Availability and costs of medicines for the treatment of tuberculosis in Europe

ObjectivesTo evaluate the access to comprehensive diagnostics and novel antituberculosis medicines in European countries.MethodsWe investigated the access to genotypic and phenotypic Mycobacterium tuberculosis drug susceptibility testing and the availability of antituberculosis drugs and calculated the cost of drugs and treatment regimens at major tuberculosis treatment centres in countries of the WHO European region where rates of drug-resistant tuberculosis are the highest among all WHO regions. Results were stratified by middle-income and high-income countries.ResultsOverall, 43 treatment centres from 43 countries participated in the study. For WHO group A drugs, the frequency of countries with the availability of phenotypic drug susceptibility testing was as follows: (a) 75% (30/40) for levofloxacin, (b) 82% (33/40) for moxifloxacin, (c) 48% (19/40) for bedaquiline, and (d) 72% (29/40) for linezolid. Overall, of the 43 countries, 36 (84%) and 24 (56%) countries had access to bedaquiline and delamanid, respectively, whereas only 6 (14%) countries had access to rifapentine. The treatment of patients with extensively drug-resistant tuberculosis with a regimen including a carbapenem was available only in 17 (40%) of the 43 countries. The median cost of regimens for drug-susceptible tuberculosis, multidrug-resistant/rifampicin-resistant tuberculosis (shorter regimen, including bedaquiline for 6 months), and extensively drug-resistant tuberculosis (including bedaquiline, delamanid, and a carbapenem) were €44 (minimum–maximum, €15–152), €764 (minimum–maximum, €542–15152), and €8709 (minimum–maximum, €7965–11759) in middle-income countries (n = 12) and €280 (minimum–maximum, €78–1084), €29765 (minimum–maximum, €11116–40584), and €217591 (minimum–maximum, €82827–320146) in high-income countries (n = 29), respectively.DiscussionIn countries of the WHO European region, there is a widespread lack of drug susceptibility testing capacity to new and repurposed antituberculosis drugs, lack of access to essential medications in several countries, and a high cost for the treatment of drug-resistant tuberculosis.     

Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients

IntroductionPrescribing medication is an important aspect of almost all in-hospital treatment regimes. Besides their obviously beneficial effects, medicines can also cause adverse drug events (ADE), which increase morbidity, mortality and health care costs. Partially, these ADEs arise from medication errors, e.g. at the prescribing stage. ADEs caused by medication errors are preventable ADEs. Until now, medication ordering was primarily a paper-based process and consequently, it was error prone. Computerized Physician Order Entry, combined with basic Clinical Decision Support System (CPOE/CDSS) is considered to enhance patient safety. Limited information is available on the balance between the health gains and the costs that need to be invested in order to achieve these positive effects. Aim of this study was to study the balance between the effects and costs of CPOE/CDSS compared to the traditional paper-based medication ordering.MethodsThe economic evaluation was performed alongside a clinical study (interrupted time series design) on the effectiveness of CPOE/CDSS, including a cost minimization and a cost-effectiveness analysis. Data collection took place between 2005 and 2008. Analyses were performed from a hospital perspective. The study was performed in a general teaching hospital and a University Medical Centre on general internal medicine, gastroenterology and geriatric wards. Computerized Physician Order Entry, combined with basic Clinical Decision Support System (CPOE/CDSS) was compared to a traditional paper based system. All costs of both medication ordering systems are based on resources used and time invested. Prices were expressed in Euros (price level 2009). Effectiveness outcomes were medication errors and preventable adverse drug events.ResultsDuring the paper-based prescribing period 592 patients were included, and during the CPOE/CDSS period 603. Total costs of the paper-based system and CPOE/CDSS amounted to €12.37 and €14.91 per patient/day respectively. The Incremental Cost-Effectiveness Ratio (ICER) for medication errors was 3.54 and for preventable adverse drug events 322.70, indicating the extra amount (€) that has to be invested in order to prevent one medication error or one pADE.ConclusionsCPOE with basic CDSS contributes to a decreased risk of preventable harm. Overall, the extra costs of CPOE/CDSS needed to prevent one ME or one pADE seem to be acceptable.     

Detecting adverse drug reactions to improve patient outcomes.

Adverse drug reactions and inappropriate administration of medications account for poor outcomes for patients. They place patients in life-threatening situations, lead to increased health care costs, extend length of stay in hospitals, as well as increasing litigation. This paper will highlight the incidence of adverse drug events (ADE) in health care and show the low rate of detection within conventional medical records. I will also show how electronic medical records (EMR) improve detection of ADE, enhance clinician compliance to their management, improve patient outcomes, and reduce health care costs.     

Diet in phenylketonuria: a snapshot of special dietary costs and reimbursement systems in 10 international centers

Background and aimsTo gather exploratory data on the costs and reimbursement of special dietary foods used in the management of phenylketonuria (PKU) from ten international specialist PKU centers.MethodsExperts from each center provided data on retail costs of the three most frequently used phenylalanine-free protein substitutes and low-protein foods at their center; reimbursement of protein substitutes and low-protein foods; and state monetary benefits provided to PKU patients.ResultsThe mean annual cost of protein substitutes across 4 age groups (2 y, 8 y, 15 y and adults) ranged from €4273 to €21,590 per patient. The cost of low-protein products also differed; the mean cost of low-protein bread varied from €0.04 to €1.60 per 100 kcal. All protein substitutes were either fully reimbursed or covered by health insurance. However, reimbursement for low-protein products varied and state benefits differed between centers.ConclusionsThe variation in the cost and reimbursement of diet therapy and the level of additional state benefits for PKU patients demonstrates the large difference in expenditure on and access to PKU dietary products. This highlights the inequality between healthcare systems and access to special dietary products for people with PKU, ultimately leading to patients in some countries receiving better care than others.     

The Cost Effectiveness of Biologic Therapy for the Treatment of Chronic Plaque Psoriasis in Real Practice Settings in Italy

Background and Objectives

Biologic therapies are considered to be cost effective by leading Health Technology Assessment (HTA) agencies and, therefore, eligible for reimbursement by public health services. However, biologic therapies entail sizable incremental costs and, besides, have a considerable financial impact that in Italy amounts to 13.7 % of the national health service’s pharmaceutical expenditure. In the reimbursability decision process, an important role is played by both the drug efficacy data observed in pre-licensing RCTs and the economic modelling assumptions, as they give evidence on cost effectiveness. The administration of therapies in real practice settings is likely to produce a significant deviation from the results predicted by the models, theoretically outweighing the assumption on which the decision process is founded. This is a matter of concern for public health services and, consequently, an interesting topic to investigate.

Methods

To overcome the lack of knowledge concerning the actual cost effectiveness of biologic therapies for the treatment of plaque psoriasis in the clinical practice setting in Italy, an observational study was conducted in 12 specialist centres on patients switching to biologic therapy within a 6-month enrolment window.

Results

The study confirms in clinical practice the efficacy of the switch to biologic therapies, analysed using a number of clinical [Psoriasis Area and Severity Index (PASI), pain visual analogue scale (VAS) and itching VAS] and quality-of-life parameters. A general health-related quality of life (HR-QOL) improvement, with a 0.23 quality-adjusted life-year (QALY) mean gain per patient, has been reported in the 6-month observation period. The direct medical costs to treat plaque psoriasis with biologic therapies amount to €15,073.7 per year (prior to their enrolment, the same patients cost €2,166.2 on an annual basis). After the switch to biologic agents, the cost per QALY during the first year of treatment amounts to €28,656.3.

Conclusion

At least in the short-term, the clinical practice of the specialised Italian centres taking part in the study confirms that switching patients to a biologic drug produces an incremental cost-effectiveness ratio comparable with the values predicted by the HTA bodies.     

Possible adverse drug events leading to hospital admission in a Brazilian teaching hospital

OBJECTIVES:

Drug safety problems can lead to hospital admission. In Brazil, the prevalence of hospitalization due to adverse drug events is unknown. This study aims to estimate the prevalence of hospitalization due to adverse drug events and to identify the drugs, the adverse drug events, and the risk factors associated with hospital admissions.

METHOD:

A cross-sectional study was performed in the internal medicine ward of a teaching hospital in São Paulo State, Brazil, from August to December 2008. All patients aged ≥18 years with a length of stay ≥24 hours were interviewed about the drugs used prior to hospital admission and their symptoms/complaints/causes of hospitalization.

RESULTS:

In total, 248 patients were considered eligible. The prevalence of hospitalization due to potential adverse drug events in the ward was 46.4%. Overprescribed drugs and those indicated for prophylactic treatments were frequently associated with possible adverse drug events. Frequently reported symptoms were breathlessness (15.2%), fatigue (12.3%), and chest pain (9.0%). Polypharmacy was a risk factor for the occurrence of possible adverse drug events.

CONCLUSION:

Possible adverse drug events led to hospitalization in a high-complexity hospital, mainly in polymedicated patients. The clinical outcomes of adverse drug events are nonspecific, which delays treatment, hinders causality analysis, and contributes to the underreporting of cases.     

苏州吴江区社区医院2017年降压药使用情况分析

目的 通过收集2017年各类降压药销售金额和患者购买情况,分析各类降压药使用情况,以便进一步优化社区降压药的销售品种。方法 采用回顾性分析的方法,收集社区2017年全年门诊降压药的使用数据。计算各类药物的销售金额、用药频度（DDDs）、药物日均费用（DDDc）,并通过各药的DDDs排序（A）和用药金额排序（B）,计算比值（B/A）。结果 苯磺酸左旋氨氯地平片、厄贝沙坦片、盐酸贝那普利（洛汀新）、缬沙坦分散片（达乐）、非洛地平缓释片（波依定）DDDs值较高,临床对该类药的选择倾向性大,使用频率高。苯磺酸左旋氨氯地平片的B/A值为1.00、尼莫地平胶囊、琥珀酸美托洛尔缓释片、盐酸贝那普利（洛汀新）以及利尿剂的B/A值接近1,这些药同步性较好,药品的价格与患者的接受程度相一致。结论 门诊高血压患者最常用的降压药物是钙拮抗剂,其次为ACEI和ARB,应用最少的是利尿剂。我院降压药的使用情况基本合理,随着医疗卫生体制改革的变化,降压药的使用结构会越发合理。     

呼吸机中心的集中化管理

医院的呼吸机中心集中化管理可以充分提高呼吸机的利用率,解决呼吸机的供需矛盾,提高呼吸机的应用水平。作者以其所在单位为例,阐述了从呼吸机的购置、维修与维护直至报废全过程中应如何加强呼吸机中心的管理。论述结果说明呼吸机中心的集中化管理有利于医院呼吸机的统一调配,实现了全院呼吸机和专业人才资源共享,减少了资源浪费,解决了供需不平衡的矛盾,大大降低了医院采购呼吸机和维修呼吸机的成本。因此医院加强呼吸机中心的管理十分重要。     

Drug-induced hemolytic anemia: Pharmacological aspects

Drug-induced hemolytic anemia is a very rare but potentially lethal adverse drug reaction, which can take the form of oxidative damage to vulnerable erythrocytes (as in glucose-6-phosphate dehydrogenase deficiency), drug-induced thrombotic microangiopathy, or immune-mediated hemolytic anemia. For each form, distinctive drugs are documented as potential triggers. When a formal diagnosis of hemolytic anemia is made following drug administration, a structured approach is recommended to assess the plausibility of an adverse drug reaction based on chronological sequence, epidemiological data, objective evidence (when available), and ruling out of non-drug causes. For suspicions of immune-mediated hemolytic anemia, investigations by a laboratory with specific expertise are crucial given the complexity of the field. If there is good reason to believe hemolytic anemia is drug-induced, immediate drug discontinuation is necessary and corticosteroid administration can be considered. The clinical pharmacology specialist can support evaluation of drug imputability and report the case to the pharmacovigilance system, an important last step in managing such events.     

Cutting the nation's health care costs

In 1984 health care expenditures totaled $387.4 billion, and may reach $757.9 billion by 1990. The following factors and their annual cost overrun price tags are the prime forces behind this rapidly growing expense: professional liability insurance, litigations, and defensive medicine, $30 billion; hospital administrative management and employee excess, $6.3 billion; community hospital profits, $8.3 billion; oversupply and duplication of drugs and drug sundries, $22.5 billion; the oversupply of physician specialists, at least $10 to $15 billion; unsolicited physician interpretation of routine, unsophisticated tests, $13.2 billion; and, finally, an American lifestyle adversely affected by illicit drugs ($60 billion), alcohol ($117 billion), and automobile accidents ($43.3 billion), for a total cost of $220 billion yearly.     

The costs associated with adverse event procedures for an international HIV clinical trial determined by activity-based costing

OBJECTIVE: To determine costs for adverse event (AE) procedures for a large HIV perinatal trial by analyzing actual resource consumption using activity-based costing (ABC) in an international research setting. METHODS: The AE system for an ongoing clinical trial in Uganda was evaluated using ABC techniques to determine costs from the perspective of the study. Resources were organized into cost categories (eg, personnel, patient care expenses, laboratory testing, equipment). Cost drivers were quantified, and unit cost per AE was calculated. A subset of time and motion studies was performed prospectively to observe clinic personnel time required for AE identification. RESULTS: In 18 months, there were 9028 AEs, with 970 (11%) reported as serious adverse events. Unit cost per AE was $101.97. Overall, AE-related costs represented 32% ($920,581 of $2,834,692) of all study expenses. Personnel ($79.30) and patient care ($11.96) contributed the greatest proportion of component costs. Reported AEs were predominantly nonserious (mild or moderate severity) and unrelated to study drug(s) delivery. CONCLUSIONS: Intensive identification and management of AEs to conduct clinical trials ethically and protect human subjects require expenditure of substantial human and financial resources. Better understanding of these resource requirements should improve planning and funding of international HIV-related clinical trials.     

Short-term cost and efficiency analysis of raltegravir versus atazanavir/ritonavir or darunavir/ritonavir for treatment-naive adults with HIV-1 infection in Spain

Introduction: The AIDS Clinical Trial Group (ACTG) 5257 clinical trial showed that raltegravir (RAL) was superior to atazanavir/ritonavir (ATV/r) and darunavir/ritonavir (DRV/r), when used in combination with emtricitabine/tenofovir DF (FTC/TDF), in a 96-week composite endpoint combining virologic efficacy and tolerability for treatment-naive adults with HIV-1 infection. This study aimed to estimate the efficiency associated with these three regimens in Spain.

Methods: An economic model was developed to estimate costs for antiretroviral drugs, adverse event management, and HIV care for individuals initiating first-line therapy. Antiretroviral drug costs were based on hospital costs with mandatory discounts applied. Adverse event management costs and HIV care costs were obtained from published sources and inflated to 2015 euros. Head-to-head efficacy and safety data (discontinuation rates, mean CD4 cell-count changes, adverse event incidence) up to 96 weeks for each regimen were obtained from the clinical trial. The efficiency of each regimen, as measured by the cost per successfully treated patient (i.e. on first-line therapy for 96 weeks), was estimated and examined in sensitivity analyses. All cost outcomes were discounted at 3.0% annually.

Results: Total costs per successfully treated patient were €22,377 for RAL, €26,629 for ATV/r, and €23,928 for DRV/r. These results were found to be robust in sensitivity analyses.

Discussion: RAL has the lowest cost per successfully treated patient when compared with DRV/r and ATV/r, each used in combination with FTC/TDF, for treatment-naive adults with HIV-1 infection in Spain. This economic evidence complements the clinical benefits of RAL reported in the ACTG 5257 clinical trial.     

长期使用芬太尼透皮贴剂的疗效和安全性分析

 背景：芬太尼透皮贴剂与口服吗啡控释片的止痛效果相近,近年来已被广泛用于晚期癌痛止痛治疗,但与芬太尼相关的严重不良反应事件屡有报道,其长期使用的安全性受到某些质疑。 目的：探讨长期接受芬太尼透皮贴剂治疗对罹患晚期癌痛患者的临床疗效,并分析其安全性。 方法：纳入309例晚期癌痛患者,其中男143例,女166例,年龄26-72岁,前2周使用口服缓释吗啡止痛,第3周开始改用芬太尼透皮贴剂止痛,直至第12周。采用自身前后对照方法,比较两种药物的止痛效果、使用过程中的不良反应和毒性反应及患者的接受程度。 结果与结论：患者在使用口服缓释吗啡及芬太尼透皮贴剂期间疼痛均获得良好控制。使用口服吗啡缓释片治疗后,出现的不良反应依次为便秘、恶心、疲劳和食欲减退。在转换为芬太尼透皮贴后,便秘(χ²=5.22,P=0.02)、恶心(χ²=4.38,P=0.04)症状较口服吗啡缓释片治疗明显减轻,呕吐症状虽有所减轻但差异无显著性意义  (χ²=2.7,P=0.10);有2.3%患者出现皮肤反应,更换贴片区域后好转,皮肤反应在使用后2-10周时有所减轻,一些不常见的不良反应如头痛、腹泻、呼吸困难、出汗增多等症状在增加剂量后初期出现。与口服缓释吗啡相比,91%患者偏爱或强烈偏爱芬太尼透皮贴剂止痛治疗。说明芬太尼透皮贴剂可以稳定地控制疼痛,减轻口服药物的不良反应,具有良好的患者依从性。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Drug-induced bronchopulmonary pleural disease

More than 75 drugs are known to have adverse effects on the bronchopulmonary pleural system. Many of these drug reactions are fatal unless they are recognized, administration is stopped, and other measures are instituted. No data exist on the number of adverse drug reactions on the lung, because there is no mandatory reporting system in the United States. Probably less than 5% are reported. The clinician should be aware of the drugs that can produce adverse reactions on the lungs and stop the administration as soon as possible. In this article, I have classified the drugs known to produce adverse pulmonary effects as follows: chemotherapeutic, cardiovascular, antibiotic, and anti-inflammatory agents, drugs known to induce systemic lupus erythematosus, inhalants, illicit drugs such as heroin, and miscellaneous drugs. There are no blood tests or other means of diagnosing adverse drug effects on the lung. Chest roentgenographic findings are nonspecific. Pulmonary function abnormalities generally correlate with the degree of dyspnea and chest roentgenographic changes. Therefore, the clinician trying to explain the onset of pulmonary symptoms must be aware of the drugs the patient is taking.     

Evaluation of methods for recording adverse drug reactions in clinical trials

Four methods used for obtaining information from patients on adverse drug reactions are reviewed on the basis of personal experience. In the development of new therapeutic drugs the method which records all events experienced by a patient during drug treatment is to be preferred as it increases the possibility of detecting unanticipated or previously unreported adverse reactions. Disadvantage of this method is that a high number of events not related to drug treatment may be recorded, causing problems in analysis of the data.     

Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management: review of the EAACI/ENDA(#) and GA2LEN/HANNA*

Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for 21-25% of reported adverse drug events which include immunological and nonimmunological hypersensitivity reactions. This study presents up-to-date information on pathomechanisms, clinical spectrum, diagnostic tools and management of hypersensitivity reactions to NSAIDs. Clinically, NSAID hypersensitivity is particularly manifested by bronchial asthma, rhinosinusitis, anaphylaxis or urticaria and variety of late cutaneous and organ-specific reactions. Diagnosis of hypersensitivity to a NSAID includes understanding of the underlying mechanism and is necessary for prevention and management. A stepwise approach to the diagnosis of hypersensitivity to NSAIDs is proposed, including clinical history, in vitro testing and/or provocation test with a culprit or alternative drug depending on the type of the reaction. The diagnostic process should result in providing the patient with written information both on forbidden and on alternative drugs.     

Cost effective prescribing of proton pump inhibitors (PPI's) in the GMS Scheme

Total expenditure under the Community Drugs Schemes in Ireland on the proton pump inhibitors (PPI's) used for the management of patients with dyspepsia was approximately 64 million Euro in 2002, an 8-fold increase since 1995. As PPI maintenance therapy accounts for the majority of this expenditure we determined potential cost savings to the GMS scheme should the prescribing of these drugs for maintenance therapy follow published clinical and cost effectiveness guidelines. Substitution, in accordance with therapeutic indication, of the PPI with the greatest individual cost i.e. omeprazole (Losec Mups) with any of the alternative agents particularly the generic omeprazole preparations Ulcid & Lopraz, rabeprazole (Pariet) and pantoprazole (Protium) would be expected to produce cost savings in excess of 5 million Euro per annum. These savings may be further enhanced by increasing the step down from healing to maintenance doses of these drugs.     

Prediction of clinical risks by analysis of preclinical and clinical adverse events

This study examines the ability of nonclinical adverse event observations to predict human clinical adverse events observed in drug development programs. In addition it examines the relationship between nonclinical and clinical adverse event observations to drug withdrawal and proposes a model to predict drug withdrawal based on these observations. These analyses provide risk assessments useful for both planning patient safety programs, as well as a statistical framework for assessing the future success of drug programs based on nonclinical and clinical observations.Bayesian analyses were undertaken to investigate the connection between nonclinical adverse event observations and observations of that same event in clinical trial for a large set of approved drugs. We employed the same statistical methods used to evaluate the efficacy of diagnostic tests to evaluate the ability of nonclinical studies to predict adverse events in clinical studies, and adverse events in both to predict drug withdrawal. We find that some nonclinical observations suggest higher risk for observing the same adverse event in clinical studies, particularly arrhythmias, QT prolongation, and abnormal hepatic function. However the lack of these events in nonclinical studies is found to not be a good predictor of safety in humans. Some nonclinical and clinical observations appear to be associated with high risk of drug withdrawal from market, especially arrhythmia and hepatic necrosis. We use the method to estimate the overall risk of drug withdrawal from market using the product of the risks from each nonclinical and clinical observation to create a risk profile.