Jason Gordon

A comparison of intermediate and long-acting insulins in people with type 2 diabetes starting insulin: an observational database study

Aims:  Insulin is normally added to oral glucose‐lowering drugs in people with type 2 diabetes when glycaemic control becomes suboptimal. We evaluated outcomes in people starting insulin therapy with neutral protamine Hagedorn (NPH), detemir, glargine or premixed insulins.

A cost-utility study of the use of pregabalin in treatment-refractory neuropathic pain.

Abstract Objectives: A small but significant proportion of patients with peripheral neuropathic pain (NeP) are refractory to the typical treatments applied in clinical practice, including amitriptyline and gabapentin. Thus, they continue to suffer the debilitating effects of NeP. This study aimed to evaluate the cost-effectiveness of pregabalin in comparison to usual care, in patients with refractory NeP, from a third party payer’s perspective (NHS). Methods: A stochastic simulation model was constructed, using clinical data from four non-randomized studies, to generate pain pathways of patients receiving usual care and pregabalin. Treatment effect (pain reduction) was converted to quality-of-life (QoL) data, using a regression analysis based on new utility data, collected from a survey of refractory NeP patients presenting to pain clinics in Cardiff, Wales. All relevant direct costs were estimated using resource use from the survey data (where available) and unit costs from the British National Formulary (BNF). The analysis was run over a 5-year time horizon, with costs and benefits discounted at 3.5%. Study limitations: The use of non-randomized (observational) data to characterize the effectiveness of treatments for NeP. Exclusion of productivity costs and consequences from the analysis. Results: In the base case analysis, an incremental cost-effectiveness ratio (ICER) of £10,803 per quality adjusted life year (QALY) was attained. This result was found to be reasonably insensitive to variations in the key input parameters, with ICERs ranging from £8505 to £22,845 per QALY gained. Conclusions: The analysis shows that pregabalin is a cost-effective alternative to usual care in patients with refractory NeP, with an ICER well below the threshold typically adopted by UK health technology assessment groups, such as NICE.

The cost-effectiveness of daclatasvir-based regimens for the treatment of hepatitis C virus genotypes 1 and 4 in the UK.

Objective This study aimed to determine the cost-effectiveness of daclatasvir in combination with other medicinal products for the treatment of patients with hepatitis C virus genotypes 1 and 4 and advanced liver disease in the UK. Methods A published and validated Markov model designed to simulate the natural history of chronic hepatitis C was used to compare daclatasvir with relevant treatment options for patients with hepatitis C virus genotypes 1 and 4 and a METAVIR score of F3–F4. Patients were defined according to their treatment status; that is, naive, experienced or interferon ineligible/intolerant. Data inputs for the analysis were derived from published sources, UK-specific where possible. A lifetime horizon was used, with costs and benefits discounted at 3.5%. Results Daclatasvir-based regimens are estimated to be cost-effective versus no treatment and established standard-of-care regimens, including telaprevir in combination with pegylated interferon-&agr;+ribavirin (PR), boceprevir in combination with PR and PR alone (incremental cost-effectiveness ratio range: £3715–£15 408). The cost-effectiveness of daclatasvir-based regimens versus emerging regimens (sofosbuvir or simeprevir based) is less consistent, but was dominant or cost-effective (incremental cost-effectiveness ratio range: £1394–£28 393) in all except two scenarios. Conclusion Daclatasvir-based regimens are expected to be highly cost-effective for the majority patients with advanced disease versus relevant comparator regimens, including newer direct-acting antiviral regimens.

Characterizing unmet medical need and the potential role of new biologic treatment options in patients with ulcerative colitis and Crohn's disease: a systematic review and clinician surveys.

Objectives Comparative outcomes of patients with ulcerative colitis (UC) and Crohn’s disease (CD) prescribed a biologic therapy are inconclusive. The aim of this research was to characterize the degree of unmet medical need in patients with UC or CD and to identify the potential role for new therapies. Methods A systematic literature review was undertaken of studies reporting outcomes associated with the use of existing biologic therapies in patients with UC or CD, focusing on the nature and rate of treatment failure. To complement the systematic review, contemporaneous data were obtained from a survey of practising gastroenterologists in the UK and France. Data were qualitatively combined in a narrative framework to evaluate the degree of unmet medical need among patients with UC or CD. Results Studies identified in the systematic review (n=120) were heterogeneous, particularly with respect to the definitions of treatment failure; estimates of treatment failure were high but uncertain. On the basis of standardized definitions, estimates of treatment failure provided by clinicians (n=102) were high, and they were higher for second-line treatment failure (primary: ⩽37%; secondary: ⩽41%) compared with first-line treatment failure (primary: ⩽26%; secondary: ⩽28%). The majority of the systematic review and survey data were reflective of outcomes with infliximab and adalimumab. Conclusion High treatment failure rates associated with existing biologics, identified by the review and clinician surveys, indicate a need for other biologic treatment options to improve the management and outcomes for people with UC and CD. Outcomes associated with existing and new biologic treatments should be investigated in head-to-head randomized trials in the context of their likely uses in clinical practice.

A cost comparison of long-acting insulin analogs vs NPH insulin-based treatment in patients with type 2 diabetes using routinely collected primary care data from the UK

Abstract Aim: The aim of this analysis was to investigate total healthcare costs, HbA1c, and weight changes over a 36-month period in patients with type 2 diabetes initiated on NPH or long-acting insulin analogs. Methods: Electronic patient data from 479 general practices in the UK (THIN database) were examined for new users of glargine (n = 794), detemir (n = 252), or NPH insulin (n = 430). Annualized healthcare costs and clinical outcomes in years 1, 2, and 3 following insulin initiation were quantified and compared with baseline, using ANOVA and linear regression models. Results: A significant difference (p < 0.05) in total healthcare costs increases at year 1 vs baseline was observed between glargine and detemir, detemir and NPH, but not between glargine and NPH (increase: +£486, +£635, and +£420 for glargine, detemir, and NPH users, respectively). However, increases by year 3 were not significantly different between the insulins. A propensity score analysis comparing analog and NPH insulin showed that, following insulin initiation, increases in costs were higher with insulin analogs at year one (+£220), but this difference decreased over time in each year following insulin initiation (+£168 and +£146, respectively, for years 2 and 3). HbA1c reductions were not significantly different between the groups at all time points. Differences in weight gain between glargine and NPH were statistically significant at year 1 (0.87 kg vs 1.11 kg) and year 3 (1.15 kg vs 1.57 kg), but other estimates of between-group differences in weight gain were non-significant. Conclusions: Following insulin initiation, the difference in healthcare costs of long-acting analogs compared to NPH insulin was transient. By year 3, the cost differences were not significantly different between the two cohorts, driven by an observed reduction in the cost of self-monitoring of blood glucose (SMBG) in the analog group and an increase in the cost of bolus insulin in the NPH group.

Hepatitis C disease transmission and treatment uptake: impact on the cost-effectiveness of new direct-acting antiviral therapies

BackgroundHepatitis C virus (HCV) treatment can reduce the incidence of future infections through removing opportunities for onward transmission. This benefit is not captured in conventional cost-effectiveness evaluations of treatment and is particularly relevant in patient groups with a high risk of transmission, such as those people who inject drugs (PWID), where the treatment rates have been historically low. This study aimed to quantify how reduced HCV transmission changes the cost-effectiveness of new direct-acting antiviral (DAA) regimens as a function of treatment uptake rates.MethodsAn established model of HCV disease transmission and progression was used to quantify the impact of treatment uptake (10–100%), within the PWID population, on the cost-effectiveness of a DAA regimen versus pre-DAA standard of care, conducted using daclatasvir plus sofosbuvir in the UK setting as an illustrative example.ResultsThe consequences of reduced disease transmission due to treatment were associated with additional net monetary benefit of £24,304–£90,559 per patient treated at £20,000/QALY, when 10–100% of eligible patients receive treatment with 100% efficacy. Dependent on patient genotype, the cost-effectiveness of HCV treatment using daclatasvir plus sofosbuvir improved by 36–79% versus conventional analysis, at 10–100% treatment uptake in the PWID population.ConclusionsThe estimated cost-effectiveness of HCV treatment was shown to improve as more patients are treated, suggesting that the value of DAA regimens to the NHS could be enhanced by improved treatment uptake rates among PWID. However, the challenge for the future will lie in achieving increased rates of treatment uptake, particularly in the PWID population.

Evaluation of Insulin Use and Value for Money in Type 2 Diabetes in the United Kingdom

IntroductionIt is unclear as to whether human or long-acting analog insulins represent the most efficient use of health and non-healthcare resources in the management of type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the value for money relationship associated with the use of these insulins in the UK setting.MethodsA literature search was performed for studies reporting expenditure associated with the use of human and analog insulins. Data from this review informed a budget impact assessment model. Costs were converted to a common currency and results are reported in 2011 British pounds sterling (GBP) values.ResultsAnnual diabetes-related medication expenditure and patients total expenditure associated with the management of T2DM were estimated to be £397 million and £3,901 million, respectively. Substitution of human insulin for analog insulins was associated with a drug acquisition cost saving of between £5 million and £23 million each year. Overall, though, total expenditure increased significantly with increased use of human insulin by £34 million to £136 million each year depending on the degree of substitution.ConclusionsOn the face of it, analog insulins are more expensive, prompting questions about potential cost savings to health services in the UK from direct substitution to the less expensive human preparation. The current analysis illustrates that the increased use of human insulin and decreased use of analog insulin would, however, increase the overall net societal cost of managing insulin-treated patients with T2DM. Governments and decision makers should consider that total healthcare expenditure would not necessarily fall when decisions are based solely on the use of cheaper products.

Value of Sustained Virologic Response in Patients with Hepatitis C as a Function of Time to Progression of End-Stage Liver Disease.

BackgroundTargeted intervention in patients with hepatitis C virus (HCV) closest to end-stage liver disease (ESLD) progression may offer an approach to treatment prioritisation whilst delivering benefits for patients and the healthcare system. In contrast to previous HCV economic analyses, this study aimed to estimate the health economic value of sustained virologic response (SVR) stratified by the patient’s propensity to progress to ESLD.MethodsAn HCV natural history model was adapted to estimate the value of avoiding ESLD complications following SVR, assessed as cost offsets and quality-adjusted life year (QALY) gains, as a function of time to ESLD at treatment initiation. These outcomes were used to estimate the financial value of achieving SVR, defined as the maximum investment that could be allocated without exceeding a willingness-to-pay threshold of £20,000/QALY.ResultsRegardless of time to ESLD onset, achieving SVR was beneficial, resulting in cost offsets and QALY gains, due to avoidance of ESLD complications. The value of achieving SVR was greatest in patients closest to ESLD onset, resulting in increased cost offsets and QALY gains (up to £50,901 and 9.56 QALYs). In patients closest to ESLD onset, the financial value of achieving SVR was £242,051, compared with £127,116 in patients furthest from onset.ConclusionsStandard cost-effectiveness evaluations may underestimate the value of treatment in HCV patients closest to ESLD development. Targeted intervention would promote efficient allocation of limited healthcare resources and reconcile concerns surrounding the affordability of new direct-acting antivirals, by minimising the number-needed-to-treat to maximise health benefit, whilst minimising healthcare expenditure.

Treatment choice, medication adherence and glycemic efficacy in people with type 2 diabetes: a UK clinical practice database study

Objective Using primary care data obtained from the UK Clinical Practice Research Datalink, this retrospective cohort study examined the relationships between medication adherence and clinical outcomes in patients with type 2 diabetes. Research design and methods Data were extracted for patients treated between 2008 and 2016, and stratified by oral antihyperglycemic agent (OHA) line of therapy (mono, dual or triple therapy). Patients were monitored for up to 365 days; associations between medication possession ratio (MPR) and outcomes at 1 year (glycated hemoglobin A1c (HbA1c), weight and hypoglycemia incidence) were assessed using linear regression modeling and descriptive analyses. Results In total, 33 849 patients were included in the study (n=23 925 OHA monotherapy; n=8406 OHA dual therapy; n=1518 OHA triple therapy). One-year change in HbA1c was greater among adherent (−0.90 to −1.14%; −9.8 to −12.5 mmol/mol) compared with non-adherent patients (−0.49 to −0.69%; −5.4 to −7.5 mmol/mol). On average, adherent patients had higher hypoglycemia event rates than non-adherent patients (rate ratios of 1.24, 1.10 and 2.06 for OHA mono, dual and triple therapy cohorts, respectively) and experienced greater weight change from baseline. A 10% improvement in MPR was associated with −0.09% (−1.0 mmol/mol), −0.09% (−1.0 mmol/mol) and −0.21% (−2.3 mmol/mol) changes in HbA1c for OHA mono, dual and triple therapy cohorts, respectively. Conclusions For patients with type 2 diabetes, increasing medication adherence can bring about meaningful improvements in HbA1c control as the requirement for treatment escalation increases. Regimens associated with weight loss and the avoidance of hypoglycemia were generally associated with better medication adherence and improved glycemic control.