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 CuredSame CuredSame Blinding Blocking

Variations in Basic Design -1 Run-in Design Admission On placeboCompliers randomised Cross-over Design Recruitment Randomised Treatment 1 Treatment 2 ASSESSASSESS ASSESSASSESS

Variations in Basic Design - II Time - Series Design RecruitmentTreatment Assess No Treatment Assess Treatment Assess Factorial Design RecruitmentRandomise 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 Difference in Outcome by Chance? Generalisability Other Populations Rigour of study