Recent independent analyses of the National Cancer Institute?s (NCI) clinical trials systems have indicated an urgent need to re-evaluate engrained processes for developing and implementing phase 1-3 protocols (Dilts DM et al. Steps and time to process clinical trials at the Cancer Therapy Evaluation Program. J Clin Oncol 2009 27:1761-1766). It is critical to find novel solutions to speeding up the excessive time it currently takes to activate an NCI-sponsored clinical trial if investigators are to take full advantage of scientific opportunities available today for clinical research. The Division of Cancer Treatment and Diagnosis (DCTD), primarily through its Cancer Therapy Evaluation Program (CTEP) and Cancer Imaging Program (CIP), and the Division of Cancer Prevention sponsor multi-institution clinical trial organizations (NCI Cooperative Groups) that conduct both early phase and late phase multi-institutional trials that evaluate anticancer therapies and imaging modalities designed to improve multiple outcomes including quality of life, delay in cancer progression and overall survival. The NCI also supports a critical network of university-based and free-standing cancer centers that conduct a large number of NCI-supported clinical trials. The focus of this initiative will be on improving the timelines involved in activating NCI-sponsored Cooperative Group phase 3 trials and in activating CTEP-held IND studies of all phases as well as investigator-initiated trials at NCI-designated Cancer Centers. . Based upon recommendations from the Clinical Trials Working Group report (http://restructuringtrials.cancer.gov/files/ctwg-report.pdf), an Operational Efficiency Working Group (OEWG) was constituted under the leadership of an extramural co-chair, Dr. Gabriel Hortobagyi, and an intramural NCI co-chair, Dr. James Doroshow. The OEWG membership was broad and diverse, including 10 Cooperative Group Chairs, 8 Cancer Center Directors, multiple clinical investigators and statisticians, protocol/Trial Specialists, Community Oncologists, representatives from Pharma/Biotech, Patient Advocates, FDA, CMS, CTSU as well as NCI Clinical Trials Leadership and Staff from DCTD, CTEP, DCP, CCR, NCICB, CCCT, and Cancer Centers. The interim report of the OEWG was presented to the Clinical Trials Advisory Committee (CTAC) on November 4, 2009. The report reviewed the current timelines for development of Cooperative Group phase 3 trials (Appendix 1 ? slide 1). Based upon these data, the medium time to phase 3 protocol activation is currently 830 days. It is clear that this prolonged development process often leads to trials which accrue poorly due to intervening scientific changes that can cause the original trial question to become stale or less relevant by the time the protocol opens. The OEWG dissected the current process into its components (Appendix 1 ? slides 2&3). The phases that require the most improvement encompass concept approval to protocol submission and protocol submission to protocol approval. To improve these timelines, the OEWG recommended a revised process for developing and implementing protocols. All stakeholders involved in the process, Cooperative Groups, NCI ?designated Cancer Centers, NCI/DCTD/CTEP, NCI/ DCP, and other collaborators such as the FDA and pharmaceutical companies will have to work in concert if the overall process is to improve. Following acceptance by NCI?s Clinical Trials and Translational Science Advisory Committee (CTAC), a decision was made to implement OEWG?s recommendations. Most importantly, it was agreed that phase 3 Cooperative Group trials would target 300 days to go from concept receipt to trial activation. While the Groups and CTEP will work together to develop new processes that help achieve the targeted timeline during 2010, it was decided that a deadline of 2 years will become mandatory as of January 1, 2011. All phase 3 trials currently in development will have to meet this 2-year timeline or they will be disapproved. Similarly, for CTEP-held IND phase 1-2 trials, the target was set at 210 days from LOI receipt to trial activation. A firm deadline of 18 months will become mandatory as of January 1, 2011, after which any trial proposal (new or currently in development) that exceeds this deadline would be disapproved irrespective of the reason for the delay. A target of 90 days was set for investigator-initiated trials at Cancer Centers. However, Cancer Centers will determine appropriate deadlines for their studies individually. For the Groups, CTEP and the Cancer Centers to meet these new protocol development timelines, the OEWG made several recommendations regarding the type of additional resources that would be required.
