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Assessing the current utilization status of wearable devices in clinical research Clin. Trials (IF 2.7) Pub Date : 2024-03-15 Takashi Miyakoshi, Yoichi M Ito
Background/AimsInformation regarding the use of wearable devices in clinical research, including disease areas, intervention techniques, trends in device types, and sample size targets, remains elusive. Therefore, we conducted a comprehensive review of clinical research trends related to wristband wearable devices in research planning and examined their applications in clinical investigations.MethodsAs
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A safety estimand for late phase clinical trials where the analysis period varies over the subjects Clin. Trials (IF 2.7) Pub Date : 2024-03-01 Katarina Hedman, Vera Lisovskaja, Per Nyström
Background/AimsEvaluating safety is as important as evaluating efficacy in a clinical trial, yet the tradition for safety analysis is rudimentary. This article explores more complex methodologies for safety evaluation, with the aim of improving the interpretability, as well as generalizability, of the results.MethodsFor studies where the analysis periods vary over the subjects, using the International
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Assessing the impact of risk-based data monitoring on outcomes for a paediatric multicentre randomised controlled trial Clin. Trials (IF 2.7) Pub Date : 2024-02-29 Renate Le Marsney, Kerry Johnson, Jenipher Chumbes Flores, Shelley Coetzer, Jennifer Darvas, Carmel Delzoppo, Arielle Jolly, Kate Masterson, Claire Sherring, Hannah Thomson, Endrias Ergetu, Patricia Gilholm, Kristen S Gibbons
Background/AimsRegulatory guidelines recommend that sponsors develop a risk-based approach to monitoring clinical trials. However, there is a lack of evidence to guide the effective implementation of monitoring activities encompassed in this approach. The aim of this study was to assess the efficiency and impact of the risk-based monitoring approach used for a multicentre randomised controlled trial
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Public involvement in Australian clinical trials: A systematic review Clin. Trials (IF 2.7) Pub Date : 2024-02-27 Tessa-May Zirnsak, Ashley H Ng, Catherine Brasier, Richard Gray
BackgroundPublic involvement enhances the relevance, quality, and impact of research. There is some evidence that public involvement in Australian research lags other countries, such as the United Kingdom. The purpose of the systematic review was to establish the rates and describe the characteristics of public involvement in Australian clinical trials.MethodsWe reviewed evidence of public involvement
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The patient perspective on dose optimization for anticancer treatments: A new era of cancer drug dosing—Challenging the “more is better” dogma Clin. Trials (IF 2.7) Pub Date : 2024-02-22 Julia Maués, Anne Loeser, Janice Cowden, Sheila Johnson, Martha Carlson, Shing Lee
The Patient-Centered Dosing Initiative, a patient-led effort advocating for a paradigm shift in determining cancer drug dosing strategies, pioneers a departure from traditional oncology drug dosing practices. Historically, oncology drug dosing relies on identifying the maximum tolerated dose through phase 1 dose escalation methodology, favoring higher dosing for greater efficacy, often leading to higher
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Rethinking the clinical research protocol: Lessons learned from the COVID-19 pandemic and recommendations for reducing noncompliance Clin. Trials (IF 2.7) Pub Date : 2024-02-17 Matthew J Gooden, Gina Norato, Katherine Landry, Sandra B Martin, Avindra Nath, Lauren Reoma
Background/AimsSince the onset of the coronavirus disease 2019 (COVID-19) pandemic, 103.4 million cases and 1.1 million deaths have occurred nationally as of November 2023. Despite the benefit of mitigating measures, the pandemic’s effect on participant safety is rarely documented.MethodsThis study assessed noncompliance occurring from July 2019 to August 2021 that were stratified by the date of noncompliance
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Patient-reported measures of tinnitus for individuals with neurofibromatosis type 2–related schwannomatosis: Recommendations for clinical trials Clin. Trials (IF 2.7) Pub Date : 2024-02-07 Heather L Thompson, Jane Grabowski, Barbara Franklin, Kimberley S Koetsier, D Bradley Welling
BackgroundNeurofibromatosis type 2–related schwannomatosis is a genetic disease characterized by the development of bilateral vestibular schwannomas, ependymomas, meningiomas, and cataracts. Mild to profound hearing loss and tinnitus are common symptoms reported by individuals with neurofibromatosis type 2. While tinnitus is known to have a significant and negative impact on the quality of life of
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New strategies for confirmatory testing of secondary hypotheses on combined data from multiple trials Clin. Trials (IF 2.7) Pub Date : 2024-02-05 Marc Vandemeulebroecke, Dieter A Häring, Eva Hua, Xiaoling Wei, Dong Xi
Background:Pivotal evidence of efficacy of a new drug is typically generated by (at least) two clinical trials which independently provide statistically significant and mutually corroborating evidence of efficacy based on a primary endpoint. In this situation, showing drug effects on clinically important secondary objectives can be demanding in terms of sample size requirements. Statistically efficient
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Is inadequate risk stratification diluting hazard ratio estimates in randomized clinical trials? Clin. Trials (IF 2.7) Pub Date : 2024-02-02 Devan V Mehrotra, Rachel Marceau West
In randomized clinical trials, analyses of time-to-event data without risk stratification, or with stratification based on pre-selected factors revealed at the end of the trial to be at most weakly associated with risk, are quite common. We caution that such analyses are likely delivering hazard ratio estimates that unwittingly dilute the evidence of benefit for the test relative to the control treatment
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The use of linked administrative data in Australian randomised controlled trials: A scoping review Clin. Trials (IF 2.7) Pub Date : 2024-02-02 Salma Fahridin, Neeru Agarwal, Karen Bracken, Stephen Law, Rachael L Morton
Background/Aims:The demand for simplified data collection within trials to increase efficiency and reduce costs has led to broader interest in repurposing routinely collected administrative data for use in clinical trials research. The aim of this scoping review is to describe how and why administrative data have been used in Australian randomised controlled trial conduct and analyses, specifically
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Research encouraging off-label use of quetiapine: A systematic meta-epidemiological analysis Clin. Trials (IF 2.7) Pub Date : 2024-01-29 Peter Grabitz, Lana Saksone, Susanne Gabriele Schorr, Johannes Schwietering, Merlin Bittlinger, Jonathan Kimmelman
Background:Researchers often conduct small studies on testing a drug’s efficacy in off-label indications. If positive results from these exploratory studies are not followed up by larger, randomized, double-blinded trials, physicians cannot be sure of a drug’s clinical value. This may lead to off-label prescriptions of ineffective treatments. We aim to describe the way clinical studies fostered off-label
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The symbolic two-step method applied to cancer care delivery research: Safeguarding against designing an underpowered cluster randomized trial with a continuous outcome by accounting for the imprecision in the within- and between-center variation Clin. Trials (IF 2.7) Pub Date : 2024-01-20 David Zahrieh, Blaize W Kandler, Jennifer Le-Rademacher
Background:Knowing the predictive factors of the variation in a center-level continuous outcome of interest is valuable in the design and analysis of parallel-arm cluster randomized trials. The symbolic two-step method for sample size planning that we present incorporates this knowledge while simultaneously accounting for patient-level characteristics. Our approach is illustrated through application
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Statistical and practical considerations in planning and conduct of dose-optimization trials Clin. Trials (IF 2.7) Pub Date : 2024-01-20 Ying Yuan, Heng Zhou, Suyu Liu
The U.S. Food and Drug Administration launched Project Optimus with the aim of shifting the paradigm of dose-finding and selection toward identifying the optimal biological dose that offers the best balance between benefit and risk, rather than the maximum tolerated dose. However, achieving dose optimization is a challenging task that involves a variety of factors and is considerably more complicated
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Adaptive Bayesian information borrowing methods for finding and optimizing subgroup-specific doses Clin. Trials (IF 2.7) Pub Date : 2024-01-20 Jingyi Zhang, Ruitao Lin, Xin Chen, Fangrong Yan
In precision oncology, integrating multiple cancer patient subgroups into a single master protocol allows for the simultaneous assessment of treatment effects in these subgroups and promotes the sharing of information between them, ultimately reducing sample sizes and costs and enhancing scientific validity. However, the safety and efficacy of these therapies may vary across different subgroups, resulting
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A Bayesian adaptive design approach for stepped-wedge cluster randomized trials Clin. Trials (IF 2.7) Pub Date : 2024-01-19 Jijia Wang, Jing Cao, Chul Ahn, Song Zhang
Background:The Bayesian group sequential design has been applied widely in clinical studies, especially in Phase II and III studies. It allows early termination based on accumulating interim data. However, to date, there lacks development in its application to stepped-wedge cluster randomized trials, which are gaining popularity in pragmatic trials conducted by clinical and health care delivery researchers
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Adaptive phase I–II clinical trial designs identifying optimal biological doses for targeted agents and immunotherapies Clin. Trials (IF 2.7) Pub Date : 2024-01-11 Yong Zang, Beibei Guo, Yingjie Qiu, Hao Liu, Mateusz Opyrchal, Xiongbin Lu
Targeted agents and immunotherapies have revolutionized cancer treatment, offering promising options for various cancer types. Unlike traditional therapies the principle of “more is better” is not always applicable to these new therapies due to their unique biomedical mechanisms. As a result, various phase I–II clinical trial designs have been proposed to identify the optimal biological dose that maximizes
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Hierarchical Bayesian modeling of heterogeneous outcome variance in cluster randomized trials Clin. Trials (IF 2.7) Pub Date : 2024-01-10 Guangyu Tong, Jiaqi Tong, Yi Jiang, Denise Esserman, Michael O Harhay, Joshua L Warren
Background:Heterogeneous outcome correlations across treatment arms and clusters have been increasingly acknowledged in cluster randomized trials with binary endpoints, where analytical methods have been developed to study such heterogeneity. However, cluster-specific outcome variances and correlations have yet to be studied for cluster randomized trials with continuous outcomes.Methods:This article
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Adherence to key recommendations for design and analysis of stepped-wedge cluster randomized trials: A review of trials published 2016-2022. Clin. Trials (IF 2.7) Pub Date : 2023-11-21 Pascale Nevins,Mary Ryan,Kendra Davis-Plourde,Yongdong Ouyang,Jules Antoine Pereira Macedo,Can Meng,Guangyu Tong,Xueqi Wang,Luis Ortiz-Reyes,Agnès Caille,Fan Li,Monica Taljaard
BACKGROUND/AIMS The stepped-wedge cluster randomized trial (SW-CRT), in which clusters are randomized to a time at which they will transition to the intervention condition - rather than a trial arm - is a relatively new design. SW-CRTs have additional design and analytical considerations compared to conventional parallel arm trials. To inform future methodological development, including guidance for
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Evaluating whether the proportional odds models to analyse ordinal outcomes in COVID-19 clinical trials is providing clinically interpretable treatment effects: A systematic review. Clin. Trials (IF 2.7) Pub Date : 2023-11-20 Masuma Uddin,Nasir Z Bashir,Brennan C Kahan
BACKGROUND After an initial recommendation from the World Health Organisation, trials of patients hospitalised with COVID-19 often include an ordinal clinical status outcome, which comprises a series of ordered categorical variables, typically ranging from 'Alive and discharged from hospital' to 'Dead'. These ordinal outcomes are often analysed using a proportional odds model, which provides a common
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Perspectives of adults with neurofibromatosis regarding the design of psychosocial trials: Results from an anonymous online survey. Clin. Trials (IF 2.7) Pub Date : 2023-11-14 Pamela L Wolters,Nour Al Ghriwati,Melissa Baker,Staci Martin,Dale Berg,Gregg Erickson,Barbara Franklin,Vanessa L Merker,Beverly Oberlander,Stephanie Reeve,Claas Rohl,Tena Rosser,Ana-Maria Vranceanu
BACKGROUND/AIMS Individuals with neurofibromatosis, including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2)-related schwannomatosis (SWN), and other forms of SWN, often experience disease manifestations and mental health difficulties for which psychosocial interventions may help. An anonymous online survey of adults with neurofibromatosis assessed their physical, social, and emotional well-being
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Leveraging the functionality of Research Electronic Data Capture (REDCap) to enhance data collection and quality in the Opioid Analgesic Reduction Study. Clin. Trials (IF 2.7) Pub Date : 2023-11-14 Janine Fredericks-Younger,Patricia Greenberg,Tracy Andrews,Pamela B Matheson,Paul J Desjardins,Shou-En Lu,Cecile A Feldman
BACKGROUND The Opioid Analgesic Reduction Study is a double-blind, prospective, clinical trial investigating analgesic effectiveness in the management of acute post-surgical pain after impacted third molar extraction across five clinical sites. Specifically, Opioid Analgesic Reduction Study examines a commonly prescribed opioid combination (hydrocodone/acetaminophen) against a non-opioid combination
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Determining a risk-proportionate approach to the validation of statistical programming for clinical trials. Clin. Trials (IF 2.7) Pub Date : 2023-11-13 Carrol Gamble,Steff Lewis,Deborah Stocken,Edmund Juszczak,Mike Bradburn,Caroline Doré,Sharon Kean
BACKGROUND The contribution of the statistician to the design and analysis of a clinical trial is acknowledged as essential. Ability to reconstruct the statistical contribution to a trial requires rigorous and transparent documentation as evidenced by the reproducibility of results. The process of validating statistical programmes is a key requirement. While guidance relating to software development
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Gene-targeted therapy for neurofibromatosis and schwannomatosis: The path to clinical trials. Clin. Trials (IF 2.7) Pub Date : 2023-11-08 Verena Staedtke,Kara Anstett,David Bedwell,Marco Giovannini,Kim Keeling,Robert Kesterson,YooRi Kim,Bruce Korf,André Leier,Miranda L McManus,Herb Sarnoff,Jeremie Vitte,James A Walker,Scott R Plotkin,Deeann Wallis
Numerous successful gene-targeted therapies are arising for the treatment of a variety of rare diseases. At the same time, current treatment options for neurofibromatosis 1 and schwannomatosis are limited and do not directly address loss of gene/protein function. In addition, treatments have mostly focused on symptomatic tumors, but have failed to address multisystem involvement in these conditions
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Unresolved issues with noninferiority pragmatic trials: Results of a literature survey. Clin. Trials (IF 2.7) Pub Date : 2023-11-05 Maria M Ciarleglio,Jiaxuan Li,Peter Peduzzi
BACKGROUND Issues with specification of margins, adherence, and analytic population can potentially bias results toward the alternative in randomized noninferiority pragmatic trials. To investigate this potential for bias, we conducted a targeted search of the medical literature to examine how noninferiority pragmatic trials address these issues. METHODS An Ovid MEDLINE database search was performed
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Shedding light on data monitoring committee charters on ClinicalTrials.gov. Clin. Trials (IF 2.7) Pub Date : 2023-11-04 Anna M Fine,Elisa Golfinopoulos,Tony Tse
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Industry payments and brand-name tyrosine kinase inhibitor use amid generic entry. Clin. Trials (IF 2.7) Pub Date : 2023-10-31 Q Wilton Sun,Howard P Forman,Joseph S Ross
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What influences trust in and understanding of clinical trials? An analysis of information and communication technology use and online health behavior from the Health Information National Trends Survey. Clin. Trials (IF 2.7) Pub Date : 2023-10-31 Aurora Occa,Allison S Merritt,Allison Leip,Jerod L Stapleton
BACKGROUND Using information and communication technologies to seek, discuss, and share health-related information influences people's trust and knowledge of several health practices. However, we know little about the associations between individuals' information and communication technology use and their perceptions of trust and knowledge of clinical trials. Examining these associations may lead to
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Recommendations for the collection and annotation of biosamples for analysis of biomarkers in neurofibromatosis and schwannomatosis clinical trials. Clin. Trials (IF 2.7) Pub Date : 2023-10-31 R Taylor Sundby,Steven D Rhodes,Edina Komlodi-Pasztor,Herb Sarnoff,Vito Grasso,Meena Upadhyaya,AeRang Kim,D Gareth Evans,Jaishri O Blakeley,C Oliver Hanemann,Chetan Bettegowda
INTRODUCTION Neurofibromatosis 1 and schwannomatosis are characterized by potential lifelong morbidity and life-threatening complications. To date, however, diagnostic and predictive biomarkers are an unmet need in this patient population. The inclusion of biomarker discovery correlatives in neurofibromatosis 1/schwannomatosis clinical trials enables study of low-incidence disease. The implementation
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When should factorial designs be used for late-phase randomised controlled trials? Clin. Trials (IF 2.7) Pub Date : 2023-10-31 Ian R White,Alexander J Szubert,Babak Choodari-Oskooei,A Sarah Walker,Mahesh Kb Parmar
BACKGROUND A 2×2 factorial design evaluates two interventions (A versus control and B versus control) by randomising to control, A-only, B-only or both A and B together. Extended factorial designs are also possible (e.g. 3×3 or 2×2×2). Factorial designs often require fewer resources and participants than alternative randomised controlled trials, but they are not widely used. We identified several issues
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Statistical rules for safety monitoring in clinical trials. Clin. Trials (IF 2.7) Pub Date : 2023-10-25 Michael J Martens,Brent R Logan
BACKGROUND/AIMS Protecting patient safety is an essential component of the conduct of clinical trials. Rigorous safety monitoring schemes are implemented for these studies to guard against excess toxicity risk from study therapies. They often include protocol-specified stopping rules dictating that an excessive number of safety events will trigger a halt of the study. Statistical methods are useful
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Design of a clinical trial using generalized pairwise comparisons to test a less intensive treatment regimen. Clin. Trials (IF 2.7) Pub Date : 2023-10-25 Mickaël De Backer,Manju Sengar,Vikram Mathews,Samuel Salvaggio,Vaiva Deltuvaite-Thomas,Jean-Christophe Chiêm,Everardo D Saad,Marc Buyse
BACKGROUND/AIMS Showing "similar efficacy" of a less intensive treatment typically requires a non-inferiority trial. Yet such trials may be challenging to design and conduct. In acute promyelocytic leukemia, great progress has been achieved with the introduction of targeted therapies, but toxicity remains a major clinical issue. There is a pressing need to show the favorable benefit/risk of less intensive
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Do recruitment SWAT interventions have an impact on participant retention in randomised controlled trials? A systematic review. Clin. Trials (IF 2.7) Pub Date : 2023-10-25 Catherine E Arundel,Laura Clark
BACKGROUND Evidence-based methods for randomised controlled trial recruitment and retention are extremely valuable. Despite increased testing of these through studies within a trial, there remains limited high-certainty evidence for effective strategies. In addition, there has been little consideration as to whether recruitment interventions also have an impact on participant retention. METHODS A systematic
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Development and pilot validation of a novel disfigurement severity scale for plexiform neurofibromas in children with neurofibromatosis type 1. Clin. Trials (IF 2.7) Pub Date : 2023-10-25 Liny John,Gurbani Singh,Eva Dombi,Pamela L Wolters,Staci Martin,Andrea Baldwin,Seth M Steinberg,Jessica Bernstein,Patricia Whitcomb,Dominique C Pichard,Anne Dufek,Andy Gillespie,Kara Heisey,Miriam Bornhorst,Michael J Fisher,Brian D Weiss,AeRang Kim,Brigitte C Widemann,Andrea M Gross
BACKGROUND/AIMS We developed an observer disfigurement severity scale for neurofibroma-related plexiform neurofibromas to assess change in plexiform neurofibroma-related disfigurement and evaluated its feasibility, reliability, and validity. METHODS Twenty-eight raters, divided into four cohorts based on neurofibromatosis type 1 familiarity and clinical experience, were shown photographs of children
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Estimating counterfactual placebo HIV incidence in HIV prevention trials without placebo arms based on markers of HIV exposure. Clin. Trials (IF 2.7) Pub Date : 2023-10-25 Yifan Zhu,Fei Gao,David V Glidden,Deborah Donnell,Holly Janes
INTRODUCTION Developing alternative approaches to evaluating absolute efficacy of new HIV prevention interventions is a priority, as active-controlled designs, whereby individuals without HIV are randomized to the experimental intervention or an active control known to be effective, are increasing. With this design, however, the efficacy of the experimental intervention to prevent HIV acquisition relative
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The impact of feedback training on prediction of cancer clinical trial results. Clin. Trials (IF 2.7) Pub Date : 2023-10-24 Adélaïde Doussau,Patrick Kane,Jeffrey Peppercorn,Aden C Feustel,Sylviya Ganeshamoorthy,Natasha Kekre,Daniel M Benjamin,Jonathan Kimmelman
INTRODUCTION Funders must make difficult decisions about which squared treatments to prioritize for randomized trials. Earlier research suggests that experts have no ability to predict which treatments will vindicate their promise. We tested whether a brief training module could improve experts' trial predictions. METHODS We randomized a sample of breast cancer and hematology-oncology experts to the
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A critique on "A randomized evaluation of on-site monitoring nested in a multinational randomized trial". Clin. Trials (IF 2.7) Pub Date : 2023-09-30 Reem AlSowaiegh,Alastair O'Brien,Nicholas Freemantle
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Advancing neurofibromatosis and schwannomatosis clinical trial design: Consensus recommendations from the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration. Clin. Trials (IF 2.7) Pub Date : 2023-09-29 Vanessa L Merker,Andrea M Gross,Brigitte C Widemann,Scott R Plotkin
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Potential endpoints for assessment of bone health in persons with neurofibromatosis type 1. Clin. Trials (IF 2.7) Pub Date : 2023-09-29 Andrea M Gross,Scott R Plotkin,Nelson B Watts,Michael J Fisher,Laura J Klesse,Andrés J Lessing,Miranda L McManus,A Noelle Larson,Beverly Oberlander,Jonathan J Rios,Herb Sarnoff,Brittany N Simpson,Nicole J Ullrich,David A Stevenson
Neurofibromatosis type 1 is a genetic syndrome characterized by a wide variety of tumor and non-tumor manifestations. Bone-related issues, such as scoliosis, tibial dysplasia, and low bone mineral density, are a significant source of morbidity for this population with limited treatment options. Some of the challenges to developing such treatments include the lack of consensus regarding the optimal
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Controls, comparator arms, and designs for critical care comparative effectiveness research: It's complicated. Clin. Trials (IF 2.7) Pub Date : 2023-08-24 Verity J Ford,Harvey G Klein,Robert L Danner,Willard N Applefeld,Jeffrey Wang,Irene Cortes-Puch,Peter Q Eichacker,Charles Natanson
BACKGROUND Comparative effectiveness research is meant to determine which commonly employed medical interventions are most beneficial, least harmful, and/or most costly in a real-world setting. While the objectives for comparative effectiveness research are clear, the field has failed to develop either a uniform definition of comparative effectiveness research or an appropriate set of recommendations
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Assessing the use of observational methods and real-world data to emulate ongoing randomized controlled trials. Clin. Trials (IF 2.7) Pub Date : 2023-08-17 Joshua D Wallach,Yihong Deng,Eric C Polley,Sanket S Dhruva,Jeph Herrin,Kenneth Quinto,Charu Gandotra,William Crown,Peter Noseworthy,Xiaoxi Yao,Molly Moore Jeffery,Timothy D Lyon,Joseph S Ross,Rozalina G McCoy
BACKGROUND/AIMS There has been growing interest in better understanding the potential of observational research methods in medical product evaluation and regulatory decision-making. Previously, we used linked claims and electronic health record data to emulate two ongoing randomized controlled trials, characterizing the populations and results of each randomized controlled trial prior to publication
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Site staff perspectives on communicating trial results to participants: Cost and feasibility results from the Show RESPECT cluster randomised, factorial, mixed-methods trial. Clin. Trials (IF 2.7) Pub Date : 2023-07-29 Annabelle South,Julia Bailey,Barbara E Bierer,Eva Burnett,William J Cragg,Carlos Diaz-Montana,Katie Gillies,Talia Isaacs,Nalinie Joharatnam-Hogan,Claire Snowdon,Matthew R Sydes,Andrew J Copas
BACKGROUND/AIMS Sharing trial results with participants is an ethical imperative but often does not happen. Show RESPECT (ISRCTN96189403) tested ways of sharing results with participants in an ovarian cancer trial (ISRCTN10356387). Sharing results via a printed summary improved patient satisfaction. Little is known about staff experience and the costs of communicating results with participants. We
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Assessing the representativeness of cluster randomized trials: Evidence from two large pragmatic trials in United States nursing homes. Clin. Trials (IF 2.7) Pub Date : 2023-07-26 Nina R Joyce,Sarah E Robertson,Ellen McCreedy,Jessica Ogarek,Edward H Davidson,Vincent Mor,Stefan Gravenstein,Issa J Dahabreh
BACKGROUND/AIMS When the randomized clusters in a cluster randomized trial are selected based on characteristics that influence treatment effectiveness, results from the trial may not be directly applicable to the target population. We used data from two large nursing home-based pragmatic cluster randomized trials to compare nursing home and resident characteristics in randomized facilities to eligible
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The Targeted Agent and Profiling Utilization Registry Study: A pragmatic clinical trial. Clin. Trials (IF 2.7) Pub Date : 2023-07-25 Pam K Mangat,Elizabeth Garrett-Mayer,Jacqueline K Perez,Richard L Schilsky
The conceptual framework of pragmatism in clinical trials is explored using the American Society of Clinical Oncology's pragmatic, non-randomized, phase II, multi-center basket clinical trial, the Targeted Agent and Profiling Utilization Registry Study (NCT02693535) as a model. The Targeted Agent and Profiling Utilization Registry Study aims to identify signals of drug activity when Food and Drug Administration
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Randomized controlled dose-escalation design to evaluate the safety of a novel pharmacological cardiopulmonary resuscitation strategy. Clin. Trials (IF 2.7) Pub Date : 2023-07-24 Sydney Benson,Demetri Yannopoulos,Tom P Aufderheide,Thomas A Murray
BACKGROUND/AIMS The motivating randomized controlled phase I trial evaluates three sodium nitroprusside doses in a novel sodium nitroprusside-enhanced cardiopulmonary resuscitation strategy for improved end-organ perfusion relative to local standard of care. Sodium nitroprusside is a vasodilator with an established safety profile in other indications, whereas the local standard of care uses vasoconstrictors
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The net benefit for time-to-event outcome in oncology clinical trials with treatment switching. Clin. Trials (IF 2.7) Pub Date : 2023-07-16 Musashi Fukuda,Kentaro Sakamaki,Koji Oba
BACKGROUND The net benefit is an effect measure for any type of endpoint, including the time-to-event outcome, and can provide intuitive and clinically meaningful interpretation. It is defined as the probability of a randomly selected subject from the experimental arm surviving by at least a clinically relevant time longer than a randomly selected subject from the control arm. In oncology clinical
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Informative cluster size in cluster-randomised trials: A case study from the TRIGGER trial. Clin. Trials (IF 2.7) Pub Date : 2023-07-13 Brennan C Kahan,Fan Li,Bryan Blette,Vipul Jairath,Andrew Copas,Michael Harhay
BACKGROUND Recent work has shown that cluster-randomised trials can estimate two distinct estimands: the participant-average and cluster-average treatment effects. These can differ when participant outcomes or the treatment effect depends on the cluster size (termed informative cluster size). In this case, estimators that target one estimand (such as the analysis of unweighted cluster-level summaries
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A randomized comparison of two-stage versus traditional one-stage consent for a low-stakes randomized trial. Clin. Trials (IF 2.7) Pub Date : 2023-07-04 Andrew J Vickers,Emily A Vertosick,Mia Austria,Christopher D Gaffney,Sigrid V Carlsson,Scott Yh Kim,Behfar Ehdaie
BACKGROUND/AIMS It has been proposed that informed consent for randomized trials should be split into two stages, with the purported advantage of decreased information overload and patient anxiety. We compared patient understanding, anxiety and decisional quality between two-stage and traditional one-stage consent. METHODS We approached patients at an academic cancer center for a low-stakes trial of
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Futility monitoring for randomized clinical trials with non-proportional hazards: An optimal conditional power approach. Clin. Trials (IF 2.7) Pub Date : 2023-06-27 Xiaofei Wang,Stephen L George
BACKGROUND Standard futility analyses designed for a proportional hazards setting may have serious drawbacks when non-proportional hazards are present. One important type of non-proportional hazards occurs when the treatment effect is delayed. That is, there is little or no early treatment effect but a substantial later effect. METHODS We define optimality criteria for futility analyses in this setting
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Data monitoring committees in pediatric randomized controlled trials registered in ClinicalTrials.gov. Clin. Trials (IF 2.7) Pub Date : 2023-06-27 Tiago Machado,Beatrice Mainoli,Daniel Caldeira,Joaquim J Ferreira,Ricardo M Fernandes
BACKGROUND Data monitoring committees advise on clinical trial conduct through appraisal of emerging data to ensure participant safety and scientific integrity. While consideration of their use is recommended for trials performed with vulnerable populations, previous research has shown that data monitoring committees are reported infrequently in publications of pediatric randomized controlled trials
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The influence of political ideology on clinical trial knowledge, invitation, and participation among adults in the United States. Clin. Trials (IF 2.7) Pub Date : 2023-06-22 Henry Onyeaka,Daniel B Weber,Onyema Chido-Amajuoyi,Chioma Muoghalu,Hermioni L Amonoo
BACKGROUND Clinical trials remain a critical component of medical innovation. Evidence suggests that individuals' political ideologies may impact their health behaviors. However, there is a paucity of literature examining the relationship between political ideologies and clinical trial knowledge and participation. METHODS Study data were derived from Health Information National Trends Survey 5 Cycle
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Chronic pain trials often exclude people with comorbid depressive symptoms: A secondary analysis of 346 randomized controlled trials. Clin. Trials (IF 2.7) Pub Date : 2023-06-22 Darren K Cheng,Maarij Hannan Ullah,Henry Gage,Rahim Moineddin,Abhimanyu Sud
BACKGROUND Chronic pain and depression are common comorbid conditions, but there is limited evidence-based guidance for management of the two conditions together. In recent years, there has been an increase in the number of chronic pain randomized controlled trials that collect depression outcomes, but it is unknown how often these trials include people with depression or significant depressive symptoms
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A comparison of different population-level summary measures for randomised trials with time-to-event outcomes, with a focus on non-inferiority trials. Clin. Trials (IF 2.7) Pub Date : 2023-06-20 Matteo Quartagno,Tim P Morris,Duncan C Gilbert,Ruth E Langley,Matthew G Nankivell,Mahesh Kb Parmar,Ian R White
BACKGROUND The population-level summary measure is a key component of the estimand for clinical trials with time-to-event outcomes. This is particularly the case for non-inferiority trials, because different summary measures imply different null hypotheses. Most trials are designed using the hazard ratio as summary measure, but recent studies suggested that the difference in restricted mean survival
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Use of comprehensive recruitment strategies in the glycemia reduction approaches in diabetes: A comparative effectiveness study (GRADE) multi-center clinical trial. Clin. Trials (IF 2.7) Pub Date : 2023-06-17 Andrea L Cherrington,Heidi Krause-Steinrauf,Vanita Aroda,John B Buse,Basma Fattaleh,Stephen P Fortmann,Stephanie Hall,Sophia H Hox,Alexander Kuhn,Tina Killean,Amy Loveland,Lawrence S Phillips,Analyn Uy Jackson,Andrea Waltje,M Diane McKee,
BACKGROUND/AIMS We present and describe recruitment strategies implemented from 2013 to 2017 across 45 clinical sites in the United States, participating in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study, an unmasked, randomized controlled trial evaluating four glucose-lowering medications added to metformin in individuals with type 2 diabetes mellitus (duration of
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Pragmatic guidance for embedding pragmatic clinical trials in health plans: Large simple trials aren't so simple. Clin. Trials (IF 2.7) Pub Date : 2023-06-15 Noelle M Cocoros,Jerry H Gurwitz,Mark J Cziraky,Christopher B Granger,Thomas Harkins,Kevin Haynes,Xiaojuan Li,Lauren Parlett,John D Seeger,Sonal Singh,Cheryl N McMahill-Walraven,Richard Platt
BACKGROUND There are unique opportunities related to the design and conduct of pragmatic trials embedded in health insurance plans, which have longitudinal data on member/patient demographics, dates of coverage, and reimbursed medical care, including prescription drug dispensings, vaccine administrations, behavioral healthcare encounters, and some laboratory results. Such trials can be large and efficient
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BASIC: A Bayesian adaptive synthetic-control design for phase II clinical trials. Clin. Trials (IF 2.7) Pub Date : 2023-06-14 Liyun Jiang,Peter F Thall,Fangrong Yan,Scott Kopetz,Ying Yuan
BACKGROUND Randomized controlled trials are considered the gold standard for evaluating experimental treatments but often require large sample sizes. Single-arm trials require smaller sample sizes but are subject to bias when using historical control data for comparative inferences. This article presents a Bayesian adaptive synthetic-control design that exploits historical control data to create a
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Data-driven strategies for increasing patient diversity in Bristol Myers Squibb-sponsored US oncology clinical trials. Clin. Trials (IF 2.7) Pub Date : 2023-06-13 Lorena Kuri,Sagar Setru,Gengyuan Liu,Diane Moniz Reed,David Weigand,Aparna Surampudi,Susan Berger,David Paulucci,Angshu Rai,Venkat Sethuraman,Blythe Vito,Helen Kellar-Wood,Mariann Micsinai Balan
BACKGROUND/AIMS Determining whether clinical trial findings are applicable to diverse, real-world patient populations can be challenging when the full demographic characteristics of enrolled patients are not consistently reported. Here, we present the results of a descriptive analysis of racial and ethnic demographic information for patients in Bristol Myers Squibb (BMS)-sponsored oncology trials in
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Handling intercurrent events and missing data in non-inferiority trials using the estimand framework: A tuberculosis case study. Clin. Trials (IF 2.7) Pub Date : 2023-06-05 Sunita Rehal,Suzie Cro,Patrick Pj Phillips,Katherine Fielding,James R Carpenter
INTRODUCTION The ICH E9 addendum outlining the estimand framework for clinical trials was published in 2019 but provides limited guidance around how to handle intercurrent events for non-inferiority studies. Once an estimand is defined, it is also unclear how to deal with missing values using principled analyses for non-inferiority studies. METHODS Using a tuberculosis clinical trial as a case study
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Considerations for identifying the "right" subgroup in adaptive enrichment trials. Clin. Trials (IF 2.7) Pub Date : 2023-06-03 Noah Simon
Adaptive Enrichment Trials aim to make efficient use of data in a pivotal trial of a new targeted therapy to both (a) more precisely identify who benefits from that therapy and (b) improve the likelihood of successfully concluding that the drug is effective, while controlling the probability of false positives. There are a number of frameworks for conducting such a trial and decisions that must be
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Partner engagement for planning and development of non-pharmacological care pathways in the AIM-Back trial. Clin. Trials (IF 2.7) Pub Date : 2023-06-02 Lindsay A Ballengee,Heather A King,Corey Simon,Trevor A Lentz,Kelli D Allen,Catherine Stanwyck,Micaela Gladney,Steven Z George,S Nicole Hastings
BACKGROUND/AIMS Embedded pragmatic clinical trials are increasingly recommended for non-pharmacological pain care research due to their focus on examining intervention effectiveness within real-world settings. Engagement with patients, health care providers, and other partners is essential, yet there is limited guidance for how to use engagement to meaningfully inform the design of interventions to
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Poor effort on cognitive testing in voluntary research predicts failure in US Army Ranger School: Implications for clinical trial design. Clin. Trials (IF 2.7) Pub Date : 2023-06-02 Travis H Turner,Jill C Newman,Bernadette P Marriott
INTRODUCTION Failure to provide effortful performance on cognitive testing is not uncommon for participants in clinical trials and can significantly impact sensitivity to treatment effect. Whether poor effort on cognitive testing might relate to other behaviors of interest is unknown. In the current investigation, we examined whether effort on baseline cognitive testing in a randomized controlled trial