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Denis Snegovskikh,1 Mark C Kendall,1 Andrew Levinson,2 Ravi Sarpatwari,2 Dominic Pisano,1 Klaus Görlinger,3,4 Gildasio De Oliveira1 1Department of Anesthesiology, The Warren Alpert Medical School of Brown University, Providence, RI, USA; 2Department of Medicine, The Warren Alpert Medical School of Brown University, Providence, RI, USA; 3Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany; 4Medical Department, Tem Innovations, Munich, GermanyCorrespondence: Mark C Kendall, Department of Anesthesiology, The Warren Alpert Medical School of Brown University, 593 Eddy Street, Davol #129, Providence, RI, 02903, USA, Tel +1 414-444-5172, Fax +1 414-444-5090, Email mark.kendall@lifespan.orgBackground: The aim of this study was to assess changes in hemostasis and associated outcome of hospitalized patients with COVID-19 infection and mild hypoxemia.Methods: Adult patients with COVID-19 infection and hypoxemia admitted to ICU were included in this prospective observational study. The primary outcome was defined as an unfavorable course of the disease if a patient: (1) developed a thromboembolic event while receiving anticoagulation prophylaxis, (2) had prolonged ICU stay, or (3) died. Demographic data, laboratory parameters and thromboelastometry (ROTEM) test results were collected.Results: Twenty-five patients were recruited into the study. There were 16 patients with an unfavorable course of the disease. Compared to the 9 patients in the favorable course group, patients with an unfavorable course had a lower platelet count, median difference of 154 (95% CI, 26 to 223 x109/L), P = 0.012, and lower clot firmness parameters in EXTEM assay: amplitude at 20 minutes (A20), median difference of 7 (95% CI, 2 to 11) P = 0.006, maximum clot firmness (MCF), median difference of 6 (95% CI, 3 to 10) P = 0.006 and area under the curve (AUC) with a median difference of 671 (95% CI, 244 to 1029) P = 0.005. They also demonstrated suppression of fibrinolysis: higher lysis index 60, median difference of − 3 (95% CI, − 6 to 0), P = 0.023. Results of functional fibrinogen (FIBTEM) assay were similar between the groups.Conclusion: The platelet count and the results of EXTEM assay, but not FIBTEM assay, were associated with the difference in clinical outcome among patients with COVID-19 infection and hypoxemia. The role of platelets in the outcome of COVID-19 infection calls for further investigation. Future studies on adjusting anticoagulant therapy based on the results of viscoelastic testing may be beneficial.Keywords: intensive care unit, thromboelastometry, coronavirus disease 2019, hypoxemia, hemostasis, thrombosis, recovery, mortality

In an analysis of risk evaluation and mitigation strategies for teratogenic drugs, Ameet Sarpatwari, Beatrice Brown and Aaron Kesselheim explore the variation in primary and secondary prevention measures.

PurposeThe US Food and Drug Administration (FDA) Amendments Act of 2007 authorized the FDA to require risk evaluation and mitigation strategy (REMS) programs for drugs with important safety concerns. REMS can have elements to assure safe use (ETASU), such as patient registries, dispensing restrictions, and physician training and certification requirements. We aimed to understand physician experiences with and perceptions of a selection of ETASU REMS.MethodsPhysicians prescribing 1 of 4 ETASU REMS-covered drugs: natalizumab, riociguat, sodium oxybate, and vigabatrin.Study designDescriptive phenomenological study based on semi-structured phone interviews.Data collection/extraction methodsQualitative content analysis to summarize physician responses to open-ended questions.ResultsOf 31 physicians (14 female), 6 prescribed riociguat, 6 vigabatrin, 7 sodium oxybate, and 12 natalizumab (5 for Crohn's disease, 7 for multiple sclerosis), most demonstrated good understanding of the rationale for and requirements of the ETASU REMS but believed that the programs had limited effect on clinical practice. Some physicians reported that the ETASU REMS made them more comfortable with prescribing covered drugs due to heightened oversight, facilitated discussions about treatment, and were likely more beneficial for non-specialists. Concerns were raised about the administrative effort needed to comply with the programs and the potential misuse of patient health information transmitted to manufacturers.ConclusionsPhysicians are generally aware of ETASU REMS and get reassurance from the additional oversight, but the programs can be better integrated into clinical workflows and can be designed to better protect patient health information.

Author(s): Beatrice L. Brown, Aaron S. Kesselheim, Ameet Sarpatwari * Key points Teratogenicity is a common reason for the US Food and Drug Administration (FDA) to apply risk evaluation and [...]

Importance: The Federal Trade Commission's (FTC) oversight role in the pharmaceutical market is critical to the health of patients and the health care system. This study characterized the FTC's policy on the pharmaceutical market in recent decades, identifying the types of actions it has favored, barriers it has faced, and authorities that remain untested. Objective: To review FTC legal actions in the pharmaceutical market from 2000-2022. Evidence Review: Legal actions were determined through manual review of search results from the FTC's online Legal Library as well as a 2023 FTC report on pharmaceutical actions. The alleged misconduct, type of legal action taken, timing, and outcome were collected from press releases, complaints, orders, and other legal documents. Findings: From 2000-2022, the FTC challenged 62 mergers, brought 22 enforcement actions against allegedly unlawful business practices, and made 1 rule related to pharmaceuticals. Alleged misconduct in enforcement actions involved anticompetitive settlements in patent litigation (n = 11), unilateral actions by brand manufacturers to delay generic competition (n = 6), noncompete agreements (n = 4), and monopolization (n = 3), with 10 outcomes involving monetary payment, totaling $1.6 billion. Of the 62 mergers the FTC challenged, 61 were allowed to continue, 58 after divesting certain drugs to third-party competitors. The FTC's reliance on drug divestitures decreased from 18 drugs per year from 2000-2017 to 4.3 per year from 2017-2023. Conclusions and Relevance: The FTC brought about 1 enforcement action and 3 merger actions per year against pharmaceutical manufacturers from 2000-2022, pursuing a small fraction of the estimated misconduct and consolidation in the pharmaceutical marketplace. Although the FTC faces substantial legal and practical limitations, important tools remain untested, including a rule defining "unfair methods of competition," that may allow it to more effectively prevent repetitive patterns of anticompetitive behavior. This Special Communication examines the Federal Trade Commission's policy and legal actions related to alleged misconduct, consolidation, and anticompetitive behavior in the pharmaceutical market between 2000 and 2022. [ABSTRACT FROM AUTHOR]

This document presents a study on the impact of skinny-label generic competition on Medicare Part D spending from 2015 to 2021. Skinny-label generics are generic drugs that are approved for a subset of the indications of the brand-name drug. The study found that skinny-label generic competition saved Medicare approximately $14.6 billion during this period. The savings were highest for drugs such as Crestor, Lyrica, and Gleevec. The study suggests that skinny-label generics can improve patient access to lower-cost medications and recommends reinforcing the skinny-label pathway to encourage timely generic competition. [Extracted from the article]

In January 2023, Moderna announced its intent to increase the price of the COVID-19 vaccine it co-developed with the National Institutes of Health (NIH) by 400%. The federal government should pressure Moderna to change course and resume buying doses for all Americans, leveraging its purchasing power to obtain a fair price. [ABSTRACT FROM AUTHOR]

BackgroundSome experts have proposed combating rising drug prices by promoting brand-brand competition, a situation that is supposed to arise when multiple US Food and Drug Administration (FDA)-approved brand-name products in the same class are indicated for the same condition. However, numerous reports exist of price increases following the introduction of brand-name competition, suggesting that it may not be effective. We performed a systematic literature review of the peer-reviewed health policy and economics literature to better understand the interplay between new drug entry and intraclass drug prices.Methods and findingsWe searched PubMed and EconLit for original studies on brand-brand competition in the US market published in English between January 1990 and April 2019. We performed a qualitative synthesis of each study's data, recording its primary objective, methodology, and results. We found 10 empirical investigations, with 1 study each on antihypertensives, anti-infectives, central nervous system stimulants for attention deficit/hyperactivity disorder, disease-modifying therapies for multiple sclerosis, histamine-2 (H2) blockers, and tumor necrosis factor (TNF) inhibitors; 2 studies on cancer medications; and 2 studies on all marketed or new drugs. None of the studies reported that brand-brand competition lowers list prices of existing drugs within a class. The findings of 2 studies suggest that such competition may help restrain how new drug prices are set. Other studies found evidence that brand-brand competition was mediated by the relative quality of competing drugs and the extent to which they are marketed, with safer or more effective new drugs and greater marketing associated with higher intraclass list prices. Our investigation was limited by the studies' use of list rather than net prices and the age of some of the data.ConclusionsOur findings suggest that policies to promote brand-brand competition in the US pharmaceutical market, such as accelerating approval of non-first-in-class drugs, will likely not result in lower drug list prices absent additional structural reforms.

BackgroundTo the extent that outcomes are mediated through negative perceptions of generics (the nocebo effect), observational studies comparing brand-name and generic drugs are susceptible to bias favoring the brand-name drugs. We used authorized generic (AG) products, which are identical in composition and appearance to brand-name products but are marketed as generics, as a control group to address this bias in an evaluation aiming to compare the effectiveness of generic versus brand medications.Methods and findingsFor commercial health insurance enrollees from the US, administrative claims data were derived from 2 databases: (1) Optum Clinformatics Data Mart (years: 2004-2013) and (2) Truven MarketScan (years: 2003-2015). For a total of 8 drug products, the following groups were compared using a cohort study design: (1) patients switching from brand-name products to AGs versus generics, and patients initiating treatment with AGs versus generics, where AG use proxied brand-name use, addressing negative perception bias, and (2) patients initiating generic versus brand-name products (bias-prone direct comparison) and patients initiating AG versus brand-name products (negative control). Using Cox proportional hazards regression after 1:1 propensity-score matching, we compared a composite cardiovascular endpoint (for amlodipine, amlodipine-benazepril, and quinapril), non-vertebral fracture (for alendronate and calcitonin), psychiatric hospitalization rate (for sertraline and escitalopram), and insulin initiation (for glipizide) between the groups. Inverse variance meta-analytic methods were used to pool adjusted hazard ratios (HRs) for each comparison between the 2 databases. Across 8 products, 2,264,774 matched pairs of patients were included in the comparisons of AGs versus generics. A majority (12 out of 16) of the clinical endpoint estimates showed similar outcomes between AGs and generics. Among the other 4 estimates that did have significantly different outcomes, 3 suggested improved outcomes with generics and 1 favored AGs (patients switching from amlodipine brand-name: HR [95% CI] 0.92 [0.88-0.97]). The comparison between generic and brand-name initiators involved 1,313,161 matched pairs, and no differences in outcomes were noted for alendronate, calcitonin, glipizide, or quinapril. We observed a lower risk of the composite cardiovascular endpoint with generics versus brand-name products for amlodipine and amlodipine-benazepril (HR [95% CI]: 0.91 [0.84-0.99] and 0.84 [0.76-0.94], respectively). For escitalopram and sertraline, we observed higher rates of psychiatric hospitalizations with generics (HR [95% CI]: 1.05 [1.01-1.10] and 1.07 [1.01-1.14], respectively). The negative control comparisons also indicated potentially higher rates of similar magnitude with AG compared to brand-name initiation for escitalopram and sertraline (HR [95% CI]: 1.06 [0.98-1.13] and 1.11 [1.05-1.18], respectively), suggesting that the differences observed between brand and generic users in these outcomes are likely explained by either residual confounding or generic perception bias. Limitations of this study include potential residual confounding due to the unavailability of certain clinical parameters in administrative claims data and the inability to evaluate surrogate outcomes, such as immediate changes in blood pressure, upon switching from brand products to generics.ConclusionsIn this study, we observed that use of generics was associated with comparable clinical outcomes to use of brand-name products. These results could help in promoting educational interventions aimed at increasing patient and provider confidence in the ability of generic medicines to manage chronic diseases.

This cross-sectional study identifies the prevalence of patents on risk evaluation and mitigation strategies and their association with delaying generic competition. [ABSTRACT FROM AUTHOR]