Unequal allotment of patients in phase III oncology clinical trials

Abstract

Patient enrollment in cancer clinical trials has traditionally been limited to an equal distribution between cases and controls, however recently some clinical trials have utilized an unequal distribution between the case and control arms. Trends and proportion of phase 3 cancer clinical trials that have an unequal allocation between the years 2010 and 2019 were studied from data extracted from clinicaltrials.gov. 323 trials with two arms and 35 trials with 3 arms were identified as randomized control trials with the primary purpose of a cancer-related treatment that provided allocation data. Amongst the trials with two arms, 238 trials had equal allocation and 85 trials had unequal allocation. Therefore, cancer clinical trials with unequal allocation represent about one in four 2-arm phase 3 trials. Amongst the eligible trials with three arms, 26 trials had equal allocation and 9 trials had unequal allocation. There was no significant difference in the annual proportion of trials with unequal allocation from 2010 to 2019. The categories of cancer which had the highest number of unequally allotted two-arm clinical trials were: gastrointestinal, breast, and genitourinary malignancies. This shift may represent a new trend in clinical trial design to help enhance closer monitoring of adverse events despite higher costs and lower statistical power attached to this method.

Keywords: Unequal allotment; randomized controlled trials; trends.

Figure 1

Process of determining phase 3 cancer clinical trials to be included in a study on trends in randomization allocations (PRISMA diagram). Data collected from clinicaltrials.gov and any linked articles on a trial’s profile.

Figure 2

Percentage of phase 3 cancer clinical trials with equal allocation (1:1) in comparison to the total number of two-arm trials from 2010 to 2017. While no particular pattern emerges on use of equal or unequal allocation trial design, overall about 1 in 4 trials may be using unequal allocation in the past decade.