The use of unequal randomisation ratios in clinical trials: A review

Objective: To examine reasons given for the use of unequal randomisation in randomised controlled trials (RCTs). Main Measures: Setting of the trial; intervention being tested; randomisation ratio; sample size calculation; reason given for randomisation. Methods: Review of trials using unequal randomisation. Databases and sources: Cochrane library, Medline, Pub Med and Science Citation Index. Results: A total of 65 trials were identified; 56 were two-armed trials and nine trials had more than two arms. Of the two-arm trials, 50 trials recruited patients in favour of the experimental group. Various reasons for the use of unequal randomisation were given. Six studies stated that they used unequal randomisation to reduce the cost of the trial, with one screening trial limited by the availability of the intervention. Other reasons for using unequal allocation were: avoiding loss of power from drop-out or crossover, ethics and the gaining of additional information on the treatment. Thirty seven trials papers (57%) did not state why they had used unequal randomisation and only 14 trials (22%) appeared to have taken the unequal randomisation into account in their sample size calculation. Conclusion: Although unequal randomisation offers a number of advantages to trials the method is rarely used and is especially under-utilised to reduce trial costs. Unequal randomisation should be considered more in trial design especially where there are large differences between treatment costs. (c) 2005 Elsevier Inc. All rights reserved.