Randomized trials i dr.wah

1. Randomized Trials
Dr. Win Aye Hlaing
Lecturer
Department of Epidemiology
University of Public Health, Yangon

2. Objectives
1. To modify the natural history of disease so as
to prevent or delay death or disability
2. To improve the health of the patient or the
population

3. • Randomized Control Trial (RCT)
• Ideal design
• For evaluating the new forms of intervention
(effectiveness & side effects)
• Community based trial

4. Unplanned trial
• 1510- Pare’
• People with numerous wounds
• Give digestive medicament- wounds- better
• Give burnt oil- wounds- worse- swollen &
inflammed

5. Planned trial
• 1747- James Lind
• Scurvy in seamen
• Got quicker recovery in men who had eaten
orange & lemon than in men who had not
eaten these

6. Use of RCT
• For evaluating new drug & other treatments
of disease including test of new health and
medical care technology
• To assess new programs for screening and
early detection or new ways of organizing and
delivering health services

7. Design of RCT

8. • May choose two or more groups receiving
different therapies
• Compare New treatment with Current
treatment
• Compare New treatment with No treatment

9. RCT
1. Selection of Subjects
2. Allocating subjects to treatment groups
without Randomization
 Studies without Comparison
 Studies with Comparison
o Historical Controls
o Simultaneous Non-randomized Controls

10. 3. Allocating subjects using Randomization
 Stratified Randomization
4. Data collection on subjects
 Treatment (Assigned & Received)
 Outcome
 Masking (Blinding)

11. 1. Selection of Subjects
• Precision in writing before the study is begun
(written criteria)
• No subjective decision-making on investigator
in deciding who is included or not included in
the study

12. 1. Selection of Subjects
• Sometimes- with laboratory experiments
• Difficult in dealing with relatively large
population
• Therefore, selection Criteria must be precisely
stated

13. 2. Allocating subjects to treatment groups
without Randomization

14. 2a. Studies without Comparison
• Some alternative to Randomization
Case study or case series
no comparison
untreated group treated groups
or

15. 2b. Studies with Comparison
• Anti-nausea pills --- ship --- test
• Captain said that – control – untreated – ILL
-- subject – treated -- WELL
• How he had chosen the controls and subjects
• He gave pills to his seamen (subjects) & no pill
to passengers (controls)
• No Randomization !!

16. Example (1)
• Anti-coagulant therapy after World War II
(A) – ODD day hospitalized – Treated
(B) – EVEN day hospitalized – Untreated

17. Example (1)
• More hospitalized patients on odd days
• The investigator knew the odd day admitted
patients are treated and also the routinely
hospitalized person did
• So, they used to hospitalized at odd day
instead of even day
Bias

18. 2b. Studies with Comparison
• Goal of Randomization
– To eliminate the possibility that the investigator
will know what the assignment at which
day/group (To eliminate Bias)
Blinding

19. Example (2)
• BCG vaccination in children
(A) – from educated parents (health
conscious) –Treated – (3) die
(B) – from non-educated parents (no health
conscious) – Untreated (Control) – (18) die

21. 2b. Studies with Comparison
• The mortality higher in controls (untreated)
• Because group (A) parents are educated &
more likely to be conscious of health
• So, group (A) with or without vaccination—
lower risk of mortality
• Because not only vaccination itself but also
they are from health conscious families

22. Example (2)
• Group (A) – from educated parents (health
conscious) – Untreated (Control)– (8) die
• Group (B) – from non-educated parents (no
health conscious) – Treated – (8) die
• No Difference !!

24. 3. Allocating subjects using Randomization
• Randomization is the beat approach in design
of trial
• Randomization means tossing a coin to decide
the assignment of a patient to a study group
• Critical element of randomization -----
unpredictability of next assignment
• Today, for large trials, randomization is carried
out using computer

25. 3. Allocating subjects using Randomization
• How to use the table for random numbers
– Every ODD – t/m (A)
– Every EVEN – t/m (B)
– Close eyes– put a finger on table – write down the
numbers – it is starting point or number
– Move – up, down, right, left

26. Allocating subjects using Randomization
• How to use the random number
– ODD – (A)
– EVEN – (B)
– Random number & t/m – written on the card
– Cared is placed inside the opaque envelope
– Envelope – labeled on outside (e.g. patient 1, patient
2, etc.)
– E.g. 1st random no. = 2 – t/m (B) – written on card –
put inside 1st envelope – Patient 1 – next random
no. = 7 – t/m (A) – card – 2nd env – Patient 2
– Envelopes are sealed

28. Main Purpose of Randomization
• To prevent any potential biases on the part of
the investigator from influencing the
assignments of participants to different t/m
groups
• These biases that might be introduced
consciously or subconsciously by the
investigator into the assignments

29. 4. Data collection on Subjects
• It is essential that the data collected for each
of the study groups be of the same quality
• We don’t need any difference due to
differences in the quality or completeness of
data between the groups

30. Treatment (Assigned & Received)
• We must know which t/m group the patient
was assigned
• We must know which therapy the patient
actually received
• E.g. patient – assigned to t/m (A) after
agreement to be randomized – but later
changes his/her mind – refuse t/m (A) –
assigned t/m (B) on his/her own (without
realizing it)

31. Outcome
• Outcome – desired effect (improvement)
-- side effects
• To prevent the more carefulness in receiving
new drug group than in current therapy group
Blinding (Masking) !!

32. Masking (Blinding)
1. Subject – not know which group they are
assigned to (“Single Blinding”) – e.g. use
“Placebo”
2. Observer or data collector + Subject (“Double
Blinding”)
prevent subconscious or conscious Biases!!

33. Factorial Design
• ͠ cross tabulation
• 2x2 factorial design
• (A) terminates, but (B) continues & vice versa
• 4 groups – a, b, c, d

41. Non-compliance
• Patients – agree to be randomized
• 1st problem --- but not comply with assigned
t/m – overt or convert – refusal to comply or
stop participating – “Droup-outs”
• Stop – without admitting this to the
investigator or study stuff
• 2nd problem --- take the drug or t/m from
other group – “Drop-ins”

42. Non-compliance
• Because t/m group include some who did not
receive therapy
• No t/m group include some who received therapy
• Difference in the effects if t/ms – much smaller
• Less compliance – no significance difference
between T/m & control groups
• More compliance – significance difference
between T/m & control groups

43. • Randomization reduces selection bias
• RCT - “Gold standard” of study design
- to assess the strength of the available
evidence supporting clinical & public
health policy
- designed to shield the study from any
preconceptions and biases of the
investigator and of others in the study
- and from other biases that might
inadvertently be introduced

44. 6/26/2017 44
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