Cost-effectiveness of novel relapsed-refractory multiple myeloma therapies in Norway: lenalidomide plus dexamethasone vs bortezomib.

OBJECTIVE: To estimate the cost-effectiveness (cost per additional life-year [LY] and quality-adjusted life-year [QALY] gained) of lenalidomide plus dexamethasone (LEN/DEX) compared with bortezomib for the treatment of relapsed-refractory multiple myeloma (rrMM) in Norway. METHODS: A discrete-event simulation model was developed to predict patients? disease course using patient data, best response, and efficacy levels obtained from LEN/DEX MM-009/-010 trials and the bortezomib (APEX) published clinical trial. Predictive equations for time-to-progression (TTP) and post-progression survival (PPS) were developed by identifying the best fitting parametric survival distributions and selecting the most significant predictors. Disease and adverse event management was obtained via survey from Norwegian experts. Costs, derived from official Norwegian pricing data bases, included drug, administration, monitoring, and adverse event management costs. RESULTS: Complete or partial responders were 65% for LEN/DEX compared to 43% for bortezomib. Derived median TTP was 11.45 months for LEN/DEX compared to 5.15 months for bortezomib. LYs and QALYs were higher for LEN/DEX (4.06 and 2.95, respectively) than for bortezomib (3.11 and 2.19, respectively). The incremental costs per QALY and LY gained from LEN/DEX were NOK 247,978 and NOK 198,714, respectively, compared to bortezomib. Multiple sensitivity analyses indicated the findings were stable. The parameters with the greatest impact were 4-year time horizon (NOK 441,457/QALY) and higher bound confidence intervals for PPS (NOK 118,392). LIMITATIONS: The model analyzed two therapies not compared in head-to-head trials, and predicted results using an equation incorporating patient-level characteristics. It is a limited estimation of the costs and outcomes in a Norwegian setting. CONCLUSIONS: The simulation model showed that treatment with LEN/DEX leads to greater LYs and QALYs when compared to bortezomib in the treatment of rrMM patients. The incremental cost-effectiveness ratio indicated treatment with LEN/DEX to be cost-effective and was the basis of the reimbursement approval of LEN/DEX in Norway.

Cost-effectiveness of diabetes case management for low-income populations.

OBJECTIVE: To evaluate the cost-effectiveness of Project Dulce, a culturally specific diabetes case management and self-management training program, in four cohorts defined by insurance status. DATA SOURCES/STUDY SETTING: Clinical and cost data on 3,893 persons with diabetes participating in Project Dulce were used as inputs into a diabetes simulation model. STUDY DESIGN: The Center for Outcomes Research Diabetes Model, a published, peer-reviewed and validated simulation model of diabetes, was used to evaluate life expectancy, quality-adjusted life expectancy (QALY), cumulative incidence of complications and direct medical costs over patient lifetimes (40-year time horizon) from a third-party payer perspective. Cohort characteristics, treatment effects, and case management costs were derived using a difference in difference design comparing data from the Project Dulce program to a cohort of historical controls. Long-term costs were derived from published U.S. sources. Costs and clinical benefits were discounted at 3.0 percent per annum. Sensitivity analyses were performed. PRINCIPAL FINDINGS: Incremental cost-effectiveness ratios of $10,141, $24,584, $44,941, and $69,587 per QALY gained were estimated for Project Dulce participants versus control in the uninsured, County Medical Services, Medi-Cal, and commercial insurance cohorts, respectively. CONCLUSIONS: The Project Dulce diabetes case management program was associated with cost-effective improvements in quality-adjusted life expectancy and decreased incidence of diabetes-related complications over patient lifetimes. Diabetes case management may be particularly cost effective for low-income populations.

An evaluation of patient preference for an alternative insulin delivery system compared to standard vial and syringe.

BACKGROUND: Diabetes mellitus (DM) affects over 18.2 million Americans and diabetes-related medical costs exceed 132 billion dollars per year, totaling more than 12% of the United States healthcare budget. The Diabetes Control and Complications Clinical Trial demonstrated that intensive insulin therapy and the control of plasma glucose can significantly reduce the incidence of late diabetic complications and delay the progression of existing conditions in type 1 diabetes. Optimal glycemic control often requires intensive insulin therapy to maintain a hemoglobin A(1C) (A1C) of less than 7% as recommended by the American Diabetes Association. It is estimated that more than half of the approximately 7 million Americans using insulin do so with suboptimal treatment and while administering one or two insulin injections per day. Non-adherence may be a contributing factor in suboptimal treatment. For a variety of reasons, many patients diagnosed with diabetes and treated with insulin are non-adherent. SCOPE: The primary objective of this study was to evaluate preference for an insulin delivery system comparing a disposable doser (InnoLet) to the standard vial/syringe. In a prospective, randomized, open-label, two-period, crossover study, 260 patients were enrolled (age > or = 18 years, with type 1 or 2 diabetes, and receiving NPH or regular or 70/30 insulin for at least 6-months). A total of 162 patients completed both treatment arms. Excluded were those unable to read/write English or administer their own injections, pregnant/lactating women, those using antipsychotics, and those with a history of alcohol abuse or cognitive impairment. Patients completed the eight-item Diabetes Fear of Self-Injection Questionnaire at baseline, week 12 and week 24. Items were rated on a 4-point Likert scale (1 = almost never; 4 = almost always) with a maximum fear score of 32. At week 24, patients completed a preference survey. FINDINGS: Of the 162 patients completing both treatment arms, 89 (55.0%) were in the vial/syringe to disposable doser treatment arm, 50% were female and mean age was 60 +/- 11 years. Patients in both treatment arms displayed little significant differences in baseline characteristics. Patients reported significantly lower fear of self-injection after using the disposable doser compared to vial/syringe (mean +/- SEM: 9.5 +/- 0.2 vs. 11.2 +/- 0.4; p < 0.0001). Most patients (71.5%) indicated a preference for the disposable doser compared to the vial/syringe method (p < 0.0001). CONCLUSION: The majority of patients preferred the disposable doser, and reported significantly less fear of self-injection using this delivery system. There are some potential limitations to consider. A randomization bias may have been present, patients who enrolled in this study were those who were actively seeking medical treatment for diabetes, insulin pens and cartridges are not available for all types of insulin regimens, pre-filled pens and cartridges may not be altered and, in general, alternative insulin delivery systems tend to be more costly than insulin sold in traditional vials. However, insulin may have greater patient acceptance and less psychological distress when administered via an alternative delivery system.

Short-term economic impact associated with occupational needlestick injuries among acute care nurses.

PURPOSE: Recent survey data have reported the incidence rate of needlestick injuries (NIs) and NIs which draw blood sustained by nurses caring for patients with diabetes in an in-patient hospital setting. The purpose of this study was to deduce the potential short-term annual economic impact resulting from such NI, and to project the potential national economic burden of NI among this population of health care workers (HCWs). METHODS: Data were obtained from a recently published, IRB-approved, Internet-based survey in which nurses routinely treating patients with diabetes self-reported outcomes of their experience with NI (N = 400). A micro-costing approach was adopted. Direct costs comprised post-exposure testing (PET) for infection, post-exposure health care services utilization, and NI-induced post-exposure prophylactic (PEP) drug utilization. Indirect costs were derived from missed workdays and associated lost productivity. These data were combined with data related to the national epidemiology and total incidence of NIs among HCWs and risk-associated populations to project the national burden. RESULTS: Among 400 nurses, 110 sustained at least one NI in the past year, with 73 punctures drawing blood. The ensuing total short-term costs of these NIs were calculated to range from 25,896 US dollars to 36,066 US dollars. Indirect costs accounted for 44-62% of this total cost. Average short-term costs per NI ranged from 145 to 201 US dollars, and average short-term costs of NI per injured nurse ranged from 235 to 328 US dollars. Assuming mean values from published literature on the incidence and distribution of NI among nursing populations, an annual national burden of 65 million US dollars was calculated for costs in the immediate period following NI. CONCLUSIONS: These data suggest substantial economic burden immediately following NI on a national and individual hospital level occurring among acute-care nurses treating patients with diabetes. Long-term treatment costs would add to the overall economic burden.

Long-term clinical and cost outcomes of treatment with biphasic insulin aspart 30/70 versus insulin glargine in insulin naïve type 2 diabetes patients: cost-effectiveness analysis in the UK setting.

OBJECTIVES: To evaluate the long-term clinical and cost outcomes associated with biphasic insulin aspart 30/70 (BIAsp 30/70, premixed 30% soluble and 70% protaminated insulin aspart in one injection) compared to insulin glargine treatment in insulin-naïve type 2 diabetes patients failing oral antidiabetic agents in the UK, based on findings recently reported from the INITIATE clinical trial. METHODS: The CORE Diabetes Model, a published, peer-reviewed and validated model of diabetes, was used to evaluate life expectancy, quality-adjusted life expectancy, cumulative incidence of complications and direct medical costs over patient lifetimes. The model simulates the range of diabetic complications and disease progression within a series of sub-models (cardiovascular disease, neuropathy, renal and eye disease) based on published data. Baseline cohort characteristics (54.5% male, mean age 52.45 years, mean diabetes duration 9 years, mean HbA(1c) 9.77%) and treatment effects were based on INITIATE. Costs were derived from published UK sources. The analysis was run over a 35-year time horizon (patient lifetime) from a third party payer perspective. Costs and clinical benefits were discounted at 3.5% per annum. Sensitivity analyses were performed. RESULTS: BIAsp 30/70 was associated with projected improvements in discounted life expectancy (0.19 +/- 0.20 years) and quality-adjusted life expectancy (0.19 +/- 0.14 quality-adjusted life years [QALYs]), as well as a reduced incidence of retinopathy and nephropathy complications, versus glargine. Total lifetime direct costs were 1319 pounds higher with BIAsp 30/70 than with glargine leading to an incremental cost-effectiveness ratio of 6951 pounds per QALY gained. CONCLUSIONS: This study is the first to address the long-term health economic implications of treating type 2 diabetes patients failing oral anti-diabetics with a biphasic insulin mix versus long-acting insulin. Our projections indicate that improved HbA1c levels with BIAsp 30/70 treatment are associated with improvements in life expectancy and quality-adjusted life expectancy, and that BIAsp 30/70 represents excellent value for money compared to insulin glargine in the UK.

Needlestick injury in acute care nurses caring for patients with diabetes mellitus: a retrospective study.

OBJECTIVE: To quantify the incidence and assess the risk of needlestick injury (NI) in nurses caring for patients with diabetes mellitus. METHODS: A total of 400 nurses caring for patients with diabetes in 381 different hospitals throughout the United States over a period of at least 1 year voluntarily completed an Internet-based data collection instrument. The nurses self-reported comprehensive data on their experience with NI, focusing on those occurring within the past year. If respondents experienced multiple NI during this period, detailed data were collected on the most recent event. RESULTS: Of the 400 nurses, 313 (78.3%) reported experiencing at least one NI, 110 (27.5%) reported at least one NI within the last 12 months, and 44 (40% of 110) reported multiple NI. Nearly two-thirds of these injuries (n = 73/110; 66.4%) were punctures that drew blood, resulting in one case of contracted hepatitis C. The cumulative annual incidence of NI events was 448 NI per 1000 nurses. Nurses reported the injury in adherence with existing regulations and policies in only 21.8% of the cases. Disposable syringes were involved in 88 (80%) of the NI events. In half of the injuries (n = 55), the needled device was equipped with a safety feature that was ineffective, primarily because it was not fully activated (n = 47/55; 85.5%) or it malfunctioned (n = 2-5; 3.6-9.1%). NI most commonly occurred while nurses were injecting insulin (n = 33; 30%). In the 2 weeks following their NI, 60.1% of nurses noted that they were more afraid of needled devices than before the injury and 41.8% felt anxious, depressed, or stressed. As a direct result of the NI, nurses missed 77 days of work. CONCLUSIONS: This study is the first to show the relatively high risk both of NI and of NI that draws blood among nurses injecting insulin with a disposable syringe and confirms previous incidence estimates of NI among nurses. Additionally, this study reveals significant post-NI emotional distress, suggests significant under-reporting of NI to hospital officials, and demonstrates the need for a more effective needle safety device.

Needlestick injuries in the United States. Epidemiologic, economic, and quality of life issues.

Best evidence from prospective studies with aggressive monitoring suggests that the incidence of needlestick injuries is significantly higher than reported through passive surveillance, ranging from 14 to 839 needlestick injuries per 1,000 health care workers per year. The economic cost of managing these injuries is substantial, ranging from dollars 51 to dollars 3,766 (2002 U.S. dollars). This amount excludes the cost of treating the long-term complications of needlestick injuries, such as HIV and hepatitis B and C infections, each of which can cost several hundreds of thousands of dollars to manage. In addition, health care workers experience significant fear, anxiety, and emotional distress following a needlestick injury, sometimes resulting in occupational and behavior changes. Despite the availability of engineered injury prevention devices, the implementation of these new technologies has been mixed in part because of the perception that these devices are costly and cost ineffective. However, widespread use of safety devices might be more easily justified on economic grounds when the full clinical and economic benefits of these new technologies are considered, especially within the context of injury prevention.

Comparing the long-term cost-effectiveness of repaglinide plus metformin versus nateglinide plus metformin in type 2 diabetes patients with inadequate glycaemic control: an application of the CORE Diabetes Model in type 2 diabetes.

OBJECTIVES: As an example application of the CORE Diabetes Model in type 2 diabetes, we simulated the cost-effectiveness of repaglinide/metformin combination therapy versus nateglinide/metformin for treatment of individuals with type 2 diabetes with an inadequate response to sulphonylurea, metformin, or fixed dose glyburide/metformin. METHODS: The CORE Diabetes Model was used to simulate long-term outcomes for a cohort of individuals with type 2 diabetes treated with either repaglinide/metformin or nateglinide/metformin. HbA1c changes for each regimen were taken from a comparative study. At the end of the study, changes in HbA1c from baseline were -1.28% points and -0.67% points for repaglinide/metformin and nateglinide/metformin, respectively. Median final doses were 5.0 mg/day for repaglinide, 360 mg/day for nateglinide and 2000 mg/day metformin in each treatment arm. Costs were calculated as the annual costs for drugs plus costs of complications (US Medicare perspective) over a 30-year period. Life expectancy (LE) and quality-adjusted life expectancy (QALE) were calculated. Outcomes and costs were discounted at 3% annually. RESULTS: With repaglinide/metformin, improved glycaemic control led to projected decreases in complication rates, improvement of LE and QALE by 0.15 and 0.14 years respectively, and total cost savings of 3,662 dollars/person over the 30-year period. Repaglinide/metformin had a 96% probability that the incremental costs per quality-adjusted life year gained would be 20,000 dollars or less, and a 66% probability that repaglinide/metformin would be cost-saving compared to nateglinide/metformin. Sensitivity analyses supported the validity and reliability of the results. CONCLUSIONS: In the health economic context, repaglinide/metformin combination was dominant to nateglinide/metformin. The CORE Diabetes Model is a tool to help third-party reimbursement payers identify treatments for type 2 diabetes that are good value for money.

Deleterious effects of increased body weight associated with intensive insulin therapy for type 1 diabetes: increased blood pressure and worsened lipid profile partially negate improvements in life expectancy.

OBJECTIVE: Weight gain is an unwanted side effect of improved glycaemic control in type 1 diabetes, associated with increased blood pressure (BP) and worsening lipid profiles. While improved glycaemic control per se should improve long-term patient outcomes, increases in BP and worsening lipid profiles may counteract these benefits. The aim of this modelling study was to assess whether the increased body weight and associated worsening of lipid profile and blood pressure would negate the improvements in glycaemic control seen with intensive therapy in patients with type 1 diabetes. METHODS: A validated diabetes model projected life expectancy (LE), quality-adjusted LE (QALE) and total lifetime costs of complications in type 1 diabetes cohorts with the characteristics of patients from the Diabetes Control and Complications Trial (DCCT). The following four cohorts (A-D) were created based on increased body weight under either conventional or intensive therapy: A) conventional glycaemic control in the subgroup with lowest weight-gain quartile after 6.5 years (HbA1c increased by 11% from baseline); B) conventional control in the highest weight-gain quartile (no change in HbA1c from baseline); C) intensive control in the lowest quartile of weight gain (with 16.1% decrease in HbA1c, but no increase in weight or associated BP, and improved lipid profile); D) intensive control in the highest quartile of weight gain (with 21% decrease in HbA1c, increased systolic BP of 6 mmHg, and worsened lipid profile). Data were derived from DCCT and other published sources. RESULTS: Intensive control, even with weight gain, led to major improvements in LE and QALE, and reduction in costs of complications versus conventional therapy. Intensive therapy with no weight increase led to a higher LE (increased by 0.57 years) and higher QALE (increased by 0.28 years) and lower costs of complications (reduced by 523 dollars/patient), compared to intensive therapy with the highest quartile of weight gain. CONCLUSIONS: Concerns about weight gain should not deter intensive insulin therapy. However, the value of improving glycaemic control without increasing body weight (and associated increased BP and worsening of lipid profile) has been confirmed.

Preference and resource utilization in elderly patients: InnoLet versus vial/syringe.

InnoLet is a disposable insulin injection device with a large easy-to-read dial, large push button for injection, and audible clicks for each unit injected. This clinical trial assessed patient preference, satisfaction, and utilization of healthcare resources (estimated nursing care) for InnoLet and vial/syringe. Patients with diabetes mellitus (N=79, mean age 68.2+/-8.6 years, duration of diabetes 16.5+/-10.9 years) having visual and/or motor disabilities and having difficulty (or required caregiver assistance) for previous injections by vial/syringe were randomized to use of either InnoLet or vial/syringe for 6 weeks, then switched to the alternate regimen for 6 weeks. At the end of the study, utilization of healthcare resources was assessed in terms of the caregiver time required to assist in preparation, storage, and disposal of each device. For vial/syringe, 60% of patients required assistance in drawing up the appropriate dosage in the syringe, and 36% of patients required assistance when injecting insulin. A major portion of the patients (53%) could independently conduct injections (without nursing/caregiver assistance) during use of InnoLet, versus 20% for vial/syringe. As a result, mean daily nursing costs associated with the injection regimen were US$ 114 for the InnoLet device, and US$ 196 for vial/syringe (P<0.001). A majority of patients (82%) indicated a preference for the InnoLet device (P<0.001).

A comparison of costs for four oral antidiabetic regimens within a managed care population.

A retrospective database analysis compared costs among patients with type 2 diabetes receiving four antidiabetic regimens: (1) repaglinide monotherapy, (2) metformin monotherapy, (3) repaglinide and metformin in combination, or (4) metformin and glyburide in combination. Pharmacy, medical, and total costs were measured for each cohort over a nine-month period. Although not statistically significant, total adjusted costs were lowest for the repaglinide-metformin combination ($8,924), followed by metformin monotherapy ($9,448), metformin and glyburide ($9,576), and repaglinide monotherapy ($11,910). These results must be confirmed in larger populations, but they imply that differences in pharmacy costs of repaglinide-metformin therapy are offset by measurable medical cost savings.