A Near-Term Solution: NCI And COG Agree on Plan to Maintain Enrollment
By Peter C. Adamson
As funding issues surrounding the NCI’s new National Clinical Trials Network (NCTN) have been a prominent topic of recent news and discussions, to help inform the cancer research community, we are taking this opportunity to share data regarding NCTN funding to the Children’s Oncology Group (COG).
The COG was the recipient of three NCTN grants: a Network Operations Center grant, a Network Statistics & Data Center grant, and an Integrated Translational Science Center (ITSC) grant. Similar to other members of the NCTN, the funding support and restrictions on utilization of that support provided under the Network Operations Center grant created an unparalleled fiscal challenge for the COG.
As originally issued, the Notice of Award (NOA) for this grant resulted in a $6.9M budget gap relative to FY13, a budget gap that would have resulted in closure of a major component of ongoing clinical trials and delayed or prevented the activation of approved new studies.
However, over the past several weeks, we have worked closely with NCI-CTEP leadership to develop a series of solutions to narrow this budget gap. A path forward has been defined that in the near term should allow COG to continue enrollment to all studies within its current clinical trial portfolio.
Here we provide details of the budget cuts to the COG and the agreed-upon bridging strategy geared towards lessening the negative impact these cuts will have for childhood cancer research and children with cancer.
Childhood Cancer Research Funding Landscape
In the United States, approximately 60% of funding for all biomedical research stems from the biopharmaceutical sector.
The next largest funder is the NIH, which supports approximately 25% of biomedical research. For childhood cancer, however, the private sector has an almost negligible investment, resulting in virtually all research funding emanating from the NCI, with lesser but vital components of funding emerging from private foundations and other philanthropic sources.
This funding landscape is directly relevant to the fiscal challenge that arose under the new NCTN. As there is no second revenue stream from the biopharmaceutical industry capable of supporting a childhood cancer clinical trial program in this country, any cut from the NCI to childhood cancer research is magnified.
Simply put, the clinical childhood cancer research enterprise is essentially entirely dependent upon funding from the NCI to conduct clinical-translational research.
Funding to the COG has declined significantly over the past 10 years (Figure 1). Since 2004, adjusting for inflation, COG incurred a 30% decrease in its base funding from NCI. This steady erosion of research support, amplified further by 2014 budget cuts, will delay progress in improving the outcome for a spectrum of cancers that effect children.
COG Funding Differences
The COG, formed 14 years ago through the voluntary merger of four existing pediatric cooperative groups, is the only group in the NCTN devoted exclusively to childhood and adolescent cancer research.
Since its formation, the more than 220 member sites of COG agreed that a centralized mechanism of funding for sites, administered through a single primary grant, would prove the most cost effective and equitable way to manage available resources. Decisions on distribution of resources to member sites would be based on performance and not be reliant on a federated system of grants to individual institutions.
In 2014, of the four primary grant mechanisms available to support NCTN groups, only three mechanisms, the Network Operations Center, Network Statistics & Data Center and the Integrated Translational Science Center (ITSC), were available to COG; the Lead Academic Participating Site (LAPS) awards were only available to the adult cancer groups.
The decision not to provide resources through the LAPS mechanism aligned with COG’s successful model of centralized support, with a clear understanding that in place of LAPS, the NCI was to provide a comparable component of funding for sites through the Network Operations Center grant.
This approach would allow COG to continue to provide a limited component of resources to support sites’ clinical research infrastructure based on an annual assessment of performance.
Historically, COG’s higher performing sites received a limited amount of additional funding generally used to offset a degree of salary support for a lead CRA or site lead PI.
The lack of LAPS grants for COG is important to understand in the context of the current fiscal challenges.
First, understanding the funds flow for COG is relatively straightforward, as there is only a single pediatric group with two primary grants available for support.
Second, given the limited number of grants, NCI may have greater flexibility in addressing specific budgetary gaps in the program.
Indeed, it was this latter point that helped narrow in the near-term the large FY14 budget gap in the Network Operations Center grant.
NCTN Funding to COG in FY14
Total COG funding via the two primary grants (the sum of the Network Operations Center and Network Statistics & Data Center grants) decreased by approximately $2M in FY14 relative to FY13, but even more concerning was how that funding was originally partitioned.
Excluding funding restricted by NCI to support sites through the per case reimbursement (PCR) mechanism, the original FY14 Network Operations Center NOA resulted in a $6.9M budget gap (Figure 2), a 39% decrease relative to FY13 (there was a $1M increase to the Network Statistics & Data Center grant).
While the fiscal trajectory of the original award under the Network Operations Center grant would be devastating to the entire program, it was equally clear that such an outcome was never the intent of the NCI.
Discussions that ensued were collaborative, with both COG and NCI suggesting potential mechanisms that could address the formidable fiscal challenges required to narrow the gap.
Beyond the topline $3M cut to the Network Operations Center grant, a major driver of the budget gap relative to FY13 was the increase in PCR costs resulting from the proposed $4,000 rate of reimbursement to high performance sites (Figure 3).
Without additional programmatic funding, there did not, and does not, appear to be any meaningful way for NCI to pay for this increased expense without negatively impacting other key areas of research.
From our perspective, COG was in a less than zero-sum situation. If we attempted to fund the higher payments, we would have to close studies.
Closing studies would be highly problematic not only from the ethical and scientific perspectives, but from a fiscal perspective as well. Fewer studies would mean fewer accruals, and fewer funds would flow to sites.
COG thus decided the best path forward would be to fund all therapeutic accruals at the standard rate of $2,250 per subject. That change would return $3.6M to support other mission critical components of the program.
To be clear, the fiscal challenges to COG member sites are formidable, and this decision does not provide for a long-term solution. It should be noted that how COG accounts for this adjustment to the overall budget (paying all sites at the standard PCR rate) might differ from how the NCI accounts for the adjustment; the net budgetary effect, however, is the same.
The COG was also successful in a recent Biomarker, Imaging and Quality of Life Studies Program (BIQSFP) application to support an integral study in a frontline acute lymphoblastic leukemia study, which offset a past expense incurred by our COG ALL reference laboratory (such critically important reference laboratories remarkably are no longer supported under the NCTN).
Other adjustments made to the NOA included the shifting of allowable expenses to the two other grants available awarded to the COG: the Network Statistics & Data Center and the Integrated Translational Science Center (ITSC). The fiscal impact of shifts to these grants is significant, but in the near term we anticipate should be manageable.
Unfortunately, the change to the ITSC will require a major narrowing of specific aims, as the budget requested, $800,000, was originally awarded at $400,000 and now will have only $200,000 available in total costs. No increase in funding was made to any of COG’s awards.
In the United States, cancer remains the leading cause of death from disease in children.
The advances made to transform childhood cancers from incurable diseases to diseases with overall 5-year survival now exceeding 80% resulted in large measure from a sustained investment by the NCI in clinical research.
And what is arguably amongst the greatest returns on investment ever made by the NCI, investment in the childhood cancer cooperative group system must be included. Thus we are thankful to NCI leadership for their willingness and responsiveness to help provide short-term measures to address the unprecedented fiscal challenges that occurred with implementation of the NCTN.
We must emphasize that the short-term fiscal work-around arrived upon does not address the topline budget cuts, let alone the need for increased investment, to the overall program.
These significant budget cuts not only steepen the increasingly downward slope in research funding for children with cancer, but also perhaps inevitably, now result in fundamental changes to our research mission that should indeed raise alarm.
The original projections on how to fund the NCTN to meet its stated objectives not only required $25M in increased funding, but also projected the need to decrease total patient accrual to NCTN clinical trials.
Childhood cancers are comprised of well over one hundred different types of cancer, many of which still have unacceptably low cure rates. Moreover, too many children continue to suffer from the substantial acute and long-term morbidity of therapy. The advent of molecularly targeted therapy and the emergence of precision medicine have the prospect to transform the therapeutic landscape for all children and adolescents with cancer.
To plan for less participation of children and families in well designed clinical research studies is an anathema to pediatric oncology researchers and the childhood cancer community alike.
Advances in today’s science will only translate into improved outcomes through increased and sustained investment in collaborative and productive clinical-translational research enterprises—team science at its best.
The NCTN should have brought increased investment to childhood cancer research; the patients and families we care for deserve no less.
The author is chair of the Children’s Oncology Group.