NEWS

Central Clinical Trials Effort Draws Praise, Criticism

Linda Wang

In 1997, a review group convened by the National Cancer Institute recommended that the NCI’s clinical trials system be restructured to update its antiquated processes, take advantage of new technologies, and broaden patient access to clinical trials. One answer to that call was an ambitious 5-year, $50 million pilot project called the Cancer Trials Support Unit (CTSU).

There is anecdotal evidence that the CTSU is working. And many people in the cancer research community genuinely believe that the CTSU is a worthwhile effort, one that will ultimately pay off in fewer administrative burdens and more clinical options.

However, the program is entering its final year and has yet to be fully embraced by the cooperative groups, which historically have been charged with carrying out clinical trials. In addition, low accrual numbers are raising questions as to whether the system is making any difference at all.

Major Overhaul

The 1997 recommendations touched off a major overhaul of the NCI’s clinical trials system. "Inherent in the recommendations was the idea that we should take advantage of new technology that had become available to modernize the NCI system so that we could become more efficient and more competitive," said Jeffrey Abrams, M.D., senior investigator with NCI’s Cancer Therapy Evaluation Program and project officer for the CTSU.



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Dr. Jeffrey Abrams

 
The NCI launched several pilot projects, including the state-of-the-science meetings, the central institutional review board (see News, Vol. 95, No. 9, p. 636), and the CTSU. Considered pieces of a puzzle, these new initiatives were meant to speed new ideas from the laboratory to the clinic, streamline administrative tasks and data reporting, and increase physician and patient participation in clinical trials.

The CTSU would provide investigators with access to trials from all nine of the adult cooperative groups. Previously, a cooperative group trial was available only to members of that particular cooperative group. In addition, the CTSU would simplify regulatory and data collection procedures through the use of standard forms and reporting mechanisms.

"The idea behind the CTSU was that it would be a cooperative venture between the cooperative groups," said Alan Lyss, M.D., director of the cancer center and clinical research at the Missouri Baptist Medical Center, St. Louis, Mo.

In September 1999, the NCI selected Westat Corp., a contract research organization in Rockville, Md., to be the primary contractor for developing and managing the CTSU. The Coalition of National Cancer Cooperative Groups, Philadelphia, and Oracle Corp., a computer database management group in Redwood City, Calif., were chosen as partners in the project.

The groups wasted no time. By November 2000, the CTSU had set up a Web site containing a menu of available protocols and had begun enrolling patients in a handful of trials. (To qualify for participation in the CTSU, an academic institution or cancer center initially had to be a member of a cooperative group.) And in May 2002, the CTSU opened to qualified physicians who are not affiliated with a cooperative group.

Steve Riordan, project director of CTSU at Westat, said that one of the biggest challenges in the beginning was getting the nine adult cooperative groups, which for decades had worked independently, up to speed with the new system. "Among the nine different groups, there’s nine different ways of doing things," he reflected. "We’ve had to adapt to each one of those."

To date, there are more than 40 phase III trials included on the CTSU menu, representing all of the major adult cancer types (pediatric cancer trials are not included in the CTSU). The CTSU has enrolled roughly 1,700 patients at around 150 patients a month, a rate that has been increasing sharply. "We’re projecting that by the end of this year, we’ll be accruing about 300 patients a month," said Abrams.

Low Accrual

But some researchers say this is not good enough. In fact, total patient accrual in the entire cooperative group system is down from previous years. "So far, we see [the CTSU] as a very expensive, new undertaking that has yet to demonstrate its real value," said Richard Schilsky, M.D., chair of the Cancer and Leukemia Group B (CALGB) and a professor of medicine at the University of Chicago.

He pointed out that under the traditional intergroup mechanism, where several cooperative groups would contribute patients and resources to one trial, one popular breast adjuvant therapy trial might register 120 patients a month. In comparison, the CTSU is registering 150 patients per month—on 40 trials.

"It seems clear to us that the registration of patients through the CTSU is much slower than what it might have been had we just stayed with the old system. And that’s a major problem because obviously we’re not going to be able to get these protocols completed nearly as quickly as we would like," Schilsky said.

He pointed out that many academic institutions belong to several cooperative groups and already have an adequate assortment of trials to choose from. He suggests that the CTSU instead focus on trials of rare cancers for which patients are more difficult to accrue.

Yet, without a formal review, researchers can only speculate as to why accrual has not been higher. Hyman Muss, M.D., a professor of medicine at the University of Vermont College of Medicine in Burlington, said that the problem may not be a lack of need, but a lack of time to learn the new system.



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Dr. Hyman Muss

 
"The CTSU infrastructure is well done, and it’s a great Web site, but it’s another thing to do at the end of a busy day," he said, explaining that when oncologists are given the choice between a CTSU study—which requires learning a new system—or an alternative study from their cooperative group, the cooperative group study may seem just that much more appealing, even if the CTSU trial may be a better fit for the patient.

"Ultimately, the CTSU could be more efficient," said Muss. Rather than allowing the CTSU to passively diffuse through the system, he suggested that the NCI take a more proactive approach to helping physicians learn the system.

"I think, if done right, the CTSU has great potential," he said. "In the long run, it’s the right model for the NCI to use to improve accrual and give patients perhaps in rural areas or smaller practices opportunities to get on trials."

Robert Comis, M.D., president and chairman of the National Coalition of Cooperative Groups, Philadelphia, attributed the low accrual numbers to forces outside of the CTSU: budget cuts, competition from industry-sponsored trials, and bills in Congress that threaten to decrease reimbursement for chemotherapy drugs.

"You layer on top of that an adjustment in the system like the CTSU, and there are a lot of other huge forces and factors, which could hurt accrual in spite of everyone’s best efforts," said Comis.

Time Shall Tell

Yet, around the country, there is anecdotal evidence that the CTSU is making a difference.

Take, for instance, Martha Jefferson Hospital’s Cancer Care Center in Charlottesville, Va. "The CTSU has enhanced our ability to add new protocols that we would not have access to without CTSU," said Meg Helsley, a protocol nurse coordinator. Since January of this year, the cancer center has enrolled seven patients into four CTSU trials.

Comis pointed out that community cancer centers are the key engine for accrual to clinical trials in the United States. "Anything we can do to help them will help everybody," he said.

The CTSU also allows community cancer centers to apply CTSU enrollments to the accrual minimum they need to maintain membership in their cooperative groups. Martha Jefferson Cancer Center, which had membership to both the CALGB and the Radiation Therapy Oncology Group (RTOG), recently lost its membership to RTOG because the cancer center was not able to meet enrollment requirements. But participation in the CTSU does not guarantee access to every cooperative group trial. There are still trials that Helsley can access only through her cancer center’s membership in the CALGB.

Anita Leonard, a nurse and research coordinator at Stormont Vail HealthCare in Topeka, Kan., has shared a similarly positive experience with the CTSU and has enrolled 25 patients into CTSU trials. "I feel like we’re on the ground level of something here and we’re all kind of putting this together as we go," she said.

Finding Common Ground

Another aspect of the CTSU is the Regulatory Support System (RSS), available since January 6. This is a central database that consolidates all of the groups’ regulatory data by using a unified data collection process. "We felt that there was a lot of duplication of effort, a lot of added expense to the system that could be reduced and made more efficient by combining things through the CTSU," said NCI’s Abrams.

The common forms will allow investigators to feel more comfortable participating in studies from different cooperative groups, said Missouri Baptist’s Lyss, who has enrolled a number of his patients into CTSU trials. "The CTSU has really been the lightning rod for trying to get many of the cooperative groups to find commonality," he said.

This year, the CTSU is focusing on converting to a Web-based data collection process. A couple of protocols are already open for Web-based data collection and several more will open soon.

Comis said it may only be a matter of time before there is an increase in use of CTSU. As more and more large trials are added to the CTSU menu, physicians are going to have to get acquainted with it, he said. The NCI has extended Westat’s contract by 9 months (now scheduled to end July 2005) to give them more time to evaluate the project and for the NCI to determine what the next contract should look like.

"We have 12 months to see if in fact there will be a brisk usage of the CTSU system," said Comis. "I think the next 12 months are going to be absolutely crucial."



             
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