Implementation of timeline reforms speeds initiation of National Cancer Institute-sponsored trials

Abstract

Background: The National Cancer Institute (NCI) organized the Operational Efficiency Working Group in 2008 to develop recommendations for improving the speed with which NCI-sponsored clinical trials move from the idea stage to a protocol open to patient enrollment.

Methods: Given the many stakeholders involved, the Operational Efficiency Working Group advised a multifaceted approach to mobilize the entire research community to improve their business processes. New staff positions to monitor progress, protocol-tracking Web sites, and strategically planned conference calls were implemented. NCI staff and clinical teams at Cooperative Groups and Cancer Centers strived to achieve new target timelines but, most important, agreed to abide by absolute deadlines. For phase I-II studies and phase III studies, the target timelines are 7 months and 10 months, whereas the absolute deadlines were set at 18 and 24 months, respectively. Trials not activated by the absolute deadline are automatically disapproved.

Results: The initial experience is encouraging and indicates a reduction in development times for phase I-II studies from the historical median of 541 days to a median of 442 days, an 18.3% decrease. The experience with phase III studies to date, although more limited (n = 25), demonstrates a 45.7% decrease in median days.

Conclusions: Based upon this progress, the NCI and the investigator community have agreed to reduce the absolute deadlines to 15 and 18 months for phase I-II and III trials, respectively. Emphasis on initiating trials rapidly is likely to help reduce the time it takes for clinical trial results to reach patients in need of new treatments.

Figure 1.

Key steps in the National Cancer Institute (NCI) clinical trial review process. FDA = US Food and Drug Administration; IRB = institutional review board; LOI = letter of intent.

Figure 2.

Comparison of pre–Operational Efficiency Working Group (OEWG) and post-OEWG timelines: early-phase studies. Kaplan–Meier plots of time from letter of intent (LOI) submission to trial activation (n = 525 pre-OEWG trials and n = 159 post-OEWG trials). Vertical solid line represents the absolute deadline, and the vertical dashed line represents the target timeline.

Figure 3.

Comparison of pre–Operational Efficiency Working Group (OEWG) and post-OEWG timelines: phase III studies. Kaplan–Meier plots of time from concept submission to trial activation (n = 112 pre-OEWG trials and n = 25 post-OEWG trials). Vertical solid line represents the absolute deadline, and the vertical dashed line represents the target timeline.

Figure 4.

Early-phase trial development stage timelines pre–Operational Efficiency Working Group (OEWG) vs post-OEWG. Data shown as median days, with the bars representing the first and third quartiles of the distributions. For letter of intent (LOI) submission to LOI approval, there were 525 pre-OEWG trials and 159 post-OEWG trials with submitted LOIs. For LOI approval to protocol submission, there were 524 pre-OEWG trials and 152 post-OEWG trials with approved LOIs. For protocol submission to trial activation, there were 522 pre-OEWG trials and 143 post-OEWG trials with submitted protocols.

Figure 5.

Components of stage 3: protocol submission to protocol approval and protocol approval to protocol activation. Data shown are median days, with the bars representing the first and third quartiles of the distributions. For protocol submission to protocol approval, there were 522 pre–Operational Efficiency Working Group (OEWG) trials and 143 post-OEWG trials. For protocol approval to trial activation, there were 489 pre-OEWG trials and 109 post-OEWG trials. Protocol approval is defined as Cancer Therapy Evaluation Program approval of the protocol document.