Since the release of the ICH E9(R1) (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Addendum on Estimands and Sensitivity Analysis in Clinical Trials to the Guideline on Statistical Principles for Clinical Trials) document in 2019, the estimand framework has become a fundamental part of clinical trial protocols. In parallel, complex innovative designs have gained increased popularity in drug development, in particular in early development phases or in difficult experimental situations. While the estimand framework is relevant to any study in which a treatment effect is estimated, experience is lacking as regards its application to these designs. In a basket trial for example, should a different estimand be specified for each subpopulation of interest, defined, for example, by cancer site? Or can a single estimand focusing on the general population (defined, for example, by the positivity to a certain biomarker) be used? In the case of platform trials, should a different estimand be proposed for each drug investigated? In this work we discuss possible ways of implementing the estimand framework for different types of complex innovative designs. We consider trials that allow adding or selecting experimental treatment arms, modifying the control arm or the standard of care, and selecting or pooling populations. We also address the potentially data-driven, adaptive selection of estimands in an ongoing trial and disentangle certain statistical issues that pertain to estimation rather than to estimands, such as the borrowing of nonconcurrent information. We hope this discussion will facilitate the implementation of the estimand framework and its description in the study protocol when the objectives of the trial require complex innovative designs.
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http://dx.doi.org/10.1002/cpt.2575 | DOI Listing |
JMIR Serious Games
January 2025
School of Computing, Engineering and Mathematical Sciences, Optus Chair Digital Health, La Trobe University, Melbourne, Australia.
Background: This review explores virtual reality (VR) and exercise simulator-based interventions for individuals with attention-deficit/hyperactivity disorder (ADHD). Past research indicates that both VR and simulator-based interventions enhance cognitive functions, such as executive function and memory, though their impacts on attention vary.
Objective: This study aimed to contribute to the ongoing scientific discourse on integrating technology-driven interventions into the management and evaluation of ADHD.
Org Lett
January 2025
State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, China.
Highly asymmetric (3+3) annulation of diaziridines with oxiranes via C-N bond cleavage in diaziridine was achieved under 10 mol % of chiral copper(II) complex as the catalyst under mild reaction conditions. With Cu(OTf) as the Lewis acid and C-symmetric imidazolidine-pyrroloimidazolone pyridine as the ligand, diverse tetrahydro-[1,3,4]-oxadiazines were obtained by stereospecific C-N/C-O bond formation in moderate to good yields (up to 93% yield) and high diastereo- (>20:1 dr) and enantioselectivities (up to 92% ee). The catalytic cycle and stereochemical model were proposed by DFT calculation.
View Article and Find Full Text PDFEur Radiol
January 2025
Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Objectives: To analyze the CT imaging features of extranodal natural killer/T (NK/T)-cell lymphoma, nasal type (ENKTCL-NT) involving the gastrointestinal tract (GI), and to compare them with those of Crohn's disease (CD) and diffuse large B-cell lymphoma (DLBCL).
Materials And Methods: Data were retrospectively collected from 17 patients diagnosed with GI ENKTCL-NT, 68 patients with CD, and 47 patients with DLBCL. The CT findings of ENKTCL-NT were analyzed and compared with those of CD and DLBCL.
Drug Deliv Transl Res
January 2025
Kinimmune, Inc. St. Louis, 63141, Missouri, USA.
PD-L1/PD-1 checkpoint inhibitors (CPIs) are mainstream agents for cancer immunotherapy, but the prognosis is unsatisfactory in solid tumor patients lacking preexisting T-cell reactivity. Adjunct therapy strategies including the intratumoral administration of immunostimulants aim to address this limitation. CpG oligodeoxynucleotides (ODNs), TLR9 agonists that can potentiate adaptive immunity, have been widely investigated to tackle PD-L1/PD-1 resistance, but clinical success has been hindered by inconsistent efficacy and immune-related toxicities caused by systemic exposure.
View Article and Find Full Text PDFMater Horiz
January 2025
School of Materials Scicence and Engineering, South China University of Technology, Guangzhou, 510640, China.
Multifunctional devices based on van der Waals heterojunctions have drawn significant attention owing to their portable size, low power consumption and various application scenarios. However, high fabrication equipment requirements, complex device structures and limited operating conditions hinder their potential value. Herein, multifunctional UV photodetect-memristors based on GaS/graphene/GaN van der Waals heterojunctions area selective deposition have been proposed for the first time.
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