What is it? Why is it important?

Randomisation is the act of randomly allocating study participants to different treatment groups (e.g. study intervention versus control group). The allocation is entirely by chance with no regard to potential preference of the researcher (i.e. SP-INV, Site-INV) or a participant’s first choice.

 

In order to decide on the study’s allocation sequence, the following factors must be defined:

  • The allocation ratio (e.g. in a 1:1 ratio, half the participant are assigned to the intervention and the other half to the control group)
  • Stratification factor(s). Stratification helps to ensure a balanced representation of a specific characteristics (i.e. the stratification factors) in different treatment groups

 

Stratification helps to ensure, that during the randomisation process, the different treatment groups remain comparable by having an equal representation of specific characteristics (e.g. age, co-morbidities).

 

By ensuring treatment groups are comparable in terms of stratification factors, the risk of bias is minimised (i.e. thereby avoiding having differences between the control and intervention group caused by something other than the intervention).

What do I need to do?

As a SP-INV, consult a statistician to discuss the randomisation process of your study. Aspects to consider include:

  • The required allocation ratio
  • Applicable stratification factor(s)

 

Stratification factor(s) are selected based on their relevance to the research question, and their potential to impact treatment outcome. A given study can have 0, 1, or even more than 1 stratification factors.

 

Example of a stratified randomization

The study: assesses the effect of a new drug on cancer survival.

Potential bias: Previous work has shown a strong correlation between cancer severity and survival. Hence, an un-balanced distribution of severe cancer cases between the control and the intervention group could be a potential bias, resulting in a higher mortality rate in the group with more severe cancer cases.

Stratification factor: in order to minimize bias, the randomisation process will be stratified using cancer severity as a stratification factor.

Where can I get help?

Your local CTU can support you with experienced staff regarding this topic

References

ICH Topic E9 statistical Principles for Clinical Trials – see in particular

  • 2.3.2 Randomisation

ICH Topic E8(R1) on general considerations for clinical studies - see in particular

  • 5.5 Methods to reduce bias

Publication PubMed – see in particular

  • PMID: 20332511 David Moher et. al. CONSORT 2010 Explanation and Elaboration: Updated Guidelines for Reporting Parallel Group Randomised Trials..
Abbreviations
  • CTU – Clinical Trials Unit
  • ICH – International Council for Harmonisation
  • Site-INV – Site Investigator
  • SP-INV – Sponsor Investigator
Basic ↦ Statistic Methodology ↦ Study Design ↦ Randomization
Study
Basic

Provides some background knowledge and basic definitions

Basic Monitoring
Basic Drug or Device
Concept

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Statistic Methodology
Concept Drug or Device
Development

Starts with confidence that the study is feasible

Ends after having received ethics and regulatory approval

Development Drug or Device
Set-Up

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Ethics and Laws
Set-Up Statistic Methodology
Set-Up Quality and Risk
Set-Up Drug or Device
Conduct

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Statistic Methodology
Conduct Drug or Device
Completion

Starts with last study visit completed

Ends after study publication and archiving

Completion Statistic Methodology
Completion Drug or Device
Current Path (click to copy): Basic ↦ Statistic Methodology ↦ Study Design ↦ Randomization

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