复方血栓通系列品种中四种皂苷通用检测方法研究

目的统一复方血栓通颗粒、片、滴丸和软胶囊中三七皂苷R1、人参皂苷Rg1、人参皂苷Re和人参皂苷Rb1的含量测定方法。方法采用高效液相色谱法,使用Thermo ODS2(5μm,150.0 mm×4.6 mm)色谱柱,柱温为20℃,以乙腈-水为流动相进行梯度洗脱,流速为1.0 ml/min,检测波长为203 nm。结果三七皂苷R1在0.0518~2.5900(r=0.9996)、人参皂苷Rg1在0.2090~8.3588(r=0.9991)、人参皂苷Re在0.0507~2.5371(r=0.9990)、人参皂苷Rb1在0.2044~8.1752(r=0.9995)范围内与峰面积线性关系良好;精密度、重复性、稳定性及加样回收率结果均能满足分析要求。结论该方法简单可行,为复方血栓通品种中三七皂苷R1、人参皂苷Rg1、人参皂苷Re和人参皂苷Rb1含量测定方法的统一提供了可靠的依据。     

Glycemic control among patients with type 2 diabetes who initiate basal insulin: a retrospective cohort study

Objective:

To examine changes in glycemic control for patients with type 2 diabetes mellitus (T2DM) after initiation of basal insulin and factors associated with improved glycemic control.

Methods:

An analysis of retrospective medical records of patients with T2DM was examined using Humedica’s electronic medical records database (January 2007–August 2012). Patients with T2DM, initiating basal insulin, age ≥21 years, with a recorded HbA1c test in both the 1 year prior and the 2 years post-initiation were included. A multivariate regression examined factors associated with changes in glycemic control. Logistic regressions examined factors associated with improvements or worsening of glycemic control, compared to relatively unchanged glycemic control.

Results:

Many (14,457) individuals met the inclusion–exclusion criteria. Multivariate analyses revealed that older age (p?p?p?=?0.0138), and higher household income (p?=?0.0065) were associated with improved glycemic control. Patients diagnosed with comorbid peripheral vascular disease (p?=?0.0072), cancer (p?=?0.0019), obesity (p?=?0.0002), moderate (p?=?0.0103), and severe chronic kidney disease (p?p?=?0.0075) in the pre-period were found to have significantly improved glycemic control in the post-period. Use of prandial insulin (p?=?0.0087), pre-mix insulin (p?=?0.0003) in the pre-period, a higher pre-period HbA1c score (p?p?Limitations:

Analyses rely on electronic medical records which cannot capture patient healthcare utilization occurring outside of the data capture system. Analyses do not control for insulin dosage or type of basal insulin prescribed.

Conclusions:

Among patients with T2DM treated with basal insulin, a number of factors may influence glycemic outcomes. These findings suggest a role for a more personalized approach to the treatment of patients with T2DM.     

Cost-effectiveness of switching to insulin degludec from other basal insulins in real-world clinical practice in Italy

Abstract

Aims: The costs associated with insulin therapy and diabetes-related complications represent a significant and growing economic burden for healthcare systems. The aim of this study was to evaluate the cost-effectiveness of switching to insulin degludec (degludec) vs continuing previous basal insulin, in Italian patients with type 1 (T1D) or type 2 (T2D) diabetes, using a long-term economic model.

Materials and methods: Data were retrieved from a real-world population of patients from clinical practice in Italy. Clinical parameters included in the base-case model were change from baseline in HbA_1c, rates of hypoglycemia, and basal and bolus insulin dose, at 6?months following switch to degludec. Costs of treatments were taken from official Italian pharmaceutical list prices and costs of hypoglycemia were based on the literature. The data were used to populate a long-term (lifetime) IQVIA CORE Diabetes Model to evaluate the incremental cost-effectiveness ratio (ICER) – cost per quality-adjusted life-year (QALY). The robustness of these results was tested with extensive sensitivity analyses by varying the time horizons and abolishing each of the treatment differences and previous basal insulins.

Results: The total incremental cost for degludec vs previous basal insulin was €–6,310 and €–2,682 for patients with T1D and T2D, respectively; the switch to degludec resulted in a QALY gain of 0.781 and 0.628. The long-term ICER for degludec vs continuing the previous basal insulin regimen showed that degludec was dominant for both T1D and T2D, meaning that patient health was improved in terms of QALYs with lower healthcare costs. Sensitivity analyses showed that degludec remained dominant in most scenarios including after elimination of any benefit in non-severe hypoglycemia and insulin dose, in both T1D and T2D.

Conclusions: Under routine care, switching to degludec is dominant, compared with continuing previous basal insulin, in Italian patients with T1D or T2D.     

药物制剂生产技术实训教学中存在的安全问题与对策

针对药物制剂生产技术实训教学中存在的安全问题进行了阐述,并提出了相应的对策,确保学生在实训教学中,做到安全操作,无隐患,不出人身、设备和产品质量等方面的事故。安全问题既是教学中的重要课题,也是每位实训老师的首要任务。     

Effects of Incumbency and R&D Affiliation on the Legitimation of Electric Vehicle Technologies

Non-economic forces distort “rational” competitions among emerging technologies and associated trajectories. For example, incumbent and credibly affiliated firms use their legitimacy to promote their technological preferences and denigrate the efforts of less legitimate firms. This article reports results of a study which examined these dynamics in the competition among emerging electrochemical innovations aimed at the electric vehicle industry. It also presents the first-known use of the technology forecasting technique called morphological analysis in business academia. Similarities and differences between media representations of innovation activities, versus actual industry-wide developments, were found to have theoretical and practitioner implications. It was found that (1) incumbent firms were not participating meaningfully, rendering that variable largely moot; (2) effects of R&D affiliation were marginally significant; that while (3) performance advantages and disadvantages were reported in the media much more frequently than respective cost-price advantages and disadvantages, that (4) the relative performance advantages and disadvantages of competing innovations were reported in a balanced way, but that (5) the pattern of reports concerning cost-price was unbalanced in a way that favored the dominant design plus relatively modest departures from it. The overall interpretation indicated that relatively modest types of innovations were “winning” the early battle in a subtle but important way, despite representing a trajectory that was not certain to be the most rational, from a performance and/or cost-price focus.     

An analysis of the cost-effectiveness of switching from biphasic human insulin 30, insulin glargine,or neutral protamine Hagedorn to biphasic insulin aspart 30 in people with type 2 diabetes

Abstract

Aims:

The aim of this analysis was to assess the cost-effectiveness of switching from biphasic human insulin 30 (BHI), insulin glargine (IGlar), or neutral protamine Hagedorn (NPH) insulin (all?±?oral glucose-lowering drugs [OGLDs]) to biphasic insulin aspart 30 (BIAsp 30) in people with type 2 diabetes in India, Indonesia, and Saudi Arabia.

Methods:

The IMS CORE Diabetes Model was used to determine the clinical outcome, costs, and cost-effectiveness of switching from treatment with BHI, IGlar, or NPH to BIAsp 30 over a 30-year time horizon. A 1-year analysis was also performed based on quality-of-life data and treatment costs. Incremental cost-effectiveness ratios (ICERs) were expressed as a fraction of gross domestic product (GDP) per capita, and cost-effectiveness was defined as ICER <3-times GDP per capita.

Results:

Switching treatment from BHI, IGlar, or NPH to BIAsp 30 was associated with an increase in life expectancy of >0.7 years, reduction in all diabetes-related complications, and was considered as cost-effective or highly cost-effective in India, Indonesia, and Saudi Arabia (BHI to BIAsp 30, 0.26 in India, 1.25 in Indonesia, 0.01 in Saudi Arabia; IGlar to BIAsp 30, ?0.68 in India, ?0.21 in Saudi Arabia; NPH to BIAsp 30, 0.15 in India, ?0.07 in Saudi Arabia; GDP per head per annum/quality-adjusted life-year). Cost-effectiveness was maintained in the 1-year analyses.

Conclusions:

Switching from treatment with BHI, IGlar, or NPH to BIAsp 30 (all?±?OGLDs) was found to be cost-effective in India, Indonesia, and Saudi Arabia, both in the long and short term.     

Insulin degludec versus insulin glargine U100 for patients with type 1 or type 2 diabetes in the US: a budget impact analysis with rebate tables

Background and aims: Drug rebates are almost universally negotiated privately between the manufacturer and the payer in the US. The aim of the present study was to illustrate the use of a “rebate table” to improve the transparency and utility of published budget impact analyses in the US by modeling ranges of hypothetical rebates for two comparators. Worked examples were conducted to illustrate the budgetary implications of using insulin degludec (IDeg) relative to insulin glargine (IGlar) U100 in patients with type 1 or 2 diabetes.

Methods: A short-term (1-year) budget impact model was developed to evaluate the costs of switching to IDeg from IGlar in patients with type 1 or 2 diabetes on basal-bolus and basal-only insulin, respectively. The analysis used insulin dose and hypoglycemia data from recent randomized trials, data on the prevalence of diabetes, and estimates of the proportion of patients using each insulin regimen. The model was configured to run multiple rebate scenarios to generate a rebate table in a hypothetical 1 million member commercial plan.

Results: Relative to IGlar, IDeg resulted in reductions in non-severe and severe hypoglycemia incidence and costs both in patients with type 1 and patients with type 2 diabetes. Insulin acquisition costs were higher, and respective rebates of 7.3% and 10.6% were required for IDeg to break-even with IGlar at the full list price. Incremental per member per month IDeg costs without a rebate were USD 0.04 in type 1 diabetes and USD 0.80 in type 2 diabetes.

Conclusions: Using IDeg instead of IGlar at list price could result in a modest increase in costs when considering insulin and hypoglycemia costs alone, but modest incremental rebates with IDeg would result in cost neutrality relative to IGlar. In addition, IDeg would result in reduced incidence of severe and non-severe hypoglycemia.     

Preferences for improvements in attributes associated with basal insulin: a time trade-off and willingness-to-pay survey of a diabetic and non-diabetic population in Sweden

Objective: Apart from improved health outcomes, treatment convenience per se may have a value to individuals. This is sometimes referred to as process utility and can be estimated in terms of willingness-to-pay (WTP) or quality-adjusted life-years (QALYs). Previous research has produced multiple studies on QALY gains and WTP estimates of insulin-related attributes. There are, however, significant variations between studies, and it is not clear to what extent the value is a reflection of the true preferences or a consequence of the methodological approach. The aim of this study is to estimate the preferences for treatment attributes associated with basal insulin (administration frequency, administration flexibility, and treatment-induced weight gain) using both QALYs—elicited using time trade-off (TTO) and WTP—among a sample of the Swedish general population and among a sample of the Swedish diabetes population.

Methods: Data was collected using web-based surveys which were distributed to members of internet panels. The WTP survey presented five hypothetical scenarios with an offer to pay the incremental cost to receive basal insulin with improved attributes. The TTO survey presented six hypothetical scenarios where the respondent could choose between living for the rest of his/her life with diabetes and receiving treatment with a basal insulin with certain attributes or live for a shorter time with full health. The scenarios were combined with either a basal or a basal–bolus treatment regimen. Results from the TTO analysis were translated into monetary estimates using a threshold value of SEK500,000 per QALY.

Results: In total, 2012 responses were included. The ratings of the attributes were almost identical, irrespective of method for the general population, while it differed to some extent for the diabetes population. The methods produced the same value for flexibility, but the estimates generated with the TTO approach were higher for one less injection and avoided weight gain. The general population assigned a higher utility gain to convenience attributes, while the diabetes population assigned a higher utility gain to avoiding weight gain.

Limitations: About a quarter of the respondents did not accept the scenario in the WTP survey, i.e. protesters.

Conclusions: The ranking of the attributes was generally independent of evaluation method, but the TTO method resulted in similar or higher values compared to the WTP method.     

Comparison of treatment costs in inadequately controlled type 2 diabetes in Germany based on the APOLLO trial with insulin glargine

Abstract

Objective: A cost analysis of once-daily insulin glargine versus three-times daily insulin lispro in combination with oral antidiabetic drugs (OADs) for insulin-naive type 2 diabetes patients in Germany based on the APOLLO trial (A Parallel design comparing an Oral antidiabetic drug combination therapy with either Lantus once daily or Lispro at mealtime in type 2 diabetes patients failing Oral treatment).

Methods: Annual direct treatment costs were estimated from the perspective of the German statutory health insurance (SHI). Costs accounted for included insulin medication, disposable pens and consumable items (needles, blood glucose test strips and lancets). Sensitivity analyses (on resource use and unit costs) were performed to reflect current German practice.

Results: Average treatment costs per patient per year in the base case were €1,073 for glargine and €1,794 for lispro. Insulin costs represented 65% vs. 37% of total costs respectively. Acquisition costs of glargine were offset by the lower costs of consumable items (€380 vs. €1,139). Sensitivity analyses confirmed the robustness of the results in favour of glargine. All scenarios yielded cost savings in total treatment costs ranging from €84 to €727.

Conclusions: Combination therapy of once-daily insulin glargine versus three-times daily insulin lispro both with OADs, in the management of insulin-dependent type 2 diabetes offers the potential for substantial cost savings from the German SHI perspective.     

Long-term cost-effectiveness analysis shows that IDegLira is associated with improved outcomes and lower costs compared with insulin glargine U100 plus insulin aspart in the US

Abstract

Aims: The clinical and economic impact of diabetes is growing in the US. Choosing therapies that are both effective and cost-effective is becoming increasingly important. The aim of the present analysis was to assess the long-term cost-effectiveness of IDegLira for treatment of patients with type 2 diabetes mellitus not meeting glycemic targets on basal insulin, vs insulin glargine U100 plus insulin aspart, in the US setting.

Materials and methods: Long-term projections of cost-effectiveness outcomes were made using the IQVIA CORE Diabetes Model. Clinical inputs were based on the DUAL VII trial, with costs (accounted from a healthcare payer perspective) and utilities based on published sources. Future costs and clinical benefits were discounted at 3% annually.

Results: IDegLira was associated with increased discounted life expectancy by 0.02 years and increased discounted quality-adjusted life expectancy by 0.22 quality-adjusted life years compared with insulin glargine U100 plus insulin aspart. Evaluation of direct medical costs suggested that the mean cost per patient with IDegLira was $3,571 lower than with insulin glargine U100 plus insulin aspart. The cost saving was driven predominantly by the lower acquisition cost of IDegLira compared with insulin glargine U100 plus insulin aspart, with further cost savings identified as a result of avoided treatment of diabetes-related complications. IDegLira was associated with improved clinical outcomes at a reduced cost compared with insulin glargine U100 plus insulin aspart.

Conclusions: Based on clinical trial data, the present analysis suggests that IDegLira is associated with improved clinical outcomes and cost savings compared with treatment with insulin glargine U100 plus insulin aspart for patients with type 2 diabetes not achieving glycemic control on basal insulin in the US. Therefore, IDegLira is likely to be considered dominant (cost saving and more effective) and, consequently, highly cost-effective in the US setting.