Study designs.

Kate O’DonnellGeneral Practice & Primary Care

Epidemiological questions.

How common is the problem?

What are the risks of further problems?

Are treatments effective?

What are the causes of the problems described?

How effective are services?

Underpinning concepts.

What concepts underpin these types of questions?

Risk

EffectivenessAssociation

Likelihood

Population level data applied to individuals

What can studies do?

Describe the situation: Descriptive.

Explain the situation: Analytical.

Compare approaches: Experimental.

Study designs.

Descriptive

Cross-sectional, longitudinal.

Analytic

Case-control studies.

Cohort studies.

Quasi-experimental

Natural experiments, policy interventions.

Experimental

Randomised controlled trial.

Type of Study Descriptive Analytical Experimental

Case study Yes No No

Case series Yes No No

Cross-sectional Yes Yes No

Case-control Yes Yes No

Cohort Yes Yes No

Natural experiment Yes Yes Quasi

Randomised control trial Yes Yes Yes

Study designs

Prevalence Cross-sectional

Cause/Aetiology

Cross-sectional;Case-control;Cohort.

Prognosis Cohort.

Harm Case-control;Cohort.

Effectiveness Randomised controlled trial.

Present FuturePast

Cross-sectional

Case-control

Cohort

From Altman. Practical Statistics for Medical Research, 1991.

Sample

Randomise

Intervention group

Control group

Randomised controlled trial

Case control studies: Key features.

Retrospective, i.e. backward looking.

Relate an effect or outcome to a probable cause.

Individuals with disease (cases) compared to individuals without disease (controls).

Case control study.

From: http://library.downstate.edu/EBM2/2500.htm

Advantages & disadvantages

Advantages Disadvantages

Quicker than cohort studies No measure of incidence

Relatively small study population required

Can only investigate one disease at a time & no temporal association

Good for rare diseases – can select all known cases

Retrospective, so data may be biased, e.g. poor records; memory recall

Case selection bias – must define cases very explicitly

Control selection bias

Matching controls to cases can be difficult

Can only determine the odds ratio, not relative risk

Appraising case control studies

Methodological approach:

Are cases and controls similar, except for exposure to the putative cause?

Is collection of retrospective data objective?

Is there evidence of “causation”?

Statistical reporting:

Type of data – influences statistical analysis.

Reporting of risk.

Cohort studies: Key features.

Prospective, i.e. forward looking.

Follow a population sample over a period of time, often years.

Record new disease events, i.e. the disease incidence.

Cohorts can be selected in either of two ways.

Selection of a cohort: External controls.

i. A cohort of individuals that have been exposed to a postulated causal factor of disease. The cohort is followed up and all new cases of the disease recorded. In this type of study, the exposed group would be compared to a matched, unexposed group and the incidence of disease in the two groups compared, i.e. an external control.

ii. An example would be a study to record the incidence of mesothelioma in factory workers exposed, or not, to asbestos.

Cohort studies.

From: http://www.socialresearchmethods.net/tutorial/Cho2/cohort.html

Selection of a cohort: Internal controls.

A population cohort can be selected and followed up over many years to determine the incidence of disease(s). In this type of study, those in the cohort who do not develop the disease act as the controls for those who do, i.e. an internal control.

An example would be the MIDSPAN study.

Cohort studies.

From: http://www.socialresearchmethods.net/tutorial/Cho2/cohort.html

Advantages & disadvantages

Advantages Disadvantages

Calculate incidence Need a large population

Don’t have to select controls Follow-up can take many years, so expensive

Prospective data collection, so less bias

Not good for rare diseases

Can study more than one disease or outcome

Lose individuals in follow-up

Temporal association Potential for bias in recruitment, assessment and follow-up.

Standardised assessment Assessment criteria may “drift” with time

Can estimate relative risk May become irrelevant before the end of the study

Appraising cohort studies

Methodological approach:

Representativeness of the inception cohort.

Characterisation at study baseline.

Nature and completeness of follow-up.

Statistical reporting:

Type of data – influences statistical analysis.

Reporting of risk.

Prevalence Cross-sectional

Cause/Aetiology

Cross-sectional;Case-control;Cohort.

Prognosis Cohort.

Harm Case-control;Cohort.

Effectiveness Randomised controlled trial.

Randomised controlled trials

A clinical trial in which:

• at least two treatments, programmes, interventions are compared.

• one of these is a control group.

• allocation uses a random, unbiased method.

Population

Group 1

Group 2

Outcome

Outcome

New treatment

Control treatmentFrom: Critical Appraisal Skills Programme (CASP), Oxford.

Randomised controlled trials

Explanatory trials

Measure efficacy:

the benefit a treatment produces under ideal conditions.

e.g. Phase III drug trials.

Pragmatic trials

Measure effectiveness:

the benefit a treatment produces in routine clinical

practice.

Aim to inform choices between treatments.

Patients should be analysed in the group to which they were initially randomised, i.e. intention to treat analysis.

Intention to treat analysis

All patients allocated to one arm of a RCT are analysed in that arm, whether or not they completed the prescribed treatment/regimen.

Two by two table

Outcome event Total

Yes No

Experimental group

a b a + b

Control group c d c + d

Total a + c b + d a + b +c + d

Appraising RCTs

Methodological approach:

Was assignment to the different groups randomised?

Was the randomisation process/list concealed?

Was everyone who entered the trial accounted for at the end?

Were subjects and assessors “blind” to treatment allocation when assessing outcomes?

Were groups similar at start of trial and treated similarly throughout the study?

Appraising RCTs

Statistical reporting:

Were subjects analysed in the group to which they were randomised: intention to treat analysis.

Type of data – influences statistical analysis.

Reporting of risk: RRR vs ARR.