External data required timely response by the Trial Steering-Data Monitoring Committee for the NALoxone InVEstigation (N-ALIVE) pilot trial.
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ABSTRACT:
SUBMITTER: Bird SM
PROVIDER: S-EPMC5389338 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:CONTEXT:The Prostate Imaging-Reporting and Data System (PI-RADS) v2 analysis system for multiparametric magnetic resonance imaging (mpMRI) detection of prostate cancer (PCa) is based on PI-RADS v1, accumulated scientific evidence, and expert consensus opinion. OBJECTIVE:To summarize the accuracy, strengths and weaknesses of PI-RADS v2, discuss pathway implications of its use and outline opportunities for improvements and future developments. EVIDENCE ACQUISITION:For this consensus expert opinion from the PI-RADS steering committee, clinical studies, systematic reviews, and professional guidelines for mpMRI PCa detection were evaluated. We focused on the performance characteristics of PI-RADS v2, comparing data to systems based on clinicoradiologic Likert scales and non-PI-RADS v2 imaging only. Evidence selections were based on high-quality, prospective, histologically verified data, with minimal patient selection and verifications biases. EVIDENCE SYNTHESIS:It has been shown that the test performance of PI-RADS v2 in research and clinical practice retains higher accuracy over systematic transrectal ultrasound (TRUS) biopsies for PCa diagnosis. PI-RADS v2 fails to detect all cancers but does detect the majority of tumors capable of causing patient harm, which should not be missed. Test performance depends on the definition and prevalence of clinically significant disease. Good performance can be attained in practice when the quality of the diagnostic process can be assured, together with joint working of robustly trained radiologists and urologists, conducting biopsy procedures within multidisciplinary teams. CONCLUSIONS:It has been shown that the test performance of PI-RADS v2 in research and clinical practice is improved, retaining higher accuracy over systematic TRUS biopsies for PCa diagnosis. PATIENT SUMMARY:Multiparametric magnetic resonance imaging (MRI) and MRI-directed biopsies using the Prostate Imaging-Reporting and Data System improves the detection of prostate cancers likely to cause harm, and at the same time decreases the detection of disease that does not lead to harms if left untreated. The keys to success are high-quality imaging, reporting, and biopsies by radiologists and urologists working together in multidisciplinary teams.
| S-EPMC6292742 | biostudies-literature
Project description:ObjectiveTo determine whether two specific criteria in Uniform Requirements for Manuscripts (URM) created by the International Committee of Medical Journal Editors (ICMJE)--namely, including the trial ID registration within manuscripts and timely registration of trials, are being followed.Materials and methodsObservational study using computerized analysis of publicly available Medline article data and clinical trial registry data. We analyzed a purposive set of five ICMJE founding journals looking at all trial articles published in those journals during 2010-2011, and data from the ClinicalTrials.gov (CTG) trial registry. We measured adherence to trial ID inclusion policy as the percentage of trial journal articles that contained a valid trial ID within the article (journal-based sample). Adherence to timely registration was measured as the percentage of trials that registered the trial before enrolling the first participant within a 60-day grace period. We also examined timely registration rates by year of all phase II and higher interventional trials in CTG (registry-based sample).ResultsTo determine trial ID inclusion, we analyzed 698 clinical trial articles in five journals. A total of 95.8% (661/690) of trial journal articles included the trial ID. In 88.3% the trial-article link is stored within a structured Medline field. To evaluate timely registration, we analyzed trials referenced by 451 articles from the selected five journals. A total of 60% (272/451) of articles were registered in a timely manner with an improving trend for trials initiated in later years (eg, 89% of trials that began in 2008 were registered in a timely manner). In the registry-based sample, the timely registration rates ranged from 56% for trials registered in 2006 to 72% for trials registered in 2011.DiscussionAdherence to URM requirements for registration and trial ID inclusion increases the utility of PubMed and links it in an important way to clinical trial repositories. This new integrated knowledge source can facilitate research prioritization, clinical guidelines creation, and precision medicine.ConclusionsThe five selected journals adhere well to the policy of mandatory trial registration and also outperform the registry in adherence to timely registration. ICMJE's URM policy represents a unique international mandate that may be providing a powerful incentive for sponsors and investigators to document clinical trials and trial result publications and thus fulfill important obligations to trial participants and society.
| S-EPMC3715364 | biostudies-literature
Project description:BackgroundInterim analysis of accumulating trial data is important to protect participant safety during randomized controlled trials (RCTs). Data Monitoring Committees (DMCs) often undertake such analyses, but their widening role may lead to extended use of interim analysis or recommendations that could potentially bias trial results.MethodsSystematic search of eight major publications: Annals of Internal Medicine, BMJ, Circulation, CID, JAMA, JCO, Lancet and NEJM, including all randomised controlled trials (RCTs) between June 2000 and May 2005 to identify RCTs that reported use of interim analysis, with or without DMC involvement. Recommendations made by the DMC or based on interim analysis were identified and potential sources of bias assessed. Independent double data extraction was performed on all included trials.ResultsWe identified 1772 RCTs, of which 470 (27%; 470/1772) reported the use of a DMC and a further 116 (7%; 116/1772) trials reported some form of interim analysis without explicit mention of a DMC. There were 28 trials (24 with a formal DMC), randomizing a total of 79396 participants, identified as recommending changes to the trial that may have lead to biased results. In most of these, some form of sample size re-estimation was recommended with four trials also reporting changes to trial endpoints. The review relied on information reported in the primary publications and methods papers relating to the trials, higher rates of use may have occurred but not been reported.ConclusionThe reported use of interim analysis and DMCs in clinical trials has been increasing in recent years. It is reassuring that in most cases recommendations were made in the interest of participant safety. However, in practice, recommendations that may lead to potentially biased trial results are being made.
| S-EPMC2279143 | biostudies-literature
Project description:Anticancer drugs are combined in an effort to treat a heterogeneous tumor or to maximize the pharmacodynamic effect. The development of combination regimens, while desirable, poses unique challenges. These include the selection of agents for combination therapy that may lead to improved efficacy while maintaining acceptable toxicity, the design of clinical trials that provide informative results for individual agents and combinations, and logistic and regulatory challenges. The phase I trial is often the initial step in the clinical evaluation of a combination regimen. In view of the importance of combination regimens and the challenges associated with developing them, the Clinical Trial Design (CTD) Task Force of the National Cancer Institute Investigational Drug Steering Committee developed a set of recommendations for the phase I development of a combination regimen. The first two recommendations focus on the scientific rationale and development plans for the combination regimen; subsequent recommendations encompass clinical design aspects. The CTD Task Force recommends that selection of the proposed regimens be based on a biologic or pharmacologic rationale supported by clinical and/or robust and validated preclinical evidence, and accompanied by a plan for subsequent development of the combination. The design of the phase I clinical trial should take into consideration the potential pharmacokinetic and pharmacodynamic interactions as well as overlapping toxicity. Depending on the specific hypothesized interaction, the primary endpoint may be dose optimization, pharmacokinetics, and/or pharmacodynamics (i.e., biomarker).
| S-EPMC4135521 | biostudies-literature
Project description:High-quality evidence shows that MRI in biopsy-naive men can reduce the number of men who need prostate biopsy and can reduce the number of diagnoses of clinically insignificant cancers that are unlikely to cause harm. In men with prior negative biopsy results who remain under persistent suspicion, MRI improves the detection and localization of life-threatening prostate cancer with greater clinical utility than the current standard of care, systematic transrectal US-guided biopsy. Systematic analyses show that MRI-directed biopsy increases the effectiveness of the prostate cancer diagnosis pathway. The incorporation of MRI-directed pathways into clinical care guidelines in prostate cancer detection has begun. The widespread adoption of the Prostate Imaging Reporting and Data System (PI-RADS) for multiparametric MRI data acquisition, interpretation, and reporting has promoted these changes in practice. The PI-RADS MRI-directed biopsy pathway enables the delivery of key diagnostic benefits to men suspected of having cancer based on clinical suspicion. Herein, the PI-RADS Steering Committee discusses how the MRI pathway should be incorporated into routine clinical practice and the challenges in delivering the positive health impacts needed by men suspected of having clinically significant prostate cancer.
| S-EPMC6677282 | biostudies-other
Project description:A novel virus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a pandemic called Coronavirus disease 2019 (COVID-19). According to the World Health Organization, COVID-19 was first detected in Wuhan city in December 2019 and has affected 216 countries with 9473214 confirmed cases and 484249 deaths globally as on June 26th, 2020. Also, this outbreak continues to grow in many countries like the United States of America (U.S.), Brazil, India, and Russia. To ensure rapid surveillance and better decision-making by government authorities in different countries, it is vital to identify alive and emerging hotspots within a country promptly. State-of-the-art methods based on space-time scan statistics (like SaTScan) are not geographically robust. Also, due to the enumeration of many Spatio-temporal cylinders, the computation cost of Spatio-temporal SaTScan (ST-SaTScan) is very high. In the applications like COVID-19 where we need to detect the emerging hotspots daily as soon as the new count of cases gets updated, ST-SaTScan seems inefficient. Therefore, this paper proposes a Particle Swarm Optimizer-based scheme to timely detect geographically robust, alive, and emerging COVID-19 hotspots in a country. Timely detection can help government officials design better control strategies like increasing testing in hotspots, imposing stricter containment rules, or setting up temporary hospital beds. Performance of ST-SaTScan and proposed scheme have been analyzed for four worst-hit U.S. states for the incubation period of 14 days between June 11th, 2020, and June 24th, 2020. Results indicate that the proposed scheme detects hotspots of a higher likelihood ratio (a measure to indicate the significance of hotspot) than ST-SaTScan in significantly less time. We also applied the proposed scheme to detect the emerging COVID-19 hotspots in all states of the U.S. During the study period, the proposed scheme has detected 104 emerging COVID-19 hotspots.
| S-EPMC9127146 | biostudies-literature
Project description: Not available
| S-EPMC4732953 | biostudies-literature
Project description:As the immuno-oncology field continues the rapid growth witnessed over the past decade, optimising patient outcomes requires an evolution in the current response-assessment guidelines for phase 2 and 3 immunotherapy clinical trials and clinical care. Additionally, investigational tools-including image analysis of standard-of-care scans (such as CT, magnetic resonance, and PET) with analytics, such as radiomics, functional magnetic resonance agents, and novel molecular-imaging PET agents-offer promising advancements for assessment of immunotherapy. To document current challenges and opportunities and identify next steps in immunotherapy diagnostic imaging, the National Cancer Institute Clinical Imaging Steering Committee convened a meeting with diverse representation among imaging experts and oncologists to generate a comprehensive review of the state of the field.
| S-EPMC10119769 | biostudies-literature
Project description: Not available
| S-EPMC1117916 | biostudies-literature
Project description:PurposeTo share better practice in establishing data monitoring committees (DMCs) for observational, retrospective safety studies with joint-industry sponsorship.MethodsA DMC model was created to monitor data from an observational, retrospective, post-authorization safety study investigating risk of medullary thyroid cancer in patients treated with long-acting glucagon-like peptide-1 receptor agonists (LA GLP-1RAs) (NCT01511393). Sponsors reviewed regulatory guidelines, best practice and sponsors' standard operation procedures on DMCs. Discussions were held within the four-member consortium, assessing applicability to observational, retrospective, real-world studies. A DMC charter was drafted based on a sponsor-proposed, adapted DMC model. Thereafter, a kick-off meeting between sponsors and DMC members was held to receive DMC input and finalize the charter.ResultsDue to this study's observational, retrospective nature, assuring participant safety - central for traditional explanatory clinical trial models - was not applicable to our DMC model. The overall strategy and key indication for our real-world model included preserving study integrity and credibility. Therefore, DMC member independence and their contribution of expert knowledge were essential. To ensure between-sponsor data confidentiality, all study committees/corporations and sponsors, besides the DMC, received blinded data only (adapted to refer to data blinding that revealed the specific marketed LA GLP-1RA/sponsor). Communication and blinding/unblinding of these data were facilitated by the contract research organization, which also provided crucial operational oversight.ConclusionsTo our knowledge, we have established the first DMC model for joint industry-sponsored, observational, retrospective safety studies. This model could serve as a precedent for others performing similar post-marketing, joint industry-sponsored pharmacovigilance activities.
| S-EPMC8247341 | biostudies-literature