2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

economies of scale, no predetermined metrics were developed
and no resources were made available to collect and
analyze data to evaluate success. In fact, annual budget
reductions after the merger precluded any comprehensive,
detailed self-assessment.
There were considerable immediate challenges in the
transition process of unifying culturally and organizationally
distinct, procedurally and operationally disparate, competing
clinical trial networks. COG leadership focused
initially on individual, discipline-specific, and institutional
membership requirements; financial planning and new models
for funds distribution (given the planned discontinuation
of institutional U-10 awards); consolidation of administrative
functions; and coordination of data management and
statistical operations. The last of these was particularly
problematic since three separate sites served as statistics
and data management centers using different and noncompatible,
internally generated, electronic, Web-based remote
data entry and registration systems. The importance of
providing adequate and centralized IT support and an
enterprise-wide Clinical Data Management System cannot
be overemphasized.
It was a priority to maintain active legacy study conduct
(80 phase III, 22 phase II, and 7 phase I) open studies using
different data management platforms while planning for the
importation of all legacy as well as new data to a single
common platform. Of equal and—given resource constraints—competing
priority was the development and implementation
of new biologically based and hypothesisdriven
clinical trials.
Despite the lack of prespecified metrics, many successes
were realized as a direct result of the consolidation. Three
years after the merger, annual enrollment on therapeutic
studies increased by more than 25% and enrollment on
KEY POINTS
● The merger of the legacy pediatric cooperative groups
was self-motivated and self-directed.
● No preestablished metrics of success were developed
other than to maintain focus and achieve mission
success.
● Supplemental resources during a challenging transition
period were not made available.
● The lack of supplemental resources precluded the
Children’s Oncology Group’s ability to perform a
detailed assessment of evaluating efficiency, and progressive
budget reductions made evaluation of any
cost-effectiveness impossible.
● Significant accomplishments in pediatric cancer were
made possible only as a direct result of its planned
consolidation and successful integration.
Author’s Disclosure of Potential Conflicts of Interest
Author
Gregory H. Reaman*
*No relevant relationships to disclose.
150
Employment or
Leadership
Positions
Consultant or
Advisory Role
nontherapeutic (epidemiology and biology) studies more
than doubled compared with combined enrollment statistics
of the legacy groups. 4 COG became the largest childhood
cancer research organization in the world and expanded its
international collaborations. New clinical and biologically
based classification systems were developed for both acute
lymphoblastic and myeloid leukemia and neuroblastoma.
5,6,7 Cytogenetic and molecular genetic predictors of
outcome were defined for these same diseases as well as for
Wilms tumor and medulloblastoma. The prognostic significance
of minimal residual disease in a number of tumor
systems (acute leukemia, lymphoma, neuroblastoma) was
established and incorporated into the expansion of riskadjusted
treatment approaches to these diseases. 6,7 Expanding
active programs in biomarker development for patient
enrichment and risk classification was made possible by
the retrospective analysis of independent data sets from
legacy groups as test and validation cohorts. Early in its
history, COG opened a frontline, randomized clinical trial
for osteosarcoma, designed and conducted in collaboration
with multiple European cooperative groups, which led to the
development of the Cancer Therapy Evaluation Program
guidelines for performance of international clinical trials.
By consolidating legacy bio-specimen banks, COG’s Biopathology
Center has become the national and international
resource for clinically well-annotated specimens of virtually
every type of pediatric cancer. Important genomic investigations
in collaboration with the NCI’s Cancer Genome
Atlas and the TARGET initiative have been made possible
through this resource. These investigations have identified
novel genetic lesions in acute leukemia and neuroblastoma,
which are being evaluated as predictive biomarkers and
for their potential therapeutic exploitation. 7-11 Since the
consolidation, statistically significant improvements in
5-year event-free survival rates have been achieved in all
prognostic subgroups of acute lymphoblastic leukemia,
acute myeloid leukemia, high-risk neuroblastoma, and medulloblastoma.
7,8,12,13 COG has developed Long-Term
Follow-Up Guidelines for childhood cancer survivors, which
are regularly updated in accordance with increasing evidence
and utilized worldwide. 7 Relevant portions of these
exposure-dependent risk assessments and recommended
surveillance parameters have been extrapolated for adult
cancer survivors.
Despite the initial challenges and anxiety experienced
during the early days of the consolidation, and despite the
criticism in response to the reduction in healthy competition,
COG has emerged as more successful and impactful
than the sum of its legacy groups. With thoughtful transition,
focus on mission, assurance of adequate centralized
resources and utilization of well-constructed, predetermined
metrics, the current cooperative group reorganization
should be viewed as a real opportunity to further advance
clinical and translational research.
Stock
Ownership Honoraria
Research
Funding
Expert
Testimony
GREGORY H. REAMAN
Other
Remuneration