The document provides an overview of randomization methods used in clinical trials, emphasizing the importance of unbiased treatment group allocation and comparability. It details various randomization techniques including simple randomization, random allocation, block randomization, stratification, and minimization. Additionally, the document discusses considerations for sample size, data collection, and monitoring management to ensure the integrity of clinical trial results.

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PRESENTED BY- AMEENA MEHABOOB
METHODS OF RANDOMIZATION OF CLINICAL TRIALS

3. • Clinical trials are research studies that test how well new
medical approaches work in people.
• Randomization is the process by which allocation of
subjects to treatment groups is done by chance, without
the ability to predict who is in what group.
• A randomized clinical trial is a clinical trial in which
participants are randomly assigned to separate groups that
compare different treatments.
INTRODUCTION
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5. PURPOSE OF RANDOMIZATION
• Primary purpose- To prevent bias in allocating
subjects to treatment groups.
• Secondary purpose- To achieve comparability
between the groups.
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6. METHODS OF
RANDOMIZATION
SIMPLE
RANDOMIZATI
ON
RANDOM
ALLOCATION
BLOCK
RANDOMIZATI
ON
STRATIFICATIO
N
MINIMIZATION
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7. 1. SIMPLE RANDOMIZATION
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8. • If there are 50 (N) number of subjects, the
treatment plans are divided equally ie, 25(n1)
and 25 (n2). Such that n1+n2= N.
• The envelopes with the treatment plans are
labelled and shuffled.
• The order of the envelopes give the order of
treatment of subjects.
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9. • Random allocation is a procedure in which
identified sample participants are randomly
assigned to a treatment and each participant
has the same probability of being assigned to
any particular treatment.
• If the design is based on N participants and n1
are to be assigned to Treatment 1 then all
possible samples of size n1 have the same
probability of being assigned to Treatment 1.
2. RANDOM ALLOCATION
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10. • Block randomization is commonly used in the two
treatment situation where sample sizes for the two
treatments are to be equal or approximately equal.
• The process involves recruiting participants in short
blocks and ensuring that half of the participants within
each block are allocated to treatment “A” and the other
half to “B”.
3. BLOCK RANDOMIZATION
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11. • There are six different ways that four patients
can be split evenly between two treatments:
1. AABB 4. BAAB
2. ABAB 5. BABA
3.ABBA 6. BBAA
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12. • The next step is to select randomly amongst
these six different blocks for each group of four
participants that are recruited.
• The random selection can be done using a list of
random numbers generated using statistical
software e.g. SPSS, Excel, Minitab, Stata, SAS. Eg-
9795270571964604603256331708242973...
• Since there are only six different blocks-
52516464632563312423...
• Blocks are selected according to the above
sequence.
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13. 5. BABA 2. ABAB 5. BABA
1. AABB 6. BBAA 4. BAAB
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14. A stratification factor is a categorical covariate
which divides the patient population
according to its levels e.g.
‐sex, 2 levels: Male, Female
‐age, 3 levels: <40, 40‐59, ≥ 60 years
‐recruitment centres
‐Menopausal status
‐any other known prognostic factor
4. STRATIFICATION
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16. • Using this method, the first patient is truly
randomly allocated; for each subsequent
patient, the treatment allocation is identified,
which minimizes the imbalance between
groups at that time.
5. MINIMIZATION
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17. • The number of subjects in a clinical trial should always
be large enough to provide a reliable answer to the
questions addressed. This number is usually
determined by the primary objective of the trial. If the
sample size is determined on some other basis, then
this should be made clear and justified.
• The sample size of an equivalence trial should be based
on the objective of obtaining a confidence interval for
the treatment difference that shows that the
treatments differ at most by a clinically acceptable
difference.
• The exact sample size in a group sequential trial cannot
be fixed in advance because it depends upon the play
of chance in combination with the chosen stopping
guideline and the true treatment difference.
SAMPLE SIZE
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18. • The collection of data and transfer of data from the investigator to
the sponsor can take place through a variety of media, including
paper case record forms, remote site monitoring systems, medical
computer systems, and electronic transfer.
• Whatever data capture instrument is used, the form and content of
the information collected should be in full accordance with the
protocol and should be established in advance of the conduct of the
clinical trial.
DOCUMENTATION
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19. • The process of data capture, through to database
finalization, should be carried out in accordance
with good clinical practice (GCP). Documentation
for all subjects for whom trial procedures (e.g.,
run-in period) were initiated may be useful.
• The computer software used for data
management and statistical analysis should be
reliable, and documentation of appropriate
software testing procedures should be available.
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20. • Careful conduct of a clinical trial according to the protocol
has a major impact on the credibility of the results. Careful
monitoring can ensure that difficulties are noticed early
and their occurrence or recurrence minimized.
• There are two distinct types of monitoring that generally
characterize confirmatory clinical trials sponsored by the
pharmaceutical industry. One type of monitoring concerns
the oversight of the quality of the trial, while the other
type involves breaking the blind to make treatment
comparisons. Both types of trial monitoring, in addition to
entailing different staff responsibilities, involve access to
different types of trial data and information, and thus
different principles apply for the control of potential
statistical and operational bias.
MONITORING MANAGEMENT
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21. • International conference on harmonization of
technical requirements for registration of
pharmaceuticals for human use, General
considerations for clinical trials, E8-E9.
• Randomized clinical trials, Sukon Kanchanaraksa,
PhD, Johns Hopkins University.
• Rndomization of clinical trials, University of the
West of England.
• Journal for clinical studies.
• www.wikipedia.com
REFERENCES
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