Economic impact of generic substitution of lamotrigine: projected costs in the US using findings in a Canadian setting

ABSTRACT

Background: Generic substitution may not always save health care costs for antiepileptic drugs (AED).

Objective: (1) To examine the economic impacts of generic substitution of lamotrigine in Canada; and (2) to convert observed Canadian costs to a United States (US) setting.

Methods: Health claims from Québec's health plan (RAMQ) between 08/2002 and 07/2006 were analyzed. Patients with ≥ 1 epilepsy claim and treated with branded lamotrigine (Lamictal) before generic entry were selected. Health care costs ($/person-year) were compared during periods of branded and generic use of lamotrigine. Two cost-conversion methods were employed; one using purchasing power parities, US/Canada service use ratios, and exchange rate, and another employing Canadian health care utilization and US unit costs.

Results: 671 patients were observed during 1650.9 and 291.2 person-years of branded and generic use of lamotrigine, respectively. The generic-use period was associated with an increase in overall costs (2006 constant Canadian dollars) relative to brand use (C$7902 vs. C$6419/person-year; cost ratio (CR) = 1.22; p = 0.05), despite the lower cost of generic lamotrigine. Non-lamotrigine costs were 33% higher in the generic period (?p = 0.013). Both conversion methods yielded increases in total projected health care costs excluding lamotrigine (2006 constant US dollars) during the generic period (Method 1: cost difference: US$1758/person-year, CR = 1.33, p = 0.01); Method 2: cost difference: US$2516, CR = 1.39, p = 0.004).

Limitations: Study limitations pertain to treatment differences, indicators used for conversion and possible claim inaccuracies.

Conclusion: Use of generic lamotrigine in Canada was significantly associated with increased overall medical costs compared to brand use. Projected overall US health care costs would likely increase as well.     

The experiences of implementing generic medicine policy in eight countries: A review and recommendations for a successful promotion of generic medicine use

Generic medicines are clinically interchangeable with original brand medicines and have the same quality, efficacy and safety profiles. They are, nevertheless, much cheaper in price. Thus, while providing the same therapeutic outcomes, generic medicines lead to substantial savings for healthcare systems. Therefore, the quality use of generic medicines is promoted in many countries. In this paper, we reviewed the role of generic medicines in healthcare systems and the experiences of promoting the use of generic medicines in eight selected countries, namely the United States (US), the United Kingdom (UK), Sweden, Finland, Australia, Japan, Malaysia and Thailand. The review showed that there are different main policies adopted to promote generic medicines such as generic substitution in the US, generic prescribing in the UK and mandatory generic substitution in Sweden and Finland. To effectively and successfully implement the main policy, different complementary policies and initiatives were necessarily introduced. Barriers to generic medicine use varied between countries from negative perceptions about generic medicines to lack of a coherent generic medicine policy, while facilitators included availability of information about generic medicines to both healthcare professionals and patients, brand interchangeability guidelines, regulations that support generic substitution by pharmacists, and incentives to both healthcare professionals and patients.     

丙戊酸托吡酯治疗儿童特发性全身性癫痫疗效比较研究

目的：评价丙戊酸和托吡酯治疗儿童特发性全身性癫痫的疗效及耐受性。方法：对1999年10月至2003年4月来我院的152例首诊特发性全身性癫痫并接受丙戊酸或/和托吡酯治疗的病人进行随访。并对结果进行分析。结果：丙戊酸单药治疗完全控制率为63．41％。托吡酯单药治疗完全控制率40．00％,二者有显著差异;丙戊酸部分控制者添加托吡酯治疗31．25％完全控制,托吡酯治疗部分控制者添加丙戊酸后36．84％发作停止。无显著差异。两种药物的不良反应均较轻且耐受性较好。结论：丙戊酸是治疗儿童特发性全身性癫痫的最有效药物之一。如丙戊酸未能完全控制发作。添加托吡酯治疗疗效好。     

Potential economic impact of increasing low dose aspirin usage on CVD in the US

Abstract

Background:

Cardiovascular disease (CVD) is a leading cause of death in the US and Western Europe, but regular use of preventive low-dose aspirin has proven effective in preventing CVD events. The purpose of this study was to explore the potential economic impact in the US if preventive aspirin usage were to be increased in line with clinical guidelines for primary and secondary prevention.     

The economic implications of generic substitution of antiepileptic drugs: a review of recent evidence

Background: The US Food and Drug Administration (FDA) considers generic and branded drugs to be therapeutically equivalent if they are pharmaceutically equivalent and bioequivalent. The American Academy of Neurology (AAN) disagrees and opposes generic substitution of branded antiepileptic drugs (AEDs) without physician and patient approval due to the risk of loss of seizure control. Objective: To review the evidence to date surrounding the economic impact of brand-to-generic substitutions of AEDs. Methods: A systematic search of PubMed and MEDLINE was conducted; the bibliographies of key articles obtained from the search were used to identify additional sources. Results/conclusion: Current literature suggests statistically higher overall healthcare costs during periods of generic AED use than during periods when branded AED are used, consistently demonstrated across different countries (Canada and the USA) and in both stable and unstable epilepsy patients, with more pronounced cost increases in patients receiving multiple generic versions. Brand-to-generic substitutions of AEDs do not necessarily reduce overall healthcare costs and may even increase them.     

Timely confirmation of gastro-esophageal reflux disease via pH monitoring: estimating budget impact on managed care organizations*

ABSTRACT

Background: Current guidelines recommend the use of pH monitoring to confirm the diagnosis of acid reflux in patients with a normal endoscopy. This analysis evaluated the financial impact of pH monitoring with the wireless pH capsule on a managed care organization (MCO) in the United States.

Methods: A decision model was constructed to project total 1-year costs to manage GERD symptoms with and without the adoption of wireless pH capsules in a hypo­thetical MCO with 10?000 eligible adult enrollees, of whom 600 presented with GERD-like symptoms. Costs of GERD diagnosis, treatment, and symptom management for those in whom a GERD diagnosis was ruled out by pH monitor­ing were assessed. The incremental per-member-per-month (PMPM) and per-treated-member-per-month (PTMPM) costs were the primary outcomes. Data sources included literature, expert input, and standardized fee schedules.

Results: An increase of 10 percentage points in the use of pH monitoring with wireless pH capsules yielded incremental PMPM and PTMPM costs of $0.029 and $0.481, respectively. The costs of proton pump inhibitor (PPI) therapy to the plan dropped to $236?363 from $238?086, while increases were observed in pH monitor­ing (from $16?739 to $21?973) and non-GERD therapy costs (from $1392 to $1740). The results were sensitive to the percentage of patients requiring repeat endoscopy before wireless pH monitoring and the cost of PPIs.

Conclusions: Timely and increased use of pH monitor­ing as recommended in published guidelines leads to less unnecessary use of PPIs with a modest budgetary impact on health plans.     

左氧氟沙星仿制药与原研药用于非重症社区获得性肺炎的疗效及安全性回顾性对比研究

目的 探讨左氧氟沙星仿制药和原研药治疗非重症社区获得性肺炎(CAP)的疗效和安全性.方法 回顾性分析124例非重症CAP患者的病历资料,根据用药种类不同分为仿制组和原研组,各62例.仿制组采取仿制盐酸左氧氟沙星注射液治疗,原研组采取原研左氧氟沙星氯化钠注射液治疗.对比两组患者临床疗效、痰培养转阴率、退热时间、住院时间、...     

A systematic review of the clinical and economic impact of drug information services on patient outcome

Aim: to establish what is known about the clinical and economic impact of drug information (DI) services on patient outcome. Method: a systematic review and critical appraisal of world literature on work conducted by Drug Information Centres and UK Schools of Pharmacy.Results: six relevant published articles were recovered – three from the UK, two from the US and one from Canada; just one was prospective in design. Four were single-centre and two were multi-centre studies. Four studies relied heavily on questionnaire surveys of the enquirer to establish an effect; only one monitored patient outcome independently and used peer review to assess impact.Conclusion: the clinical and economic impact of drug information consultation and provision on patient care has not been investigated rigorously. A research methodology for such an investigation is suggested.     

Investigation on the need of multiple dose bioequivalence studies for prolonged-release generic products

In the European Union multiple dose bioequivalence studies are required for the approval of generic prolonged-release products, but they are not required by the US-FDA. In order to investigate if the multiple dose bioequivalence studies are necessary, the bioequivalence studies assessed in the Spanish Agency for Medicines and Health Care Products in the last 10 years were searched to find all reasons for rejection and identify those cases where the multiple dose study had failed to show bioequivalence and the single dose study had shown bioequivalence. In these latter cases, the plasma concentration at the end of the dosing interval (C_τ) in the single dose study was assessed to investigate its sensitivity to predict non-bioequivalence in the steady state.The search identified six cases where the non-equivalence in the multiple dose study was not detected by the corresponding single dose study. C_τ was not able to detect the difference in five cases and in general it was more variable than conventional metrics. In conclusion, the multiple dose bioequivalence study is necessary to ensure therapeutic equivalence and the use of C_τ would be counterproductive, increasing the sample size of the studies without enough sensitivity to detect differences in the steady state.     

Clinical and economic impact of clinical pharmacist interventions regarding antimicrobials on critically ill patients

BackgroundIncorporating in the Intensive Care Unit (ICU) a clinical pharmacist who performs interventions on antimicrobials may be cost-effective.ObjectivesTo evaluate the clinical and economic impact of clinical pharmacist interventions on antimicrobials in an ICU. To identify drug related problems and medication errors detected by the pharmacist.MethodsA retrospective observational study was performed to analyze drug related problems, medication errors and clinical pharmacist interventions related to antimicrobials in adults admitted to an ICU in a 5-month period. The economic impact of pharmacist interventions was estimated considering difference in cost derived from antimicrobial treatment, adverse drug events and clinical pharmacist time.ResultsA total of 212 drug related problems were detected in 114 patients, 18 being medication errors. Clinical pharmacist developed one intervention for each problem identified. 204 interventions (96.2%) were considered important with improved patient care and 7 (3.3%) very important. No negative impact of any intervention was identified. Physicians accepted 97.6% of the interventions. A potential saving of 10,905 € was estimated as a result of pharmacist interventions and 4.8 € were avoided per euro invested in a clinical pharmacist.ConclusionsA clinical pharmacist performing interventions on antimicrobials in the ICU has a positive impact on patient care and decreases costs.     

The effect of new biosimilars in rheumatology and gastroenterology specialities on UK healthcare budgets: Results of a budget impact analysis

Background

The approval of new biosimilars of infliximab, etanercept and adalimumab by the European Medicines Agency is expected to produce further cost savings to the healthcare system budget.

基于畅销药影响因素的定量研究

药品能否成为畅销药通常是制药企业在进行产品研发时最关注的问题。文中随机抽取1993-2009年FDA批准的所有新分子实体(NMEs)和新生物制品(BLAs)中的100个药物,按所选取的代理评价指标进行相关和回归分析。是否老年病、是否富贵病、是否难治愈疾病以及药品的首度研发药企是否世界500强公司这4个指标以高拟合度(R2=0.834)构成预测药物是否畅销的模型。所选取的评价指标对预测未来畅销药有一定参考意义。     

Effects of carbamazepine, phenytoin, valproic acid, oxcarbazepine, lamotrigine, topiramate and vinpocetine on the presynaptic Ca2+ channel-mediated release of [3H]glutamate: comparison with the Na+ channel-mediated release

The effect of carbamazepine, phenytoin, valproate, oxcarbazepine, lamotrigine and topiramate, that are among the most widely used antiepileptic drugs (AEDs), and of the new putative AED vinpocetine on the Ca(2+) channel-mediated release of [(3)H]Glu evoked by high K(+) in hippocampal isolated nerve endings was investigated. Results show that carbamazepine, oxcarbazepine and phenytoin reduced [(3)H]Glu release to high K(+) to about 30% and 55% at concentrations of 500 microM and 1500 microM, respectively; lamotrigine and topiramate to about 27% at 1500 microM; while valproate failed to modify it. Vinpocetine was the most potent and effective; 50 microM vinpocetine practically abolished the high K(+) evoked release of [(3)H]Glu. Comparison of the inhibition exerted by the AEDs on [(3)H]Glu release evoked by high K(+) with the inhibition exerted by the AEDs on [(3)H]Glu release evoked by the Na(+) channel opener, veratridine, shows that all the AEDs are in general more effective blockers of the presynaptic Na(+) than of the presynaptic Ca(2+) channel-mediated response. The high doses of AEDs required to control seizures are frequently accompanied by adverse secondary effects. Therefore, the higher potency and efficacy of vinpocetine to reduce the permeability of presynaptic ionic channels controlling the release of the most important excitatory neurotransmitter in the brain must be advantageous in the treatment of epilepsy.     

Centralized Pan-European survey on the under-treatment of hypercholesterolaemia (CEPHEUS): overall findings from eight countries

Abstract

Background:

Surveys evaluating plasma lipid goal attainment in patients with coronary heart disease have shown that hypercholesterolaemia is inadequately treated. Limited data account for the reasons behind this. The aim of the CEntralized Pan-European survey on tHE Under-treatment of hypercholeSterolaemia (CEPHEUS) survey was to evaluate the current use and efficacy of lipid-lowering drugs (LLD), and to identify possible patient/physician characteristics associated with failure to achieve low-density lipoprotein cholesterol (LDL-C) targets recommended by the 2003 European guidelines (Third Joint Task Force).     

Donepezil in Alzheimer's disease: an evidence-based review of its impact on clinical and economic outcomes

INTRODUCTION: Donepezil is indicated for the symptomatic treatment of mild to moderate Alzheimer's disease. It is a specific and reversible inhibitor of acetylcholinesterase (AChE); by increasing levels of available acetylcholine, donepezil may compensate for the loss of functioning cholinergic brain cells. AIMS: This review evaluates the clinical impact of donepezil by assessing randomized controlled and open-label naturalistic trials, as well as observational studies. A broad perspective is gained of its effectiveness on various outcomes. EVIDENCE REVIEW: There is strong evidence that donepezil has efficacy against the three major domains of Alzheimer's disease symptoms, namely functional ability, behavior, and cognition. The strongest evidence is for improvement or less deterioration in global outcomes and cognition in the short to medium term. There is limited evidence that improved global outcomes are maintained in the long term and clear evidence to support long-term maintenance of cognitive benefits. Also, donepezil appears to maintain function in the long term and there is some level 1 and 2 evidence of improved or limited deterioration in behavior or mood in the short to medium term. Despite donepezil's effects on major symptoms of Alzheimer's disease, its impact on patients' quality of life has not been consistently demonstrated, perhaps reflecting the difficulty of assessing this aspect in this patient population. Donepezil may also lessen caregiver burden. Donepezil has some effect on markers of brain function, but more data are needed to confirm a neuroprotective effect. There is limited and conflicting evidence that long-term donepezil treatment delays time to institutionalization. There is some evidence that donepezil may be cost effective, especially when unpaid caregiver costs are considered. Donepezil is generally safe and well tolerated. CLINICAL VALUE: AChE inhibitors are the only agents recommended for the treatment of cognitive decline in patients with mild to moderate Alzheimer's disease. Donepezil is more effective than placebo and is well tolerated in improving the major symptoms of this disease. Improvements are usually modest, although stabilization of cognitive and functional symptoms with donepezil can also be considered an important clinical outcome. Donepezil may lessen caregiver burden. Donepezil may also be cost effective, especially when unpaid caregiver costs are considered. More data are required from randomized controlled trials with long-term follow-up to confirm its cost effectiveness and impact on quality of life, disease progression, and time to institutionalization.     

欧洲药品局对在第三国进行临床试验的伦理和GCP问题的考虑

众所周知,欧洲药品管理局(EMA)是欧盟的一个非集权实体,主要职责是通过审评和监督人用药品和兽用药品保护并促进公众和动物健康。欧洲药品管理局负责对药品的欧洲上市许可申请(集中程序)进行技术审评。对来源于欧盟以外的临床研究数据,如何保证受试者的合法权益,保证临床研究符合伦理和GCP的要求,成为欧洲药品局关注的一个问题。2009年,EMA起草了"对在第三国进行的人用药品临床试验中以及向欧洲药品管理局递交的上市许可申请中的伦理和GCP草案"并广泛征求意见,2010年9月在伦敦召开会议对草案进行了讨论。本文主要介绍该草案的基本情况以及会议讨论要点。     

欧盟药物临床试验质量管理规范检查启动因素及结果研判的概述

如何有效地利用有限的监管资源,提高药物临床试验质量管理规范(GCP)检查的质量和效率,保证药物临床试验的质量和合规性,成为我国及其他各国药监机构所面临的挑战.本文以欧洲药物管理局(EMA)负责的集中审批程序的药品注册申请为例,对启动GCP检查的风险因素以及结果研判进行总结分析,以期为国内启动临床试验现场核查工作以及审评...     

Clinical and economic impact of using macrogol 3350 plus electrolytes in an outpatient setting compared to enemas and suppositories and manual evacuation to treat paediatric faecal impaction based on actual clinical practice in England and Wales

ABSTRACT

Objective: To estimate the clinical and economic impact of using macrogol 3350 plus electrolytes (macrogol 3350; Movicol; Movicol Paediatric Plain) in an outpatient setting compared to enemas and suppositories and manual evacuation to treat paediatric faecal impaction.

Methods: A chart review was undertaken to extract clinical outcomes and resource use from the case notes of a cohort of children aged 2–11 years with faecal impaction who initially received either macrogol 3350 (in an outpatient setting) or enemas and suppositories or manual evacuation for initial disimpaction. Five centres across England and Wales participated in the study. These data were used to inform a decision model which depicted the management of children during the disimpaction phase and for a period of 12 weeks following initial disimpaction. Unit resource costs at 2005/2006 prices were applied to the resource utilisation estimates within the model, enabling the incremental costs and consequences of using macrogol 3350 in an outpatient setting, compared to the other treatments, to be estimated.

Results: 112 patients treated with macrogol 3350, 101 who received enemas and suppositories and 11 who underwent a manual evacuation were eligible for analysis. Ninety-seven per cent of children treated with macrogol 3350 were successfully disimpacted within 5 days, compared to 73% of those who received enemas and suppositories and 89% of those who underwent a manual evacuation (?p < 0.001). There were no significant differences in reported adverse events between the different treatments for disimpaction, with the exception of vomiting which was significantly higher among those who underwent a manual evacuation (18% versus 2% with the other treatments; p < 0.01). There were no significant differences in the number of clinician outpatient visits between treatments. However, macrogol 3350-treated patients had significantly fewer hospital admissions than those who received the other interventions (0.1 versus 1.4 and 1.0 for enemas and suppositories and manual evacuation respectively; p < 0.05) and occupied fewer bed days. The total NHS cost of disimpaction and subsequent maintenance of children initially treated with macrogol 3350 was estimated to be £694 (95% CI: £496; £892). This compared with £2759 (95% CI: £1266; £4252) and £2333 (95% CI: £1609; £3058) for those who initially received enemas and suppositories or underwent a manual evacuation, respectively. Hence, using macrogol 3350 instead of enemas and suppositories and manual evacuation to disimpact the whole annual cohort of faecally impacted children aged 2–11 years in England could potentially reduce annual NHS expenditure on this condition by 59% (£5 million) and reduce the annual number of paediatric hospital admissions for this condition by 92% (4330).

Conclusion: Within the limitations of our model, macrogol 3350 affords the NHS a clinically effective and cost-effective treatment for the disimpaction of children suffering from faecal impaction compared to enemas and suppositories or a manual evacuation, and has the potential to release healthcare resources for alternative use within the system.