Dear Drs. Varmus and Doroshow,






  • The transformation is essentially a single‐armed trial with an ambiguous schema – If scientists identify a new molecule with an exciting mechanism of action in vitro, the molecule would be taken through Phase I and Phase II trials to establish dose and efficacy in vivo. The investigators would then be required to show that the new treatment is superior to the standard of care in a randomized Phase III trial. Large- scale business transformations with far less at stake and similar issues about the feasibility of rigorous multi‐phase trials substitute financial and operations modelling to choose among available alternatives and develop clear implementation plans. This effort appears to be going straight to implementation without adequate solution design, business case (cost/benefit) analysis, or migration planning

  • There is no dose modification plan—Clinical trial protocols make explicit provisions for adapting the treatment plan in response to adverse events (e.g., reducing doses in the event of dangerous cytopenias.) There does not appear to be any explicit criteria for what would constitute a dangerous or unanticipated consequence that would require adaptation of the implementation program. This, coupled with the lack of metrics and clear endpoints is deeply concerning

  • The data monitoring plan is weak-- While there is a stated intent to manage performance to reach a higher level, ambiguity surrounding metrics and the lack of baselines and targets threatens to confound this intent. Essentially, we have no effective way of measuring performance levels for the status quo and no definition of what constitutes success (i.e., the targeted level of improvement.) It is important to note that metrics played a crucial role in recent successes with protocol development timeframes and CIRB throughput. Metrics can be difficult to develop and often aren’t perfect, but they inform action and provide clear incentives and feedback

  • Reliance on secondary endpoints—Trials are ideally designed to achieve primary endpoints that indicate clinical benefit, such as overall survival. Secondary endpoints, like response rates, are viewed as not necessarily indicative of true clinical benefit and are frowned upon where there are primary endpoints that can readily be measured. There is a presumption of benefit from reducing the number of groups from ten to four. However, there is no evidence that there will be benefits. We have not seen analyses to project the magnitude of any benefits and what specifically will be required to achieve them. Similar assumptions are made relative to consolidation of decision‐making into national committees. However, the is no evidence that this will be the case and no metrics defined to assess the effect on outcomes



  • Re-evaluating NCI’s role in the clinical trial system and shifting from hands-on leadership and oversight to funding the clinical trials process

  • Allocating a larger portion of the NCI research portfolio to the Clinical Trials Cooperative Group Program

  • Enhancing trial participant diversity through support for Minority‐Based Community Clinical Oncology Programs, Patient Navigator Research Program and other NCI programs. Our constituents ask that NCI Enforce NIH Policy and Guidelines on the Inclusion of Women and Minorities in Clinical Research as prescribed in the NIH Revitalization Act of 1993, PL 103-43

  • Increasing the per case reimbursement rate and adequately funding the costs of conducting trials

  • Mandating the submission of annotated bio‐specimens

  • There was no cooperative group advocate on the IOM task force that developed the recommendations

  • Meetings to present the program and work out details have excluded cooperative group advocates from key sessions, most notably from NCI’s many meetings with the Cooperative Group Chairs