A review and validation of overall survival extrapolation in health technology assessments of cancer immunotherapy by the National Institute for Health and Care Excellence: how did the initial best estimate compare to trial data subsequently made available?

Background: Validation of overall survival (OS) extrapolations of immune-checkpoint inhibitors (ICIs) during the National Institute for Health and Care Excellence (NICE) Single Technology Assessment (STA) process is limited due to data still maturing at the time of submission. Inaccurate extrapolation may lead to inappropriate decision-making. The availability of more mature trial data facilitates a retrospective analysis of the plausibility and validity of initial extrapolations. This study compares these extrapolations to subsequently available longer-term data.

Methods: A systematic search of completed NICE appraisals of ICIs from March 2000 to December 2017 was performed. A targeted search was also undertaken to procure published OS data from the pivotal clinical trials for each identified STA made available post-submission to NICE. Initial Kaplan-Meier curves and associated extrapolations from NICE documentation were extracted to compare the accuracy of OS projections versus the most mature data.

Results: The review identified 11 STAs, of which 10 provided OS data upon submission to NICE. The extrapolations undertaken considered parametric or piecewise survival models. Additional data cut-offs provided a mean of 18 months of OS beyond the end of the original data. Initial extrapolations typically under-estimated OS from the most mature data cut-off by 0.4–2.7%, depending on the choice of assessment method and use of the manufacturer- or ERG-preferred extrapolation.

Conclusion: Long-term extrapolation of OS is required for NICE STAs based on initial immature OS data. The results of this study demonstrate that the initial OS extrapolations employed by manufacturers and ERGs generally predicted OS reasonably well when compared to more mature data (when available), although on average they appeared to underestimate OS. This review and validation shows that, while the choice of OS extrapolation is uncertain, the methods adopted are generally aligned with later-published follow-up data and appear appropriate for informing HTA decisions.     

Economic modelling of costs associated with outcomes reported for type 2 diabetes mellitus (T2DM) patients in the CANVAS and EMPA-REG cardiovascular outcomes trials

Aims: To model direct medical costs associated with reductions in cardiovascular disease (CVD) events in T2DM patients reported in the CANVAS and EMPA-REG trials, which assessed the cardiovascular safety of canagliflozin and empagliflozin, respectively.

Materials and methods: Costs were modeled from a US managed care organization (MCO) perspective for the CVD outcomes included in both trials: three-point major adverse cardiovascular event (MACE) and its components (cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke), as well as heart failure requiring hospitalization. The rate of CVD events averted (difference between study drug and placebo) was projected to the portion of an MCO T2DM population matching the respective trial’s inclusion criteria. A targeted literature search for paid amounts directly associated with each CVD event provided the unit costs, which were applied to the projected number of events averted, to calculate costs avoided per member per year (PMPY). One-way sensitivity analyses were performed on events averted, unit costs, and percentages of trial-applicable patients.

Results: Based on three-point MACE events averted, costs avoided PMPY of $6.17 (range: $1.27–$10.94) for CANVAS and $2.75 ($0.19–$4.83) for EMPA-REG were estimated. Costs avoided for individual components of MACE ranged from $0.77 to $3.84 PMPY for CANVAS and from -$0.97 (additional costs) to $1.54 for EMPA-REG. PMPY costs avoided for heart failure were $2.72 for CANVAS and $1.32 for EMPA-REG.

Limitations and conclusions: Models assumed independent, non-recurrent outcomes and were restricted to medical costs directly associated with the trial-reported events. The reductions in CVD events in T2DM patients reported for both CANVAS and EMPA-REG project to a positive cost avoidance for these events in an MCO population. The analysis did not include an assessment of the impact on total cost, as the costs associated with adverse events, drug utilization or other clinical outcomes were not examined.     

Understanding Motivations,Inhibitors, and Facilitators of Association Members in Attending International Conferences

Abstract

This study examined the motivations, inhibitors, and facilitators that influence association members in attending international conferences. Mailed questionnaires were sent to conference participants of the 2000 International Council of Hotel, Restaurant Industry Educators (CHRIE) conference. It was found that “Sightseeing,” “Self-enhancement,” and “Business and association activities” are the underlying dimensions of the conference motivations. The underlying dimensions of conference inhibitors are “Conference and personal constraints” and “Distance, time, and money.” The study also revealed that “Affordability and availability of time,” “Family/spouse,” and “Distance and ease of access” are major conference facilitators.     

The management of acid-related disorders: the burden of disease and the need for effective treatment

Summary

A large and increasing number of people suffer from acid-related disorders such as dyspepsia, gastro-oesophageal reflux disease (GORD), and peptic ulcer disease. In 1994 alone, about 2 million patients consulted their family doctor for an acid-related disorder. Treatment of these patients represents a high cost to the NHS in terms of medications, consultations, referrals and treatment of complications. UK government statistics also indicate that there is a huge economic burden associated with acid-related disorders in terms of lost productivity.

Effective management of acid-related disorders is required to ensure that the available resources are used efficiently and to the benefit of the NHS, society and the patient.

Proton pump inhibitors are the most effective and predictable therapy available for acid-related disorders and many clinical studies have demonstrated their superior efficacy over H2-receptor antagonists in the management of these conditions. These therapeutic advantages translate into economic gains. Several economic studies have shown that it is more cost-effective to treat GORD and peptic ulcer disease with the proton pump inhibitor omeprazole than with H2-receptor antagonists.     

零售企业破坏性创新及其制约因素：一个理论框架

自中国零售市场对外开放以来，本土零售企业一直在复制与模仿外资零售企业的道路上艰难前行，虽有发展，但始终无法超越外资零售企业，更无法获得可持续的竞争优势。文章认为，本土零售企业只有走破坏性创新道路才有可能获得长足发展，进而阐述了本土零售企业进行破坏性创新的空间基础和破坏性创新过程，并对阻碍零售企业破坏性创新的因素进行了探讨，这些因素可分为四类：行为采纳障碍、思想障碍、风险障碍、创新过程的先期障碍。     

Large-scale participatory co-shaping of technological developments: First experiments with PARDIZIPP

A future-oriented participatory procedure on the basis of the Delphi method was developed and empirically tested a first time with the goal to improve the shaping of technological developments. The technology under study here was micro-electronics or rather their relationship with labor and the test took place in NorthRhine-Westphalia.Today problems exist in all walks of life. There is a lot of talk about today's problems as if they were new, though one has heard similar arguments throughout history. How do we assess if we are really in danger of bringing the world to an end? Although this danger appears real, it would not be the first time in history that people have thought and felt like this--However, one thing that is new are the consequences of modern sciences and technology, which are not suited to given social and environmental requirements. They have given rise to questions concerning the quality of the decision-makers. The questioning of many of these decisions has increased for some time and is now getting more and more specific, with a demand for quality and information rather than managerial skills and competitiveness from the decision-makers. The term ‘decision-maker’ describes those who determine the application of technology, science and technical equipment which has either existed for a long time already or has recently been developed.--It is not easy to change the structures and processes of decision-making so that new structures and processes will be more suited to social and environmental requirements. We have tested our ideas as to how this could be done, in an empirical project. Although we called it ‘Project NRW-2000’, it would probably be better described as an experiment.--We persuaded 90 ordinary people to participate in this project as ‘experts on daily life and work’. This group was asked to work in six regional sub-groups and discuss, with reference to three given normative societal scenarios for the year 2020, the relationship between microelectronics and labour markets of the year 2020, on the basis of a participatory Delphi procedure. Before we elaborate on the concept of our project in Section 3, we would like to outline it in terms of the mainstream of the sociology of technology as well as with research on ‘acceptance’ in Section 1. In Section 2 we will briefly illustrate the framework of the research programme ‘Socially Oriented Shaping of Technology’ of the state of Northrhine-Westphalia, which funded our research project. Section 4 particularly deals with the participatory elements of our project, while Section 5 is devoted to the development of the scenarios. Section 6 sums up the results of the ‘scenario-construction’. Regarding specific elements, we restrict ourselves to topics concerning technology, labour, and the relationship between women workers/employees and technology. As a final outlook we deal with the political implications of our approach. All that is left is to remind our readers that we regard this project as a first application or experiment within our overall approach.     

Healthcare and economic burden of adverse events among patients with chronic myelogenous leukemia treated with BCR-ABL1 tyrosine kinase inhibitors

Objectives: BCR-ABL1 tyrosine kinase inhibitors (TKIs) are established treatments for chronic myelogenous leukemia (CML); however, they are associated with infrequent, but clinically serious adverse events (AEs). The objective of this analysis was to assess healthcare resource utilization and costs associated with AEs, previously identified using the FDA Adverse Event Reporting System (FAERS) in another study, among TKI-treated patients.

Methods: Adult patients with ≥1 inpatient or ≥2 outpatient ICD-9-CM diagnosis codes for CML and ≥1 claim for a TKI treatment between January 1, 2006 and September 30, 2012 were identified from the Commercial and Medicare MarketScan databases. The first claim for a TKI was designated as the index event. Patients were required to have no TKI treatment during a 12-month baseline period. Healthcare resource utilization and costs associated with select AEs having the strongest association with TKI treatment (femoral arterial stenosis [FAS], peripheral arterial occlusive disease [PAOD], intermittent claudication, coronary artery stenosis [CAS], pericardial effusion, pleural effusion, malignant pleural effusion, conjunctival hemorrhage) were evaluated during a 12-month follow-up period.

Results: The study sample included 2,005 CML patients receiving TKI therapy (mean age?=?56 years; 56% male). Among all evaluated AEs, the highest mean inpatient healthcare costs were observed for FAS ($16,800 per patient) and PAOD ($14,263 per patient), which had total mean medical costs (inpatient?+?outpatient) of $17,015 and $15,154 per patient, respectively. Mean outpatient healthcare costs were highest for CAS ($1,861 per patient), followed by intermittent claudication ($947 per patient), PAOD ($891 per patient), and pleural effusion ($890 per patient). Total mean medical costs for fluid retention-related AEs, including pericardial effusion and pleural effusion, were $2,797 and $1,908 per patient, respectively.

Conclusions: The healthcare costs of AEs identified in the FAERS as having the strongest association with TKI treatment are substantial. Vascular stenosis-related AEs, including FAS and PAOD, have the highest cost burden.     

Economic modeling to evaluate the impact of chronic myeloid leukemia therapy management on the oncology care model in the US

Abstract

Objective: To develop an economic model to evaluate changes in healthcare costs driven by restricting usage of branded tyrosine kinase inhibitors (TKIs) through substitution with generic imatinib among chronic myeloid leukemia (CML) patients in a typical Oncology Care Model (OCM) practice, and examine the impact on Performance-Based Payment (PBP) eligibility.

Methods: An Excel-based economic model of an OCM practice with 1,000 cancer patients during a 6-month episode of care was developed. Cancer types and proportions of patients treated in the practice were estimated from an OCM report. All-cause healthcare costs were obtained from published literature. It was assumed that if a practice restricts usage of branded TKIs for newly-diagnosed CML patients, 80% of the market share of branded imatinib and 50% of the market shares of 2^nd-gen TKIs would shift to generic imatinib. Among established TKI-treated patients, it was assumed that 80% of the market share of branded imatinib and no patients treated with 2^nd-gen TKIs would shift to the generic.

Results: Four CML patients were estimated for a 1,000-cancer patient OCM practice with a total baseline healthcare cost of $51,345,812 during a 6-month episode. If the practice restricts usage of branded TKIs, the shift from 2^nd-gen TKIs to generic imatinib would reduce costs by $12,970, while shifting from branded to generic imatinib lowers costs by $25,250 during a 6-month episode. Minimum reductions of $3,013,832 in a one-sided risk model and $2,372,010 in a two-sided risk model are required for PBP eligibility; the shift from 2^nd-gen TKIs to generic imatinib would account for 0.4% and 0.5% of the savings required for a PBP, respectively.

Conclusions: This analysis indicates that the potential cost reduction associated with restricting branded TKI usage among CML patients in an OCM setting will represent only a small proportion of the cost reduction needed for PBP eligibility.     

A Pilot Study of Motivations,Inhibitors, and Facilitators of Association Members in Attending International Conferences

Abstract

This study examined motivation, inhibitors, and facilitators of association members in attending international conferences. A survey questionnaire was used to measure the importance of those factors in influencing the subjects during the conference attendance decision process. The study revealed that opportunities for travel to overseas destinations, outdoor recreation, business or political activities, change of pace, networking, and education were important factors which motivated the respondents in attending international conferences. Perceived risks of safety, inconvenience, and unfamiliarity with overseas destinations, distance, time, money, health problems, and possible security problems of overseas destinations inhibit people from attending conferences. The respondents considered deals on overseas travel packages, opportunities to do activities with family at overseas destinations, and costs covered by their employer as important factors that facilitate their attendance at international conferences.     

陕西省优秀竞技健美操运动员冬训期机能监控

本文通过对陕西省优秀竞技健美操运动员冬训期Hb、CK、BUN、T的跟踪监控,试图分析与研究其训练特点和相关生理生化指标的变化规律。研究结果表明其基本上适应训练计划负荷,训练安排比较合理科学,机能监控发挥了非常重要的作用。