Phase III clinical trial development: a process of chutes and ladders.
OBJECTIVE
The Institute of Medicine report on cooperative groups and the National Cancer Institute (NCI) report from the Operational Efficiency Working Group both recommend changes to the processes for opening a clinical trial. This article provides evidence for the need for such changes by completing the first comprehensive review of all the time and steps required to open a phase III oncology clinical trial and discusses the effect of time to protocol activation on subject accrual.


METHODS
The Dilts and Sandler method was used at four cancer centers, two cooperative groups, and the NCI Cancer Therapy Evaluation Program. Accrual data were also collected.


RESULTS
Opening a phase III cooperative group therapeutic trial requires 769 steps, 36 approvals, and a median of approximately 2.5 years from formal concept review to study opening. Time to activation at one group ranged from 435 to 1,604 days, and time to open at one cancer center ranged from 21 to 836 days. At centers, group trials are significantly more likely to have zero accruals (38.8%) than nongroup trials (20.6%; P < 0.0001). Of the closed NCI Cancer Therapy Evaluation Program-approved phase III clinical trials from 2000 to 2007, 39.1% resulted in <21 accruals.


CONCLUSIONS
The length, variability, and low accrual results demonstrate the need for the NCI clinical trials system to be reengineered. Improvements will be of only limited effectiveness if done in isolation; there is a need to return to the collaborative spirit with all parties creating an efficient and effective system. Recommendations put forth by the Institute of Medicine and Operational Efficiency Working Group reports, if implemented, will aid this renewal.
Knight Cancer Institute, Center for Management Research in Healthcare, Division of Management, School of Medicine, Oregon Health and Science University, 3303 SW Bond Avenue, Portland, OR 97239, USA. dilts@ohsu.edu
David M
DM
Dilts
Steven K
SK
Cheng
Joshua S
JS
Crites
Alan B
AB
Sandler
James H
JH
Doroshow
D017326:Clinical Trials, Phase III as Topic / Q000379:methods* / Q000592:standards; D006801:Humans; D054547:National Cancer Institute (U.S.); D009369:Neoplasms / Q000628:therapy; D013997:Time Factors; D014481:United States