Methods of Randomization

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. It is done in clinical trials. This presentation describes the methods of randmization used in clinical trials.

1. WELCOME 1

2. 2 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 3

4. 4

5. PURPOSE OF RANDOMIZATION Primary purpose- To prevent bias in allocating subjects to treatment groups. Secondary purpose- To achieve comparability between the groups. 5

6. 6

7. 1. SIMPLE RANDOMIZATION N n1 n2 7

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. 8

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 ALLOC ATION 9

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 RANDOMIZ ATION 10

11. There are six different ways that four patients can be split evenly between two treatments: 11

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. 12

13. 13

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 14

15. 15

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 16

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 17

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 18

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. 19

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 20

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 21

22. 22 THANK YOU