Dear all,

A researcher has developed a new treatment for some medical condition. A clinical trial is being planned, in which 60 subjects are to be enrolled, 30 to each treatment group (treatment and control), therefore, a randomization is needed to minimize bias from various sources.

The trial is multi-center trial, with 4 different sites in which the treatment will be given. A block randomization with stratification by center, yields the same amount of blocks (each block is randomized for treatment and control) for each center, i.e. the same amount of subjects in each center (default of the software). However, some sites are bigger than others, and the sponsor wish to enroll more subjects in sites A and B, and less in C and D.

Randomization need to make sure that baseline characteristics are more or less equal between the two treatment groups, and to ensure that the investigator remains blinded. I wanted to ask you, how to solve the problem of wanting to stratify by center on one hand, but wishing to have more subjects in specific centers due to the fact that they are bigger, enroll faster, etc...Is it legal to give more blocks to some centers? I couldn't find such an example in the FDA guidelines.

For the sake of the example, let's say that I use blocks of 4 subjects, I need 60 overall (30*2), and got 4 centers. How should I do a stratified block randomization without forcing the investigator to enroll an equal number of subject in each site? Can I maintain balance within center and not between centers?

Thank you !