Browsing by Subject "clinical trials"
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Item Open Access A Decade On: Systematic Review of ClinicalTrials.gov Infectious Disease Trials, 2007-2017.(Open forum infectious diseases, 2019-06) Jaffe, Ian S; Chiswell, Karen; Tsalik, Ephraim LBackground:Registration of interventional trials of Food and Drug Administration-regulated drug and biological products and devices became a legal requirement in 2007; the vast majority of these trials are registered in ClinicalTrials.gov. An analysis of ClinicalTrials.gov offers an opportunity to define the clinical research landscape; here we analyze 10 years of infectious disease (ID) clinical trial research. Methods:Beginning with 166 415 interventional trials registered in ClinicalTrials.gov from 2007-2017, ID trials were selected by study conditions and interventions. Relevance to ID was confirmed through manual review, resulting in 13 707 ID trials and 152 708 non-ID trials. Results:ID-related trials represented 6.9%-9.9% of all trials with no significant trend over time. ID trials tended to be more focused on treatment and prevention, with a focus on testing drugs, biologics, and vaccines. ID trials tended to be large, randomized, and nonblinded with a greater degree of international enrollment. Industry was the primary funding source for 45.2% of ID trials. Compared with the global burden of disease, human immunodeficiency virus/AIDS and hepatitis C trials were overrepresented, and lower respiratory tract infection trials were underrepresented. Hepatitis C trials fluctuated, keeping with a wave of new drug development. Influenza vaccine trials peaked during the 2009 H1N1 swine influenza outbreak. Conclusions:This study presents the most comprehensive characterization of ID clinical trials over the past decade. These results help define how clinical research aligns with clinical need. Temporal trends reflect changes in disease epidemiology and the impact of scientific discovery and market forces. Periodic review of ID clinical trials can help identify gaps and serve as a mechanism to realign resources.Item Open Access Acquisition, Analysis, and Sharing of Data in 2015 and Beyond: A Survey of the Landscape: A Conference Report From the American Heart Association Data Summit 2015.(J Am Heart Assoc, 2015-11-05) Antman, Elliott M; Benjamin, Emelia J; Harrington, Robert A; Houser, Steven R; Peterson, Eric D; Bauman, Mary Ann; Brown, Nancy; Bufalino, Vincent; Califf, Robert M; Creager, Mark A; Daugherty, Alan; Demets, David L; Dennis, Bernard P; Ebadollahi, Shahram; Jessup, Mariell; Lauer, Michael S; Lo, Bernard; MacRae, Calum A; McConnell, Michael V; McCray, Alexa T; Mello, Michelle M; Mueller, Eric; Newburger, Jane W; Okun, Sally; Packer, Milton; Philippakis, Anthony; Ping, Peipei; Prasoon, Prad; Roger, Véronique L; Singer, Steve; Temple, Robert; Turner, Melanie B; Vigilante, Kevin; Warner, John; Wayte, Patrick; American Heart Association Data Sharing Summit AttendeesBACKGROUND: A 1.5-day interactive forum was convened to discuss critical issues in the acquisition, analysis, and sharing of data in the field of cardiovascular and stroke science. The discussion will serve as the foundation for the American Heart Association's (AHA's) near-term and future strategies in the Big Data area. The concepts evolving from this forum may also inform other fields of medicine and science. METHODS AND RESULTS: A total of 47 participants representing stakeholders from 7 domains (patients, basic scientists, clinical investigators, population researchers, clinicians and healthcare system administrators, industry, and regulatory authorities) participated in the conference. Presentation topics included updates on data as viewed from conventional medical and nonmedical sources, building and using Big Data repositories, articulation of the goals of data sharing, and principles of responsible data sharing. Facilitated breakout sessions were conducted to examine what each of the 7 stakeholder domains wants from Big Data under ideal circumstances and the possible roles that the AHA might play in meeting their needs. Important areas that are high priorities for further study regarding Big Data include a description of the methodology of how to acquire and analyze findings, validation of the veracity of discoveries from such research, and integration into investigative and clinical care aspects of future cardiovascular and stroke medicine. Potential roles that the AHA might consider include facilitating a standards discussion (eg, tools, methodology, and appropriate data use), providing education (eg, healthcare providers, patients, investigators), and helping build an interoperable digital ecosystem in cardiovascular and stroke science. CONCLUSION: There was a consensus across stakeholder domains that Big Data holds great promise for revolutionizing the way cardiovascular and stroke research is conducted and clinical care is delivered; however, there is a clear need for the creation of a vision of how to use it to achieve the desired goals. Potential roles for the AHA center around facilitating a discussion of standards, providing education, and helping establish a cardiovascular digital ecosystem. This ecosystem should be interoperable and needs to interface with the rapidly growing digital object environment of the modern-day healthcare system.Item Open Access An innovative educational program for addressing health disparities in translational cancer research.(Journal of clinical and translational science, 2020-11) Oldham, Carla E; Gathings, MJ; Devi, Gayathri R; Patierno, Steven R; Williams, Kevin P; Hough, Holly J; Barrett, Nadine JNorth Carolina Central University (NCCU) and Duke Cancer Institute implemented an NCI-funded Translational Cancer Disparities Research Partnership to enhance translational cancer research, increase the pool of underrepresented racial and ethnic group (UREG) researchers in the translational and clinical research workforce, and equip UREG trainees with skills to increase diversity in clinical trials. The Cancer Research Education Program (C-REP) provided training for UREG graduate students and postdoctoral fellows at Duke and NCCU. An innovative component of C-REP is the Translational Immersion Experience (TIE), which enabled Scholars to gain knowledge across eight domains of clinical and translational research (clinical trials operations, data monitoring, regulatory affairs, UREG accrual, biobanking, community engagement, community outreach, and high-throughput drug screening). Program-specific evaluative metrics were created for three broad domains (clinical operations, basic science/lab research, and population-based science) and eight TIE domains. Two cohorts (n = 13) completed pre- and post-surveys to determine program impact and identify recommendations for program improvement. Scholars reported statistically significant gains in knowledge across three broad domains of biomedical research and seven distinct areas within TIE. Training in translational research incorporating immersions in clinical trials operation, biobanking, drug development, and community engagement adds value to career development of UREG researchers.Item Open Access Characteristics of pediatric pulmonary hypertension trials registered on ClinicalTrials.gov.(Pulm Circ, 2017-04) Awerbach, Jordan D; Krasuski, Richard A; Hill, Kevin DThe investigation of pediatric pulmonary hypertension (PH) drugs has been identified as a high priority by the United States National Institutes of Health (NIH). Studying pediatric PH is challenging due to the rare and heterogeneous nature of the disease. We sought to define the pediatric PH clinical trials landscape, to evaluate areas of trial success or failure, and to identify potential obstacles to the study of pediatric PH drugs. Interventional pediatric (ages 0-17 years) PH trials registered on ClinicalTrials.gov from June 2005 through December 2014 were analyzed. There were 45 pediatric PH trials registered during the study period. Median (IQR) projected trial enrollment was 40 (24-63), with seven trials (16%) targeting > 100 participants. Industry was the most common trial sponsor (n = 23, 50%), with only two (4.4%) NIH-sponsored trials. Phosphodiesterase inhibitors were the most frequently studied drug (n = 18, 39%). Single group study designs were used in 44% (n = 20) with an active comparator (parallel, factorial, or cross-over designs) in 25 trials, including 22 with randomization and ten that were double-blinded. Study outcomes varied markedly with inconsistent use of known surrogate and composite endpoints. One-third of trials (n = 15, 33%) were terminated, predominantly due to poor participant enrollment. Of the 17 completed trials, 11 had published results and only three efficacy trials met their primary endpoint. There are unique challenges to drug development in pediatric PH, including enrolling patients, identifying appropriate study endpoints, and conducting randomized, controlled, double-blind trials where the likelihood of meeting the study endpoint is optimized.Item Open Access Development and evaluation of a novel training program to build study staff skills in equitable and inclusive engagement, recruitment, and retention of clinical research participants.(Journal of clinical and translational science, 2022-01) Cranfill, Jessica R; Freel, Stephanie A; Deeter, Christine E; Snyder, Denise C; Naggie, Susanna; Barrett, Nadine J; Roberts, Jamie NBackground
Adequate equitable recruitment of underrepresented groups in clinical research and trials is a national problem and remains a daunting challenge to translating research discoveries into effective healthcare practices. Engagement, recruitment, and retention (ER&R) training programs for Clinical Research Professionals (CRPs) often focus on policies and regulations. Although some training on the importance of diversity and inclusion in clinical research participation has recently been developed, there remains a need for training that couples critical equity, diversity, and inclusion (EDI) concepts with skill development in effective recruitment and retention strategies, regulations, and best practices.Approach and methods
We developed the ER&R Certificate program as a holistic approach to provide Duke University CRPs the opportunity to build competency in gap areas and to increase comfort in championing equitable partnerships with clinical research participants. The thirteen core and elective courses include blended learning elements, such as e-learning and wiki journaling prompts, to facilitate meaningful discussions. Pre- and post-assessments administered to CRP program participants and their managers assessed program impact on CRP skills in ER&R tasks and comfort in equitable, diverse, and inclusive engagement of clinical research participants.Results and discussion
Results from the first two cohorts indicate that CRPs perceived growth in their own comfort with program learning objectives, especially those centered on participant partnership and EDI principles, and most managers witnessed growth in competence and responsibility for ER&R-related tasks. Results suggest value in offering CRPs robust training programs that integrate EDI and ER&R training.Item Open Access Factors influencing longitudinal changes of circulating liver enzyme concentrations in subjects randomized to placebo in four clinical trials.(American journal of physiology. Gastrointestinal and liver physiology, 2019-03) Nunez, Derek J; Alexander, Myriam; Yerges-Armstrong, Laura; Singh, Gurparkash; Byttebier, Geert; Fabbrini, Elisa; Waterworth, Dawn; Meininger, Gary; Galwey, Nicholas; Wallentin, Lars; White, Harvey D; Vannieuwenhuyse, Bart; Alazawi, William; Kendrick, Stuart; Sattar, Naveed; Ferrannini, EleLiver enzyme concentrations are measured as safety end points in clinical trials to detect drug-related hepatotoxicity, but little is known about the epidemiology of these biomarkers in subjects without hepatic dysfunction who are enrolled in drug trials. We studied alanine and aspartate aminotransferase (ALT and AST) in subjects randomized to placebo who completed assessments over 36 mo in a cardiovascular outcome trial [the Stabilisation of Atherosclerotic Plaque by Initiation of Darapladib Therapy ("STABILITY") trial; n = 4,264; mean age: 64.2 yr] or over 12 mo in three trials that enrolled only subjects with type 2 diabetes (T2D) [the DIA trials; n = 308; mean age: 62.4 yr] to investigate time-dependent relationships and the factors that might affect ALT and AST, including body mass index (BMI), T2D, and renal function. Multivariate linear mixed models examined time-dependent relationships between liver enzyme concentrations as response variables and BMI, baseline T2D status, hemoglobin A1c levels, and renal function, as explanatory variables. At baseline, ALT was higher in individuals who were men, <65 yr old, and obese and who had glomerular filtration rate (GFR) >60 ml·min-1·1.73 m-2. ALT was not significantly associated with T2D at baseline, although it was positively associated with HbA1c. GFR had a greater impact on ALT than T2D. ALT concentrations decreased over time in subjects who lost weight but remained stable in individuals with increasing BMI. Weight change did not alter AST concentrations. We provide new insights on the influence of time, GFR, and HbA1c on ALT and AST concentrations and confirm the effect of sex, age, T2D, BMI, and BMI change in subjects receiving placebo in clinical trials. NEW & NOTEWORTHY Clinical trials provide high-quality data on liver enzyme concentrations from subjects randomized to placebo that can be used to investigate the epidemiology of these biomarkers. The adjusted models show the influence of sex, age, time, renal function, type 2 diabetes, HbA1c, and body mass index on alanine aminotransferase and aspartate aminotransferase concentrations and their relative importance. These factors need to be considered when assessing potential signals of hepatotoxicity in trials of new drugs and in clinical trials investigating subjects with nonalcoholic fatty liver disease.Item Open Access Interfaces between Bayesian and Frequentist Multiplte Testing(2015) Chang, Shih-HanThis thesis investigates frequentist properties of Bayesian multiple testing procedures in a variety of scenarios and depicts the asymptotic behaviors of Bayesian methods. Both Bayesian and frequentist approaches to multiplicity control are studied and compared, with special focus on understanding the multiplicity control behavior in situations of dependence between test statistics.
Chapter 2 examines a problem of testing mutually exclusive hypotheses with dependent data. The Bayesian approach is shown to have excellent frequentist properties and is argued to be the most effective way of obtaining frequentist multiplicity control without sacrificing power. Chapter 3 further generalizes the model such that multiple signals are acceptable, and depicts the asymptotic behavior of false positives rates and the expected number of false positives. Chapter 4 considers the problem of dealing with a sequence of different trials concerning some medical or scientific issue, and discusses the possibilities for multiplicity control of the sequence. Chapter 5 addresses issues and efforts in reconciling frequentist and Bayesian approaches in sequential endpoint testing. We consider the conditional frequentist approach in sequential endpoint testing and show several examples in which Bayesian and frequentist methodologies cannot be made to match.
Item Open Access NRG Oncology Survey on Practice and Technology Use in SRT and SBRT Delivery.(Frontiers in oncology, 2020-01) Chetvertkov, Mikhail; Monroe, James Ira; Boparai, Jaskaran; Solberg, Timothy D; Pafundi, Deanna H; Ruo, Russell L; Gladstone, David J; Yin, Fang-Fang; Chetty, Indrin J; Benedict, Stanley; Followill, David S; Xiao, Ying; Sohn, Jason WPurpose
To assess stereotactic radiotherapy (SRT)/stereotactic body radiotherapy (SBRT) practices by polling clinics participating in multi-institutional clinical trials.Methods
The NRG Oncology Medical Physics Subcommittee distributed a survey consisting of 23 questions, which covered general technologies, policies, and procedures used in the Radiation Oncology field for the delivery of SRT/SBRT (9 questions), and site-specific questions for brain SRT, lung SBRT, and prostate SBRT (14 questions). Surveys were distributed to 1,996 radiotherapy institutions included on the membership rosters of the five National Clinical Trials Network (NCTN) groups. Patient setup, motion management, target localization, prescriptions, and treatment delivery technique data were reported back by 568 institutions (28%).Results
97.5% of respondents treat lung SBRT patients, 77.0% perform brain SRT, and 29.1% deliver prostate SBRT. 48.8% of clinics require a physicist present for every fraction of SBRT, 18.5% require a physicist present for the initial SBRT fraction only, and 14.9% require a physicist present for the entire first fraction, including set-up approval for all subsequent fractions. 55.3% require physician approval for all fractions, and 86.7% do not reposition without x-ray imaging. For brain SRT, most institutions (83.9%) use a planning target volume (PTV) margin of 2 mm or less. Lung SBRT PTV margins of 3 mm or more are used in 80.6% of clinics. Volumetric modulated arc therapy (VMAT) is the dominant delivery method in 62.8% of SRT treatments, 70.9% of lung SBRT, and 68.3% of prostate SBRT.Conclusion
This report characterizes SRT/SBRT practices in radiotherapy clinics participating in clinical trials. Data made available here allows the radiotherapy community to compare their practice with that of other clinics, determine what is achievable, and assess areas for improvement.Item Open Access Sibling umbilical cord blood infusion is safe in young children with cerebral palsy.(Stem cells translational medicine, 2021-09) Sun, Jessica M; Case, Laura E; Mikati, Mohamad A; M Jasien, Joan; McLaughlin, Colleen; Waters-Pick, Barbara; Worley, Gordon; Troy, Jesse; Kurtzberg, JoannePreclinical and early phase clinical studies suggest that an appropriately dosed umbilical cord blood (CB) infusion has the potential to help improve motor function in young children with cerebral palsy (CP). As many children with CP do not have their own CB available, use of allogeneic cells would extend access to this potentially beneficial therapy to more children. In this phase I, open-label study, 15 children, aged 1 to 6 years, with moderate to severe spastic CP were treated with a single intravenous infusion of allogeneic human leukocyte antigen (HLA) matched or partially matched sibling CB with a cell dose of ≥2.5 × 107 cells/kg based on the pre-cryopreservation count (median infused cell dose, 3.3 × 107 ; range, 1.8-5.2 × 107 ). There were a total of 49 adverse events (AEs) over a 2-year time period, but there were no AEs related to the CB infusions. Specifically, there were no acute infusion reactions and no antibody formation against platelets, red blood cells, or donor-specific HLA antigens. Donor cells were not detected in peripheral blood 6 months later. Six months after infusion, participants were assessed for response and experienced a mean ± SD increase of 4.7 ± 2.5 points on the Gross Motor Function Measure-66 and 1 ± 2.9 points on the Peabody Gross Motor Quotient. Appropriately dosed, allogeneic partially or fully HLA-matched sibling CB infusion is well tolerated and potentially beneficial in young children with CP.Item Open Access The Challenge of Community Representation.(J Empir Res Hum Res Ethics, 2016-10) Lawrence, Carlton; Stewart, KearsleyAlthough community advisory boards (CABs) are widely used in clinical research, there is limited data regarding their composition and structure, especially in Africa. Our research provides the first qualitative study of the membership practices, selection methods, and qualifications of the six major HIV research centers that comprise the Ugandan National CAB Network (UNCN). Researchers conducted interviews ( n = 45) with CAB members and research liaisons at each of the sites. While selection practices and demographics varied between the sites, all six CABs exclusively followed a broad community membership model. Results suggest successful CABs are context dependent and thus distinct guidelines may be needed based on variables including CAB funding level, representation model, and research focus.