The two trials paradigm plays a prominent role in drug development and has been widely and controversially discussed. Its purpose is to ensure replicability or substantiation of study results. This note investigates a simple generalization of the paradigm to more than two trials that preserves the project wise type-I error rate and power.
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http://dx.doi.org/10.1007/s43441-022-00471-4 | DOI Listing |
Jpn J Ophthalmol
January 2025
Department of Ophthalmology, Eye center, China Medical University Hospital, Taichung City, Taiwan.
Purpose: To compare the efficac and safety of a dual-blade 20,000 cuts per minute (cpm) vitrectomy probe with a single-blade 10,000 cpm probe for primary rhegmatogenous retinal detachment (RRD).
Study Design: Prospective, randomized controlled clinical trial.
Methods: Evaluations were conducted preoperatively, intraoperatively, and at three months postoperatively.
HSS J
February 2025
Department of Spine Surgery, Hospital for Special Surgery, New York, NY, USA.
The scope of existing annular closure device (ACD) studies examining long-term follow-up data is limited. There is a paucity of studies that report and analyze recent outcomes data following ACD use. We sought to summarize the available long-term follow-up data on postoperative outcomes of the Barricaid (Intrinsic Therapeutics) ACD.
View Article and Find Full Text PDFTher Adv Neurol Disord
January 2025
Department of Neurology, Ulm University, Ulm, Germany.
The advent of antisense oligonucleotide (ASO) therapies in neurodegenerative disorders is associated with enormous hope. Nusinersen treatment was a breakthrough intervention in the recessive disease spinal muscular atrophy, and superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS) seems to be the paradigm disease in dominant degenerative diseases. The results of treatment with the ASO tofersen in SOD1-ALS show that the drug has a convincing beneficial effect on ALS caused by SOD1 mutations, that preclinical studies in rodents predicted the therapeutic effect in the human disease, and that clinical efficacy is associated with a specific sequence of effects of the drug on mechanistic and degenerative biomarkers and, subsequently, functional outcomes such as weight stabilization and ALSFRS-R.
View Article and Find Full Text PDFCancer J
January 2025
From the Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center, Columbus, OH.
There has been a significant paradigm shift in the clinical management of lower-grade glioma patients given the recent updates to the 2021 World Health Organization classification along with long-term results from randomized phase III clinical trials. As a result, we are now better able to diagnose and assign patients to the most appropriate treatment course. This review provides a comprehensive summary of the most robust and reliable molecular biomarkers for adult lower-grade gliomas and discusses current challenges facing this patient population that future correlative biology studies combined with advancements in technologies could help overcome.
View Article and Find Full Text PDFElife
January 2025
Integrative Model-Based Cognitive Neuroscience Research Unit, University of Amsterdam, Amsterdam, Netherlands.
This study investigates the functional network underlying response inhibition in the human brain, particularly the role of the basal ganglia in successful action cancellation. Functional magnetic resonance imaging (fMRI) approaches have frequently used the stop-signal task to examine this network. We merge five such datasets, using a novel aggregatory method allowing the unification of raw fMRI data across sites.
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