The other randomization - methods for labeling drug kits.

PURPOSE

Most phases 2 and 3 blinded randomized clinical trials package study drug, e.g., active and placebo, into drug kits for distribution to investigational sites. Kits are made so that it is not possible to determine the type of drug in the kit. This enables investigators to administer drug to patients in a manner that blinds investigators and patients. Kits are labeled with unique kit IDs that code for the drug type. Kit lists contain the assignment of kit IDs to drug. Algorithms for making kit lists, like algorithms for randomizing patients, incorporate randomness to ensure investigators and patients are blind to the process. This paper reviews three types of kit list: blocked, double randomized, and scrambled, and discusses the operational benefits of what a pharmaceutical company might obtain using scrambled lists along with an overview of the challenges of generating and extending the lists for large trials.

METHODS

We reviewed the operational characteristics of three types of kit list: blocked, double randomized, and scrambled.

RESULTS

Blocked kit lists were a popular choice until their unblinding and operational deficiencies became well known. The many difficulties associated with blocked kit lists are unnecessary and can be avoided by using a double randomized kit list or a scrambled kit list. Compared to double randomized kit lists, scrambled kit lists can be more easily extended due to their advantage of having randomly sized gaps between kit IDs.

CONCLUSIONS

Among the three types of kit list, scrambled kit lists offer the most flexibility. The adoption of scrambled kit lists has in practice provided the many operational benefits described in this paper.