With publicly funded correlative science in the nation's Cancer Cooperative Groups reduced to a trickle, Group leaders propose implementing a long-standing National Academy of Medicine recommendation to bring new money to this area of research through public-private partnerships. They also recommend major process changes to remove significant barriers for researchers to access the biological samples contributed by patients. The current Journal of Clinical Oncology issue features 'Correlative Science in the Cooperative Group System—Re-Engineering for Success.'
This Position Paper represents consensus among Evanthia Galanis, MD, DSc for the Alliance for Clinical Trials in Oncology, Janet Dancey, MD for the Canadian Cancer Trials Group, Douglas S. Hawkins, MD for the Children's Oncology Group, Peter J. O'Dwyer, MD and Mitchell D. Schnall, MD, PhD for the ECOG-ACRIN Cancer Research Group, Norman Wolmark, MD, Robert Mannel, MD, and Quynh-Thu Le, MD for NRG Oncology, and Charles Blanke, MD, for the SWOG Cancer Research Group. The Cooperative Groups and their leaders are integral to the National Cancer Institute (NCI) and the National Clinical Trials Network.
In a statement, the Group Chairs share the rationale for proposing a new approach:
- "The Cooperative Group Chairs have observed the risk and reality of underfunding for correlative science, which has resulted in unused patient samples accumulating in our tissue banks. Unused samples have an opportunity cost in losing the full value of these independent trials, and we fail our patients by not extracting the maximum information from the valuable samples they provide. The focus of this Position Paper is to reorder processes at multiple levels so as to bring new funding into a dynamic and real-time correlative science program."
The National Academy of Medicine (NAM, formerly the Institute of Medicine) first recognized the value of correlative science in 2010, recommending "the incorporation of innovative science into cancer clinical trials through the support and use of biorepositories." A specific recommendation was that the NCI should facilitate "the creation of more public-private partnerships" and "the development of appropriate hybrid funding models, in which NCI and industry support… (would define) …components of trials that are of mutual interest." Since then, NAM has reiterated these goals on multiple occasions.
In the new publication, the Group Chairs state:
- "In this Position Paper, with a sense of urgency on the basis of funding and efficiency limitations of the current system, [we] propose a series of modifications to correlative science funding (with the encouragement of the most recent NCI Directors)...[and] the key starting point for progress will be the institution of a public-private partnership to expand funding support to translational science."
Publicly funded clinical trials conducted by the Cooperative Groups have had a substantial public health impact as measured by life-years saved for people with cancer (Unger JM et al. J Clin Oncol. 2023). The National Institutes of Health (NIH) grants that provide federal resources for these groups to evaluate new cancer treatments also contain goals for studying the biospecimens and tumor samples from trial participants (tumor tissues, normal tissues, certain body fluids, etc.).
Correlative studies for clinical trials explore relationships between molecular biology (biomarkers such as genes and proteins) and clinical outcomes (such as disease progression). They are the promise of precision oncology. Correlative research leads to knowledge beyond the initial trial itself. For example, by studying hundreds or thousands of biospecimens, researchers can uncover which groups of patients do or do not benefit from a particular therapy, identify novel subsets of cancers, or define which patients may be at risk of side effects from treatment.
However, under current rules, investigators encounter enormous difficulties gaining access to biospecimens and tumor tissue for correlative studies. The Group Chairs say that given the rising concerns by stakeholders, it is clear that access to samples needs to be facilitated:
- "Correlative research on Group tissue samples is almost at a standstill because of these barriers to access. Not alone does this represent an opportunity cost; the barriers are a disincentive to the participation of early- and mid-career translational and basic scientists whose expertise and engagement the system needs the most, and so there is a future loss to science and careers in cancer research."
The authors also highlight that the Cooperative Groups are diversifying. For example, programs are underway to increase the efficiency and accuracy of data collection from electronic health records. The Groups are beginning to acquire real-world data outside of clinical trials, to meet the US Food and Drug Administration's goals for collecting real-world evidence for approved cancer treatments. Also, the Groups are testing artificial intelligence (AI) approaches to interpreting the results of clinical trials, which can greatly extend their value.
- "It may be argued that the preferred interface between Federal funding and these activities should be the public-private partnership since agreements can be fit for the appropriate purpose and have a responsiveness that meets the needs of the current information cycles," they state.
The Group Chairs have proposed the legal framework within the paper. The principles of a public-private partnership require that the Cooperative Groups be free to enter into agreements for sample collection and/or disposition with sponsoring entities and have custody of the biological samples. They conclude:
- "There is an opportunity to achieve two major goals with this proposal. The first is to create structures that will facilitate translational research alongside the clinical trials with an impact that can reach far into the future. The current system, though well intentioned, has been rendered nonfunctional, weighed down by barriers to getting the research done by the people most capable of doing it. The second is that in common with other research organizations, the Cooperative Groups are diversifying in ways that recognize and leverage the data-rich and rapidly changing information ecosystem in order to create the benefits that a learning environment can bring to tailoring individual treatment plans for patients."
About the Cooperative Groups
The six Cooperative Groups are all part of the National Clinical Trials Network (NCTN). We are groups of researchers, cancer centers, and community doctors who are involved in studies that test new ways to screen, prevent, diagnose, and treat cancer. Clinical trials run by Cooperative Groups are funded and supported by the National Cancer Institute (NCI), and large numbers of patients take part in many locations.
- Alliance for Clinical Trials in Oncology (Alliance) develops and conducts clinical trials with promising new cancer therapies, and utilizes the best science to develop optimal treatment and prevention strategies for cancer, as well as research methods to alleviate side effects of cancer and cancer treatments. In addition to its role in the NCTN, it serves as a research base for the NCI Community Research Oncology Program (NCORP).The Alliance comprises nearly 10,000 cancer specialists at hospitals, medical centers, and community clinics across the United States and Canada. Chair: Evanthia Galanis, MD, DSc. Learn more at AllianceforClinicalTrialsinOncology.org.
- Canadian Cancer Trials Group (CCTG) is a cancer clinical trials research cooperative that runs phase I-III trials to test anti-cancer and supportive therapies at over 85 hospitals and cancer centres across Canada. From their operations centre at Queen's University, CCTG has supported more than 600 trials enrolling 100,000 patients from 40 countries on 6 continents through a global network of 20,000 investigators and clinical trial staff. CCTG is the Canadian Coordinating Clinical Trial Network for NCTN and a national program of the Canadian Cancer Society with the aim is to improve survival and quality of life for all people with cancer. Chair: Janet Dancey, MD. Learn more at cctg.ca.
- Children's Oncology Group (COG) is the world's largest organization devoted exclusively to childhood and adolescent cancer research. COG unites over 10,000 experts in childhood cancer at more than 200 leading children's hospitals, universities, and cancer centers across North America, Australia, and New Zealand in the fight against childhood cancer. Today, more than 90% of the 16,000 children and adolescents diagnosed with cancer each year in the United States are cared for at COG member institutions. Research performed by COG institutions over the past 50 years has transformed childhood cancer from a virtually incurable disease to one with a combined 5-year survival rate of 80%. COG's mission is to improve the cure rate and outcomes for all children with cancer. Chair: Douglas S. Hawkins, MD. Learn more at ChildrensOncologyGroup.org.
- ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) is an expansive membership-based scientific organization that designs and conducts research studies involving adults who have or are at risk of developing cancer. The Group comprises nearly 1400 member institutions and 21,000 research professionals in the United States and around the world. ECOG-ACRIN is known for advancing precision medicine and biomarker research through its leadership of major national clinical trials integrating cutting-edge genomic approaches. In addition to its role in the NCTN, it serves as a research base for the NCI Community Research Oncology Program (NCORP). Co-Chairs: Peter J. O'Dwyer, MD and Mitchell D. Schnall, MD, PhD. Learn more at ecog-acrin.org.
- NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology's extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. Chairs: Norman Wolmark, MD, Robert Mannel, MD, and Quynh-Thu Le, MD. Learn more at nrgoncology.org
- SWOG Cancer Research Network (SWOG) is part of the NCI's NCTN and NCORP, and is part of the the oldest and largest publicly funded cancer research network in the nation. SWOG has 20,000 members in 45 states and eight other countries who design and conduct clinical trials to improve the lives of people with cancer. SWOG trials have directly led to the approval of 14 cancer drugs, changed more than 100 standards of cancer care, and saved more than 3 million years of human life. Chair: Charles Blanke, MD. Learn more at swog.org.
DOI: 10.1200/JCO.24.00527
