Research Design: RCT and Cohort Studies

John Q. Wong, MD, MSc22 Jun 2010

PH Course Requirement

Two research proposals◦RCT◦Cohort

No need to implement

Objective

At the end of the session, the students will be able to:◦Design a randomized controlled trial (RCT)◦Design a cohort study

Session outline

RCT◦Example◦Exercise

Cohort Study◦Example◦Exercise

Design elements

Research hypothesisStudy designOutcome variableExposure variableMethods of analysisPossible sources of bias and confounding

Design elements

Research hypothesis◦ Clear statement

Study design◦ Appropriate for the

hypothesis◦ Sampling ◦ Randomization

Outcome variable◦ Relevant to clinical

practice◦ Diagnosis test used◦ Accuracy of diagnosis

Exposure variable◦ Measurement of

exposure ◦ Accuracy

Methods of analysis◦ Sample size

computation◦ Statistical test

Possible sources of bias and confounding◦ Potential biases

Magnitude and direction◦ Potential confounding

RCT Example

Hypothesis

To assess whether supplementation with calcium cholecalciferol (vitamin D3) reduces the risk of fracture in women with one or more risk factors for fracture of the hip

Study design

Randomized controlled trialStratified randomization by practice

Outcome variable

Primary outcome measure◦All clinical fractures

Secondary outcome measure◦Adherence to treatment◦Falls◦Quality of life

Exposure variable

Intervention◦Daily oral supplementation using 1000 mg

calcium with 800 IU cholecalciferol and information leaflet on dietary calcium intake and prevention of falls (experimental group)

◦Leaflet only (control group)Pill count

Methods of analysis: sample size computation

Incidence of outcome (fractures) among unexposed (control group) = 10%

Difference in outcome between groups detectable = 34%

Power = 80%Level of confidence = 95%, two-tailedDropout rate = 20%

Methods of analysis: statistical tests

Intention-to-treat analysisComparison of groups at baseline

◦Chi-square◦T-test

Survival analysis: time to first fracture

Potential sources of bias and confounding

Potential bias◦Follow-up bias◦Selection bias◦Information bias

Potential confounders◦Age, weight, previous fracture, smoker, health

status, maternal hip fracture, fall in previous 12 months, SF-12 scores, estimated dietary calcium intake

RCT Exercise

Hypothesis◦To evaluate whether treating personal

clothing/sheets worn by nomads is protective against malaria infection

Cohort Example

Hypothesis

To identify determinants of vaccine-associated paralytic poliomyelitis (VAPP)

Study design

Retrospective cohort studyAll cases of acute flaccid paralysis

reported in Poliomyelitis Eradication Surveillance System (PESS)

Outcome variable

Occurrence of VAPPClinical classification criteria

Exposure variable

Having received OPV between 4 and 40 days before the onset of AFP (exposed)

Had not received the vaccine or who received it outside of this period (non-exposed)

Methods of analysis

No sampling doneIncidence of VAPPRR of VAPP occurrence in relation to

◦First OPV dose ◦Total number of vaccine doses given◦Exposure to OPV

Logistic regression

Potential sources of bias and confounding

Bias◦Selection bias due to incompleteness of the

PESS◦Misclassification bias in diagnosis of VAPP

Confounders◦Gender, fever, GI and upper respiratory signs,

months of onset, extremity paralyzed, number of OPV doses received before the paralysis, type of vaccine poliovirus isolated, age in years

Cohort Exercise

To determine the association between social networks and all-cause and cause-specific mortality among middle-aged Japanese