Challenges to accrual predictions to phase III cancer clinical trials: A survey of study chairs and lead statisticians of 248 NCI-sponsored trials

Abstract

6562 Background: Trial closure due to inadequate accrual presents a common problem in cancer research. We sought to identify factors related to trial design common to trials with successful versus unsuccessful accrual. Methods: In 2008, a 30-question web-based survey was sent to the study chair (SC) and lead statistician (LS) for all 248 phase III trials open in 1993–2002 by five national cooperative groups (NCG). SC and LS level of experience, trial design elements, accrual predictions, and perceived accrual influences were queried. Accrual success was categorized based on NCG records: successful trials (ST) closed with complete accrual or at interim analysis while unsuccessful trials (UT) closed due to inadequate accrual. Responses were analyzed by respondent role (SC/LS) and accrual success. Results: 309 eligible responses were included (response rate, 62%: LS 81%, SC 45%). Respondents represented ST (65%) and UT (35%) with no response bias by accrual success. SC academic rank was not linked to accrual success. Literature review, SC experience, and expert opinion within NCG most commonly influenced control arm selection, but did not impact accrual success. NCG experience had the greatest influence on accrual predictions in both ST and UT. Trials comparing novel with established therapies were more likely to be ST (72%) than UT (28%); head-to-head comparisons of established therapies were more equally divided between ST (59%) and UT (41%). Among the 41% of respondents citing significant accrual difficulties, no factors negatively influencing accrual were consistently identified. Among respondents not citing accrual difficulties, factors credited with positively influencing accrual were clinical relevance of study question, lack of competing trials, and protocol paralleling normal practice. Conclusions: No consistent factors were identified to explain poor trial accrual, suggesting that reasons for poor accrual are not well understood and warrant further study. An objective measure of clinical relevance would be useful to inform trial prioritization practices. Research into alternative strategies for accrual prediction is needed since NCG experience is linked to both successful and unsuccessful accrual. [Table: see text]