The United States is a relatively free-pricing market for pharmaceutical manufacturers to set list prices at the product launch. Few drug price controls exist, and federal price negotiation as a ...policy has historically been politically untenable. After decades of debate on whether the federal government, specifically the Medicare program, should more actively manage drug prices, the US Congress passed legislation authorizing Medicare to directly negotiate prices with manufacturers. The purpose of this article is to describe elements and implementation of the price negotiation provisions and then comment on the potential impacts on payers, innovations, and the pharmaceutical industry. While impacting only a few drugs each year in the beginning, price negotiation in the Medicare program will have secondary and long-term effects in the US market and beyond. It is clear that in the United States, the Medicare market for drugs will no longer be a free-pricing environment in the industry.
Increases in prescriptions of opioid medications for chronic pain have been accompanied by increases in opioid overdoses, abuse, and other harms and uncertainty about long-term effectiveness.
To ...evaluate evidence on the effectiveness and harms of long-term (>3 months) opioid therapy for chronic pain in adults.
MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, PsycINFO, and CINAHL (January 2008 through August 2014); relevant studies from a prior review; reference lists; and ClinicalTrials.gov.
Randomized trials and observational studies that involved adults with chronic pain who were prescribed long-term opioid therapy and that evaluated opioid therapy versus placebo, no opioid, or nonopioid therapy; different opioid dosing strategies; or risk mitigation strategies.
Dual extraction and quality assessment.
No study of opioid therapy versus no opioid therapy evaluated long-term (>1 year) outcomes related to pain, function, quality of life, opioid abuse, or addiction. Good- and fair-quality observational studies suggest that opioid therapy for chronic pain is associated with increased risk for overdose, opioid abuse, fractures, myocardial infarction, and markers of sexual dysfunction, although there are few studies for each of these outcomes; for some harms, higher doses are associated with increased risk. Evidence on the effectiveness and harms of different opioid dosing and risk mitigation strategies is limited.
Non-English-language articles were excluded, meta-analysis could not be done, and publication bias could not be assessed. No placebo-controlled trials met inclusion criteria, evidence was lacking for many comparisons and outcomes, and observational studies were limited in their ability to address potential confounding.
Evidence is insufficient to determine the effectiveness of long-term opioid therapy for improving chronic pain and function. Evidence supports a dose-dependent risk for serious harms.
Agency for Healthcare Research and Quality.
Abstract Clinical trials evaluating medicines, medical devices, and procedures now commonly assess the economic value of these interventions. The growing number of prospective clinical/economic ...trials reflects both widespread interest in economic information for new technologies and the regulatory and reimbursement requirements of many countries that now consider evidence of economic value along with clinical efficacy. As decision makers increasingly demand evidence of economic value for health care interventions, conducting high-quality economic analyses alongside clinical studies is desirable because they broaden the scope of information available on a particular intervention, and can efficiently provide timely information with high internal and, when designed and analyzed properly, reasonable external validity. In 2005, ISPOR published the Good Research Practices for Cost-Effectiveness Analysis Alongside Clinical Trials: The ISPOR RCT-CEA Task Force report. ISPOR initiated an update of the report in 2014 to include the methodological developments over the last 9 years. This report provides updated recommendations reflecting advances in several areas related to trial design, selecting data elements, database design and management, analysis, and reporting of results. Task force members note that trials should be designed to evaluate effectiveness (rather than efficacy) when possible, should include clinical outcome measures, and should obtain health resource use and health state utilities directly from study subjects. Collection of economic data should be fully integrated into the study. An incremental analysis should be conducted with an intention-to-treat approach, complemented by relevant subgroup analyses. Uncertainty should be characterized. Articles should adhere to established standards for reporting results of cost-effectiveness analyses. Economic studies alongside trials are complementary to other evaluations (e.g., modeling studies) as information for decision makers who consider evidence of economic value along with clinical efficacy when making resource allocation decisions.
Net prices of new antiobesity medications Hernandez, Inmaculada; Sullivan, Sean D.
Obesity (Silver Spring, Md.),
March 2024, 2024-Mar, 2024-03-00, 20240301, Letnik:
32, Številka:
3
Journal Article
Recenzirano
Objective
Glucagon‐like peptide‐1 receptor agonists (GLP1s) are effective antiobesity drugs and the subject of intense debate around insurance coverage due to the large prevalence of obesity and ...overweight. The estimation of the budget impact associated with GLP1 insurance coverage requires estimates of GLP1 prices that account for manufacturer discounts. The authors applied a peer‐reviewed method to estimate the net prices of GLP1s after manufacturer discounts.
Methods
The authors estimated manufacturer discounts for each product as the difference between the gross sales estimated at list price and manufacturer‐reported revenue. From this difference, the authors subtracted discounts to government programs, including 340B, Medicaid, and the Medicare Part D coverage gap, and attributed the remaining amount to manufacturer discounts provided in the commercial market.
Results
Manufacturer discounts for GLP1s approved for obesity were estimated at 41%, which translated into net prices of $717 to $761 per month of supply. Manufacturer discounts for GLP1s approved for type 2 diabetes ranged from 54% to 59%, which translated into net prices of $312 to $469 per month of supply.
Conclusions
The magnitude of manufacturer discounts underscores the need to consider net price information in studies that inform private and public payers' decision‐making around coverage of GLP1s for obesity.
Opioid overdose is a leading cause of accidental death in the United States.
To estimate the cost-effectiveness of distributing naloxone, an opioid antagonist, to heroin users for use at witnessed ...overdoses.
Integrated Markov and decision analytic model using deterministic and probabilistic analyses and incorporating recurrent overdoses and a secondary analysis assuming heroin users are a net cost to society.
Published literature calibrated to epidemiologic data.
Hypothetical 21-year-old novice U.S. heroin user and more experienced users with scenario analyses.
Lifetime.
Societal.
Naloxone distribution for lay administration.
Overdose deaths prevented and incremental cost-effectiveness ratio (ICER).
In the probabilistic analysis, 6% of overdose deaths were prevented with naloxone distribution; 1 death was prevented for every 227 naloxone kits distributed (95% CI, 71 to 716). Naloxone distribution increased costs by $53 (CI, $3 to $156) and quality-adjusted life-years by 0.119 (CI, 0.017 to 0.378) for an ICER of $438 (CI, $48 to $1706).
Naloxone distribution was cost-effective in all deterministic and probabilistic sensitivity and scenario analyses, and it was cost-saving if it resulted in fewer overdoses or emergency medical service activations. In a "worst-case scenario" where overdose was rarely witnessed and naloxone was rarely used, minimally effective, and expensive, the ICER was $14 000. If national drug-related expenditures were applied to heroin users, the ICER was $2429.
Limited sources of controlled data resulted in wide CIs.
Naloxone distribution to heroin users is likely to reduce overdose deaths and is cost-effective, even under markedly conservative assumptions.
National Institute of Allergy and Infectious Diseases.
Summary Background Chronic obstructive pulmonary disease (COPD) is a growing cause of morbidity and mortality worldwide, and accurate estimates of the prevalence of this disease are needed to ...anticipate the future burden of COPD, target key risk factors, and plan for providing COPD-related health services. We aimed to measure the prevalence of COPD and its risk factors and investigate variation across countries by age, sex, and smoking status. Methods Participants from 12 sites (n=9425) completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors. COPD prevalence estimates based on the Global Initiative for Chronic Obstructive Lung Disease staging criteria were adjusted for the target population. Logistic regression was used to estimate adjusted odds ratios (ORs) for COPD associated with 10-year age increments and 10-pack-year (defined as the number of cigarettes smoked per day divided by 20 and multiplied by the number of years that the participant smoked) increments. Meta-analyses provided pooled estimates for these risk factors. Findings The prevalence of stage II or higher COPD was 10·1% (SE 4·8) overall, 11·8% (7·9) for men, and 8·5% (5·8) for women. The ORs for 10-year age increments were much the same across sites and for women and men. The overall pooled estimate was 1·94 (95% CI 1·80–2·10) per 10-year increment. Site-specific pack-year ORs varied significantly in women (pooled OR=1·28, 95% CI 1·15–1·42, p=0·012), but not in men (1·16, 1·12–1·21, p=0·743). Interpretation This worldwide study showed higher levels and more advanced staging of spirometrically confirmed COPD than have typically been reported. However, although age and smoking are strong contributors to COPD, they do not fully explain variations in disease prevalence—other factors also seem to be important. Although smoking cessation is becoming an increasingly urgent objective for an ageing worldwide population, a better understanding of other factors that contribute to COPD is crucial to assist local public-health officials in developing the best possible primary and secondary prevention policies for their regions.
Abstract Background Budget impact analyses (BIAs) are an essential part of a comprehensive economic assessment of a health care intervention and are increasingly required by reimbursement authorities ...as part of a listing or reimbursement submission. Objectives The objective of this report was to present updated guidance on methods for those undertaking such analyses or for those reviewing the results of such analyses. This update was needed, in part, because of developments in BIA methods as well as a growing interest, particularly in emerging markets, in matters related to affordability and population health impacts of health care interventions. Methods The Task Force was approved by the International Society for Pharmacoeconomics and Outcomes Research Health Sciences Policy Council and appointed by its Board of Directors. Members were experienced developers or users of BIAs; worked in academia and industry and as advisors to governments; and came from several countries in North America and South America, Oceania, Asia, and Europe. The Task Force solicited comments on the drafts from a core group of external reviewers and, more broadly, from the membership of the International Society for Pharmacoeconomics and Outcomes Research. Results The Task Force recommends that the design of a BIA for a new health care intervention should take into account relevant features of the health care system, possible access restrictions, the anticipated uptake of the new intervention, and the use and effects of the current and new interventions. The key elements of a BIA include estimating the size of the eligible population, the current mix of treatments and the expected mix after the introduction of the new intervention, the cost of the treatment mixes, and any changes expected in condition-related costs. Where possible, the BIA calculations should be performed by using a simple cost calculator approach because of its ease of use for budget holders. In instances, however, in which the changes in eligible population size, disease severity mix, or treatment patterns cannot be credibly captured by using the cost calculator approach, a cohort or patient-level condition-specific model may be used to estimate the budget impact of the new intervention, accounting appropriately for those entering and leaving the eligible population over time. In either case, the BIA should use data that reflect values specific to a particular decision maker’s population. Sensitivity analysis should be of alternative scenarios chosen from the perspective of the decision maker. The validation of the model should include at least face validity with decision makers and verification of the calculations. Data sources for the BIA should include published clinical trial estimates and comparator studies for the efficacy and safety of the current and new interventions as well as the decision maker’s own population for the other parameter estimates, where possible. Other data sources include the use of published data, well-recognized local or national statistical information, and, in special circumstances, expert opinion. Reporting of the BIA should provide detailed information about the input parameter values and calculations at a level of detail that would allow another modeler to replicate the analysis. The outcomes of the BIA should be presented in the format of interest to health care decision makers. In a computer program, options should be provided for different categories of costs to be included or excluded from the analysis. Conclusions We recommend a framework for the BIA, provide guidance on the acquisition and use of data, and offer a common reporting format that will promote standardization and transparency. Adherence to these good research practice principles would not necessarily supersede jurisdiction-specific BIA guidelines but may support and enhance local recommendations or serve as a starting point for payers wishing to promulgate methodology guidelines.
Use of epidural corticosteroid injections is increasing.
To review evidence on the benefits and harms of epidural corticosteroid injections in adults with radicular low back pain or spinal stenosis ...of any duration.
Ovid MEDLINE (through May 2015), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, prior systematic reviews, and reference lists.
Randomized trials of epidural corticosteroid injections versus placebo interventions, or that compared epidural injection techniques, corticosteroids, or doses.
Dual extraction and quality assessment of individual studies, which were used to determine the overall strength of evidence (SOE).
30 placebo-controlled trials evaluated epidural corticosteroid injections for radiculopathy, and 8 trials were done for spinal stenosis. For radiculopathy, epidural corticosteroids were associated with greater immediate-term reduction in pain (weighted mean difference on a scale of 0 to 100, -7.55 95% CI, -11.4 to -3.74; SOE, moderate), function (standardized mean difference after exclusion of an outlier trial, -0.33 CI, -0.56 to -0.09; SOE, low), and short-term surgery risk (relative risk, 0.62 CI, 0.41 to 0.92; SOE, low). Effects were below predefined minimum clinically important difference thresholds, and there were no longer-term benefits. Limited evidence showed no clear effects of technical factors, patient characteristics, or comparator interventions on estimates. There were no clear effects of epidural corticosteroid injections for spinal stenosis (SOE, low to moderate). Serious harms were rare, but harms reporting was suboptimal (SOE, low).
The review was restricted to English-language studies. Some meta-analyses were based on small numbers of trials (particularly for spinal stenosis), and most trials had methodological shortcomings.
Epidural corticosteroid injections for radiculopathy were associated with immediate reductions in pain and function. However, benefits were small and not sustained, and there was no effect on long-term surgery risk. Limited evidence suggested no effectiveness for spinal stenosis.
Ocean Acidification and Human Health Falkenberg, Laura J.; Bellerby, Richard G.J.; Connell, Sean D. ...
International journal of environmental research and public health,
06/2020, Letnik:
17, Številka:
12
Journal Article
Recenzirano
Odprti dostop
The ocean provides resources key to human health and well-being, including food, oxygen, livelihoods, blue spaces, and medicines. The global threat to these resources posed by accelerating ocean ...acidification is becoming increasingly evident as the world’s oceans absorb carbon dioxide emissions. While ocean acidification was initially perceived as a threat only to the marine realm, here we argue that it is also an emerging human health issue. Specifically, we explore how ocean acidification affects the quantity and quality of resources key to human health and well-being in the context of: (1) malnutrition and poisoning, (2) respiratory issues, (3) mental health impacts, and (4) development of medical resources. We explore mitigation and adaptation management strategies that can be implemented to strengthen the capacity of acidifying oceans to continue providing human health benefits. Importantly, we emphasize that the cost of such actions will be dependent upon the socioeconomic context; specifically, costs will likely be greater for socioeconomically disadvantaged populations, exacerbating the current inequitable distribution of environmental and human health challenges. Given the scale of ocean acidification impacts on human health and well-being, recognizing and researching these complexities may allow the adaptation of management such that not only are the harms to human health reduced but the benefits enhanced.
Renal denervation lowers arterial blood pressure in both clinical populations and multiple experimental models of hypertension. This therapeutic effect is partly attributed to the removal of ...overactive renal sensory nerves. The TRPV1 (transient receptor potential vanilloid 1) channel is highly expressed in renal sensory nerves and detects changes in noxious and mechanosensitive stimuli, pH, and chemokines. However, the extent to which TRPV1 channels contribute to 2-kidney-1-clip (2K1C) renovascular hypertension has not been tested.
We generated a novel Trpv1
(TRPV1 knockout) rat using CRISPR/Cas9 and 26-bp deletion in exon 3 and induced 2K1C hypertension.
The majority (85%) of rat renal sensory neurons retrogradely labeled from the kidney were TRPV1-positive. Trpv1
rats lacked TRPV1 immunofluorescence in the dorsal root ganglia, had a delayed tail-flick response to hot but not cold water, and lacked an afferent renal nerve activity response to intrarenal infusion of the TRPV1 agonist capsaicin. Interestingly, 2K1C hypertension was significantly attenuated in male Trpv1
versus wild-type rats. 2K1C hypertension significantly increased the depressor response to ganglionic blockade, total renal nerve activity (efferent and afferent), and afferent renal nerve activity in wild-type rats, but these responses were attenuated in male Trpv1
rats. 2K1C hypertension was attenuated in female rats with no differences between female strains. Finally, glomerular filtration rate was reduced by 2K1C in wild-type rats but improved in Trpv1
rats.
These findings suggest that renovascular hypertension requires activation of the TRPV1 channel to elevate renal afferent and sympathetic nerve activity, reduce glomerular filtration rate, and increase arterial blood pressure.
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