2. Definition
RCT is a study in which a group of
investigators study an intervention in a series
of individuals who receive the intervention in
a random order.
Intervention to be tested is called the
experimental group
3. The other group of participants is called the
control group.
The control can be conventional practice, a
placebo, or no intervention at all
4. Schema of a simple trial
Eligible patients
Rx group 1
Rx group 2
Randomize
5. Why Randomize?
We need to analyse groups at the end of the
trial
To ensure that difference in groups is
because of the Rx
For this you need comparable groups at the
start of trial
Purpose of randomization is to make the
treatment groups comparable
6. Value of randomization
it reduces the risk of serious imbalance in
unknown but important factors that could
influence the clinical course of the
participants.
7. RCT
‘the most powerful tool in modern clinical
research “
– Prospective
– Controlled
– unbiased
8. What is wrong with non-
randomized studies?
Two main types of studies, those with and
those without concurrent control groups
9. Non-randomized studies II
Without concurrent controls
Case series studies
Historical controls
type of patient may change, due to eligibility
criteria
environment changes
data quality often quite different between
groups
10. Non-randomized studies III
Controlled non-randomized studies
Difficult to argue that one group is different from
another but allocation is predictable, so bias can
arise from selection of patients
Randomization must be unpredictable
11. Random allocation
all participants have the same chance of
being assigned to each of the study groups
the purpose is to keep both groups as similar
to each as possible at the start of the trial.
12. Is coin tossing OK?
OK for big trials
For small trials, such ‘simple randomization’
can lead to imbalance in group sizes
13. Example: trial with 30 patients
If 30 patients are in a trial randomized using
coin tossing there is a 14% chance of 15:15
split
For 16:14 chance is 27%
‘Worse’ than 20:10 is 10%
Why ‘worse’?
Because imbalance leads to loss of power
14. We need randomization
to be done properly
to ensure similar numbers in groups
To combine with stratification -in large trials-
to ensure comparability
16. True randomization
Need to separate the person who generates
allocation from those who assess eligibility
Third party schemes
Telephone randomization service
Pharmacy randomization
Web-based service?
Envelopes
Sealed envelopes (preferably opaque)
17. Blinding
The best way to protect a trial against bias is
by keeping the people involved in the trial
unaware of the identity of the interventions
for as long as possible
18. Types of RCTs
RCTs according to whether the investigators
and participants know which intervention is
being assessed
– Open trials
– Single blind trials
– Double blind trials
– Triple blind trials
19. Blinding is difficult
Having placebo in the same shape , formula
and taste is very costly, and time consuming.
The drug side effects e.g. local reaction at
the site of injection would partially unblind .
Impossible if surgical and medical treatments
are compared.
The need for urgent unblinding code in case
of serious side effects
20. Other types of RCTs
RCTs according to how the participants are
exposed to the interventions
– Parallel trials
– Crossover trials
Trials testing one variable or factorial design
e.g (2 X2 X 2)
21. Follow up
During the trial
– Adherence to the study protocol
– Patients compliance with treatment
After finishing the intervention, follow up of
participants should be sufficiently long and
complete
22. Analysis of clinical trials
Analysis of clinical trials
Intension to treat analysis Per treatment analysis
Sub group analysis
23. Disadvantages of RCTs
expensive: time and money;
volunteer bias;
ethically problematic at times.
24. Interim Analysis
Done in large RCTs
To explore the results after recruiting of half
of the participants
If marked difference is recognized , then trial
should be stopped
Examples: WHI trial
Breech Trial
25. So, how to do RCT
Set up a protocol
Recruit your patients
Randomize (try to be blind)
Follow up
Analyze your data
Publish
26. RCTs
The gold standard for therapeutic research
Basis for Meta-analysis
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