Industry-sponsored and federally sponsored clinical trials together drive drug development and patient care. While the pharmaceutical industry conducts clinical trials to obtain new drug approvals from the U.S. Food and Drug Administration (FDA), federally sponsored oncology trials tend to take place within the cooperative groups that make up the National Cancer Institute’s (NCI) National Clinical Trials Network (NCTN).1 They result from a federal mandate to “routinely achieve change in clinical practice” by conducting trials designed by oncology specialists to meet patient needs.
Industry-sponsored and federally sponsored trials serve complementary vital functions in new treatment discovery. Unfortunately, decreased federal support threatens cooperative trials’ ability to play a critical role in identifying optimal patient care.
Different Questions Yield Different Answers
The NCTN consists of four adult groups and one large group focused on childhood cancers. The five U.S. Network Groups are the Alliance for Clinical Trials in Oncology, ECOG-ACRIN Cancer Research Group, NRG Oncology, SWOG Cancer Research Network, and Children’s Oncology Group. Each group has its own disease focus area, and the investigators who belong to the groups meet regularly to decide which trials will be funded. Researchers compete for funding to lead these cooperative trials by describing the likelihood of the results contributing to public good.
“They simply don’t have the funding to support every good idea,” said Andrew Cowan, MD, research director of multiple myeloma at Fred Hutchinson Cancer Center in Seattle.
“Federally sponsored researchers are not focused on a new drug approval, per se, but they are focused on the best treatments for patients,” said Joseph M. Unger, PhD, MS, associate professor in the Public Health Sciences Division at Fred Hutch.
Instead of seeking new drug approval, the NCI often sponsors multimodality and de-escalation trials designed to investigate less aggressive treatments. NCI trials may also address drug repurposing, cancer prevention, screening, symptom management, and health disparities, benefitting diverse patient populations.
Cooperative Trials Are Often Practice Changing
NCTN trials have had a profound impact on patient care in oncology. For example, of the 182 phase III trials conducted by SWOG Cancer Research Network over 37.5 years starting January 1, 1980, 45% had practice-influencing results, including 39% that served as the basis for recommendations in National Comprehensive Cancer Network (NCCN) guidelines.2 Just as important, however, NCTN trials often yield negative results that can be instrumental in shaping patient care. NCI, Dr. Cowan said, provides the “freedom to study questions that large pharma or biotech may not be interested in … A lot of them have been pivotal trials that have been practice changing.”
Last year, for example, researchers published in the New England Journal of Medicine results from a large NCI-funded clinical trial that indicated that treating patients with advanced-stage classic Hodgkin lymphoma (cHL) with nivolumab plus doxorubicin, vinblastine, and dacarbazine (N+AVD) resulted in longer progression-free survival than treatment with brentuximab vedotin and AVD (BV+AVD).3 The adolescents and adults with stage II or IV advanced-stage cHL treated with N+AVD also experienced a better side effect profile than those treated with BV+AVD. As a result of the findings, the NCCN guidelines now state that the immunotherapy nivolumab should be part of the initial treatment of teens and adults with advanced forms of cHL.4
An analysis of the total federal investment in the SWOG studies estimated that the federal government spent $1.36 billion in 2017 dollars for 182 trials, prompting Aaron T. Gerds, MD, MS, a hematologist at Cleveland Clinic in Ohio to write: “… the NCI-funded cooperative trials deliver as a factory of clinically meaningful results, and do so at a good value.”1 By one calculation, the NCI’s network research groups contributed to gains of 14.2 million life-years for patients with cancer over four decades at a cost to taxpayers of only $326 US (USD)/life-year.5
“NCTN tends to do trials that industry is not so motivated to do,” Dr. Unger said.
Federally funded trials also provide training for early-career investigators, including mentorship and collaboration opportunities.
Decrease in Federally Funded Trials
Cancer clinical trials can be costly. The discovery of highly remunerative cancer treatments in the 1990s drove pharmaceutical companies to invest more money in the oncology sector of the industry, Dr. Unger said. In contrast, NCI sponsorship of clinical trials has been mostly flat and has not kept up with the growing cancer incidence. Thus, the ratio of industry-sponsored to NCI-sponsored trials has more than doubled over the past decade.5 Enrollments of patients to clinical trials are now eight times more likely attributable to pharmaceutical company sponsorship than federal sponsorship.5
Congressional funding allocations to NCI help support the NCTN and determine the funding available for federally sponsored trials. While industry-sponsored cancer clinical trial enrollment doubled from 2008 to 2022, enrollment in federally funded trials has remained flat.5 One positive conclusion from this discrepancy is that there has been a significant industry investment in cancer clinical trials. In contrast, Dr. Unger said, the federal sponsorship of trials has not kept up with either industry sponsorship or the increase in cancer incidence in the population.
“It’s a very different landscape than it used to be two to three decades ago,” Dr. Unger said. Even though NCI’s Cancer Moonshot, announced by President Barack Obama in his 2016 State of the Union Address and presided over by then-Vice President Joe Biden, accelerated scientific discovery in cancer research, the time-limited effort was spread out over basic research and clinical trials. According to Dr. Unger, it did not change the fact that pharmaceutical company sponsorship of clinical trials now far exceeds that of federal sponsors.
Industry and the federal government do, in some cases, partner in trial sponsorship. Such collaborations leverage industry resources to facilitate trials by providing the drugs for use in clinical trials, the costs of which can be high and challenging for the NCI to cover with its budget. In general, the collaborations benefit both parties. “Industry gets a lot from federal sponsorship of clinical trials,” Dr. Unger explained, noting that federal sponsorship can advance early drug discoveries. “It’s an important collaboration and symbiosis,” he added. Unfortunately, when a federal sponsor tests a pharmaceutical company agent, collaborations often involve lengthy contractual negotiations.
Competition for Patients
At some level, federally and industry-sponsored trials also stand in competition. This is because patients typically can enroll in only one trial and the number of patients is limited.
“Patients and physicians may be more familiar with industry trials, particularly if there is heavy promotion from pharmaceutical companies,” said Yara Abdou, MD, assistant professor in the Division of Oncology at University of North Carolina in Chapel Hill. “Co-op trials may not be as widely advertised.”
Last year, Dr. Unger and colleagues published a study of patient enrollment in industry-sponsored versus federally sponsored cancer clinical trials from 2008 to 2022 using data from ClinicalTrials.gov.5 They documented a growing reliance on industry to conduct cancer clinical research, including pediatric cancer research. When adjusted for biomedical price inflation and indexed in constant (2020) USD, they found that the NCI’s cooperative group clinical trials budget (for adult and pediatric trials) was 6% lower in purchasing power in 2020 compared with 2010, suggesting that federal underinvestment in clinical cancer research leaves federally sponsored trials underfunded to compete for patients.
The competition for patients plays out at the level of cancer clinical trial offices (CCTOs) in cancer centers, which are charged with developing and coordinating a complex clinical research protocol. Their goal is to improve outcomes for patients with cancer while advancing the scientific field. Over time, most CCTOs have needed to activate more trials to meet patient needs with lower enrollment goals per trial, resulting in larger budgets, more staff, and longer activation times.
A recent survey of CCTOs across North America found that from 2018 to 2023, CCTO operations had larger staff sizes, larger budgets, and more trials supported but fewer patients enrolled in interventional treatment trials.6 The authors suggest that the data reflect the increasing complexity of cancer clinical trials, the importance of external funding sources, and the need for operational efficiency upgrades to provide cutting-edge cancer research and care. The Association of American Cancer Institutes’ Clinical Research Innovation program intends to repeat this survey annually to track cancer clinical research capacity and readiness in North America over time.6 The hope is that these survey results can be used to improve CCTO operational efficiencies, share best practices, and target investments in CCTO infrastructure to accelerate the translation of research discoveries to viable treatments for patients with cancer.
Dr. Unger explained that not only are CCTOs under-resourced to participate in all available trials, but a finite number of patients at each center can be enrolled in clinical trials. Because pharmaceutical companies provide a greater incentive to sites to participate in their trials, those trials often take priority with CCTOs and patients. “Industry is to be congratulated for all they do to advance clinical trials,” Dr. Unger said, adding, however, that “the playing field for recruitment of patients should be fair for federally sponsored trials.”
Funding Uncertainty
Centers that participate in federally sponsored trials often receive reimbursements that are less than the costs to participate in the trial, leaving the centers or investigators to cover the remaining costs. “We can’t meet our operating costs with those budgets,” Dr. Cowan said, adding that “some centers may have subsidies to support, but not all do … We need more funding for NCI and NCTN trials.”
Researchers at academic institutions or health care facilities seek to cover the cost of conducting a clinical trial without relying on funds from their institution. In many cases, the institutions that do move forward with the federally funded trials often must dip into institutional, operational, or philanthropic funds. “They will let us open it,” Dr. Cowan said, “but we’re the ones who have to make the finances work … We can only do as many NCTN trials as we have the funding to support.”
Dr. Abdou explained, “Industry trials are backed by pharmaceutical companies with deep financial resources, allowing them to open more sites, recruit more patients, and provide significant support for trial infrastructure. In contrast, co-op trials rely on government funding (e.g., National Institutes of Health [NIH] or NCI), which is often more limited and spread across multiple projects.” As a result, the menu of possible trials a CCTO offers patients is often weighted toward pharmaceutical industry-sponsored trials. Dr. Cowan noted that the cooperative trials are usually very appealing to patients, and it can be frustrating not to be able to offer them as an option to patients.
The financial situation became more dire on February 7, when the NIH issued supplemental guidance that eliminated negotiated indirect cost rates and established a new standard indirect cost rate of 15%, dramatically lowering the reimbursement of the facilities and administrative costs that come with conducting federal research. When asked how the NIH’s supplemental guidance will affect clinical trials, Dr. Unger referred the question to a Fred Hutch spokesperson who responded with the following statement: “Fred Hutch is closely monitoring NIH policy changes. These policies could significantly impact our ability to continue making discoveries to treat, cure, or prevent cancer and infectious diseases. We are working vigorously with our peers, partners, legislators, and trade organizations to advocate for Congressional intervention.”
Looking to the Future
As the U.S. struggles to fund practice-changing cooperative studies, other countries continue to support their cooperatives.
“In Europe, there’s funding from the European Union for some national networks,” Dr. Cowan said, explaining that Australia, Canada, and China also have networks with structures like the NCTN.
“Different countries fund co-op trials in unique ways,” Dr. Abdou said. “The Canadian Cancer Trials Group receives government funding but also leverages partnerships with industry and foundations to sustain co-op trials. Their model integrates public-private funding while maintaining independence.” While the European model is similar to Canada’s, Australia has a Medical Research Future Fund that provides dedicated funding for investigator-initiated trials, ensuring financial sustainability.
Even without the chilling effect of the February 7 supplemental guidance, the level of U.S. funding for oncology trials has left cooperatives struggling.7 “The NCI Community Oncology Research Program has increased community-based trial access, improving minority and rural enrollment, yet many sites struggle with limited resources and slow activation due to administrative hurdles,” Dr. Abdou said. “To enhance these efforts, increased federal and industry funding, dedicated financial support for community sites, and streamlined regulatory processes such as a central IRB (institutional review board) are essential to sustain trial growth and improve patient enrollment.” Unfortunately, it is unclear how the research community can continue to conduct cooperative clinical trials, let alone advance these efforts, given the uncertainty associated with the NIH policy changes.
References
- Gerds AT. Commentary: NCI-sponsored clinical trials are clinically meaningful and cost-effective. Case Comprehensive Cancer Center. December 12, 2019. Accessed March 4, 2025. https://case.edu/cancer/about-us/news/commentary-nci-sponsored-clinical-trials-are-clinically-meaningful-and-cost-effective.
- Unger JM, Nghiem VT, Hershman DL, et al. Association of National Cancer Institute-sponsored clinical trial network group studies with guideline care and new drug indications. JAMA Netw Open. 2019;4:e1910593.
- Herrera AF, LeBlanc M, Castellino SM, et al. Nivolumab+AVD in advanced-stage classic Hodgkin’s lymphoma. N Engl J Med. 2024;391(15):1379-1389.
- Phillips C. Nivolumab appears to boost cure rate in advanced Hodgkin lymphoma. National Cancer Institute. November 14, 2024. Accessed March 25, 2025. https://www.cancer.gov/news-events/cancer-currents-blog/2024/hodgkin-lymphoma-nivolumab-avd-first-line.
- Unger JM, Xiao H, Vaidya R, et al. Patient enrollment to industry-sponsored versus federally-sponsored cancer clinical trials. J Clin Oncol. 2024;42(33):3917-3925.
- Kasner M, Fritsche AH, Leong MC, et al. North American cancer clinical research capacity and benchmarking in the postpandemic era. JCO Oncology Practice. 2024;20(12):1612-1619.
- National Institutes of Health. NOT-OD-25-068: Supplemental guidance to the 2024 NIH grants policy statement: indirect cost rates. February 7, 2025. Accessed March 4, 2025. https://grants.nih.gov/grants/guide/notice-files/NOT-OD-25-068.html.
