacy3. Evaluation of screening programs4. Outbreak investigations5. Demography 6. Genetic epidemiology7. Occupational epidemiology

Advantages

1. Only realistic study design for uncovering etiology in rare diseases

2. Important in understanding new diseases3. Commonly used in outbreaks investigation4. Useful if inducing period is long5. Relatively inexpensive

Disadvantages

1. Susceptible to bias if not carefully designed 2. Especially susceptible to exposure misclassification 3. Especially susceptible to recall bias 4. Restricted to single outcome 5. Incidence rates not usually calculate 6. Cannot assess effects of matching variables