NEWS

Children’s Oncology Group Looks to Increase Efficiency, Numbers in Clinical Trials

Steve Benowitz

To many, the announced merger of four pediatric cancer clinical trials cooperative groups more than 2 years ago was long overdue. The leaders of the groups for the most part agreed that the time was right to form a new entity, which they dubbed the Children’s Oncology Group. Together, rather than separately, they said, they could cut research duplication, better use dwindling funds, and increase clinical study efficiency. The marriage of talent and resources had the blessing —even the urging—of the National Cancer Institute, the groups’ main funding agency.

In the old system, institutions conducting pediatric clinical trials belonged to either the Children’s Cancer Group or the Pediatric Oncology Group. Member institutions then might participate in trials conducted by two other groups, the Intergroup Rhabdomyosarcoma Study Group and the National Wilms’ Tumor Group.

Competition

But having two main groups meant two organizations competing for resources and a relatively small number of children with cancer, maybe 8,000 to 10,000 new cases a year. Thanks to remarkable strides in curing childhood cancer in the last 2 decades—approximately 70% of new childhood cancers are cured—increasing numbers of children are needed for studies to prove real differences in treatments, said William Crist, M.D., dean of the University of Missouri Medical School in Columbia and former interim chairman of the Children’s Oncology Group.

"The intergroup process has always been slow, awkward and difficult," said POG chairwoman Sharon Murphy, M.D., professor of pediatrics at Northwestern University Medical School and chief of the Division of Hematology/Oncology at Children’s Memorial Hospital in Chicago. She was explaining a decision made 2 years ago by the heads of the four groups at a meeting at Chicago’s O’Hare Airport.



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Dr. Sharon Murphy

 
"We had already been working together on intergroup trials on various tumors and we decided, rather than trying to fix the intergroup mechanism, why not get rid of it altogether," she said. "We felt we could increase capacity for research by combining and doing research we couldn’t do separately, such as epidemiology and health outcomes research."

No One Voice

"The groups were concerned that they were competing more and more with each other for limited funds and resources instead of speaking as a single voice in an area that’s underfunded," explained Mark Kieran, M.D., Ph.D., clinical director of pediatric medical neuro-oncology at the Dana-Farber Cancer Institute in Boston.

The Children’s Oncology Group hopes to "work more effectively with industry, private foundations and other partners," Murphy said, in addition to streamlining clinical trials development and creating a national childhood cancer registry. By merging the old groups, the new group has in effect doubled the number of institutions and doctors potentially involved in any trial, cutting the overall length for trials.

The four groups will exist until the end of their grant cycles in 2001, Murphy said. When the Children’s Oncology Group submits its first competing grant application in 2002, the four groups will be no more. The group will maintain many ongoing trials begun and based at the more than 230 member institutions, including major universities and hospitals throughout the United States and Canada, as well as some sites in Europe and Australia, she said.

Challenges Ahead

Although the group finally elected its first chairman in mid-November (results of the election were unavailable at press time), the daily organizational wrinkles of the marriage, in practice, will take some time to smooth out. Murphy sees the main challenge as creating a new infrastructure, "merging four groups, four headquarters, four chairs, four statistical centers, separate memberships and cultures, and millions in grants. We have to create something new—a new mission, new bylaws, a new organization."

Many share her concerns. "How will the groups integrate successfully, and how long will it take before we stop looking at people as CCG or POG and instead as members of COG?" asked Henry Friedman, M.D., James B. Powell Professor of Neuro-oncology at Duke University Medical Center in Durham, N.C.

Most pediatric oncologists seem excited at the new opportunities. "We’ve had a difficult time translating new drugs from the adult trials or from the lab to pediatrics," said Beverly Lange, M.D., the Yetta Dietch Novotny Professor of Pediatrics at the University of Pennsylvania School of Medicine and medical director of the Division of Oncology at Children’s Hospital of Philadelphia. "There are more opportunities to do phase I trials now than 10 years ago, so it’s a boon to us to do more things more quickly. Having one group working with CTEP (NCI’s Cancer Therapy Evaluation Program) and the FDA will allow us to move new technologies more quickly."

Joseph Mirro, M.D., executive vice president and chief medical officer, St. Jude Children’s Research Hospital in Memphis, sees the new group as an opportunity for the often overlooked adolescent cancer population, which may be better served by one pediatric oncology group. "I think this is an important component of the new group to focus on," he said, suggesting that a single group may be able to enroll a greater number of 15- to 21-year-olds, traditionally the most difficult to get to participate. About 5% to 10% of this age group enroll in trials.

Last year in an editorial in the ASCO News, Joseph Simone, M.D., senior clinical director of the Huntsman Cancer Institute and at the University of Utah, Salt Lake City, raised some concerns about the Children’s Oncology Group.



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Dr. Joseph Simone

 
"My major reservation," he wrote, "is that a scientific monopoly is inherently anti-intellectual." Because all of the pediatric oncology institutions would be in one group, both grant peer review and competition would suffer, he said. What’s more, the group would be too large and unlikely to conduct innovative clinical trials.

Merger Has Benefits

CCG chairman Archie Bleyer, M.D., Mosbacher Chair and Professor of Pediatrics at the University of Texas M.D. Anderson Cancer Center in Houston, in the same editorial, pointed to the merger’s benefits, but conceded that much of the way the new organization conducts business has yet to be worked out.

"We should be able to do more studies with the same amount of funding because we are doing the trials together," he said in an interview. "We should be more efficient because by being able to increase patients in studies and find important answers quickly, the rate of progress against pediatric cancer will accelerate. By consolidating resources, we should be able to raise the survival rate [of cancer treatment] from 70% to 80%." He also believes pediatric oncologists will be able to conduct trials in the less common cancers such as retinoblastoma, melanoma, and infrequent sarcomas because the combined groups will have more patients.

With the group’s formation, the resulting lack of competition between groups worries many. Robert Arceci, M.D., director of pediatric oncology at Johns Hopkins Oncology Center in Baltimore, believes pediatric oncologists must find a way to stoke the competitive fires and "fight any sense of self-satisfaction." Competition, which came naturally between CCG and POG —and as a direct result, innovation—are critically important for the new group to succeed.

Peer Review Logistics

Likewise, both POG and CCG relied on the other group’s members to peer review grant proposals. With the merger, Children’s Oncology Group members may have to go to competitors in Western Europe or to the adult oncology community. Bleyer agrees with Simone’s concern about managing such a large organization. No one knows if its sheer size will stifle individual expression or intimidate some of the younger investigators. "We may lose some originality and innovation and become monolithic," he said.

Another key problem will be recognition; there will be half the leadership positions, said Michael Link, M.D., chief of the Division of Pediatric Oncology, Hematology and Bone Marrow Transplantation at Stanford University School of Medicine. "There will be some unhappy people. It’s an academic career issue. Young investigators will have fewer positions to aspire to."

Still, said Link, "The benefits of working together far outweigh the benefits of working alone."



             
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