Nine-year change in statistical design, profile, and success rates of Phase II oncology trials

Abstract

We investigated nine-year trends in statistical design and other features of Phase II oncology clinical trials published in 2005, 2010, and 2014 in five leading oncology journals: Cancer, Clinical Cancer Research, Journal of Clinical Oncology, Annals of Oncology, and Lancet Oncology. The features analyzed included cancer type, multicenter vs. single-institution, statistical design, primary endpoint, number of treatment arms, number of patients per treatment arm, whether or not statistical methods were well described, whether the drug was found effective based on rigorous statistical testing of the null hypothesis, and whether the drug was recommended for future studies.

Exact tests using binary data in adaptive two or multi-stage designs

“…Ivanova et al. 11 found that “Simon’s design remained the most frequently used two-stage design in Phase II oncology trials analyzed (40%).” They also pointed out that “Increased use of Fleming’s design (Fleming 12 ), a two-stage design with a possibility to stop for futility or efficacy after stage 1, was seen, from 2% in 2005 to 11% in 2014.” Our research on type II adaptive designs includes Simon’s design as a special case but provides a lot more flexibility on possible designs by allowing a non-constant n2(Y1) in stage 2. This effort, as shown in the plots a), b) and d) of Figure 2, can greatly reduce the expected total sample size over Simon’s design while maintaining nearly the same power.…”

A Review of Perspectives on the Use of Randomization in Phase II Oncology Trials

“…However, Rubinstein et al noted in 2011 that 69 (28%) of the then active National Cancer Institute–sponsored phase II trials were randomized (19). In addition, Thezenas et al (78), Ivanova et al (79), and Langrand-Escure et al (80) have all since conducted reviews of phase II trials, each identifying a large proportion that incorporated randomization.…”

Futility stopping in clinical trials, optimality and practical considerations

“…Two-stage designs with futility stopping are widely used in single arm phase 2 trials in oncology with a binary outcome where the probability of positive response is compared to the historical response rate (Simon 1989). A survey of phase 2 oncology trials (Ivanova et al 2016) reported that 40% of phase 2 trials in oncology published in leading oncology journals in 2010-2015 used Simon's design. Futility stopping is a useful feature in other therapeutic areas, especially in phase 2 trials with the goal of evaluating efficacy of a novel therapy.…”