IOM releases recommendations for cancer clinical trials

NCI Cooperative Groups limiting trial participation, ASCO survey says.

Yesterday, the Institute of Medicine released a new report providing recommendations to strengthen and improve the National Cancer Institute’s Clinical Trials Cooperative Group Program.

The report, A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program, reviewed the role of a wide group of stakeholders and called for an overhaul of the current system.

Despite the long standing role of Cooperative Groups in developing new cancer therapies, “many stakeholders — including clinical investigators, patient advocates, Cooperative Group leadership, industry participants as well as the NCI — have expressed concerns that the program is falling short of its potential to conduct the timely, large-scale, innovative trials needed to improve patient care,” the report said.

“Improved treatments for cancer will be delayed and patient lives will be lost unnecessarily, unless the efficiency and effectiveness of the clinical trials system improves,” it said.

The report listed four goals directed at guiding improvement efforts:

Improving the speed and efficiency of the design, launch and conduct of clinical trials.
Making optimal use of scientific innovations.
Improving selection, prioritization, support and completion of clinical trials.
Fostering expanded participation of both patients and physicians.

After the release of the report, Richard L. Schilsky, MD, immediate past president of the American Society of Clinical Oncology released a statement.

“The Cooperative Clinical Research Program is the jewel of our nation’s cancer research system, and is critical to advancing progress against the disease. In fact, the majority of what we know about treating cancer has come from this program. ASCO supports the recommendations in the IOM report and we urge NCI to increase the program’s funding and make needed changes to the system,” Schilsky said.

“The report emphasizes that adequate investment is essential to the continued success of Cooperative Group trials. But today, the system is being starved of funding. In real dollars, the program receives less funding today than it did a decade ago. Considering the program’s vital importance to the nation’s fight against cancer, it is clearly not in the public interest that it receives such a small fraction of NCI’s overall budget. ASCO calls on NCI to double its support for cooperative clinical research within five years.”

ASCO survey

A group of ASCO researchers also released a study yesterday that found that one-third of NCI Cooperative Group sites plan to limit participation in federally funded clinical trials due to inadequate per-case reimbursement. Instead, these sites may increase participation in industry-sponsored trials, despite expressing a preference for conducting Cooperative Group trials.

Allison R. Baer, MD, and colleagues surveyed 509 U.S. and Canadian NCI-supported Cooperative Groups to identify the issues influencing enrollment in Cooperative Group trials.

Of the 509 sites surveyed, 33% were planning to limit their participation in these trials. Surveyed sites were asked to give the reasons for limiting participation. In addition to “other,” sites could select insufficient staffing or insufficient NCI per-case reimbursement as reasons for limiting participation. Multiple reasons could be selected.

Seventy-five percent of those sites who planned to limit participation selected insufficient NCI per-case reimbursement as a reason for limiting participation; for 40 of these sites, reimbursement was the sole reason selected.

“Baer et al remind us that the Cooperative Group per-case reimbursement of $2,000 has not increased in 10 years,” wrote Robin Zon, MD, FACP, in an accompanying editorial. “Published data from the 2005 ASCO and C-Change studies indicate that during this same time period, the average cost per enrollee was $5,000 to $6,000.”

Zon wrote that although Baer et al highlight NCI-funded clinical trial contributions, more importantly, they suggest “that the NCI may underestimate the importance of adequate funding as a means of sustaining enrollment and participation in NCI cooperative group trials.” – by Leah Lawrence

Given that the very first of the current NCI Cooperative Groups forms the legacy of today's Children's Oncology Group, the pivotal contribution to improved outcomes for childhood cancer resulting from collaborative, multicenter clinical and translational research is indeed testimony to the importance of the NCI's clinical trial enterprise to the American public and to global health. The IOM report provides convincing evidence of the need for increased federal and other support, well-planned organizational restructuring, and improved operational efficiency to assure that a robust clinical trials system can be responsive to the need and exciting opportunities for translating new genetic and genomic discoveries to improved diagnosis and treatment of cancer in the next decade. That legislators and NCI leadership take immediate steps to turn recommendations into action and that the investigators and patients who are partners in the system effect the needed transition are legitimate expectations. The very fact that meaningful changes are already being implemented prior to the report's publication is reassuring.

– Gregory H. Reaman, MD
Chair, Children's Oncology Group

At least they finally admit they have a problem; the success of any solution, however, will reside with how successfully they identify the root causes of poor enrollment and offer appropriate solutions to address the specific problems. Two key problems that need to be addressed are funding and trial design of the cooperative group trials.

– Charles H. Weaver, MD CEO
Editor, Cancer Consultants.com

There's a great deal in the IOM report that is good news for the cooperative groups. Additional per-patient funding for trial sites and added emphasis on centralizing Institutional Review Board functions, for example, would both result in faster trials. As would the OEWG recommendations the report endorses for speeding protocol development (in our cooperative group we're in the midst of a major initiative on this front, with target protocol development timelines even more ambitious than the OEWG's). My concern is that only a minority of the report's recommendations will be realized or even achievable, and if the wrong minority of recommendations is implemented, the country will be without a vibrant mechanism to provide definitive evidence to help cancer patients, families and caregivers choose among the myriad of approaches. Much of the re-engineering within cooperative groups that is proposed in this report was the result of studies commissioned by the NCI with David Dilts, PhD, MBA. Dilts has made several presentations of his data over the past couple of years, often using the analogy of the "failed" model of General Motors vs. the "successful" model of Toyota. Yet today an AP poll shows more Americans believe in the quality of Ford and GM than of Japanese manufacturers such as Toyota. The point being everyone agrees that protocol development is too slow, but there is little evidence that changing the "front offices" or "back offices" will solve these problems, nor that it will be cost effective. Yet these recommendations may be implemented for the simple reason that they can be realized by fiat, whereas the other changes, which are perhaps even more essential, may prove unachievable. It's indisputable, for instance, that more money to support trial sites would be a good thing, but how likely are we to see that added funding given the state of the U.S. economy and the federal budget deficit? Similarly, consolidating governmental agencies including the NCI, FDA and Office of Human Subjects Protection is a worthy ambition, but how likely is it that change of this magnitude can be achieved given the partisan entrenchment now gumming up Washington? Even within the NCI there are two divisions that support the cooperative groups: the Division of Cancer Treatment and Diagnosis (DCTD) and the Division of Cancer Prevention (DCP), with different standards of operation, review and engagement. How effective has the NCI leadership been over the past 10 years at harmonizing these internal divisions? We are all grateful to the IOM for performing this important evaluation. It would be worthwhile to review the several earlier evaluations by the IOM on this same subject of America's cancer cooperative group system. We can only hope that in treating what ails the system, HHS practices some evidence-based medicine rather than simply the art of the possible.

– Laurence H. Baker, DO
Professor of Medicine, University of Michigan; Chair, Southwest Oncology Group

Baer AR. J Oncol Pract. 2010;doi:10.1200/JOP.200028.

Zon R. J Oncol Pract. 2010;doi:10.1200/JOP.091093.