Improving the protocol implementation process: the National Cancer Institute's response.

TO THE EDITOR: In their recent editorial, Steensma and Kantarjian revisited the well-identified problems within the clinical trial development process, but their comments failed to mention National Cancer Institute (NCI) initiatives to rectify those problems. The NCI has implemented several major initiatives to address these issues, not the least of which was the funding and facilitation of the analyses by Dilts et al that were referred to in the editorial. In response to these analyses that were commissioned by the NCI, we formed the Operational Efficiency Working Group (OEWG) in 2008. Key stakeholders, including the cooperative groups, NCI-designated cancer centers, patient advocates, community oncologists, industry, and the US Food and Drug Administration, were represented in this 2-year effort to create a comprehensive strategy to increase efficiency in clinical trial development. The OEWG’s recommendations led to a number of changes in NCI’s Cancer Therapy Evaluation Program (CTEP) protocol development processes. Although details have been provided elsewhere, we here enumerate important changes that have already occurred. First, absolute deadlines now exist that require trials to be open to patient enrollment 18 months from submission for phase III trials and 15 months from submission for early-phase trials. Failure to meet these deadlines ends formal development of NCIsupported trials. Second, improvements have been implemented in the protocol review process, such as creation of a new review template that highlights the major scientific issues that must be resolved, as distinguished from administrative and editorial changes, the inclusion of reviewers’ comments as Track Changes in the protocol document to speed protocol revisions, and the scheduling of teleconferences between CTEP staff and investigators to decrease iterative protocol revisions and reviews. Third, new roles have been created in NCI/CTEP, cooperative groups, and some NCI-designated cancer centers to facilitate implementation of the OEWG recommendations. A medical editor expedites the protocol revision process by compiling all of the reviews and protocol documents. Clinical trials project managers facilitate all aspects of the timely review and activation of studies, assist in monitoring accrual to studies, and work with NCI staff and investigators to address the problem of trials with accrual challenges. Fourth, new information technology tools have been implemented that provide extramural investigators and NCI staff with the current status of protocols and track bottlenecks in development to allow swift intervention. These changes have led to significant improvements in the efficiency of protocol development; the median time from concept submission to activation of CTEP-sponsored phase III studies has decreased by 46% (from 727 to 388 days) since 2010. Steensma and Kantarjian also reference the delays in opening multicenter trials because of the necessity for multiple local institutional review board (IRB) approvals. Perhaps these authors are unaware of the NCI’s Central IRB Initiative, which began reviewing NCI-sponsored studies in 2001. The CIRB’s procedures were updated in parallel with the initiation of the OEWG recommendations, resulting in an over 50% reduction in the time required for IRB approval of NCI-supported trials over the last 5 years. The median time from receipt of a protocol to approval by the CIRB was reduced to 43 days in 2013, compared with 98 days in 2008. All sites participating in the new NCI National Clinical Trials Network program, which began operation March 1, 2014, will be required to join the Association for the Accreditation of Human Research Protection Programs–accredited NCI CIRB. The NCI CIRB will be used for all CTEP-supported National Clinical Trials Network phase III and phase II/III clinical trials, as well as select large phase II studies and studies in rare cancers. Finally, in April 2013, CTEP introduced a new, mandatory, shorter informed consent template. Recognizing that informed consent documents were too often unwieldy and overly detailed, the new informed consent template is shorter, concisely lists only the most important adverse events, and avoids complex medical and scientific jargon. We agree with Steensma and Kantarjian that more needs to be done to expedite protocol development and rapid trial completion so that the oncology community may bring new and effective cancer therapies more rapidly to patients. By building on the successes that have been achieved to date, we will continue to work toward that goal.