Randomized Controlled Trial

Randomized Controlled Trial Aim: testing medicines or medical procedures use randomized control the most reliable form of scientific evidence eliminates all forms of spurious causality Special condition: randomized clinical trial (RCT) clinical trial The basic idea: treatments are allocated to subjects at random different treatment groups are 'statistically equivalent'

Clinical Trial Disease Treatment No Yes Sample Placebo No Yes Population Random selection In clinical trials, the investigator applies a treatment (intervention) and observes the effect on an outcome. The major advantage of a trial over an observational study is the ability to demonstrate causality. Randomly assigning the intervention can eliminate the influence of confounding variables, and blinding the administration decreases bias ascertainment. Blinded administration

Randomized Controlled Trial STEPS: Selection of participants Random allocation to treatment or control arm Blinding of treatment or control to patient and/or clinician

Randomized Controlled Trial SAMPLING: Sample size calculation Inclusion/exclusion criteria Informed consent

Randomized Controlled Trial RANDOMIZATION To ensure even distribution of confounding factors among the two groups

Randomized Controlled Trial BLINDING To minimize placebo effect Can not be applied in particular condition Blinding Knowledge of treatment assignment Patient Clinician Investigator None Yes Single No Double Triple

Randomized Controlled Trial ETHICAL ISSUE Adopt new treatment without conducting experimental trial Continue a trial if treatment harmful What if treatment obviously effective? Conduct a trial with marginal benefit

Randomized Controlled Trial Advantages Demonstrate causality Randomization: eliminate the influence of confounding variables Blinding : decreases bias Disadvantages Expensive Compliance Selective population Ethical issue

Randomized Controlled Trial PHASES Developed by FDA for approval of new treatment After experimental trial in vitro and in animal Testing a new treatment in small group of volunteer (usually healthy people) Determine: safe dose-range, side-effect Testing to a larger group (usually RCT) Determine effectiveness, tolerability, and safety

Randomized Controlled Trial PHASES (cont…) Test the treatment in a larger group of patients Confirm effectiveness Monitor side effect Comparing with ‘old’ treatment Collect information for safe use of drug Post marketing Effect on different population Side-effect

CONSIDER……. In preparing or using the results of RCT, Quality: Reliability: replicable under ideal condition Validity: the degree to which a study reaches a correct conclusion, depends on: Method Sample Bias: systematic distortion of statistical result Selection bias Observer bias Recall bias Reporting bias Publication bias

Clinical Trial Study population : New VP shunt patients in NS Department Sample : Group 1 : VP shunt patients + A Group 2: VP shunt patients + B Variable : Infection Type of Antibiotic Dummy table : Infection Yes No A B

Clinical Trial Outcome Treatment No Yes Sample Placebo (treatment B) CONCLUSION Placebo (treatment B) No Yes Population Random selection In clinical trials, the investigator applies a treatment (intervention) and observes the effect on an outcome. The major advantage of a trial over an observational study is the ability to demonstrate causality. Randomly assigning the intervention can eliminate the influence of confounding variables, and blinding the administration decreases bias ascertainment. Blinded administration

Clinical Trial The effect of a therapy: OUTCOME Infection No infection Total Therapy a b a+b Control c d c+d a+c b+d a+b+c+d The effect of a therapy: Relative risk, risk reduction, relative risk reduction, NNT The precision : P < 0.05; 95% confidence interval

Thank you