Factors associated with successful phase III trials for solid tumors: A systematic review

It is known that the success rates of phase III trials for solid cancers are low. The aim of this study was to investigate factors related to trial design and operation that were associated with the probability of the success of phase III trials for solid cancers based on the latest comprehensive data.

Relevant clinical trials, started between September 2007 and December 2017, were retrieved from ClinicalTrials.gov. Then, variables related to the selected trials such as types of primary endpoint and duration of trial enrollment were collected from the literature and ClinicalTrials.gov. Based on the collected data, a multivariate logistic regression analysis was conducted to find factors associated with the successful results.

Four hundred phase III trials were found eligible for the study. Unsuccessful trials were 207 and successful trials were 193. As a result of multivariate logistic regression analysis, factors that presented a statistically significant relationship were primary endpoint (Odds ratio [OR]: 2.79 [95% CI: 1.59-4.89]), control arm (OR: 3.06 [95% CI: 1.39-6.73]), start year of trial (OR: 3.28 [95% CI: 1.87-5.77]), and duration of trial enrollment (OR: 0.77 [95% CI: 0.60-0.99]).

Type of primary endpoints (time-to-event endpoints other than overall survival), control arm (treatments with lower evidence level, placebo or best supportive care), and duration of trial enrollment (faster enrollment speed) were associated with phase III trial success.