General notes on the use of ActivEpi CD Rom – we will NOT do the DataDesk exercises

Different ways to describe study designs (other than experimental vs. observational):

· Directionality

· Timing

Directionality

Deals with timing of investigation of exposure and outcome

· Exposure known prior to disease – Forward directionality

· Exposure determined AFTER disease – Backward directionality

· Exposure and Disease determined simultaneously – Nondirectional

Timing

Relates to whether the study is initiated before or after the outcome.

Retrospective – the disease/outcome has already occurred when the study begins

Prospective – the disease/outcome occurs sometime after the initiation of the study

Could be a mixture or retrospective and prospective (Mixed timing)
We now go into the specific of the major study design:

Clinical trial

Cohort

Case-control

Cross-sectional

Others

Clinical Trials

Experimental design

Assess therapeutic effects/health benefits

Key features:

Randomization

Blinding

Ethical concerns

Intention to treat analysis (analyze-as-randomized, effectiveness) vs. Treatment-received analysis (efficacy)

Cohort Studies

Observational; Can be prospective or retrospective

Prospective

Retrospective

Which do you think usually provides more accurate information, prospective or retrospective?

Ways in which a cohort study might be designed:

1. Sample population, divide into exposed and nonexposed

2. Identify an exposed population – find an external, nonexposed group for comparison

Advantages of cohort studies:

Of observational studies, tends to be least prone to bias

Can address several diseases in same study

With retrospective, can be relatively low cost, quick

Can be used with rare exposures

Disadvantages of cohort studies

Loss to follow-up a potential problem

Usually larger sample size than case-control

Prospective – can be expensive & time-consuming

Prospective – inefficient with rare diseases, diseases of

long latency

Case-Control Studies

Identify cases, then sample those without disease (controls)

Ideally should be from a clearly defined source population

Controls should also be from the same source population

Can be retrospective, prospective, or mixed

Case-Control Studies - continued

Advantages:

Relative to cohort, quicker

Usually smaller sample size

Better with rare diseases than cohort

Better with diseases of long latency periods

Can evaluate multiple exposures

Disadvantages

Only one outcome can be studied (in contrast to cohort)

Does not allow direct assessment of risk

More susceptible to certain biases

Not efficient for studying rare exposures

Use of incident vs. prevalent cases in case-control studies

Incident cases preferred

With prevalent cases, exposure-disease relationship may be affected by prognostic indicators of duration of disease.

Choosing controls in a Case-Control Study

Controls should be from same source population as cases.

Population-based vs. hospital/clinic-based

Hospital vs. Population-based Case-control studies

Hospital Advantages (relative to population-based)

· Controls easily accessible

· Less expensive, less time consuming

Hospital Disadvantages (relative to population-based)

· Controls less representative of source population

· Controls are ill; possibly ill due to exposure of interest

Examples

· Reye syndrome – relation with aspirin

· Creutzfeldt-Jakob Disease – relation with animal products

Cross-Sectional Studies

Most frequently used study design.

Provides a snapshot of a population

Observational design

Variables measured at a single point in time

Examples:

· NHANES – National Health and Nutrition Examination Surveys

· BRFSS – Behavioral Risk Factor Surveillance Survey

· EPI – Expanded Program on Immunization Surveys

· MICS – UNICEF Multiple Indicator Cluster Survey

The target population could be the general population, individuals belonging to an organization (Medical Society), patients at a hospital (patient satisfaction survey), etc., etc., etc.

Advantages:

· Tends to be an inexpensive study design

· Can assess several exposures and diseases simultaneously

· Can generate hypotheses

Disadvantages

· Cannot establish whether exposure preceded disease

· In general, deals with prevalent disease (potential for survivor bias)

· Need large sample sizes for rare conditions

Example of a Cross-Sectional Study – Peripheral Vascular Disease in Scotland

Hybrid Designs

2 types described – both are variants of population-based case-control study: Case-Cohort and Nested Case-Control

Case-Cohort Study

Start with a cohort study; identify those with disease (“cases”) at a latter point in time, select subsample from nondiseased as controls using exposure information collected at the start of the study.

Example: gastric cancer and H. pylori infection

· Cohort of 9,775 men in Taiwan with blood samples at baseline.

· During study, 29 developed gastric cancer

· Selected 220 controls from those with no gastric cancer

· Compared frequency of H. pylori infections at baseline.

Nested Case-Control Study

Variation of Case-Cohort. Identify cases as they occur, select control(s) for each case. Also called density-type case control study.

Example of nested case-control: Cohort study of 5000 telephone employees

Incomplete Designs

Ecologic Studies

Also called ecologic correlations/studies; comparison based on summary or aggregate data from groups (not individuals). Subject to ecologic fallacy.

Proportional Studies

Deals only with the proportion of deaths due to a cause.

3,520 deaths among nuclear power plant workers

Do not know size of population at risk