Non-randomised trials are defined as trials where the investigator controls allocation, which is not at random. Controlled before-and-after trials are defined by pre- and post-intervention outcome assessment and a non-random group allocation that is not under the control of the investigator. A randomized controlled trial is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical techniques, medical devices, etc.

1. Randomized Controlled Trials &
Non Randomized Controlled Trials
BY: SUBHAJIT MANDAL
REGISTRATION NO. RA1922255010004
M.PHARM (PHARMACOLOGY)
SRM COLLEGE OF PHARMACY
SUBJECT: CLINICAL RESEARCH & PHARMACOVIGILANCE
DATE: 6th /02/20

2. Study Design for a Clinical Trial

3. Randomized controlled trials

4. Definition
RCT is a study in which a group of
investigators studies two interventions in a
series of individuals who receive them in a
random order.
Intervention to be tested is called the
experimental group.

5. The other intervention is regarded as a
standard of comparison or control, and the
group of participants who receive it is called
the control group.
The control can be conventional practice, a
placebo, or no intervention at all.

6. Scheme of a simple trial
Eligible patients
Rx group 1
Rx group 2
Randomize

7. Why should we Randomize?
Compare groups at the end of the trial
Difference is because of the Rx
For this you need comparable groups
Purpose of randomization is to make the
treatment groups comparable
Ensures that only difference in groups is due
to trial treatments

8. RCT (Randomised controlled Trials)
 The most powerful tool in modern clinical
Research
 Prospective
 Controlled
 Unbiased

9. FLOWCHART OF RCT:-

10. Non Randomized controlled trials

11. Control randomized controlled trails
• In a non-randomised clinical trial,
participants are allocated to different
treatment (or placebo) arms using a
non-random method. Allocation is
decided and managed by the
investigator.
• Non-random allocation can lead to bias
in the results of a trial.

12. What is wrong with non-
randomized studies?
Two main types of study, those with and
those without concurrent control groups

13. Non-randomized studies II
Without concurrent controls
Uncontrolled
cannot really make much of such studies if
there is any variation in outcomes.
Historical controls
type of patient may change, due to eligibility
criteria
environment changes, due to trial
data quality often quite different between
groups

14. Non-randomized studies III
Non-randomized concurrent controls
Alternation
Odd/Even hospital no. or date of birth
First letter of surname
Difficult to argue that one group is different
from another but allocation is predictable, so
bias can arise from selection of patients
so randomization must be unpredictable

15. 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.

16. But we need randomization
to be done properly
to ensure similar numbers in groups
To combine with stratification -in large trials-
to ensure comparability for prognostic factors

17. Pseudo-randomisation
Alternating record number
Date of birth
Geographical distribution
Open list

18. 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)

19. Value of randomization
it reduces the risk of serious imbalance in
unknown but important factors that could
influence the clinical course of the
participants.

20. Types of RCTs
RCTs according to whether the investigators
and participants know which intervention is
being assessed
Open trials & categorised into
 Single blind trials
 Double blind trials
 Triple blind trials

21. RCTs according to how the participants are
exposed to the interventions
Parallel trials
Crossover trials
Trials with factorial design

23. Blinding
The best way to protect a trial against is by
keeping the people involved in the trial
unaware of the identity of the interventions
for as long as possible.
Could be single
Could be double
Could be triple

24. 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

25. What the process should be:
Adherence to the study protocol
Patients compliance with treatment and
follow up
sufficiently long and complete

26. Analysis of clinical trials
Analysis of clinical trials
Intension to treat analysis Per protocol analysis
Sub group analysis

27. Disadvantages of RCTs
 expensive: time and money;
 volunteer bias;
 ethically problematic at times.

28. Applications
Done in large multicenter RCTs
To explore the results after recruiting of half
of the participants
If marked difference is recognized , then trial
should be stopped
Examples: WHI(Women's Health Initiative) trials
 Breech Trial
AIDS trial


29. Reference:
• https://en.wikipedia.org/wiki/Randomized_controlled_trial
• Drug Discovery & Clinical Reseach By S.K Gupta