This document discusses randomization in medical research. It defines randomization as the allocation of individuals to intervention or control groups in a clinical trial by chance. Randomization avoids selection bias and balances both known and unknown confounding factors between groups. Participants, communities, or locations can be randomized. Simple, permuted block, stratified, and adaptive randomization methods are described. Threats to randomization include non-adherence to the randomization protocol and lack of treatment equipoise. Maintaining the integrity of randomization is important for establishing causality in medical research.

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!?