Richard F. Pollock

Systematic review of the cost-effectiveness of biphasic insulin aspart 30 in type 2 diabetes

Abstract Objectives: To review the cost-effectiveness of biphasic insulin aspart (BIAsp 30) compared to other insulin regimens in the treatment of type 2 diabetes based on published literature. Methods: The electronic databases MEDLINE, EMBASE, the Cochrane Library and EconLit and a selection of congress/meeting databases were systematically searched using combinations of search terms designed to identify publications describing cost-effectiveness analyses of BIAsp 30 in patients with type 2 diabetes. Searches were limited to studies in humans, and published in the English language between January 1999 and July 2009. All records were screened for inclusion in the review. Results: Seven published cost-effectiveness analyses and ten abstracts were identified. One was a health technology assessment from the UK, which evaluated cost-effectiveness using the UKPDS Outcomes Model and meta-analysis of published clinical trials and concluded that premixed insulin analogs were unlikely to be cost-effective versus insulin glargine or biphasic human insulin. In all other studies the cost-effectiveness of BIAsp 30 versus other insulin regimens was assessed using the validated CORE Diabetes Model and outcomes from either the INITIATE randomized controlled trial, or the PRESENT or IMPROVE observational studies. However, notable limitations include the fact that all cost-effectiveness analyses to date have been performed using a single model and that a number of these are based on data from observational studies rather than randomized controlled trials. Nevertheless, long-term clinical and economic outcomes were reported for several countries: UK, US, Sweden, Saudi Arabia, Poland, South Africa, South Korea and China. BIAsp 30 was associated with improvements in quality-adjusted life expectancy in all countries. Estimates of direct costs varied according to country and comparator, but incremental cost-effectiveness ratios for the US and UK were USD 46 533 and GBP 6951 per quality-adjusted life year gained for BIAsp 30 versus insulin glargine. Conclusions: Although cost-effectiveness data on BIAsp 30 are scarce the majority of the analyses identified in this review suggest that BIAsp 30 is likely to be cost-effective compared to insulin glargine and biphasic human insulin across a wide range of settings, and under certain circumstances would be a dominant treatment option.

Evaluating the cost-effectiveness of laparoscopic adjustable gastric banding versus standard medical management in obese patients with type 2 diabetes in the UK.

To evaluate the cost‐effectiveness of laparoscopic adjustable gastric banding (LAGB) versus standard medical management (SMM) in obese patients with type 2 diabetes from a UK healthcare payer perspective.

Evaluation of the cost-utility of insulin degludec vs insulin glargine in Sweden

Abstract Objective: To evaluate the annual cost-utility of insulin degludec compared with glargine in patients with: type 1 diabetes (T1D), type 2 diabetes receiving basal-only therapy (T2D-BOT), and type 2 diabetes receiving basal-bolus therapy (T2B-BB) in Sweden. Methods: A cost-utility model was programmed in Microsoft Excel to evaluate clinical and economic outcomes. The clinical trials were designed as treat-to-target, with insulin doses adjusted in order to achieve similar glycemic control between treatments, thus long-term modeling is not meaningful. Basal and bolus insulin doses, incidence of hypoglycemic events, frequency of self-monitoring of blood glucose, and possibility for flexibility in timing of dose administration were specified for each insulin in three diabetes populations, based on data collected in Swedish patients with diabetes and a meta-analysis of clinical trials with degludec. Using these characteristics, the model estimated costs from a societal perspective and quality-adjusted life years (QALYs) in the two scenarios. Results: Use of degludec was associated with a QALY gain compared with glargine in T1D (0.31 vs 0.26 QALYs), T2D-BOT (0.76 vs 0.69 QALYs), and T2D-BB (0.56 vs 0.47 QALYs), driven by reduced incidence of hypoglycemia and possibility for flexibility around timing of dose administration. Therapy regimens containing degludec were associated with increased costs compared to glargine-based regimens, driven by the increased pharmacy cost of basal insulin, but partially offset by other cost savings. Based on estimates of cost and clinical outcomes, degludec was associated with incremental cost-effectiveness ratios of SEK 19,766 per QALY gained, SEK 10,082 per QALY gained, and SEK 36,074 per QALY gained in T1D, T2-BOT, and T2-BB, respectively. Limitations: The hypoglycemic event rates in the base case analysis were derived from a questionnaire-based study that relied on patient interpretation and recall of hypoglycemic symptoms. The relative rates of hypoglycemia with degludec compared to glargine were derived from a meta-analysis of phase III trials, which may not reflect the relative rates observed in real-world clinical practice. Both of these key limitations were explored in one-way sensitivity analyses. Conclusions: Based on reduced incidence of hypoglycemia and possibility for flexibility around timing of dose administration, use of degludec is likely to be cost-effective compared to glargine from a societal perspective in T1D, T2-BOT, and T2-BB in Sweden over a 1-year time horizon.

Evaluating the cost‐effectiveness of reduced mild hypoglycaemia in subjects with Type 1 diabetes treated with insulin detemir or NPH insulin in Denmark, Sweden, Finland and the Netherlands

Diabet. Med. 29, 303–312 (2012)

Systematic Review and Meta-Analysis of Tacrolimus versus Ciclosporin as Primary Immunosuppression After Liver Transplant

Background and Aims Several meta-analyses comparing ciclosporin with tacrolimus have been conducted since the 1994 publication of the tacrolimus registration trials, but most captured data from randomized controlled trials (RCTs) predating recent improvements in waiting list prioritization, induction protocols and concomitant medications. The present study comprised a systematic review and meta-analysis of ciclosporin and tacrolimus in liver transplant recipients using studies published since January 2000. Methods Searches of PubMed, the Cochrane Library and EMBASE identified RCTs of tacrolimus and ciclosporin as the immunosuppressant in adult primary liver transplant recipients, published between January 2000 and August 6, 2014. A random effects meta-analysis was conducted to evaluate the relative risk of death, graft loss, acute rejection (AR), new-onset diabetes after transplantation (NODAT) and hypertension with tacrolimus relative to ciclosporin at 12 months. Results The literature search identified 11 RCTs comparing ciclosporin with tacrolimus. Relative to ciclosporin, tacrolimus was associated with significantly improved outcomes in terms of patient mortality (risk ratio [RR] with ciclosporin of 1.26; 95% confidence interval [95%CI] 1.01–1.58). Tacrolimus was superior to ciclosporin in terms of hypertension (RR with ciclosporin 1.26; 95%CI 1.07–1.47), but inferior in terms of NODAT (RR with ciclosporin 0.60; 95%CI 0.47–0.77). There were no significant differences between ciclosporin and tacrolimus in terms of graft loss or AR. Conclusions Meta-analysis of RCTs published since 2000 showed tacrolimus to be superior to ciclosporin in terms of patient mortality and hypertension, while ciclosporin was superior in terms of NODAT. No significant differences were identified in terms of graft loss or AR. These findings provide further evidence supporting the use of tacrolimus as the cornerstone of immunosuppressive therapy in liver transplant recipients.

The cost effectiveness of rapid-acting insulin aspart compared with human insulin in type 2 diabetes patients: an analysis from the Japanese third-party payer perspective

Abstract Objectives: The Nippon Ultra-Rapid Insulin and Diabetic Complication Evaluation Study (NICE Study) (NCT00575172) was a 5-year, open-label, randomised controlled trial which compared cardiovascular outcomes in Japanese type 2 diabetes patients intensively treated with regular human insulin or insulin aspart (NovoRapid; Novo Nordisk A/S, Bagsværd, Denmark), a rapid-acting insulin analogue. The aim of the present analysis was to evaluate the cost effectiveness of insulin aspart versus regular human insulin from the perspective of a Japanese third-party healthcare payer. Research design and methods: A discrete event-simulation model was developed in Microsoft Excel to assess the within-trial cost effectiveness and make longer-term clinical projections in patients treated with regular human insulin or insulin aspart. In addition to severe hypoglycaemia, the model captured myocardial and cerebral infarction events and percutaneous coronary intervention and coronary artery bypass graft procedures. Within-trial mortality, incidence of severe hypoglycaemia and cardiovascular event probabilities were derived from the annual rates observed during the trial period, while post-trial outcomes were calculated using the event rates from the trial, adjusted for increasing patient age. Event costs were accounted from the healthcare payer perspective and expressed in 2008 Japanese yen (JPY), while health-related quality of life (HRQoL) was captured using event and state utilities. Future costs and clinical benefits were discounted at 3% annually. Life expectancy, quality-adjusted life expectancy, cardiovascular event rates and costs were evaluated over 5- and 10-year time horizons and sensitivity analyses were performed to assess variability in model outcomes. Results: Over 5 years of treatment, insulin aspart dominated human insulin both in incremental life expectancy and in incremental quality-adjusted life-years (QALYS). Insulin aspart was associated with a small improvement in discounted life expectancy of 0.005 years (4.688 vs. 4.684 years) and an increase of 0.023 quality-adjusted life-years (QALYs) (3.800 vs. 3.776 QALYs) when compared with regular human insulin. Insulin aspart also incurred lower costs (JPY 481,586 vs. 594,717, difference −113,131) which resulted from the decreased incidence of cardiovascular events with insulin aspart (0.013 events per patient year vs. 0.030 on regular human insulin). Breakdown of costs indicated that pharmacy costs were higher with insulin aspart (JPY 346,608 vs. 278,468), but these costs were more than offset by the reduced costs associated with cardiovascular complications and hypoglycaemia over 5 years of treatment (JPY 134,978 vs. 316,249). Sensitivity analysis showed that insulin aspart was still cost-effective in the case where only 18% of the within-trial cardiovascular and mortality benefit over regular human insulin was captured in the model (assuming a willingness-to-pay threshold of JPY 5,000,000). Limitations: The NICE study cohort was relatively small (n = 325), meaning that caution should be exercised when calculating and interpreting the incremental cost-effectiveness ratio. Also, despite the differences in cardiovascular risk profile between the Japanese and UK populations, UKPDS-derived risk equations were used to project MI outcomes and PCI and CABG procedures and UKPDS HRQoL scores were applied to all health states. While these risk formulas and HRQoL utilities may not be directly applicable to the Japanese population, no equivalent Japanese-specific data are currently available. Conclusions: In a Japanese type 2 diabetes population, prescribing rapid-acting insulin aspart significantly reduced cardiovascular complications over 5- and 10-year time horizons, resulting in increased quality of life and decreased costs when compared with human insulin.

Budget impact of switching from an immediate-release to a prolonged-release formulation of tacrolimus in renal transplant recipients in the UK based on differences in adherence

Background and aims Advagraf is a once-daily prolonged-release formulation of tacrolimus with proven noninferiority to Prograf, a twice-daily immediate-release formulation of tacroli-mus, in biopsy-proven acute rejection, graft survival and patient survival in renal transplant recipients. Advagraf is associated with improved adherence compared with Prograf, which may ultimately improve long-term outcomes. The present study assessed the budget impact of switching patients from Prograf to Advagraf in the UK. Materials and methods A budget-impact model was constructed based on published data on acute rejection, graft failure, and mortality in the UK setting. Patients were assumed to convert from Prograf to Advagraf on a 1:1 milligram:milligram basis. In a study comparing the adherence rates between once-daily versus twice-daily formulations of tacrolimus, the proportion of patients taking the prescribed number of daily doses was 88.2% in Advagraf patients and 78.8% in Prograf patients. The model applied a relative risk of graft failure of 3.47 to nonadherent patients based on data from a 2004 meta-analysis (based on graft-failure rates of 1.3%–40.0% in adherent patients, compared with 6.1%–100% in nonadherent patients). Cost data were taken from the March 2013 British National Formulary and 2012–2013 National Health Service tariff information. The analysis was performed over a 5-year time horizon and future costs were not discounted, in line with International Society for Pharmacoeconomics and Outcomes Research guidelines. Results Over a 5-year time horizon, the mean cost per patient (including tacrolimus, concomitant immunosuppressive medications, dialysis after graft failure, and treatment for acute rejection) was £29,328 (standard deviation [SD] £2,844) for Advagraf versus £33,061 (SD £3,178) for Prograf. The total cost saving of £3,733 (SD £530) was driven primarily by reduced dialysis costs arising from the lower incidence of graft failure (21.6% with Prograf versus 18.3% with Advagraf) in the larger proportion of adherent patients in the Advagraf arm. In a hypothetical transplant centre of 100 kidney-transplant recipients, this would result in cost savings approaching £375,000 over 5 years. Conclusion Conversion of renal transplant recipients from Prograf to Advagraf was associated with lower pharmacy and dialysis costs, with the reduction in dialysis costs being driven by improved adherence to Advagraf regimen and the consequent improvement in graft survival.

Long-term cost-effectiveness of insulin detemir versus NPH insulin in type 2 diabetes in Sweden

Abstract Aim: To evaluate the cost-effectiveness of insulin detemir vs. NPH insulin once daily, in patients with type 2 diabetes in the Swedish setting based on clinical data from a published randomized controlled trial. Methods: Projections of long-term outcomes were made using the IMS CORE Diabetes Model (CDM), based on clinical data from a 26-week randomized controlled trial that compared once daily insulin detemir and NPH insulin, when used to intensify insulin treatment in 271 patients with type 2 diabetes and body mass index (BMI) 25–40 kg/m2. Trial results showed that insulin detemir was associated with a significantly lower incidence of hypoglycemic events and significantly less weight gain in comparison with NPH insulin. The analysis was conducted from a third party payer perspective and the base case analysis was performed over a time horizon of 40 years and future costs and clinical outcomes were discounted at a rate of 3% per year. Results: Insulin detemir was associated with higher mean (SD) quality-adjusted life expectancy (5.42 [0.10] vs. 5.31 [0.10] quality-adjusted life years [QALYs]) and lower overall costs (SEK 378,539 [10,372] vs. SEK 384,216 [11,230]; EUR 33,794 and EUR 34,300, respectively, where 1 EUR = 11.2015 SEK) compared with NPH insulin. Sensitivity analysis showed that the principal driver of the benefits associated with insulin detemir was the lower rate of hypoglycemic events (major and minor events) vs. NPH insulin, suggesting that detemir might also be cost-saving over a shorter time horizon. Limitations of the analysis include the use of data from a trial outside Sweden in the Swedish setting. Conclusions: Based on clinical input data derived from a previously published randomized controlled trial, it is likely that in the Swedish setting insulin detemir would be cost-saving in comparison with NPH insulin for the treatment of patients with type 2 diabetes.

A long-term analysis evaluating the cost-effectiveness of biphasic insulin lispro mix 75/25 and mix 50/50 versus long-acting basal insulin analogs in the United States

Abstract Objective: To evaluate the cost-effectiveness of biphasic insulin lispro mix 75/25 (LM75/25) and mix 50/50 (LM50/50) compared with a long-acting analog insulin (LAAI) regimen from the perspective of a US healthcare payer. Methods: A published computer simulation model of diabetes was used to evaluate the cost-effectiveness of LM75/25 and LM50/50 vs a LAAI (insulin glargine) from the perspective of a US healthcare payer. Treatment effects in terms of HbA1c benefits were taken from a recent meta-analysis. Direct medical costs including pharmacy, complication, and patient management costs were obtained from published sources. All costs were expressed in 2010 US dollars and future costs and clinical benefits were discounted at 3% per annum. Sensitivity analyses were performed. Results: LM75/25 and LM50/50 were associated with improvements in life expectancy of 0.08 and 0.09 years, improvements in quality-adjusted life expectancy of 0.07 quality-adjusted life years (QALYs) and 0.08 QALYs and increases in cost of US

A UK analysis of the cost of switching renal transplant patients from an immediate-release to a prolonged-release formulation of tacrolimus based on differences in trough concentration variability

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