Illustrating Emerging Good Practices for Quantitative Benefit-Risk Assessment: A Hypothetical Case Study of Systemic Biologic Treatments for Plaque Psoriasis

ObjectivesQuantitative benefit-risk assessment (qBRA) is a structured process to evaluate the benefit-risk balance of treatment options to support decision making. The ISPOR qBRA Task Force was recently established to provide recommendations for the design, conduct, and reporting of qBRA. This report presents a hypothetical case study illustrating how to apply the Task Force’s recommendations toward a qBRA to inform the benefit-risk assessment of brodalumab at the time of initial marketing approval. The qBRA evaluated 2 dosing regimens of brodalumab (210 mg or 140 mg twice weekly) compared with weight-based dosing of ustekinumab and placebo.MethodsWe followed the 5 steps recommended by the Task Force. Attributes included treatment response (≥75% improvement in Psoriasis Area and Severity Index), suicidal ideation and behavior, and infections. Performance data were drawn from pivotal clinical trials of brodalumab. The qBRA used multicriteria decision analysis and preference weights from a hypothetical discrete choice experiment. Sensitivity analyses examined the robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, consideration of a subgroup (nail psoriasis), and the maintenance phase of treatment (52 weeks instead of 12).ResultsResults from this hypothetical qBRA suggest that brodalumab 210 mg had a more favorable benefit-risk profile compared with ustekinumab and placebo. Ranking of brodalumab compared with ustekinumab was dependent on brodalumab’s dose. Sensitivity analyses demonstrated robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, as well as choice of attributes and length of follow-up.ConclusionThis case study demonstrates how to implement the ISPOR Task Force’s good practice recommendations on qBRA.     

The Brucellae and Their Success as Pathogens

Brucellae are tiny, aerobic, slow growing, catalase and oxidase positive Gram negative coccobacilli or small rods, which may reach man through exposure to tissues of mammalian hosts via cuts or aerosols, or as food infections mostly through dairy products. As parasites brucellae are extraordinarily successful, causing very long-lasting infections in all mammalian social animals, such as ungulates, canids, and rodents; recently they have been found to also cause disease in pinnipeds and cetaceans. Brucellae as members of the alpha Proteobacteria, have suffered major losses of genomic material as they adapted to their facultative intracellular parasite role, and are able to initiate infection with minimal disturbance of the innate immune system, thus reaching a privileged intracellular niche where they multiply. Brucellae are likely to be among the toughest organisms to control through public health and agricultural policies, even involving detection-slaughter strategies.     

How better is random blinded re-checking results in Revised National TB Control Programme,India?

Background: The Revised National Tuberculosis Control Programme (RNTCP) is implementing the External Quality assurance (EQA) and Random blinded re-checking (RBRC) as one of its important component. This nationwide study was conducted to determine (1) the number and types of RBRC errors and (2) the sensitivity and specificity among rechecked slides. Materials and Methods: The study was based on the monthly RBRC reports submitted by ~13,000 designated microscopy centres (DMCs) across the country under routine programmatic settings in 2010. The DMCs reports were compiled at district, state and national level. Results: A total of 11, 89,564 slides were rechecked from 11,039 DMCs. Of which 99.5% of rechecked slides did not have any errors. The sensitivity and specificity of the rechecked slides had 98% sensitivity and 100% specificity. Conclusion: RBRC is the crucial component of EQA and the results from the programme are found to be satisfactory. Based on the study findings, the earlier value of 80% sensitivity used for calculation of annual sample size for RBRC has been increased to 90% sensitivity. The annual RBRC sample size for DMCs has been increased by 1.5–2 folds.     

Monitoring the patient response as an alternative to commercial negative quality control in infectious serology

BackgroundTraditional internal quality control schemes for qualitative infectious serology mostly rely on the use of commercial positive and negative quality control materials. However, with respect to the negative control, target values provided by the manufacturer are often poorly defined and non-commutability of the commercial materials further complicates correct interpretation of control results.An alternative quality control procedure using the median patient seronegative response is presented.Study designDaily patient median responses were calculated for our Hepatitis B surface antigen, Hepatitis B core antibody, Hepatitis C antibody and HIV antigen/antibody test systems. Because of the low prevalence of these viruses in our area, most patient responses are negative. A minimum of 5 patient samples per day was required to generate a stable daily median. Control limits were calculated and daily patient medians were plotted against commercial quality control results.ResultsCommercial negative controls and daily patient medians mostly behaved in the same way. Nevertheless, for the Hepatitis B surface antigen test, patient medians frequently exceeded the calculated control limit in contrast to commercial quality controls. This confirms that target ranges provided by the manufacturer are not always adequate. Moreover, an important matrix-related interference occurred on our HIV antigen/antibody test system and correct interpretation was only possible using daily patient median results.ConclusionMonitoring the daily patient median response can be a valuable alternative to traditional commercial negative quality control. It's easy to perform, cost-free, provides additional information with respect to matrix effects and allows for the establishment of well-defined control limits.     

Patient preferences and predicted relative uptake for targeted therapies in metastatic colorectal cancer: a discrete choice experiment

Abstract

Objective

Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients’ preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies.     

上海市闵行区暂住人口结核病人诊断延迟因素定性研究

[目的]分析上海市暂住人口结核病人诊断延迟情况及因素,为防制决策服务。[方法]对闵行区结核病防治工作人员、暂住人口结核病人进行访谈,对5家医院内科门诊和6家药店进行模拟患者观察。[结果]暂住人口结核病人诊断延迟情况严重,经济条件差是暂住人口就诊延迟的重要原因,卫生服务提供方(包括医院和药店)对病人诊断延迟造成一定影响。[结论]要改善暂住人口结核病人诊断延迟严重的状况,最主要的是要对暂住人口的结核病诊疗在政策给予优惠经济上给予适当减免。鉴于暂住人口生病后在药店买药情况普遍,药店从业人员的基本医药知识的保证也是值得关注的。     

Reduction of Cracks in Marble Appeared at Hydro-Abrasive Jet Cutting Using Taguchi Method

The appearance of cracks in brittle materials in general and in marble, in particular, is a problem in the hydro-abrasive jet cutting process. In this paper is presented a method to reduce the appearance of cracks when cutting with a hydro-abrasive jet of marble by using statistical analysis. The Taguchi method was used, establishing the main parameters that influence the process. Research design was based on performing experiments by modifying the parameters that influence the process. In this way, it has been shown that the stochastic effects resulting from the marble structure can be reduced. A careful study was made of the behavior of marble under the action of the hydro-abrasive jet, and of the behavior of the whole process in the processing of brittle materials. Results of experiments confirmed the hypothesis that statistical analysis is a procedure that can lead to a decrease in the number of cracks in processing. The measurement was performed with precise instruments and analyzed with recognized software and according to the results obtained, the reduction of the number of cracks is achieved through use of low pressure, a minimum stand-off distance and a small tube diameter. In this way, the paper presents a new and effective tool for optimizing the cutting with a hydro-abrasive jet of marble.     

正交实验法优选咳喘合剂的提取工艺

<正>咳喘合剂是杭州市红十字会医院的临床经验方,由蜜麻黄、蜜款冬花、蜜紫菀、浙贝、黄芩、前胡、甘草等12味中药组成,具有宣肺平喘,止咳化痰的功效,临床用于小儿急慢性支气管炎、哮喘、过敏性咳嗽及上呼吸道感染、感冒后痒咳等症。为了规范咳喘合剂的提取工艺,确保制剂的疗效,根据处方中药物各组分的理化性质及药理特点,结合中医临床用药经验,采用正交实验法对咳喘合剂进行了提取工