Patent Monopolies and the Costs of Mismarketing Drugs

Patent monopolies have long been used as a mechanism for financing innovation and research. The logic is that the government awards a monopoly on a product or process for a limited period of time in order to reward innovation. However, in addition to providing incentives for innovation and research, patent monopolies also provide incentives for a wide-range of rent-seeking behaviors, many of which can have major social costs. This paper attempts to calculate one category of these costs for prescription drugs. It produces estimates of the costs associated with mismarketing drugs. The estimates are based on assessments of the costs in the form of increased morbidity and mortality associated with five prominent cases of mismarketing over the last two decades

The Availability of Data from Clinical Trials: The Case of Crohn's Disease

The United States spent an estimated $540 billion on prescription drugs and medical equipment in 2017 ($450 billion on prescription drugs alone). Clinical trials which evaluate prescription drugs and new devices prior to their entrance on the market are usually financed and sometimes even carried out by the company holding the intellectual property rights to the technology in question. This is problematic for several reasons. There is an obvious incentive to conceal or underreport trial data which could be harmful to a drug's sales potential or reputation.Our study seeks to briefly characterize the data made available through ClinicalTrials.gov in order to better understand what information is available to prescribers and investigators not involved in the marketing of the drug or device. In doing so, we underscore the potentially enormous value of publicly funding clinical trials in terms of both patient safety and economic cost

Heterogeneity of Scaffold Biomaterials in Tissue Engineering

Tissue engineering (TE) offers a potential solution for the shortage of transplantable organs and the need for novel methods of tissue repair. Methods of TE have advanced significantly in recent years, but there are challenges to using engineered tissues and organs including but not limited to: biocompatibility, immunogenicity, biodegradation, and toxicity. Analysis of biomaterials used as scaffolds may, however, elucidate how TE can be enhanced. Ideally, biomaterials should closely mimic the characteristics of desired organ, their function and their in vivo environments. A review of biomaterials used in TE highlighted natural polymers, synthetic polymers, and decellularized organs as sources of scaffolding. Studies of discarded organs supported that decellularization offers a remedy to reducing waste of donor organs, but does not yet provide an effective solution to organ demand because it has shown varied success in vivo depending on organ complexity and physiological requirements. Review of polymer-based scaffolds revealed that a composite scaffold formed by copolymerization is more effective than single polymer scaffolds because it allows copolymers to offset disadvantages a single polymer may possess. Selection of biomaterials for use in TE is essential for transplant success. There is not, however, a singular biomaterial that is universally optimal

Simultaneous estimation of silodosin and silodosin β-D-glucuronide in human plasma using LC-MS/MS for a pharmacokinetic study

A rapid, simple, sensitive and selective LC-MS/MS method has been developed and validated for simultaneous quantification of silodosin and silodosin β-D-glucuronide human plasma using stable labelled isotopes as internal standards. Solid phase extraction technique (SPE) was used for the extraction and the method validated over a range of 0.20 ng/mL to 100.56 ng/mL for silidisin and 0.20 ng/mL to 101.63 ng/mL for silodosin β-D-glucuronide. The chromatographic separation was achieved on Cosmicsil Adze C18 (4.6 × 100 mm, 3 µm) column using a mobile phase consisting of acetonitrile, methanol and 10 mM ammonium acetate buffer 50:20:30 (v/v/v) at a flow rate of 1.000 mL/min with run time of 4 min. The API-4500 LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. The developed assay method was successfully applied to a pharmacokinetic study in humans

Semi-xenotransplantation: the regenerative medicine-based approach to immunosuppression-free transplantation and to meet the organ demand.

Although xenografts have always held immeasurable potential as an inexhaustible source of donor organs, immunological barriers and physiological incompatibility have proved to be formidable obstacles to clinical utility. An exciting, new regenerative medicine-based approach termed "semi-xenotransplantation" (SX) seeks to overcome these obstacles by combining the availability and reproducibility of animal organs with the biocompatibility and functionality of human allografts. Compared to conventional xenotransplantation wherein the whole organ is animal-derived, SX grafts are cleansed of their antigenic cellular compartment to produce whole-organ extracellular matrix scaffolds that retain their innate structure and vascular channels. These scaffolds are then repopulated with recipient or donor human stem cells to generate biocompatible semi-xenografts with the structure and function of native human organs. While numerous hurdles must be still overcome in order for SX to become a viable treatment option for end-stage organ failure, the immense potential of SX for meeting the urgent needs for a new source of organs and immunosuppression-free transplantation justifies the interest that the transplant community is committing to the field

Computational Insight Into the Hydroamination of an Activated Olefin, As Catalyzed by a 1,2,4-Triazole-Derived Nickel(II) N‑Heterocyclic Carbene Complex

A density functional theory (DFT) investigation performed at the B3LYP/TZVP//B3LYP/6-31G­(d)-LANL2DZ level of theory on the hydroamination of dimethylamine (Me₂NH) on an activated olefin (namely, acrylonitrile (CH₂CHCN)), as catalyzed by a 1,2,4-triazol based nickel­(II) N-heterocyclic carbene complex (namely, [1,4-dimethyl-1,2,4-triazole-5-ylidene]₂ nickel dichloride) revealed that the olefin coordination pathway is favorable over the amine coordination pathway, although the initial olefin coordination step is higher in energy than the initial amine coordination step. Significantly enough, the reaction involved a crucial 1,3-proton transfer step between the resonance intermediates, i.e., the C-bound [(NHC)₂Ni­(CH­(CN)­CH₂NHMe₂)]⁺ (<b>D</b>) species or N-bound [(NHC)₂Ni­(NCCHCH₂NHMe₂)]⁺ (<b>E</b>) species and the intermediate [(NHC)₂Ni­(NCCH₂CH₂NMe₂)]⁺ (<b>F</b>), depicting the cleavage of a N–H bond and the formation of a C–H bond facilitated by a water-assisted/amine-assisted proton shuttle. Overall, among the various pathways explored, the lowest energy pathway involved alkene coordination, followed by an amine-assisted 1,3-proton transfer step

TRPV4 Mechanotransduction in Fibrosis

Fibrosis is an irreversible, debilitating condition marked by the excessive production of extracellular matrix and tissue scarring that eventually results in organ failure and disease. Differentiation of fibroblasts to hypersecretory myofibroblasts is the key event in fibrosis. Although both soluble and mechanical factors are implicated in fibroblast differentiation, much of the focus is on TGF-β signaling, but to date, there are no specific drugs available for the treatment of fibrosis. In this review, we describe the role for TRPV4 mechanotransduction in cardiac and lung fibrosis, and we propose TRPV4 as an alternative therapeutic target for fibrosis