1. Randomized Controlled Trial

2. 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'

3. 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

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

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

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

7. 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

9. 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

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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. Thank you