Cost-effectiveness analysis of exenatide once-weekly versus dulaglutide, liraglutide, and lixisenatide for the treatment of type 2 diabetes mellitus: an analysis from the UK NHS perspective.

OBJECTIVE: To assess the cost-effectiveness of exenatide 2 mg once-weekly (EQW) compared to dulaglutide 1.5 mg QW, liraglutide 1.2 mg and 1.8 mg once-daily (QD), and lixisenatide 20 µg QD for the treatment of adult patients with type 2 diabetes mellitus (T2DM) not adequately controlled on metformin. METHODS: The Cardiff Diabetes Model was applied to evaluate cost-effectiveness, with treatment effects sourced from a network meta-analysis. Quality-adjusted life years (QALYs) were calculated with health-state utilities applied to T2DM-related complications, weight changes, hypoglycemia, and nausea. Costs (GBP £) included drug treatment, T2DM-related complications, severe hypoglycemia, nausea, and treatment discontinuation due to adverse events. A 40-year time horizon was used. RESULTS: In all base-case comparisons, EQW was associated with a QALY gain per patient; 0.046 vs dulaglutide 1.5 mg; 0.102 vs liraglutide 1.2 mg; 0.043 vs liraglutide 1.8 mg; and 0.074 vs lixisenatide 20 µg. Cost per patient was lower for EQW than for liraglutide 1.8 mg (-£2,085); therefore, EQW dominated liraglutide 1.8 mg. The cost difference per patient between EQW and dulaglutide 1.5 mg, EQW and liraglutide 1.2 mg, and EQW and lixisenatide 20 µg was £27, £103, and £738, respectively. Cost per QALY gained with EQW vs dulaglutide 1.5 mg, EQW vs liraglutide 1.2 mg, and EQW vs lixisenatide 20 µg was £596, £1,004, and £10,002, respectively. In the probabilistic sensitivity analysis, the probability that EQW is cost-effective ranged from 76-99%. CONCLUSION: Results suggest that exenatide 2 mg once-weekly is cost-effective over a lifetime horizon compared to dulaglutide 1.5 mg QW, liraglutide 1.2 mg QD, liraglutide 1.8 mg QD, and lixisenatide 20 µg QD for the treatment of T2DM in adults not adequately controlled on metformin alone.

The cost-effectiveness of exenatide twice daily (BID) vs insulin lispro three times daily (TID) as add-on therapy to titrated insulin glargine in patients with type 2 diabetes.

OBJECTIVE: To evaluate the cost-effectiveness of exenatide twice daily (BID) vs bolus insulin lispro three times daily (TID) as add-on therapy when glycemic control is sub-optimal with titrated basal insulin glargine and metformin. METHODS: The analysis was based on the recent 4B Study, which compared exenatide BID and lispro TID as add-on therapies in subjects with type 2 diabetes insufficiently controlled, despite titrated insulin glargine. The Cardiff Diabetes Model was used to simulate patient costs and health benefits beyond the 4B Study. The Swedish healthcare perspective was adopted for this analysis; costs are reported in €EUR to aid interpretation. The main outcome measure was the cost per quality-adjusted life-year (QALY) gained with exenatide BID compared to lispro TID. RESULTS: Exenatide BID was associated with an incremental cost of €1,270 and a QALY increase of +0.64 compared with lispro TID over 40 years. The cost per QALY gained with exenatide BID compared with lispro TID was €1,971, which is within conventional limits of cost-effectiveness. Cost-effectiveness results were generally robust to alternative assumptions and values for key model parameters. LIMITATIONS: Extrapolation of trial data over the longer term can be influenced by modeling and parameter uncertainty. Cost-effectiveness results were generally insensitive to alternative values of key model input parameters and across scenarios. CONCLUSIONS: The addition of exenatide BID rather than insulin lispro to basal insulin is associated with similar or better clinical outcomes. Illustrated from the Swedish healthcare perspective, analysis with the Cardiff Diabetes Model demonstrated that exenatide BID represents a cost-effective treatment alternative to lispro TID as add-on therapy in type 2 diabetes patients insufficiently controlled on basal insulin.

The cost-effectiveness of candesartan-based antihypertensive treatment for the prevention of nonfatal stroke: results from the Study on COgnition and Prognosis in the Elderly.

Patients who survive a first stroke are often left with permanent disabilities, and have significant needs for rehabilitation and long-term care. Antihypertensive treatment reduces the risk of cardiovascular events such as stroke. The purpose of this study was to investigate the cost-effectiveness of candesartan-based antihypertensive treatment for the prevention of nonfatal stroke. The cost-effectiveness analysis was based on data from Study on COgnition and Prognosis in the Elderly (SCOPE), where patients were randomly assigned to receive the angiotensin receptor blocker candesartan or placebo, with open-label active antihypertensive treatment added as needed. The analysis was carried out using a Markov model, which combined clinical and resource utilization data from SCOPE with Swedish retail prices for drugs and unit costs for in-patient stays, and outpatient visits. The cost per patient was 1949 EUR in the candesartan group and 1578 EUR in the control group. The largest share of the cost was attributed to antihypertensive treatment in the candesartan group and to the long-term cost of stroke in the control group. Candesartan-based antihypertensive treatment was associated with 0.0289 additional quality-adjusted life-years (QALYs) per patient and an incremental cost per QALY gained of approximately 13,000 EUR. Sensitivity analyses showed that these results were fairly stable. In conclusion, the cost per QALY gained with candesartan-based antihypertensive treatment lies within the range of society's willingness to pay for health gains. The results indicate that candesartan-based antihypertensive treatment is cost-effective for the prevention of nonfatal stroke.

Cost-effectiveness of felodipine-metoprolol (Logimax) and enalapril in the treatment of hypertension.

We present results from a Swedish retrospective cost-effectiveness analysis of felodipine-metoprolol (Logimax) and enalapril in hypertension. In the 8-week trial, the average reduction of diastolic blood pressure (DBP) and the share of patients reaching target DBP were both significantly greater in the felodipine-metoprolol group. Cost of treatment (costs of drugs and physician visits) was somewhat higher in the felodipine-metoprolol group. After 8 weeks, an extra 4.8 mmHg reduction and an additional 22% of patients reaching target DBP were achieved with felodipine-metoprolol at the extra cost of SEK 19 (Swedish kronor, $US I=SEK 7.90). The incremental cost per mmHg reduction and per patient reaching target DBP was calculated at SEK 4 and SEK 86, respectively. Average cost-effectiveness ratios showed that the costs per mmHg reduction and per patient reaching target DBP after 8 weeks were 40 and 34% lower in the felodipine-metoprolol group, respectively. In conclusion, felodipine-metoprolol is cost-effective in the treatment of hypertension.

Contingent valuation with an open-ended follow-up question: a test of scope effects.

It has been suggested that an open-ended follow-up question should be added to the binary contingent valuation question. Before this is generally recommended, it is important to evaluate the properties of such follow-up questions. Using a split sample approach, we test whether the open-ended follow-up is sensitive to the scope of the commodity being valued. No significant scope effects were detected. It is concluded that the results obtained do not support the use of an open-ended follow-up in contingent valuation applications.

Valuation of health changes with the contingent valuation method: a test of scope and question order effects.

In recent years, there has been a growing interest in the contingent valuation method for measurement of monetary values of various commodities. However, the validity and reliability of the method need to be examined thoroughly. This paper reports results of a test of scope and question order effects in a contingent valuation experiment in the health care field. Using three binary valuation questions, data were collected on willingness to pay for superior treatment of reflux oesophagitis. To test for scope effects, different probabilities of successful short- and long-term treatments were evaluated using a split sample approach. The presence of question order effects was tested by assigning respondents to different question orders. The contingent valuation method proved sensitive to changes in scope in that the willingness to pay increased with the probability of being free from symptoms and with a reduced risk of having a relapse once recovered. Also, regression analysis indicate that people who suffer from severe reflux oesophagitis are more willing to pay for more effective treatment. No question order effects were detected in the data.

Willingness to pay for reductions in angina pectoris attacks.

To compare the costs of health care programs, with the benefits, the values of changes in health status must be expressed in monetary terms. The development of methods to estimate willingness to pay for changes in health status is therefore of interest. This paper reports the results of a contingent valuation study measuring willingness to pay for reductions in angina pectoris attacks. An innovative study design allowed analysis on the data on willingness to pay using two approaches, a binary question and a bidding-game technique. Percentage reductions in anginal attacks were varied randomly in different subsamples, and data were collected about angina pectoris status, attack rate, and income to test the internal validity of the contingent valuation method. Willingness to pay for a 50% reduction in the attack rate for three months was estimated to be about SEK 2,500 ($345) with the binary approach, and about SEK 2,100 ($290) using the bidding-game technique. Regression analyses showed that income, angina pectoris status, attack rate, and percentage reduction in attack rate were all related to willingness to pay, in agreement with the authors' hypothesis.

Inhibition of Serratia marcescens nuclease secretion by a truncated nuclease peptide.

The production of extracellular nuclease (Nuc) from the Serratia marcescens nucA chromosomal locus is inhibited in cells producing the N-terminal portion of Nuc from a multicopy plasmid. This inhibition in trans is not at the level of nucA expression, but rather at the level of secretion of the Nuc protein. Production of the periplasmic protein beta-lactamase (Bla) does not inhibit Nuc production unless fused to the nucA signal peptide and expressed from nucAp. Inhibition by either the truncated Nuc peptide (delta Nuc) or a Bla fusion protein is promoter specific and observed when expressed from nucAp; little inhibition is observed when the same protein is expressed from the lacZpo promoter-operator. This promoter specificity is also true for the secretion of Nuc itself.

The cost of angina pectoris in Sweden.

A survey of 402 Swedish patients with angina pectoris was performed to estimate the annual direct medical costs, and nonmedical costs, of a typical Swedish angina pectoris patient, and to identify those variables having the greatest impact on the direct medical costs. Data regarding the consumption of healthcare services over a 3-month period were collected through telephone interviews conducted by trained nurses at a medical marketing agency. The data were multiplied by 4 to obtain an estimate of the annual resource consumption. The annual direct medical cost of angina pectoris was estimated at 40,052 Swedish krona (SEK; $US1 approximately SEK7.20, March 1995) per patient, comparable with the cost of a myocardial infarction. As expected, however, the severity of angina pectoris was important in determining the direct medical cost. The significant variables explaining variations in direct costs were (in order of importance): (i) whether the patient had undergone cardiovascular surgery; (ii) whether the patient was treated by a general practitioner or an internist; (iii) the number of years since first diagnosis of angina pectoris; and (iv) whether the patient's angina pectoris was characterised as stable or unstable. The annual nonmedical cost of angina pectoris per patient was estimated at SEK38,225. The relatively high costs of angina pectoris underline the importance of health economic evaluations of various diseases and medical interventions.