Eastern Cooperative Oncology Group and the
American College of Radiology Imaging Network have decided to
merge, NCI is down to five adult cooperative groups.
even though the first round of mergers and alliances instigated by NCI have
taken place relatively quickly, discussion at an
Institute of Medicine/ASCO workshop last week indicates these
agreements should not be interpreted as a consensus about how the clinical
trials system should be restructured.
has said it intends to fund just four adult cooperative groups, but the last
two unpaired groups each want to remain independent. In addition, it is far
from clear how the groups that have agreed to combine intend to structure
themselves, and how much latitude they will be given by NCI to develop
organizations and set priorities that allow their investigators to answer the
kinds of clinical questions that interest them.
workshop brought together the leadership of the existing cooperatives - nine
focused on adult cancers and one on pediatric cancers - along with officials
from NCI and FDA, and representatives from industry, community hospitals and
topic was implementing IOM's recommendations for overhauling the national
clinical trials system, of which NCI's Clinical Trials Cooperative Groups
program is one component.
part of that overhaul, NCI announced in December it intended to consolidate the
nine adult groups into four multi-disease, multi-disciplinary groups, while
Children's Oncology Group (COG) in its present form.
goal is to conserve resources and reduce duplicated effort, and to improve
systemwide prioritization of the trial concepts that get funded.
stakeholders at the workshop agreed that increased collaboration is good for
the system as a whole, they raised concerns that imposing centralized
decision-making on the co-ops will squelch innovation and drive talented
also questioned whether NCI and IOM have been too focused on arriving at a
magic number of cooperative groups instead of letting scientific strategy
and NCI have put forth the Children's Oncology Group as the model for
consolidating the adult groups. In a presentation to the workshop, former COG
Chair Greg Reaman described how the organization was created in 2000 through
the merger of four smaller pediatric oncology groups.
process involved not only creating a single operations center with a new data
system, but also adopting a new constitution and new membership criteria.
far, only one of the announced combinations of adult groups definitively fits
that mold. The
American College of Surgeons Oncology Group (ACOSOG), the
North Central Cancer Treatment Group (NCCTG) and
Cancer and Leukemia Group B (CALGB) have said they will create
a new group with a single scientific agenda, constitution and bylaws, and
American College of Radiation Imaging Network (ACRIN) and the Eastern
Cooperative Oncology Group (ECOG), the most recent groups to announce their
engagement, are still working out their new structure. But the idea behind the
combination appears to be in the spirit of IOM's recommendations. Both group
chairs told BioCentury the merger will provide an opportunity to develop a
scientific strategy for biomarker-driven studies in a way that would not have
been possible as separate entities.
research portfolio has comprised several high-profile studies in screening and
early diagnosis, including the National Lung Screening Trial (NLST), which
showed low-dose helical computed tomography (CT) can significantly reduce lung
cancer-specific mortality vs. chest X-ray in patients at high risk for lung
imaging group also collaborated with CALGB to design and conduct the original
I-SPY study of contrast-enhanced MRI for assessing and predicting response to
neoadjuvant treatment in breast cancer. ACRIN is participating in a contract
role to collect similar imaging data for I-SPY 2.
group chair Mitchell Schnall said joining with ECOG is a way to improve his
group's ability to do therapeutic studies.
don't have a standing organization looking at what therapies are coming, what
markers are needed and what those opportunities are. I'd say we have spotty
interactions with colleagues in other organizations that are thinking about
these things," he told BioCentury.
merger also will promote more comprehensive thought about how imaging markers
should be used relative to other kinds of biomarkers, Schnall said.
want to get more integrated into the biology of experimental therapies so we
can optimally position markers on our own and in coordination with in vitro
markers," he said.
advantages of imaging are that it's repeatable, it can be done non-invasively,
it can be done dynamically and it can be done in real time. We want to look for
opportunities where that brings advantages," Schnall added.
Schnall said he expects uniting with ECOG will improve accrual of patients to
studies that are investigating imaging as a tool to predict and monitor
has focused primarily on therapeutic trials, with more limited participation in
studies involving screening and diagnosis. While many of the group's trials
have incorporated biomarkers, Chair Robert Comis told BioCentury merging with
ACRIN will provide the tools and expertise necessary for a more comprehensive
approach to biomarker-driven research.
has coordinated two of the largest biomarker-driven studies in cooperative
group history, TAILORx and E5202," Comis said. "But if you look at the whole
area of biomarkers - genomics, proteomics, metabolomics - you need a strong
imaging platform to really understand what is happening."
TAILORx trial is a 10-year, 10,000-patient study designed to determine the
benefit of chemotherapy for women with breast cancer with intermediate risk as
determined by Oncotype DX, a gene expression assay from Genomic
E5202 study is using molecular profiling to determine risk and treatment
strategy in patients with Stage II colorectal cancer.
added that ACRIN has been a leader in early detection and diagnostic imaging,
where ECOG has been less active. He views the merger as an opportunity for ECOG
and ACRIN clinicians to jointly develop such studies.
Form follows function
Schnall and Comis are enthusiastic about the opportunity to strengthen their
response to emerging science, both told the workshop NCI needs to be
flexible rather than require all the groups to conform to a common structure.
told BioCentury the traditional cooperative group structure, in which there is
one disease site committee for each type of cancer, may not be suitable for the
combined ECOG/ACRIN organization, which will conduct studies in screening,
diagnosis and therapy settings.
are different sets of markers and different sets of clinicians involved in
these settings," he said. "For us, the thing about how to organize ourselves is
how to get the right critical mass of people thinking about the right things."
added: "I've always been concerned that the numbers have driven this discussion
rather than the scientific strategy. It's not about whether there are four or
five or two groups. It's about how we come together and how the scientific
portfolios come together."
comments were echoed by several participants at the workshop, including Sharon
Murphy, scholar-in-residence at IOM and former chair of the Pediatric Oncology
Group, one of COG's predecessors.
four? And is there any flexibility?" Murphy asked. "We've seen a rather hasty
rush to the altar and some arranged marriages, and this was not what the IOM
fact, the report suggested one possible solution was four multidisciplinary
adult groups, each with four disease site committees, but IOM did not say how
it had arrived at the number four.
early March, a group of six directors of NCI cancer centers issued a white
paper proposing a radically different model for the clinical trials system,
which would encompass six or seven groups, each focused on a single set of
diseases (see "Centers Speak," A11).
Doroshow, director of NCI's Division of Cancer Treatment and Diagnosis, noted
NCI is considering a variety of viewpoints. "We are in the input-gathering
phase," he said. "We certainly want to understand a variety of perspectives
because we are nowhere near the place of starting to write up this RFA."
was referring to a request for applications, formally called a Funding
Opportunity Announcement (FOA), that NCI plans to issue around July 2012. The
FOA will include guidelines describing NCI's expectations for what the
cooperative groups should look like, how they should function and how they will
FOA will begin a competition among the co-ops for grants or contracts. At this
point, NCI has said four adult groups and one pediatric group will receive
Door number three
participants in the third tie-up announced to date - the
National Surgical Adjuvant Breast and Bowel Project (NSABP) and
Radiation Therapy Oncology Group (RTOG) - also made a plea for
Chair Walter Curran and NSABP Chair Norman Wolmark have described their union
as a "collaborative alliance." While the details are being worked out, it
clearly bears the least resemblance to the merger that formed COG.
thing you can infer from what's been said is that some of the newly created
relationships will look different from each other," Curran told the workshop.
"Some will be one entity, some will be a confederation/alliance of many
entities, and my hope is that the federal guidelines for review will allow such
the nine original adult groups, that leaves SWOG, which does not intend to combine with
another group, and the
Gynecologic Oncology Group (GOG).
latter has argued it should be left independent as a fifth adult group, but
also is holding discussions with NSABP and RTOG.
the meeting, gynecologic group chair Philip DiSaia told BioCentury a potential
alliance with NSABP and RTOG would look very different from the mergers other
groups have announced.
all completely different, so how the hell could we merge?" he said.
said GOG is considering a third alternative, should neither independence nor
alliance pan out - becoming an "industry-only collaborator."
pay pretty well, but you don't have quite the freedom we have now. But we've
found some things we're interested in, and so is industry," he said.
said the GOG, RTOG and NSABP feel they are being forced into a combination to
achieve NCI's vision of consolidation, which is untested and may turn out not
to be healthy for the individual groups or the system as a whole.
need to talk with NCI about some type of strategy that will allow us to
preserve our groups' integrity. They are sticking to this precept, and they
don't even know if it's going to hurt trials," he said.
uncertainty was echoed by several discussants at the workshop.
don't think any of us in this room really know what's going to work," said
Peter Adamson, chair of Children's Oncology Group. "We have to make sure the
incentives are aligned with the goals, and my overarching concern is how do we
attract the best talent?" COG Chair Peter Adamson told the roundtable.
we really don't know what's going to work, let's incentivize innovation and
leave flexibility. I don't think any of us, including the COG, have the perfect
model," he told the roundtable.
of structure, the groups made it clear they want to retain their central role
in the process of designing trials. The groups were concerned that role could
be jeopardized by NCI's proposal to form an oversight committee that would
include extramural advisors to help set priorities for the national clinical
would be in addition to NCI's 10 disease-specific scientific committees, which
are charged with prioritizing and refining concepts for Phase II and III trials
in their respective disease areas.
applaud the concept of the NCI steering committee, but what I don't want to see
is a trend for the scientific core and the development process of new and
exciting trials to shift from the group committees, where there is true
expertise," Curran said.
want the whole scientific development process to be in the group committees,"
he said, "and have the steering committee do what a steering committee should
do - and that is review rather than generate trials."
agreed the scientific leadership must remain within the groups.
have no interest in becoming CROs for the government. What we want to do is
maintain our position as part of the heart of the translational research
program of the cancer institute," he said.
Bertagnolli, chair of CALGB, said more coordination between the parts of the
NCI trials system is necessary, but not at the cost of innovation.
by committee tends toward the safe, and not to the brave and innovative. Our
work will greatly suffer if we stifle innovation," she warned.
College of Radiology Imaging Network (ACRIN), Philadelphia, Pa.
College of Surgeons Oncology Group (ACOSOG), Durham, N.C.
Society of Clnical Oncology (ASCO), Alexandria, Va.
and Leukemia Group B (CALGB), Chicago, Ill.
Oncology Group (COG), Arcadia, Calif.
Cooperative Oncology Group (ECOG), Philadelphia. Pa.
Health Inc. (NASDAQ:GHDX), Redwood City, Calif.
Oncology Group (GOG), Philadelphia, Pa.
of Medicine (IOM), Washington, D.C.
Cancer Institute (NCI), Bethesda, Md.
Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh,
Central Cancer Treatment Group (NCCTG), Rochester, Minn.
Therapy Oncology Group (RTOG), Philadelphia, Pa.
SWOG, Ann Arbor, Mich.