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PRESENTED BY- AMEENA MEHABOOB

METHODS OF RANDOMIZATION OF CLINICAL TRIALS

• Clinical trials are research studies that test how well newmedical approaches work in people.

• Randomization is the process by which allocation ofsubjects to treatment groups is done by chance, withoutthe ability to predict who is in what group.

• A randomized clinical trial is a clinical trial in whichparticipants are randomly assigned to separate groups thatcompare different treatments.

INTRODUCTION

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PURPOSE OF RANDOMIZATION

• Primary purpose- To prevent bias in allocatingsubjects to treatment groups.

• Secondary purpose- To achieve comparabilitybetween the groups.

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METHODS OF RANDOMIZATION

SIMPLE RANDOMIZATI

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RANDOM ALLOCATION

BLOCK RANDOMIZATI

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STRATIFICATION

MINIMIZATION

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1. SIMPLE RANDOMIZATION

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• If there are 50 (N) number of subjects, thetreatment plans are divided equally ie, 25(n1)and 25 (n2). Such that n1+n2= N.

• The envelopes with the treatment plans arelabelled and shuffled.

• The order of the envelopes give the order oftreatment of subjects.

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• Random allocation is a procedure in whichidentified sample participants are randomlyassigned to a treatment and each participanthas the same probability of being assigned toany particular treatment.

• If the design is based on N participants and n1are to be assigned to Treatment 1 then allpossible samples of size n1 have the sameprobability of being assigned to Treatment 1.

2. RANDOM ALLOCATION

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• Block randomization is commonly used in the twotreatment situation where sample sizes for the twotreatments are to be equal or approximately equal.

• The process involves recruiting participants in shortblocks and ensuring that half of the participants withineach block are allocated to treatment “A” and the otherhalf to “B”.

3. BLOCK RANDOMIZATION

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• 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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• The next step is to select randomly amongstthese six different blocks for each group of fourparticipants that are recruited.

• The random selection can be done using a list ofrandom numbers generated using statisticalsoftware e.g. SPSS, Excel, Minitab, Stata, SAS. Eg-

9795270571964604603256331708242973...

• Since there are only six different blocks-

52516464632563312423...

• Blocks are selected according to the abovesequence.

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5. BABA 2. ABAB 5. BABA

1. AABB 6. BBAA 4. BAAB

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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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• Using this method, the first patient is trulyrandomly allocated; for each subsequentpatient, the treatment allocation is identified,which minimizes the imbalance betweengroups at that time.

5. MINIMIZATION

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• The number of subjects in a clinical trial should alwaysbe large enough to provide a reliable answer to thequestions addressed. This number is usuallydetermined by the primary objective of the trial. If thesample size is determined on some other basis, thenthis should be made clear and justified.

• The sample size of an equivalence trial should be basedon the objective of obtaining a confidence interval forthe treatment difference that shows that thetreatments differ at most by a clinically acceptabledifference.

• The exact sample size in a group sequential trial cannotbe fixed in advance because it depends upon the playof chance in combination with the chosen stoppingguideline and the true treatment difference.

SAMPLE SIZE

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• The collection of data and transfer of data from the investigator tothe sponsor can take place through a variety of media, includingpaper case record forms, remote site monitoring systems, medicalcomputer systems, and electronic transfer.

• Whatever data capture instrument is used, the form and content ofthe information collected should be in full accordance with theprotocol and should be established in advance of the conduct of theclinical trial.

DOCUMENTATION

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• The process of data capture, through to databasefinalization, should be carried out in accordancewith good clinical practice (GCP). Documentationfor all subjects for whom trial procedures (e.g.,run-in period) were initiated may be useful.

• The computer software used for datamanagement and statistical analysis should bereliable, and documentation of appropriatesoftware testing procedures should be available.

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• Careful conduct of a clinical trial according to the protocolhas a major impact on the credibility of the results. Carefulmonitoring can ensure that difficulties are noticed earlyand their occurrence or recurrence minimized.

• There are two distinct types of monitoring that generallycharacterize confirmatory clinical trials sponsored by thepharmaceutical industry. One type of monitoring concernsthe oversight of the quality of the trial, while the othertype involves breaking the blind to make treatmentcomparisons. Both types of trial monitoring, in addition toentailing different staff responsibilities, involve access todifferent types of trial data and information, and thusdifferent principles apply for the control of potentialstatistical and operational bias.

MONITORING MANAGEMENT

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• 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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