1. Randomization and Comparative Designs
Oncology Journal Club
April 5, 2002

2. Comparative Designs “Compare”: need more than one group
Different types
historical control
two+ treatment groups
treatment and placebo groups
“Phase III”

3. Was this study comparative?
What are the “groups” that are being compared?
Treatment 1 vs. treatment 2?
Was it randomized?
What was were they randomized to?
Did they show a difference in the two groups under consideration?
Did they show that the groups being compared were comparable with regard to pertinent factors?

4. Randomization Why? What’s the big deal? Reduces potential for bias
“Ensures” that groups being compared are likely to be similar to each other.
Example of violation of randomization bias:
selection bias: the physician decides which patients are assigned to which treatment
i.e. physician decides which patients get high versus low radiotherapy!

5. Randomization
What if physicians tend to give sicker patients less radiotherapy?
Now, there is a “correlation” between being sick and treatment.
Is it so strange to imagine that the sicker patients would tend to have shorter survival?
Now that they have “confounded” sick status with treatment, they CANNOT conclude anything about treatment.

6. Randomization
Idea of Confounders: many variables may be associated with outcome. By randomly assigning individuals to treatment groups, we decrease likelihood of making an error due to a confouding variable

7. Randomization
Randomization to low versus high radiotherapy WOULD have made illness and treatment independent.
How could this have been helped?
Inclusion/exclusion criteria so that only kids who were “healthy” enough could receive full dose
Stratify by stage: ensure that comparable numbers of sick and less sick kids are in each arm.

8. Final Comments on Randomization
It does not guarantee that groups are “the same,” but the principle is that for large numbers of patients, the groups will even out.
For small studies, might be a good idea to stratify to really ensure balance.
Randomization isn’t always truly random
blocking
stratification

9. Final Comments on Comparative Trials
Selection bias: not just physician choice
center (e.g. multi-center study)
patient (think about ITT vs. actual received)
Blinding/Masking:
when possible, it is generally a good idea for patient (blinded) or patient and physician (double-blinded) to not know which group patient is assigned to
avoids sub-concious effects
avoids cross-over