What are RTCs?

• Randomised controlled trials are considered the gold standard method to assess efficacy of treatment or develop causal relationship
• Ethical requirements set out in Declaration of Helsinki, 1960
• Heath technology appraisal now requires cost to also be considered - cost-effectiveness analysis
• Power of RTC is randomisation - random allocation to intervention or control gives likely balance to all factors affecting outcome; prevents bias and allows determination of causality

Phases of drug development

• Phase 1: safety, dose finding, volunteers (3-30)
• Phase 2: safety, how effective, how often? (30-50)
• Phase 3: efficacy, safety (100+)
• Phase 4: post approval in large population (1000+)

Target population

• Trial population should include people who would get the drug/intervention if the trial is successful - representative
• Trials generally exclude children, pregnant women, elderly, and people with co-morbidity

Randomised trial designs

Parallel group

• Each subject is randomised to one of two or more distinct treatment/intervention groups
• Stratification is the partitioning of subjects and results by a factor other than the treatment given
  • Can be used to ensure equal allocation of subgroups of participants to each experimental condition, and to control for confounding variables
  • Only stratify on factors likely to have impact on the outcome e.g. tumour size
  • Most useful in small trials

Randomised factorial trial

• Two (or more) intervention comparisons are carried out simultaneously e.g. participants may be randomised to receive aspirin or placebo, and also randomised to receive a behavioural intervention or standard care

Strengths