Question

Clinical trial

(a) There are several methods to assign treatments to patients in comparative clinical trials. Commonly used methods include pure randomization ,permutted blocks and within strata.

Briefly describe each of these technique for which the institution ,the sex,and age of the patient (under 50 years of age versus over 50 years of age) are factors that could be taken into account at the time of randomization.

Answer 1

Stratified Randomisation refers to the situation in which strata are constructed based on values of prognostic variables and a randomisation scheme is performed separately within each stratum. For example, suppose that there are two prognostic variables, age and gender, such that four strata are constructed:

	Treatment A	Treatment B
Male, Age<50	12	12
Male, Age>50	36	37
Female, Age<50	13	12
Female, Age>50	40	40

The strata size usually vary (maybe there are relatively fewer young males and young females with the disease of interest). The objective of stratified randomisation is to ensure balance of the treatment groups with respect to the various combinations of the prognostic variables. Simple randomisation will not ensure that these groups are balanced within these strata so permuted blocks are used within each stratum are used to achieve balance.

If there are too many strata in relation to the target sample size, then some of the strata will be empty or sparse. This can be taken to the extreme such that each stratum consists of only one patient each, which in effect would yield a similar result as simple randomisation. Keep the number of strata used to a minimum for good effect.

Permuted Block Randomisation is a way to randomly allocate a participant to a treatment group, while maintaining a balance across treatment groups. Each “block” has a specified number of randomly ordered treatment assignments.

For example, let’s you had treatment groups A and B, and you plan to enrol 10 new patients per week. Your first 3 blocks might look like this:

• Week 1: BAAABABBAB.
• Week 2: ABABBABABA.
• Week 3: AAABBBAABB.

Note that each block has 5 As and five Bs, maintaining a balance of the two despite the random order.

If your experiment involves a number that isn’t divisible by the block size, then your treatment groups may not have the exact same amounts. For example, if you only enrolled 28 patients in this particular permuted block randomization scheme, you would have two fewer Bs than As:

• Week 1: BAAABABBAB.
• Week 2: ABABBABABA.
• Week 3: AAABBBAA.

For large trials, a small imbalance usually doesn’t make a big difference, but this is something to take into consideration for smaller trials.