Generic drug competition: The pharmaceutical industry “gaming” controversy

Among American adults 20 years and older, 59 percent take at least one prescription drug on a regular basis. Unlike most branded drugs, which are generally drugs that have a trade name and are protected by a patent, off‐patent generic drugs make up approximately 90 percent of prescriptions annually filled in the United States; yet in 2017, generic drugs made up only 23 percent of total drug costs in the U.S. The U.S. Food and Drug Administration has taken the lead in encouraging increased competition in the nation’s prescription drug marketplace, most recently with its release of the agency’s Drug Competition Action Plan, but also with its regulatory guidance and enforcement efforts to eliminate “gaming” of the regulatory process by both branded and generic pharmaceutical manufacturers. Such “gaming” activities include “pay‐for‐delay” agreements involving financial compensation between branded and generic pharmaceutical manufacturers to forestall the emergence into the market of generic pharmaceuticals to compete against a formerly patent‐protected branded drug. A combination of new enabling legislation, federal judicial guidance, and agency regulatory activities show promise in encouraging increased competition in the prescription drug marketplace, with the American consumer the ultimate beneficiary of lower health care costs and improved overall personal health.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152498/1/basr12186_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152498/2/basr12186.pd

Therapeutic Options for the Treatment of Hypertension in Children and Adolescents

Primary hypertension in children is increasing in prevalence with many cases likely going undiagnosed. The prevalence is currently estimated at between 3%–5% in the United States and may be higher in certain ethnic groups. Primary hypertension, once felt to be rare in children, is now considered to be about five times more common than secondary hypertension. This review provides information to guide physicians through an organized approach to: 1) screening children and adolescents for hypertension during routine visits; 2) using normative percentile data for diagnosis and classification; 3) performing a clinical evaluation to identify the presence of co-morbidities; 4) initiating a plan of care including subsequent follow-up blood pressure measurements, therapeutic lifestyle changes and pharmacologic therapies

Plasma bioavailability and changes in PBMC gene expression after treatment of ovariectomized rats with a commercial soy supplement

The health effects of soy supplementation in (post)menopausal women are still a controversial issue. The aim of the present study was to establish the effect of the soy isoflavones (SIF) present in a commercially available supplement on ovariectomized rats and to investigate whether these rats would provide an adequate model to predict effects of SIF in (post)menopausal women. Two dose levels (i.e. 2 and 20. mg/kg b.w.) were used to characterize plasma bioavailability, urinary and fecal concentrations of SIF and changes in gene expression in peripheral blood mononuclear cells (PBMC). Animals were dosed at 0 and 48. h and sacrificed 4. h after the last dose. A clear dose dependent increase of SIF concentrations in plasma, urine and feces was observed, together with a strong correlation in changes in gene expression between the two dose groups. All estrogen responsive genes and related biological pathways (BPs) that were affected by the SIF treatment were regulated in both dose groups in the same direction and indicate beneficial effects. However, in general no correlation was found between the changes in gene expression in rat PBMC with those in PBMC of (post)menopausal women exposed to a comparable dose of the same supplement. The outcome of this short-term study in rats indicates that the rat might not be a suitable model to predict effects of SIF in humans. Although the relative exposure period in this rat study is comparable with that of the human study, longer repetitive administration of rats to SIF may be required to draw a final conclusion on the suitability of the rat a model to predict effects of SIF in humans

The identification of a low molecular mass bacteriocin, rhamnosin A, produced by Lactobacillus rhamnosus strain 68

Aims: This study focuses on the isolation and characterization of a peptide with bacteriocin-like properties isolated from Lactobacillus rhamnosus strain 68, previously identified by 16S rRNA gene sequencing and originating from human gastrointestinal flora. Methods and Results: The peptide was isolated from a supernatant of bacteria maintained under restrictive conditions by a combination of ethanol precipitation and reversed-phase chromatography. The molecular mass of the peptide as assessed by mass spectrometry was 6433 center dot 8 Da. An isoelectric point of 9 center dot 8 was determined by 2D-PAGE. The peptide designated rhamnosin A inhibited Micrococcus lysodeikticus ATCC 4698 but did not inhibit Lactobacillus plantarum 8014 or Lact. plantarum 39268. Inhibitory activity against M. lysodeikticus at concentrations used in this study was shown to be bacteriostatic rather than bacteriolytic or bactericidal. Rhamnosin A retained biological activity after heat treatment (95 degrees C, 30 min) but was sensitive to proteolytic activity of pepsin and trypsin. Conclusions: The N-terminal sequence of rhamnosin A, as determined by Edman degradation and in more detail by blast analysis, did not show identity with any currently available Lact. rhamnosus HN001-translated protein sequences, nor any significant similarity with other sequences in the nonredundant protein sequence database. Being a small, heat-stable, nonlanthionine-containing peptide, rhamnosin A should be categorized as a class II bacteriocin. Significance and Impact of the Study: This study describes a partial bacteriocin sequence isolated from Lact. rhamnosus 68 and broadens our understanding of bacteriocins

An Analysis of Clostridium difficile Environmental Contamination During and After Treatment for C difficile Infection.

Background: Lower Clostridium difficile spore counts in feces from C difficile infection (CDI) patients treated with fidaxomicin versus vancomycin have been observed. We aimed to determine whether environmental contamination is lower in patients treated with fidaxomicin compared with those treated with vancomycin/metronidazole. Methods: The CDI cases were recruited at 4 UK hospitals (Leeds, Bradford, and London [2 centers]). Environmental samples (5 room sites) were taken pretreatment and at 2-3, 4-5, 6-8, and 9-12 days of treatment, end of treatment (EOT), and post-EOT. Fecal samples were collected at diagnosis and as often as produced thereafter. Swabs/feces were cultured for C difficile; percentage of C difficile-positive samples and C difficile bioburden were compared between different treatment arms at each time point. Results: Pre-EOT (n = 244), there was a significant reduction in environmental contamination (≥1 site positive) around fidaxomicin versus vancomycin/metronidazole recipients at days 4-5 (30% vs 50% recipients, P = .04) and at days 9-12 (22% vs 49%, P = .005). This trend was consistently seen at all other timepoints, but it was not statistically significant. No differences were seen between treatment groups post-EOT (n = 76). Fidaxomicin-associated fecal positivity rates and colony counts were consistently lower than those for vancomycin/metronidazole from days 4 to 5 of treatment (including post-EOT); however, the only significant difference was in positivity rate at days 9-12 (15% vs 55%, P = .03). Conclusions: There were significant reductions in C difficile recovery from both feces and the environment around fidaxomicin versus vancomycin/metronidazole recipients. Therefore, fidaxomicin treatment may lower the C difficile transmission risk by reducing excretion and environmental contamination

Cost effectiveness of ulcerative colitis treatment in Germany: a comparison of two oral formulations of mesalazine

<p>Abstract</p> <p>Background</p> <p>The treatment of ulcerative colitis (UC) can place a substantial financial burden on healthcare systems. The anti-inflammatory compound 5-aminosalicylic acid (5-ASA; mesalazine) is the recommended first-line treatment for patients with UC. In this analysis, the incremental cost effectiveness ratio (ICER) of two oral formulations of 5-ASA (Mezavant^®and Asacol^®) is examined in the treatment of patients with mild-to-moderate, active UC in Germany.</p> <p>Methods</p> <p>A Markov cohort model was developed to assess the cost effectiveness of Mezavant compared with Asacol over a 5-year period in the German Statutory Health Insurance (SHI). Drug pricing details for 2009 were applied throughout the model, and overall resource use was determined and also fitted to 2009 from published results of a large cross sectional study of German SHI patients. Cost per quality adjusted life year (QALY) was the primary endpoint for this study. Remission rates were obtained using data from a randomised, phase III trial of Mezavant with an active Asacol reference arm and a long-term, open label, safety and tolerability trial of Mezavant. Uncertainty in the study model was assessed using one-way and probabilistic sensitivity analyses applying a Monte Carlo simulation.</p> <p>Results</p> <p>Over a 5-year period, healthcare costs for patients receiving Mezavant were 624 Euro lower than for patients receiving Asacol. Additionally, patients receiving Mezavant gained 0.011 QALYs or 18 more days in remission compared with Asacol. One-way sensitivity analyses suggest that these results are driven by both differences in the acquisition cost between mesalazine formulations and differences in treatment efficacy. Furthermore, sensitivity analyses suggest a probability of 76% for cost savings and higher QALYs with Mezavant compared with Asacol. If adherence and its influence on the remission rates and the risk of developing colorectal cancer were included in the model, the results might have even been more favorable to Mezavant due to its once daily dosing regimen.</p> <p>Conclusions</p> <p>This model suggests that patients treated with Mezavant may achieve increased time in remission and higher QALYs, with lower direct costs to the SHI when compared with Asacol. Mezavant may therefore be a suitable first-line option for the induction and maintenance of remission in UC.</p