This comparative study of cancer clinical trial portfolios assesses differences between federal and industry sponsors in cancer clinical trial research.
Key Points
Question
How do the clinical trial portfolios of federal and industry sponsors differ in the US?
Findings
In this comparative study of cancer clinical trial portfolios among 11 681 trials registered on ClinicalTrials.gov (2008-2024), industry trials were more likely to focus on single-agent drug therapies, while US federally sponsored studies were more likely to evaluate nontreatment interventions, multimodality treatment strategies, deescalation approaches, and therapies for rare cancers and pediatric populations.
Meaning
Results of this study suggest that US federal and industry sponsors support complementary cancer clinical trial portfolios, reflecting the distinct contributions of each sponsor to the cancer clinical research enterprise.
Abstract
Importance
Industry and federal sponsors support much of the US cancer clinical trial enterprise. Industry-sponsored trials have traditionally focused on therapeutic development and regulatory approval, whereas federally sponsored trials have been viewed as addressing broader clinical and public health research questions. However, differences between these trial portfolios have not been systematically quantified.
Objective
To characterize differences between federally sponsored and industry-sponsored cancer clinical trials in the US.
Design and Setting
A comparative study of interventional cancer clinical trial portfolios registered on ClinicalTrials.gov and initiated between 2008 and 2024. US-based interventional cancer trials, including treatment and nontreatment interventions, were included.
Exposure
Lead sponsor classified as federal or industry.
Main Outcomes and Measures
Trial characteristics, including study purpose, phase, intervention type, deescalation design, rare cancer focus, and patient age category (adult vs children). Differences in trial characteristics by sponsor type were assessed using χ2 tests and described using odds ratios (ORs) with 95% CIs.
Results
Overall, 11 681 federally sponsored trials (n = 2112 [18.1%]) and industry-sponsored trials (n = 9569 [81.9%]) were analyzed. Compared with industry-sponsored trials, federally sponsored trials were less likely to be single-agent drug trials conducted for the purpose of cancer treatment (48.6% vs 77.4%; OR, 0.28; 95% CI, 0.25-0.31; P < .001). In contrast, federally sponsored trials were more likely to evaluate nontreatment interventional trials, including prevention (4.7% vs 1.1%; OR, 4.43; 95% CI, 3.32-5.92; P < .001) and supportive care (2.5% vs 0.9%; OR, 2.92; 95% CI, 2.02-4.20; P < .001). Among trials conducted for the purpose of cancer treatment, federally sponsored studies were more likely to investigate multimodality regimens combining drug and biological agents (19.1% vs 7.4%; OR, 2.98; 95% CI, 2.58-3.44; P < .001) and to combine drug and/or biological agent regimens with radiotherapy (10.5% vs 1.4%; OR, 8.22; 95% CI, 6.51-10.37; P < .001) or surgery (2.5% vs 0.2%; OR, 14.09; 95% CI, 7.95-24.98; P < .001). Federal sponsorship was also associated with greater use of deescalation trial designs (3.1% vs 0.4%; OR, 8.38; 95% CI, 5.43-12.94; P < .001) and trials conducted in rare cancers (17.5% vs 12.1%; OR, 1.54; 95% CI, 1.34-1.77; P < .001) and in children (16.1% vs 5.3%; OR, 3.43; 95% CI, 2.93-4.01; P < .001).
Conclusions
In this study, industry-sponsored trials were more likely to evaluate single-agent drug therapies, whereas US federally sponsored trials were more likely to evaluate nontreatment interventions, multimodality treatment strategies, treatment deescalation approaches, and therapies for rare cancers and pediatric populations. These findings provide an empirical characterization of the complementary and essential roles of federal and industry sponsors in the cancer clinical trial enterprise.
Introduction
Cancer clinical trials are foundational to improving outcomes for people with cancer and have contributed to decreases in cancer mortality over the past 2 decades.1,2,3 They provide the highest level of evidence for treatment efficacy, informing US Food and Drug Administration (FDA) approvals and clinical practice guidelines.4,5,6,7,8 Many of these new cancer treatments have been developed by industry sponsors.7 However, as observed in a 2010 Institute of Medicine report, industry-sponsored trials are principally focused on new drug development and meeting regulatory requirements for drug approval.6,9 Given this, clinical questions with limited commercial incentives may receive less support.10,11,12
The federal system of clinical trials, particularly those sponsored through the National Cancer Institute (NCI) and its cooperative trial networks, has played a central role in establishing standards of care across many cancers.6 Historically, federally sponsored trials have been viewed as addressing research questions that may be less attractive for industry investment, including treatment deescalation approaches, combinations of previously approved agents from different manufacturers, multimodality treatment strategies, and studies in rare or pediatric cancers.6 These questions are critical for public health.
Federal sponsorship of cancer clinical trials dominated the field 40 years ago, with most cancer clinical research supported by the NCI.13 In contrast, today the ratio of enrollments attributable to industry vs federal sponsorship is 9 to 1, a ratio that doubled from 2010 to 2020.14 In this changed landscape, differences between federally sponsored and industry-sponsored trial portfolios have not been systematically characterized. We hypothesized that federally sponsored cancer clinical trials would differ systematically from industry-sponsored trials, with less emphasis on drug trials and greater emphasis on nontreatment interventions, multimodality treatment strategies, treatment deescalation, and understudied patient populations, such as pediatric patients and those with rare cancers. Characterizing these differences provides an empirical basis for evaluating the complementary roles of federally sponsored and industry-sponsored research and for identifying how changes in the balance of sponsor support may influence the types of clinical research questions that are addressed.
Methods
This comparative study of cancer clinical trial portfolios used data from ClinicalTrials.gov, which mandates trial registration under the 2007 FDA Amendments Act.15,16 Data were downloaded in March 2025 for interventional cancer trials initiated between January 1, 2008, and December 31, 2024. Studies were eligible if they listed at least 1 US study site, regardless of whether they also included international sites. Institutional review board approval was not required per the Common Rule because this study used only publicly available, deidentified data from ClinicalTrials.gov and did not involve human participants. This study followed relevant portions of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Sponsor Classification
Each trial was classified according to the lead sponsor field in ClinicalTrials.gov, defined as the primary organization that initiates and controls the study.17,18 Trials were coded as federally sponsored if the lead sponsor was the National Institutes of Health (NIH) or another US federal agency; these designations include all NIH-supported studies, including R01-funded and cooperative group trials. Industry trials were defined as those for which the lead sponsor was a pharmaceutical or biotechnology company. Studies with lead sponsors classified as Other in ClinicalTrials.gov were excluded because this category comprises heterogeneous sponsor entities (eg, individuals, academic centers, foundations, hospitals, non-US governments) that do not constitute a coherent and readily interpretable sponsor class.19
Variables of Interest
We extracted the following trial characteristics from ClinicalTrials.gov. For study purpose, trials were classified according to the predefined ClinicalTrials.gov study-purpose categories, including cancer treatment, basic science, device feasibility, diagnostic, health services research (ie, care delivery), prevention, screening, and supportive care. For phase of trial, trials were classified as phase 1, 2, 3, 4, or not applicable. Multiphase trials (eg, phase 2/3) were categorized by the highest phase. For single modality interventions, trials were classified as behavioral, biologic, device, drug, radiotherapy, surgery or other procedure, and other intervention. For multimodality interventions, trials were categorized as drug and biologic combinations; drug or biologic agents or both combined with devices, radiotherapy, surgery, transplant, radiotherapy and surgery, or other modality; or other combinations. For deescalation trials, trials explicitly designed to test lower doses or shorter durations of therapy were classified as deescalation studies. For rare cancers, trials were considered rare cancer studies if the targeted cancer type has an annual US incidence of fewer than 40 000 new cases.12 For pediatric trials, trials were coded as pediatric if they included patients younger than 18 years.14
Statistical Analysis
Among all interventional trials, we compared the study purpose between federal and industry sponsors. To clarify interpretation within a homogeneous set of trials with a common purpose, and because treatment trials comprised more than 9 of 10 trials, remaining comparisons were made in trials conducted for the primary purpose of cancer treatment. Among these trials, we characterized differences between federal and industry sponsorship with respect to phase, type of intervention, deescalation designs, and rare and pediatric cancers (eg, special populations). Descriptive statistics were used to summarize the distribution of trial characteristics by sponsor type. For each trial characteristic, differences between federally sponsored and industry-sponsored trials were assessed using χ2 tests and described using odds ratios (ORs) with 95% CIs. P values were reported as nominal and were not adjusted for multiple comparisons. Statistical significance was set at 2-sided P < .05.
Results were further stratified by time period (2008-2012 vs 2013-2018 vs 2019-2024) to assess temporal consistency. Temporal differences in sponsor-specific trial characteristics were evaluated using logistic regression models with terms for sponsor type, time period, and their interaction; no additional covariates were included. Sensitivity analyses were conducted using alternative sponsor classification strategies (eg, primary or secondary) based on ClinicalTrials.gov sponsor fields to assess the robustness of the results.
Analyses were conducted using SAS (version 9.4; SAS Institute) and R version 4.3.2 (R Foundation for Statistical Computing). When trial-type classification was unclear, 2 independent reviewers (J.M.U., H.X.) categorized the trial by consensus, with adjudication by the lead author (J.M.U.).
Results
In total, 11 681 trials met our inclusion criteria, including 2112 (18.1%) federally sponsored trials and 9569 (81.9%) industry-sponsored trials. The overall ratio of industry to federal lead sponsorship was 4.53. This ratio increased over time from 2.72 in 2008-2012 to 5.00 in 2013-2018 to 6.44 in 2019-2024.
Among industry- and federally sponsored trials, most (n = 10 588 [90.6%]) were conducted for the purpose of cancer treatment; smaller sets of trials were conducted for basic science (n = 116 [1.0%]), device feasibility (n = 23 [0.2%]), diagnostics (n = 277 [2.4%]), health services research (n = 40 [0.3%]), prevention (n = 204 [1.7%]), screening (n = 69 [0.6%]), and supportive care (n = 134 [1.1%]) (Table).
Table. Study Characteristics.
| Characteristic and category | All interventional trials, No. (%) | ||
|---|---|---|---|
| Federal | Industry | All trials | |
| No. for all trials | 2112 | 9569 | 11 681 |
| Purpose | |||
| Basic science | 14 (0.7) | 102 (1.1) | 116 (1.0) |
| Device feasibility | 3 (0.1) | 20 (0.2) | 23 (0.2) |
| Diagnostic | 76 (3.6)a | 201 (2.1) | 277 (2.4) |
| Health services research | 25 (1.2)a | 15 (0.2) | 40 (0.3) |
| Prevention | 99 (4.7)a | 105 (1.1) | 204 (1.7) |
| Screening | 23 (1.1)a | 46 (0.5) | 69 (0.6) |
| Supportive care | 52 (2.5)a | 82 (0.9) | 134 (1.1) |
| Treatment | 1797 (85.1) | 8791 (91.9)a | 10 588 (90.6) |
| Otherb | 23 (1.1) | 207 (2.2)a | 230 (2.0) |
| Treatment trials | |||
| No. | 1797 | 8791 | 10 588 |
| Phase | |||
| 1 | 482 (26.8) | 3308 (37.6)a | 3790 (35.8) |
| 2 | 1067 (59.4)a | 3767 (42.9) | 4834 (45.7) |
| 3 | 235 (13.1) | 1557 (17.7)a | 1792 (16.9) |
| 4 | 6 (0.3) | 81 (0.9)c | 87 (0.8) |
| Not applicable | 7 (0.4) | 78 (0.9) | 85 (0.8) |
| Single modality intervention | |||
| Behavioral | 16 (0.9)a | 5 (0.1) | 21 (0.2) |
| Biologic | 127 (7.1) | 749 (8.5) | 876 (8.3) |
| Device | 9 (0.5) | 172 (2.0)a | 181 (1.7) |
| Drug | 873 (48.6) | 6802 (77.4)a | 7675 (72.5) |
| Radiotherapy | 23 (1.3)a | 11 (0.1) | 34 (0.3) |
| Surgery or other procedure | 11 (0.6)a | 5 (0.1) | 16 (0.2) |
| Other interventiond | 8 (0.4) | 65 (0.7) | 73 (0.7) |
| Multimodality intervention | |||
| D and B | 344 (19.1)a | 647 (7.4) | 991 (9.4) |
| D and/or B and device | 17 (0.9) | 73 (0.8) | 90 (0.9) |
| D and/or B and radiotherapy | 189 (10.5)a | 124 (1.4) | 313 (3.0) |
| D and/or B and surgery | 45 (2.5)a | 16 (0.2) | 61 (0.6) |
| D and/or B and transplant | 25 (1.4)a | 12 (0.1) | 37 (0.3) |
| D and/or B, surgery, and radiotherapy | 29 (1.6)a | 4 (0.0) | 33 (0.3) |
| D and/or B and other modalitye | 69 (3.8)a | 77 (0.9) | 146 (1.4) |
| Other combinations | 12 (0.7) | 29 (0.3) | 41 (0.4) |
| Dose escalation | 55 (3.1)a | 33 (0.4) | 88 (0.8) |
| Special populations | |||
| Rare cancers | 315 (17.5)a | 1068 (12.1) | 1383 (13.1) |
| Pediatric cancers | 290 (16.1)a | 467 (5.3) | 757 (7.1) |
Abbreviations: B, biologic; D, drug.
Statistically significantly greater at the P < .01 level.
Includes not applicable category.
Statistically significantly greater at the .01 ≤ P ≤ .05 level.
Includes dietary (1 industry trial) and transplant (1 federal and 1 industry trial).
Includes dietary (4 federal and 6 industry trials).
Interventional Trials
Federally sponsored interventional trials were less likely to be studies whose primary purpose was cancer treatment (85.1% vs 91.9%; OR, 0.50; 95% CI, 0.43-0.58; P < .001). In contrast, federal sponsorship was more likely to involve nontreatment interventional trials (Figure 1). Federally sponsored trials were more likely to be diagnostic trials (3.6% vs 2.1%; OR, 1.74; 95% CI, 1.31-2.29; P < .001), more likely to be health services research trials (1.2% vs 0.2%; OR, 7.63; 95% CI, 3.86-15.59; P < .001), more likely to be prevention trials (4.7% vs 1.1%; OR, 4.43; 95% CI, 3.32-5.92; P < .001), more likely to be screening studies (1.1% vs 0.5%; OR, 2.28; 95% CI, 1.32-3.85; P < .002), and more likely to be supportive care studies (2.5% vs 0.9%; OR, 2.92; 95% CI, 2.02-4.20; P < .001). There were no differences in federal vs industry sponsorship of basic science (0.7% vs 1.1%) or device feasibility (0.1% vs 0.2%) studies.
Figure 1. Bar Graph Showing the Proportion of Study Purpose by Sponsor Type for Nontreatment Interventional Trials.
OR indicates odds ratio.
Although relative differences between federal and industry sponsors were substantial for many trial categories, industry also conducts many such trials in absolute terms, given its larger portfolio (eTable 1 in Supplement 1). For example, although prevention trials represented 1.1% of industry trials and 4.7% of federal trials, the absolute numbers were similar (105 vs 99).
Treatment Trials
Among the 90.6% of all interventional trials that were conducted for the purpose of cancer treatment, the following results were found. Federal trials were less likely to be phase 1 trials (26.8% vs 37.6%; OR, 0.61; 95% CI, 0.54-0.68; P < .001) and phase 3 trials (13.1% vs 17.7%; OR, 0.70; 95% CI, 0.60-0.81; P < .001), but were more likely to be phase 2 trials (59.4% vs 42.9%; OR, 1.95; 95% CI, 1.76-2.16; P < .001) (Figure 2). With regard to trial complexity, single-agent drug trials were less common in the federal trial portfolio (48.6% vs 77.4%; OR, 0.28; 95% CI, 0.25-0.31; P < .001). In contrast, federal trials were more likely to emphasize other modalities, either alone or in combination with drug or biological agents or both. Federal trials were more likely to be single-modality radiotherapy trials (OR, 10.35; 95% CI, 5.04-21.27; P < .001) or surgery or other procedure trials (OR, 9.84; 95% CI, 3.69-26.25; P < .001) and were more likely to combine drug or biologic agents or both together (OR, 2.98; 95% CI, 2.58-3.44; P < .001) or in multimodality regimens that included radiotherapy (OR, 8.22; 95% CI, 6.51-10.37; P < .001), surgery (OR, 14.09; 95% CI, 7.95-24.98; P < .001), or transplant (OR, 10.32; 95% CI, 5.18-20.58; P < .001). Deescalation trials were more common in federally vs industry-sponsored trials (3.1% vs 0.4%; OR, 8.38; 95% CI, 5.43-12.94; P < .001). Rare cancer trials were more likely (17.5% vs 12.1%; OR, 1.54; 95% CI, 1.34-1.77; P < .001) and pediatric trials were more likely (16.1% vs 5.3%; OR, 3.43; 95% CI, 2.93-4.01; P < .001) to be conducted by federal sponsors (Figure 2).
Figure 2. Dot Plot of Federal vs Industry Sponsorship of Cancer Treatment Trials.
The vertical dotted line shows the line of equal odds.
Temporal Trends
As time periods increased from 2008-2012 to 2019-2024, nontreatment intervention studies of any kind (trend test, P = .03 for interaction), especially studies conducted for the purpose of basic science (P = .04 for interaction) and prevention (P = .04 for interaction), were increasingly more likely to be conducted by federally sponsored groups (eFigure 1, eTable 2 in Supplement 1). In contrast, trials conducted for the purpose of cancer treatment were increasingly more likely to be conducted by industry (P = .002 for interaction). Among trials whose primary purpose was cancer treatment, phase 3 trials (P = .03 for interaction), multimodality trials (P = .01 for interaction), and deescalation trials (P = .002 for interaction) were increasingly more likely to be conducted by federal sponsors. In contrast, single-agent drug trials (P = .01 for interaction), phase 1 trials (P = .009 for interaction), and trials for rare cancers (P = .02 for interaction) were increasingly more likely to be undertaken by industry. Federal sponsors consistently emphasized pediatric populations more than industry. In the most recent period (2019-2024), there was no statistically significant difference between federal and industry sponsors in the proportion of phase 3 trials (16.2% vs 17.9%; OR, 0.89, 95% CI, 0.69-1.14, P = .35).
Sensitivity Analyses
Across alternative sponsor classification strategies, the proportions and ORs remained largely consistent (eTable 3 in Supplement 1). Only 1 comparison changed statistical direction: biologic-only trials were more common among industry-led studies in the base-case analysis (8.5% vs 7.1%; P = .04) but more common with federal involvement as the primary or secondary sponsor in sensitivity analyses (7.9% vs 6.8%; P = .01).
Discussion
This study found that federally sponsored and industry-sponsored cancer clinical trials differed substantially in scope and purpose. Federally sponsored trials were more likely to investigate treatment deescalation approaches, nontreatment interventions, multimodality treatment strategies, and understudied populations, whereas industry-sponsored trials were more likely to focus on single-agent drug therapies. Many of these differences increased over time. These findings provide empirical insight into the distinct and complementary roles of federal and industry sponsors in conducting cancer clinical trials.
Consistent with prior analyses, industry sponsors were more likely to conduct phase 1 and phase 3 oncology trials, whereas federal sponsors were more likely to conduct phase 2 trials.20,21 These patterns likely reflect the differing roles of industry and federally funded research in clinical development, with industry playing a central role in first-in-human dose-finding phase 1 trials and regulatory approval, whereas federal sponsors have a broader role in early clinical development.22,23 One example is the NCI National Clinical Trials Network, which conducts basket, umbrella, and platform trials designed to efficiently evaluate promising therapies.24,25 More generally, prior work has linked NIH-funded basic and translational research to the development of many FDA-approved therapies, including all new molecular entities approved between 2010 and 2016.26
Federally sponsored trials were more likely to evaluate complex, multiagent, and multimodality treatment strategies. Examples that established standards of care include combined-modality therapy for Hodgkin lymphoma, breast-conserving surgery plus radiotherapy for early-stage breast cancer, and adjuvant chemotherapy for colorectal cancer.27,28,29,30 In recent trials such as TAILORx (Trial Assigning Individualized Options for Treatment [Rx]), RxPONDER (Rx for Positive Node, Endocrine Responsive Breast Cancer), and PROSPECT (Preoperative Radiation or Selective Preoperative Radiation and Evaluation before Chemotherapy and Total Mesorectal Excision), federally funded sponsors have used deescalation designs to show that selected patients can safely avoid chemotherapy or radiotherapy without compromising outcomes.31,32,33
Federal cooperative group networks may be particularly important in rare cancers, where limited patient populations often require national multicenter collaborations, as shown by the NCI-supported SWOG DART (Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors) trial in rare tumors.25,34,35,36,37 In pediatric oncology, NCI cooperative group pediatric oncology trials have contributed to marked improvements in outcomes for diseases such as acute lymphoblastic leukemia, sarcoma, and lymphoma.11,38,39,40,41 Notably, industry sponsorship of pediatric cancer trials has increased substantially and now accounts for more than twice the enrollment of pediatric patients compared with federal sponsors.14
Both research paradigms have contributed substantially to advances in cancer care. Population-level analyses estimate that NCI-sponsored research has contributed to 14.2 million life-years gained over 4 decades, informed clinical practice guidelines across multiple cancers, and generated extensive secondary and translational research.42,43,44,45 Likewise, industry investment has accelerated advances in precision oncology and immunotherapy, resulting in numerous treatments with demonstrated clinical benefit.46,47 For instance, population-level decreases in lung cancer mortality have been linked, in part, to the introduction of targeted therapies.48
The findings are consistent with a broader model in which federal and industry sponsors contribute complementary functions to the oncology research ecosystem (eFigure 2 in Supplement 1). In this framework, federally supported research contributes to basic science discovery, clinical trial infrastructure, and methodologic innovation. Industry, in turn, plays a central role in therapeutic development and regulatory approval while also providing biomarker platforms and access to investigational agents. The greater emphasis on multimodal treatment strategies, treatment deescalation, and research in rare and pediatric cancers among federally sponsored trials may represent downstream extensions of this research continuum. These activities are often linked through collaborative trial funding, public–private partnerships, and cooperative research mechanisms that may not be fully captured by trial registry–based sponsor classifications.49,50
Despite their complementary functions, federally sponsored trials now represent a small proportion of the national research portfolio. Between 2018 and 2022, compared with federal sponsorship, industry sponsorship accounted for 9 of 10 enrollments of adult patients with cancer.14 Because the number of patients willing to participate in clinical trials is limited, this imbalance raises concerns that research questions lacking commercial incentives may go unanswered.51,52 The adverse consequences may also extend to industry. Between 2015 and 2024, among US counties, those with NCI-funded trial sites were 9 times more likely also to host industry-sponsored trials, suggesting that federally supported clinical trial infrastructure serves as a platform for industry-sponsored research.53
Limitations
This study was limited by reliance on registry coding, which may misclassify trial characteristics. Additionally, the study did not fully account for multisponsor trials, potentially obscuring the role of collaborative partnerships. Last, this analysis focused on differences in trial portfolios at trial initiation rather than on downstream effects on clinical practice or patient outcomes, which have been examined in prior studies.7,42,44,45,46,47
Conclusions
The results from this comparative study of cancer clinical trial portfolios suggest the distinct functions of US federal and industry sponsors in the cancer clinical trial enterprise. Together, these sponsors contribute complementary strengths within an interdependent research ecosystem that translates public and private investment into tangible benefit for patients.
eTable 1. Number of trials by sponsor type
eTable 2. Proportions, odds ratios, 95% CI’s, and P values for selected domains of federal vs industry conduct of cancer studies by trial initiation time period
eTable 3. Sensitivity analyses using different sponsor type classifications
eFigure 1. Odds ratios of federal vs industry conduct of cancer studies by trial initiation time period
eFigure 2. Conceptual model of the relationship between federal and industry sponsorship of cancer clinical research
Data Sharing Statement
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eTable 1. Number of trials by sponsor type
eTable 2. Proportions, odds ratios, 95% CI’s, and P values for selected domains of federal vs industry conduct of cancer studies by trial initiation time period
eTable 3. Sensitivity analyses using different sponsor type classifications
eFigure 1. Odds ratios of federal vs industry conduct of cancer studies by trial initiation time period
eFigure 2. Conceptual model of the relationship between federal and industry sponsorship of cancer clinical research
Data Sharing Statement