Mother and Child Health: Research Methods

G.J.Ebrahim

Editor

Journal of Tropical Pediatrics, Oxford University Press.

Basic Design of Clinical Trials

Sample

Subjects

Randomise

Treatment

Placebo

Cured Same

Cured SameBlinding

Blocking

Variations in Basic Design -1

Run-in Design

Admission On placebo Compliers randomised

Cross-over Design

Recruitment Randomised

Treatment 1

Treatment 2

A

S

S

E

S

S

A

S

S

E

S

S

Variations in Basic Design - II

Time - Series Design

Recruitment Treatment

Assess

No Treatment

Assess

Treatment

Assess

Factorial Design

Recruitment Randomise

Treatment 1

Treatment 2

Low Dose

High Dose

Low Dose

High Dose

Issues of Methodology - I

Entry Criteria

Strict for Explanatory Trials. Less strict for Pragmatic Trials

Diagnosis

How accurate?

Interventions

How good a compliance achieved?

Subjects who drop-out are different from those who continue

Other competing interventions?

Issues of Methodology - II

Subject Allocation

Different rates of drop-out between groups cause under or over estimate of outcome.

Treatment Allocation

Randomisation and blinding help to remove bias. Blocking needed if outcomes vary because of age, sex or other attributes.

Challenges in Designing Clinical Trials

Control of Bias -

In allocation of subjects to treatment.

In assessment of outcome.

Sample Size

How small a difference is clinically important?

What tests of significance will be used?

What outcome is expected in the control group?

Drop-outs and Withdrawals

How to handle them during analysis?

Generalizability of Results

Population of Patients

Sample

Treated

Control

Outcome

Outcome

Difference in Outcome by Chance?

GeneralisabilityOther

Populations

Rigour of study