Experimental Studies Randomized Trials Clinical Trials.

Experimental StudiesRandomized Trials

Clinical Trials

Research Design Epidemiology

Descriptive StudiesCase ReportsCase SeriesCross Sectional Survey

Analytic StudiesObservational Studies

Case-Control or Case-ComparisonCohort Studies

Intervention StudiesClinical Trials

History

The Islamic-Persian scholar Avicenna (980–1037) was an early proponent of the technique. James Lind (1716–1794) ran a clinical trial in 1747 to compare the effects of cider, oranges and lemons and four other treatments in 12 patients suffering from scurvy (two assigned to each treatment). The two given oranges and lemons recovered. The first modern randomized clinical trials were carried out by the Medical Research Council in the United Kingdom and their prime mover was the statistician Austin Bradford Hill (1897–1991).

From Canon of Medicine

"The drug must be tested with two contrary types of diseases, because sometimes a drug cures one disease by Its essential qualities and another by its accidental ones." "The time of action must be observed, so that essence and accident are not confused." "The effect of the drug must be seen to occur constantly or in many cases, for if this did not happen, it was an accidental effect." "The experimentation must be done with the human body, for testing a drug on a lion or a horse might not prove anything about its effect on man."

Randomized Clinical Trials

TherapeuticAZT treatment for AIDSMastectomy vs. lumpectomy

InterventionMammography for early detectionCholesterol lowering drugs

PreventionSmoking cessationClean needle program

Strength of Evidence

Weaker Stronger

Case reports RandomizedCase series Trials

Observational studiesCase/Control

Cohort

Experimental Studies

General features inherent to methodology

prospectiveconcurrent control group intervention with placebo or usual care

investigator controls/ manipulates conditions studied (hence an experiment)investigator assigns exposure

Schematic diagram of a clinical trial

SampleNonparticipants

Randomization

ControlIntervention

Lost to follow-up

Measure outcome Measure outcome

Randomization types

SimpleSystematicBalanced blockStratified

Simple randomization

B B A B A B A A B B

B A A A A A A A B A

B A B A B B B B A B

A B A B A B B B B B

B A A A B A B B A A

A A B A B B B A B B

A B B A A B B B A B

B A A A B B A B B B

B A A B A B B B A B

B B A B B B B A B A

Systematic randomization

A B A B A B A B A B

A B A B A B A B A B

A B A B A B A B A B

A B A B A B A B A B

A B A B A B A B A B

A B A B A B A B A B

A B A B A B A B A B

A B A B A B A B A B

A B A B A B A B A B

A B A B A B A B A B

Balanced block randomization

1. AABB2. ABAB3. ABBA4. BBAA5. BABA6. BAAB

1 3 2 9 1

6 4 3 8 7

3 1 2 5 8

2 4 1 7 3

4 5 3 9 6



1 3 2 9 1

6 4 3 8 7

3 1 2 5 8

2 4 1 7 3

4 5 3 9 6

A A B B



1 3 2 9 1

6 4 3 8 7

3 1 2 5 8

2 4 1 7 3

4 5 3 9 6

A A B B A B B A



1 3 2 9 1

6 4 3 8 7

3 1 2 5 8

2 4 1 7 3

4 5 3 9 6

A A B B A B B A

A B A B



1 3 2 9 1

6 4 3 8 7

3 1 2 5 8

2 4 1 7 3

4 5 3 9 6

A A B B A B B A

A B A B A A B B



1 3 2 9 1

6 4 3 8 7

3 1 2 5 8

2 4 1 7 3

4 5 3 9 6

A A B B A B B A

A B A B A A B B

B A A B B B A A

A B B A A B B A

A A B B A B A B

B A B A A B B A

B B A A A A B B

A B B A B B A A

B A B A A B B A

B A A B A A B B

Confounding and Bias

By randomly assigning the exposure - reduce the risk of confounding because:““confounders - known and unknown” are confounders - known and unknown” are randomly distributed among the treatment randomly distributed among the treatment groupsgroups

By blinding (masking) assessment of outcomereduce the risk of information bias

Masking (blinding)

To avoid systematic differences between the treated and control groups during the course of the study in factors other than the one under study

Double-blindPatient, care provider, and investigator (person collecting data) all unaware of treatment assignment

Single-blindPatient unaware of treatment assignment

Blindness

Open label (unblinding)Single blinding (patients only)Double blinding (patients and investigators)Triple blinding (patients and investigators and Monitoring investigators)

Concerns in RCT

Loss to follow upLow compliancePublication bias

Experimental Studies Randomized Trials Clinical Trials.

Documents

Transcript of Experimental Studies Randomized Trials Clinical Trials.