Enhancing Adolescent and Young Adult Oncology Research Within the National Clinical Trials Network: Rationale, Progress, and Emerging Strategies.
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PROVIDER: S-EPMC4604069 | BioStudies |
REPOSITORIES: biostudies
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Project description:Over the past 30 years, adolescents and young adults (AYA, 15-39 years of age) with cancer have shown significantly less improvement in survival than younger and older patients. Because evidence suggests this may be related to their low participation in cancer clinical trials, increasing accrual to these trials has become a priority for closing this "AYA gap." This paper reviews data documenting low AYA enrollment, presents a conceptual framework for research and intervention (Clinical Trials Pathway to Enrollment) and summarizes recent developments in the United States National Cancer Institute-sponsored clinical trials enterprise that are expected to improve AYA enrollment, including the National Clinical Trials Network (NCTN) and expanded scientific collaboration between the Children's Oncology Group and adult NCTN groups. While time will be required for the effects of these changes to be fully realized, they offer a mechanism for facilitating the breadth of clinical/translational research needed for advancing AYA oncology and measuring its impact.
| S-EPMC6319956 | BioStudies
Project description:The extent to which trial-level factors differentially influence accrual to trials has not been comprehensively studied. Our objective was to evaluate the empirical relationship and predictive properties of putative risk factors for low accrual in the National Cancer Institute's (NCI's) Cooperative Group Program, now the National Clinical Trials Network (NCTN). Data from 787 phase II/III adult NCTN-sponsored trials launched between 2000 and 2011 were used to develop a logistic regression model to predict low accrual, defined as trials that closed with or were accruing at less than 50% of target; 46 trials opened between 2012 and 2013 were used for prospective validation. Candidate predictors were identified from a literature review and expert interviews; final predictors were selected using stepwise regression. Model performance was evaluated by calibration and discrimination via the area under the curve (AUC). All statistical tests were two-sided. Eighteen percent (n = 145) of NCTN-sponsored trials closed with low accrual or were accruing at less than 50% of target three years or more after initiation. A multivariable model of twelve trial-level risk factors had good calibration and discrimination for predicting trials with low accrual (AUC in trials launched 2000-2011 = 0.739, 95% confidence interval [CI] = 0.696 to 0.783]; 2012-2013: AUC = 0.732, 95% CI = 0.547 to 0.917). Results were robust to different definitions of low accrual and predictor selection strategies. We identified multiple characteristics of NCTN-sponsored trials associated with low accrual, several of which have not been previously empirically described, and developed a prediction model that can provide a useful estimate of accrual risk based on these factors. Future work should assess the role of such prediction tools in trial design and prioritization decisions.
| S-EPMC5964887 | BioStudies
Project description:Importance:National Cancer Institute Clinical Trial Network (NCTN) groups serve a vital role in identifying effective new antineoplastic regimens. However, the downstream clinical effect of their trials has not been systematically examined. Objective:To examine the association of NCTN trials with guideline care and new drug indications. Design, Setting, and Participants:This retrospective cohort study evaluated phase 3 SWOG Cancer Research Network clinical trials from January 1, 1980, through June 30, 2017. Only completed trials with published results were included. To be considered practice influential (PI), a trial must have been associated with guideline care through its inclusion in National Comprehensive Cancer Network (NCCN) clinical guidelines or US Food and Drug Administration (FDA) new drug approvals in favor of a recommended treatment. Data were analyzed from June 15, 2018, through March 29, 2019. Main Outcomes and Measures:Estimated overall rate of PI trials, as well as trends over time. The total federal investment supporting the set of trials was also determined. Results:In total, 182 trials consisting of 148 028 patients were studied. Eighty-two studies (45.1%; 95% CI, 37.7%-52.6%) were PI, of which 70 (38.5%) influenced NCCN guidelines, 6 (3.3%) influenced FDA new drug approvals, and 6 (3.3%) influenced both. The number of PI trials was 47 of 65 (72.3%) among those with positive findings and 35 of 117 (29.9%) among those with negative findings. Thus, 35 of 82 PI trials (42.7%) were based on studies with negative findings, with nearly half of these studies (17 of 35 [48.6%]) reaffirming standard of care compared with experimental therapy. The total federal investment spent in conducting the trials was $1.36 billion (2017 US dollars), a rate of $7.5 million per study or $16.6 million per PI trial. Conclusions and Relevance:Nearly half of all phase 3 trials by one of the NCTN's largest groups were associated with guideline care or new drug indications, including those with positive and negative findings. Compared with the costs of a new drug approval in pharmaceutical companies, typically estimated at more than $1 billion, the amount of federal funds invested to provide this valuable evidence was modest. These results suggest that the NCTN program contributes clinically meaningful, cost-efficient evidence to guide patient care.
2019-01-01 | S-EPMC6727679 | BioStudies
Project description:Progress toward improvement in cancer therapy relies on clinical trials. Yet, only a minority of eligible patients with cancer enroll as a result of multiple barriers at the patient, investigator, center, and national level. However, the rise of the Internet and mobile technology has created a slew of tools with medical applications, from Web sites to apps to social media platforms, all of which may aide clinicians in our quest to improve the clinical research enterprise. SWOG is one of five members in the National Cancer Institute's National Clinical Trials Network-the nation's oldest and largest publicly funded cancer research network-and is taking a leadership role in exploring and testing the promise of digital engagement through the empaneling of the Digital Engagement Committee. This article outlines the mission, principles, and priorities of the Digital Engagement Committee and proposes how this work may inform the use of digital tools for the cancer research community and, hopefully, translate to improved outcomes for our patients.
| S-EPMC6668704 | BioStudies
Project description:The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from NCI, FDA, National Clinical Trials Network (NCTN), advocacy and the pharmaceutical and biotech industry. The meeting goals and objectives were to: 1) create a collaborative environment in which the greater bladder research community can pursue future optimally designed novel clinical trials focused on the theme of molecular targeted and immune-based therapies in NMIBC; 2) frame the clinical and translational questions that are of highest priority; and 3) develop two clinical trial designs focusing on immunotherapy and molecular targeted therapy. Despite successful development and implementation of large Phase II and Phase III trials in bladder and upper urinary tract cancers, there are no active and accruing trials in the NMIBC space within the NCTN. Disappointingly, there has been only one new FDA approved drug (Valrubicin) in any bladder cancer disease state since 1998. Although genomic-based data for bladder cancer are increasingly available, translating these discoveries into practice changing treatment is still to come. Recently, major efforts in defining the genomic characteristics of NMIBC have been achieved. Aligned with these data is the growing number of targeted therapy agents approved and/or in development in other organ site cancers and the multiple similarities of bladder cancer with molecular subtypes in these other cancers. Additionally, although bladder cancer is one of the more immunogenic tumors, some tumors have the ability to attenuate or eliminate host immune responses. Two trial concepts emerged from the meeting including a window of opportunity trial (Phase 0) testing an FGFR3 inhibitor and a second multi-arm multi-stage trial testing combinations of BCG or radiotherapy and immunomodulatory agents in patients who recur after induction BCG (BCG failure).
| S-EPMC4927845 | BioStudies
Project description:In 2009, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Pediatric Terminology Harmonization Initiative to establish a core library of terms to facilitate the acquisition and sharing of knowledge between pediatric clinical research, practice, and safety reporting. A coalition of partners established a Pediatric Terminology Adverse Event Working Group in 2013 to develop a specific terminology relevant to international pediatric adverse event (AE) reporting. Pediatric specialists with backgrounds in clinical care, research, safety reporting, or informatics, supported by biomedical terminology experts from the National Cancer Institute's Enterprise Vocabulary Services participated. The multinational group developed a working definition of AEs and reviewed concepts (terms, synonyms, and definitions) from 16 pediatric clinical domains. The resulting AE terminology contains >1000 pediatric diseases, disorders, or clinical findings. The terms were tested for proof of concept use in 2 different settings: hospital readmissions and the NICU. The advantages of the AE terminology include ease of adoption due to integration with well-established and internationally accepted biomedical terminologies, a uniquely temporal focus on pediatric health and disease from conception through adolescence, and terms that could be used in both well- and underresourced environments. The AE terminology is available for use without restriction through the National Cancer Institute's Enterprise Vocabulary Services and is fully compatible with, and represented in, the Medical Dictionary for Regulatory Activities. The terminology is intended to mature with use, user feedback, and optimization.
| S-EPMC5292241 | BioStudies
Project description:Cluster randomized trials randomly assign groups of individuals to examine research questions or test interventions and measure their effects on individuals. Recent emphasis on quality improvement, comparative effectiveness, and learning health systems has prompted expanded use of pragmatic cluster randomized trials in routine health-care settings, which in turn poses practical and ethical challenges that current oversight frameworks may not adequately address. The 2012 Ottawa Statement provides a basis for considering many issues related to pragmatic cluster randomized trials but challenges remain, including some arising from the current US research and health-care regulations. In order to examine the ethical, regulatory, and practical questions facing pragmatic cluster randomized trials in health-care settings, the National Institutes of Health Health Care Systems Research Collaboratory convened a workshop in Bethesda, Maryland, in July 2013. Attendees included experts in clinical trials, patient advocacy, research ethics, and research regulations from academia, industry, the National Institutes of Health Collaboratory, and other federal agencies. Workshop participants identified substantial barriers to implementing these types of cluster randomized trials, including issues related to research design, gatekeepers and governance in health systems, consent, institutional review boards, data monitoring, privacy, and special populations. We describe these barriers and suggest means for understanding and overcoming them to facilitate pragmatic cluster randomized trials in health-care settings.
| S-EPMC4498459 | BioStudies
Project description:For the past two decades, the National Cancer Institute (NCI) has supported the involvement of patient advocates in both internal advisory activities and funded research projects to provide a patient perspective. Implementation of the inclusion of patient advocates has varied considerably, with inconsistent involvement of patient advocates in key phases of research such as concept development. Despite this, there is agreement that patient advocates have improved the patient focus of many cancer research studies. This commentary describes our experience designing and pilot testing a new framework for patient engagement at SWOG, one of the largest cancer clinical trial network groups in the United States and one of the four adult groups in the NCI's National Clinical Trials Network (NCTN). Our goal is to provide a roadmap for other clinical trial groups that are interested in bringing the patient voice more directly into clinical trial conception and development. We developed a structured process to engage patient advocates more effectively in the development of cancer clinical trials and piloted the process in four SWOG research committees, including implementation of a new Patient Advocate Executive Review Form that systematically captures patient advocates' input at the concept stage. Based on the positive feedback to our approach, we are now developing training and evaluation metrics to support meaningful and consistent patient engagement across the SWOG clinical trial life cycle. Ultimately, the benefits of more patient-centered cancer trials will be measured in the usefulness, relevance, and speed of study results to patients, caregivers, and clinicians.
| S-EPMC6005117 | BioStudies
Project description:Rare cancers account for 27% of neoplasms diagnosed each year, and 25% of cancer-related deaths in the United States. However, rare cancers show some of the highest response rates to targeted therapies, probably due to identification of oncogenic drivers with little interpatient variability. Although the low incidence of rare cancers makes large-scale randomized trials involving single histologies difficult to perform, drugs have been successfully developed in rare cancers using clinical trial designs that combine microscopic histologies. Such trials are being pursued within the National Clinical Trials Network (NCTN), which possesses unique qualifications to perform widespread molecular screening of tumors for patient enrollment onto therapeutic clinical trials. When larger clinical trials are needed to determine optimum treatment strategies in rare cancers, the NCTN's broad reach in North America and internationally, and their ability to partner with both United States-based and international research organizations, can make these challenging studies feasible.
2015-01-01 | S-EPMC4673983 | BioStudies
Project description:<h4>Background</h4>The US faces remarkable food and nutrition challenges. A new federal effort to strengthen and coordinate nutrition research could rapidly generate the evidence base needed to address these multiple national challenges. However, the relevant characteristics of such an effort have been uncertain.<h4>Objectives</h4>Our aim was to provide an objective, informative summary of 1) the mounting diet-related health burdens facing our nation and corresponding economic, health equity, national security, and sustainability implications; 2) the current federal nutrition research landscape and existing mechanisms for its coordination; 3) the opportunities for and potential impact of new fundamental, clinical, public health, food and agricultural, and translational scientific discoveries; and 4) the various options for further strengthening and coordinating federal nutrition research, including corresponding advantages, disadvantages, and potential executive and legislative considerations.<h4>Methods</h4>We reviewed government and other published documents on federal nutrition research; held various discussions with expert groups, advocacy organizations, and scientific societies; and held in-person or phone meetings with >50 federal staff in executive and legislative roles, as well as with a variety of other stakeholders in academic, industry, and nongovernment organizations.<h4>Results</h4>Stark national nutrition challenges were identified. More Americans are sick than are healthy, largely from rising diet-related illnesses. These conditions create tremendous strains on productivity, health care costs, health disparities, government budgets, US economic competitiveness, and military readiness. The coronavirus disease 2019 (COVID-19) outbreak has further laid bare these strains, including food insecurity, major diet-related comorbidities for poor outcomes from COVID-19 such as diabetes, hypertension, and obesity, and insufficient surveillance on and coordination of our food system. More than 10 federal departments and agencies currently invest in critical nutrition research, yet with relatively flat investments over several decades. Coordination also remains suboptimal, documented by multiple governmental reports over 50 years. Greater harmonization and expansion of federal investment in nutrition science, not a silo-ing or rearrangement of existing investments, has tremendous potential to generate new discoveries to improve and sustain the health of all Americans. Two identified key strategies to achieve this were as follows: 1) a new authority for robust cross-governmental coordination of nutrition research and other nutrition-related policy and 2) strengthened authority, investment, and coordination for nutrition research within the NIH. These strategies were found to be complementary, together catalyzing important new science, partnerships, coordination, and returns on investment. Additional complementary actions to accelerate federal nutrition research were identified at the USDA.<h4>Conclusions</h4>The need and opportunities for strengthened federal nutrition research are clear, with specific identified options to help create the new leadership, strategic planning, coordination, and investment the nation requires to address the multiple nutrition-related challenges and grasp the opportunities before us.
| S-EPMC7454258 | BioStudies