Challenges to accrual predictions to phase III cancer clinical trials: a survey of study chairs and lead statisticians of 248 NCI-sponsored trials.
Research on barriers to accrual has typically emphasized factors influencing participation after trial activation.
We sought to identify factors influencing trial design and accrual predictions prior to trial activation associated with sufficient accrual.
A 30-question web-based survey was sent to the study chair and lead statistician for all 248 phase III trials open in 1993-2002 by five Clinical Trials Cooperative Groups. Questions addressed prior trial experience, trial design elements, accrual predictions, and perceived accrual influences. Accrual sufficiency categorization was derived from Clinical Trials Cooperative Group records: sufficient accrual included trials closed with complete accrual or at interim analysis, insufficient accrual included trials closed with inadequate accrual. Responses were analyzed by respondent role (study chair/lead statistician) and accrual sufficiency.
Three hundred and nine eligible responses were included (response rate, 63%; lead statisticians, 81%; and study chairs, 45%), representing trials with sufficient (63%) and insufficient accruals (37%). Study chair seniority or lead statistician experience was not linked to accrual sufficiency. Literature review, study chair's personal experience, and expert opinion within Clinical Trials Cooperative Group most commonly influenced control arm selection. Clinical Trials Cooperative Group experience most influenced accrual predictions. These influences were not associated with accrual sufficiency. Among respondents citing accrual difficulties (41%), factors negatively influencing accrual were not consistently identified. Respondents credited three factors with positively influencing accrual: clinical relevance of study, lack of competing trials, and protocol paralleling normal practice.
Perceptions of lead statisticians and study chairs may not accurately reflect accrual barriers encountered by participating physicians or patients. Survey responses may be subject to recall bias.
Consistent factors explaining poor accrual were not identified, suggesting reasons for poor accrual are not well understood and warrant further study. Alternate strategies for accrual prediction are needed since Clinical Trials Cooperative Group experience is linked to successful and unsuccessful accrual.
Schroen, AT; Petroni, GR; Wang, H; Thielen, MJ; Sargent, D; Benedetti, JK; Cronin, WM; Wickerham, DL; Wang, XF; Gray, R; Cohn, WF; Slingluff, CL; Djulbegovic, B
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