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Experimental Study Designs

Dr. Birgit GreinerDep. of Epidemiology and Public Health

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Learning objectivesAt the end of this lecture you …

• Are familiar with areas of application of experimental studies

• Know different types of experimental studies

• Understand the essential components of the design

• Appreciate potential limitations • Are familiar with ethical issues in trials

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Type of Study

Alternative Name

Unit of Study

Randomised Controlled Trials

Field Trials

Community Trials

Clinical Trials

Community Intervention Studies

Patients

Healthy People

Communities

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Trials are useful for evaluating:

• New drug or other treatment for disease• New medical/health care technology• Methods of prevention• Methods of health promotion• New health protection policies• Programs for screening and diagnosis• Methods of providing health care• New health care policies

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Example of an RCT

A randomised controlled trial investigated whether preoperative

smoking intervention reduced postoperative complications in patients

undergoing hip or knee replacement

Moeller AM, Villebro N, Pedersen T. & Toennesen H. The Lancet, Vol 359 Jan 12, 2002

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Intervention Randomisation

Control Blinding

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population

group 1

group 2

Outcome

Outcome

new treatment

control treatment

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Randomised controlled trialRandomised controlled trial

Patients undergoing hip or knee replacement

Preoperative Smoking intervention

Standard care

POC

No POC

POC

No POC

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Chance - Sample Size

Bias - Randomisation/Blinding/

Standardization

Confounding - Randomisation

Overview

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Chance: Sample size

Large enough to have high probability (power) of detecting a clinically

important difference of a given size

• Size of effect

• Error level (usually 5%)

• Statistical power (usually 80%)

• Variation of outcome

Use StatCalc in the EpiInfo Software: http://www.cdc.gov/epiinfo/EI2000.htm

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BiasSystematic deviation of results from the

truth

Measurement bias

Sytematic error arising from inaccurate measurement

Selection bias

Error due to systematic differences between those selected for the

study and those who are not

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ConfoundingEffects of 2 exposures are not seperated

EXPOSURE

(coffee drinking)

DISEASE

(heart disease)

CONFOUNDING VARIABLE

(cigarette smoking)

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Validity issues

Internal validityDegree to which the investigator’s conclusions correctly describe what happened in the study

External validityDegree to which the investigator’s conclusions are appropriate when applied to the universe outside the study

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Advantages of RCTs

• Strong ability to prove causal relationships

• Risk of confounding factors minimised by randomisation

• Efficient and powerful statistical manipulation possible

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Disadvantages of RCTs

• Loss-to-follow up of patients and non-compliance might constitute major biases

• Often based on volunteer samples, results may not be generalizable to the wider population

• Not feasible/ethical for major public health questions

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Basic Ethical Principles in Biomedical Research Involving Human Subjects

• Experimental procedure clearly formulated in protocol and reviewed by independent committee

• Importance of objective is in proportion to risk to the subject

• Assessment of predictable risks in comparison with forseeable benefits to subject

• Cease intervention if hazards outweigh benefits• Informed consent from subject• Subject can withdraw at any time

Adapted from Helsinki Declaration: www.mrc.ac.uk/pdf-ctg.pdf

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Voluntary consent of human subject is absolutely essential…..free power of choice, without the intervention of …. ulterior form of constraint or coercion. Helsinki Declaration 2000

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Ethical Considerations in RCTs

• Is proposed treatment safe?• For the sake of trial, can a treatment ethically

be withheld?• What patients may be brought into trial and

allocated randomly to treatments?• Is it ethical to use a placebo or dummy

treatment?• Is it proper for the trial to be in any way

masked?Adapted from Hill (1977)

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Pooling of data from multiple studies addressing the same hypothesis.

Provide a more “precise” estimate

Watch out for publication bias

!

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Database of Systematic Reviews

Database of Abstracts of Reviews

Cochrane Collaboration Trials Registry

Cochrane Review Methodology

Cochrane Collaborationwww.cochrane.org