analyzing rcts

Analyzing RCTs

Arin BasuPrepared for

HLTH 460-46227-04-2010

Objectives

• Principles of RCT• Describe RCT• How to analyze results• Advantages of RCT• Limitations of RCT• Interpret RCT

What is an RCT?SELECT POPULATION

RANDOM ASSIGNMENT

INTERVENTION GROUPCONTROL GROUP

FOLLOW UP

COMPARE OUTCOMES FOR BOTH GROUPS

Begin with homogenous group

Individual with disease

Use randomization to split

RANDOMIZATION CAN BE DONE USING RANDOM NUMBERS TABLESOFTWARE PROGRAMME

Follow up to observe outcomes

Individuals with desired outcomes

Individuals with the disease

Comparison of results

Intervention/Control Outcome status

PRESENT ABSENT Total

INTERVENTION A B A+B

CONTROL C D C+DTotal A+C B+D A+B+C+D

Experiment Event Rate (EER) = (A / (A+B)) * 100Control Event Rate (CER) = (C / (C+D)) * 100Absolute Risk Reduction = EER - CERRelative Risk = EER/CER

Types of RCT• Parallel Group RCT• Factorial RCT• Crossover RCT• Cluster RCT• Trial types

– Superiority– Non-inferiority– Equivalence

• Pragmatic RCT vs Traditional RCT

Parallel group RCT

Initial allotment

INTERVENTION CONTROL

Final Evaluation

Diseased individuals

Individuals who got better with treatment

Factorial RCTTREATMENT X

INTERVENTION CONTROL

TREATMENT Y

INTERVENTION

CONTROL

Crossover RCT

Intervention Control

Washout Period

Trial Types based on aims

• Superiority trial– Is treatment X superior to placebo or another

treatment Y?• Non-inferiority trial

– Is treatment X not inferior or as good as another treatment Y?

• Equivalence trials– Is treatment X as good as or certainly as harmful

as no more harmful than another treatment Y?

Pragmatic RCT

• RCT tight selection criteria• Internal validity high generalizability low• Two approaches – not do RCT at all, or

observational studies• Pragmatic RCT is a good middle way• Relaxed inclusion criteria• Concealment of allocation• Appropriate for behavioural intervention studies

Cluster RCT

Clusters of individuals and unit of analysis are clusters

Why are RCTs good?

• Randomization: balancing• Control of chance by appropriate sample size

selection• Control of bias by blinding

– A process where the investigator is unaware of the allocation status (single blinding)

– When the participant is unaware of allocation status (double blinding)

• Control of confounding by randomization

Limitation of RCT

• Expensive in terms of time and money• Not generalizable• Low external validity• Otherwise, RCTs are good study designs

Example of an RCT

Cohort Study

• Observational epidemiological study• Individuals are selected on the basis of their

exposure• Exposed and non-exposed individuals are

followed up in time• Followed up to observe emergence of the

outcomes• Rates of outcomes compared

Steps of Cohort studyStudy Population

Exposure staus

Exposed Non-exposed

Rate of disease occurrence in exposed

Rate of disease occurrence in non-exposed

Type of Cohort study

• Prospective cohort study– Exposure occurs first followed by outcome but

outcome status not known at the time of exposure assignment

• Retrospective cohort study– Exposure precedes outcome– However, outcome status is known at the time of

exposure cohort assembly

Analysis of results

Exposure Outcome Total

Present Absent

Exposed A B A+B

Non exposed C D C+D

Total A+C B+D A+B+C+D

Rate of the disease among exposed = A/(A+B)Rate of disease or outcome among non-exposed = C / (C+D)Relative risk = Rate among exposed / Rate among non-exposed

Why are cohort studies good?

• Since sampling is done on exposure therefore easier to control for sample size therefore chance

• Always followed up, therefore presence of exposure before outcome is guaranteed

• Good for studying many outcomes

Limitations of cohort studies

• Risk of biased observation– Bias during cohort formation– Bias during recording of outcomes

• Role of uncontrolled for confounding is a problem

Summary

• RCTs and cohort studies are two important study designs in epidemiology and health research

• RCTs can be extended to studies beyond health care

• Pragmatic RCTs enable complex interventions to be studied

• Cohort studies are best study designs among observational studies

Example of cohort study