Randomization Types of Randomization Threats to Randomization

1. Randomization in
medical research
MPH Course - Epidemiology Module
Dr. Vignesh L, M.D. (AIIMS, New Delhi)
Senior Resident
Department of Preventive & Social Medicine
JIPMER, Puducherry

2. Outline
• What is random & randomization?
• Why to randomize?
• Whom and what to randomize?
• How to randomize?
• Threats to randomization
• References and further reading

3. Source: The Lancet 2002; 359:57-61 (DOI:10.1016/S0140-6736(02)07283-5)

7. Random
• No specific pattern
• Un predictable
• Completely guided by a ‘known’ chance

8. Randomization
Allocation of individuals to
intervention or control of a clinical
trial by chance
• Each possible assignment has a
known chance of being selected
• Treatment assignment is
unpredictable

9. Why to Randomize?
• Avoids selection bias
• Balances confounding factors between both the groups – Known and
unknown factors
• Allows to perform statistical tests for establishing causality

10. What to Randomize?
• Participants / Individual – Classical RCT
• Community / locality – Community trial or Cluster randomized trials

11. How (not) to Randomize?
• Birth date
• Hospital record number
• Hospital room number
• Day of visiting the hospital

12. How to Randomize?
• Simple randomization
• Permuted block randomization
• Stratified randomization
• Adaptive randomization

13. Block randomization
• Every block of X new participants is randomly and equally allocated to
treatment arms A & B
• Block size 4 – 6 possibilities
ABBB AABB AAAB BAAA BBAA BBBA
Advantage
• Equal assignment
Disadvantage
• If block size is known, last participant assignment can be predicted –
random/unknown block size
• Imbalance in critical variables

14. Stratified randomization
• Important variables that can affect the outcome are stratified and
randomization done separately between these strata
• E.g., Study site in multi-site trial
Advantage
• Balance of critical variables achieved
Disadvantage
• Can’t use too many variables for strata ( < 4 )

15. Threats to randomization
• Per-protocol analysis Versus Intention-to-treat analysis
• Equipoise and randomization

16. References
• Leon Gordis – Epidemiology 6th Edition
• John Last – A Dictionary of Epidemiology
• Introduction to the Principles and Practice of Clinical Research (IPPCR) –
Issues in Randomization: Video in Youtube -
https://www.youtube.com/watch?v=UgFXLk7i46c&ab_channel=NIHVideo
Cast
Topics for further reading:
• Adaptive randomization

17. Questions!?