For over half a century, courts and commentators have disagreed as to the standards governing liability for drug design cases. In the last several years, the United States Supreme Court decided two cases that will have a profound effect on whether drug design defect cases, in general, are federally preempted. In PLIVA v. Mensing and Mutual Pharmaceutical Co. v. Bartlett, the Court preempted product liability actions for failure to warn and design defect against the manufacturers of generic drugs that met the FDA standard for the brand name drug. In these cases, the Court made wide-ranging statements that are applicable to brand name drugs as well. This Essay finds the Bartlett Court erred in having read New Hampshire law too narrowly. At the same time, the Court's reasoning has opened a debate as to the scope of federal preemption for brand name drugs. This Essay argues that the sweeping language in these two cases leads to the conclusion that common law drug design cases involving brand name drugs will fall prey to federal preemption.
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JCO Clin Cancer Inform
January 2025
SimBioSys Inc, Chicago, IL.
Purpose: Perfusion modeling presents significant opportunities for imaging biomarker development in breast cancer but has historically been held back by the need for data beyond the clinical standard of care (SoC) and uncertainty in the interpretability of results. We aimed to design a perfusion model applicable to breast cancer SoC dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) series with results stable to low temporal resolution imaging, comparable with published results using full-resolution DCE-MRI, and correlative with orthogonal imaging modalities indicative of biophysical markers.
Methods: Subsampled high-temporal-resolution DCE-MRI series were run through our perfusion model and resulting fits were compared for consistency.
J Clin Oncol
January 2025
The Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW, Australia.
Purpose: Over the past 15 years, the landscape of early phase clinical trials (EPCTs) has undergone a remarkable expansion in both quantity and intricacy. The proliferation of sites, trials, sponsors, and contract research organizations has surged exponentially, marking a significant shift in research conduct. However, EPCT operations suffer from numerous inefficiencies, such as cumbersome start-up processes, which are particularly critical when drug safety and the recommended phase II dose need to be established in a timely manner.
View Article and Find Full Text PDFJ Med Chem
January 2025
Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, School of Pharmaceutical Sciences, Central University of Punjab, Bathinda 151 401, India.
The multifactorial nature of cancer requires treatment that involves simultaneous targeting of associated overexpressed proteins and cell signaling pathways, possibly leading to synergistic effects. Herein, we present a systematic study that involves the simultaneous inhibition of human topoisomerases (hTopos) and histone deacetylases (HDACs) by multitargeted quinoline-bridged hydroxamic acid derivatives. These compounds were rationally designed considering pharmacophoric features and catalytic sites of the cross-talk proteins, synthesized, and assessed for their anticancer potential.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen DK-2100, Denmark.
GABA receptors (GABARs) are the major elements of inhibitory neurotransmission in the central nervous system (CNS). They are established targets for regulation by endogenous brain neuroactive steroids (NASs) such as pregnanolone. However, the complexity of de novo synthesis of NAS derivatives has hindered attempts to circumvent the principal limitations of using endogenous NASs, including selectivity and limited oral bioavailability.
View Article and Find Full Text PDFPLoS One
January 2025
Institute of Psychiatry, Psychology & Neuroscience at King's College London, London, United Kingdom.
Fluctuation-related pain (FRP) affects more than one third of people with Parkinson's disease (PwP, PD) and has a harmful effect on health-related quality of life (HRQoL), but often remains under-reported by patients and neglected by clinicians. The National Institute for Health and Care Excellence (NICE) recommends The Parkinson KinetiGraphTM (the PKGTM) for remote monitoring of motor symptoms. We investigated potential links between the PKGTM-obtained parameters and clinical rating scores for FRP in PwP in an exploratory, cross-sectional analysis of two prospective studies: "The Non-motor International Longitudinal, Real-Life Study in PD-NILS" and "An observational-based registry of baseline PKG™ in PD-PKGReg".
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