An economic evaluation of sevelamer in patients new to dialysis

ABSTRACT

Objective: The overall objective of this study was to estimate the costs and outcomes associated with treatment with sevelamer for hyperphosphataemia compared with calcium-based binders.

Methods: Using published data on mortality and hospitalisation rates, a Markov model was developed to predict health outcomes and associated costs for the treatment of hyperphosphataemia using either sevelamer or calcium binders in chronic kidney disease patients who had recently started haemodialysis. Patient outcomes were modelled for 5 years, and incremental cost-effective ratios (ICERs) were calculated for sevelamer relative to calcium carbonate and calcium acetate binders. The perspective adopted was that of the UK National Health Service.

Results: The total 5-year discounted treatment cost for patients treated with sevelamer is £24?216, while for the calcium carbonate group total cost was £17?695. This is an incremental cost of £6521 per sevelamer-treated patient over 5 years. Patients receiving sevelamer can be expected to experience 2.70 quality-adjusted life years (QALYs) compared to 2.46 for those treated with calcium carbonate (i.e. an incremental gain of 0.24 QALYs). This results in an incremental cost per QALY of £27?120 and an incremental cost per life year gained of £15?508. Results were similar with calcium acetate.

Conclusion: Together with the unique morbidity and mortality benefits, this study suggests that treatment with sevelamer confers clinical benefits with a modest investment of additional economic resources.     

Cost-effectiveness of licensed treatment options for restless legs syndrome in the UK and Sweden

ABSTRACT

Objective: To estimate the cost-effectiveness of pramipexole versus no treatment and ropinirole in moderate to very severe idiopathic restless legs syndrome (RLS) in the UK and Sweden.

Methods: A Markov model was developed using clinical trial data for pramipexole and ropinirole. Model health states were based on the International RLS Study Group Rating Scale (IRLS) scores. Health states were: no (IRLS 0), mild (IRLS 1–14), moderate (IRLS 15–24), severe (IRLS 25–34), very severe RLS (IRLS 35–40) and death. Patients entered the model with an IRLS score?>?15 matching the trial inclusion criteria of the pramipexole trials. Resource use and utilities were based on trial data, literature, a patient survey and a panel of physicians from the UK and Sweden in the absence of published information. A healthcare sector perspective was taken for the UK and a societal perspective for Sweden using 2004–2005 unit costs. The base case analysis took a 1-year timeframe.

Results: In the UK the incremental cost per quality-adjusted life year (QALY) for pramipexole was £3349 versus no treatment and a cost-saving of £92 against ropinirole. In Sweden, pramipexole produced cost-savings of Swedish Krona (SEK) 2381 (£176) versus no treatment and SEK?3564 (£264) against ropinirole. QALY gains in both countries were 0.095 versus no treatment and 0.007 versus ropinirole. Results compare well with UK cost–effectiveness thresholds of £20?000/£30?000 per QALY and are cost-saving for Sweden. One-way and probabilistic sensitivity analyses showed results to be robust.

Conclusions: Pramipexole is cost-effective compared to no treatment and ropinirole for patients with moderate to very severe RLS.     

Cost-effectiveness of atypical antipsychotics for the management of schizophrenia in the UK

ABSTRACT

Objective: To evaluate the cost-effectiveness of atypical antipsychotic treatment sequences for the management of stable schizophrenia in the UK.

Research design and methods: A Markov model was developed to assess the cost per quality-adjusted life year (QALY) gained from 12 alternative treatment sequences each containing two of four atypical antipsychotics (aripiprazole, olanzapine, quetiapine and risperidone), followed by clozapine. The main model parameters were populated with data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study and a recent trial comparing aripiprazole with olanzapine. Patients enter the model with stable schizophrenia and may relapse, discontinue or continue and experience adverse events (AEs), or develop diabetes. Population mortality was adjusted for schizophrenia and diabetes. Utility decrements applied to stable schizophrenia, relapse, diabetes and treatment-related AEs were taken from a direct UK utility elicitation study. Resource use and unit costs were taken from published sources. A time horizon of 10 years was adopted. Results are based on 10,000 probabilistic iterations of the model.

Results: Aripiprazole followed by risperidone produced the greatest number of QALYs, an additional 0.03 compared with risperidone followed by olanzapine, at an incremental cost of £257 (incremental cost/QALY: £9,440). Aripiprazole followed by risperidone had the greatest probability among evaluated sequences of being cost-effective at a threshold of >£10,000/QALY. All other strategies were dominated by at least one of these strategies. The impact of lower pricing for risperidone (based on generic availability) did not impact results.

Conclusions: Modelling the cost-effectiveness of different treatment sequences for stable schizophrenia is appropriate given that patients rarely remain on one treatment for long periods. The treatment sequence aripiprazole followed by risperidone was the most cost-effective option for patients with stable schizophrenia in the UK.     

An economic evaluation of vasoactive agents used in the United Kingdom for acute bleeding oesophageal varices in patients with liver cirrhosis

ABSTRACT

Objective: To conduct an economic evaluation of terlipressin, octreotide and placebo in the treatment of bleeding oesophageal varices (BOV) where endotherapy could be used concomitantly.

Methods: A discrete event simulation model was created with transition states: bleeding, no bleeding, no bleeding post transjugular intrahepatic portosystemic shunt, post-salvage surgery, and death. Efficacy data on survival, re-bleeding and control of bleeding were obtained from high quality studies reported in Cochrane meta-analyses. Baseline outcomes related to the course of disease and health-state utilities were derived from published sources. Vasoactive treatment costs and all related BOV costs were obtained from published UK sources.

Results: The average aggregated treatment cost per person for all medical interventions at 1 year was lower for terlipressin-treated patients (£2623) compared with those treated using octreotide (£2758) or placebo (£2890). The incremental analysis comparing terlipressin with octreotide and placebo using a cost per quality adjusted life year (QALY) and cost per life year gained (LYG) approach indicated that terlipressin was the dominant BOV treatment option (i.e. it cost less and it was more effective). Based on a maximum willingness to pay of £20?000/QALY terlipressin was more effective and cost-saving compared to octreotide and placebo for simulations ranging from 42 days to 2 years. In point estimation analyses octreotide was dominant compared to placebo; however, probabilistic sensitivity analysis indicated that octreotide was unlikely to be cost-effective compared to placebo.

Conclusions: The findings indicated that vasoactive treatment in BOV was cost-savingcompared to no vasoactive treatment. Furthermore, terlipressin was the more cost-effective vasoactive treatment for BOV in cirrhotic patients.     

Economic evaluation of etoricoxib versus non-selective NSAIDs in the treatment of ankylosing spondylitis in the UK

ABSTRACT

Objectives: To evaluate the cost-effectiveness of etoricoxib, a cyclooxygenase (COX)‐2 selective inhibitor, versus non-selective nonsteroidal anti-inflammatory drugs (nsNSAIDs) in the treatment of ankylosing spondylitis (AS).

Methods: The cost-effectiveness of etoricoxib versus nsNSAIDs was evaluated from the UK National Health Service (NHS) and society perspective with a decision-analytic model. Patients stayed on initial therapy throughout 52 weeks unless they experienced an adverse event (AE) or lacked efficacy, in which case they switched to another nsNSAID or a tumor necrosis factor alpha antagonist. Efficacy data were obtained from a 1‐year etoricoxib clinical trial in AS. Bath AS Functional Index (BASFI) data were translated into Quality Adjusted Life Year (QALY) weights using a published data on the relation between BASFI and Short-form (SF) 36 Quality of life scores, as well as the relation between SF‐36 and utility. Safety data were based on meta-analyses of etoricoxib trials. Information on treatment pathways, resource consumption, and absenteeism from work was obtained from literature and experts. Model outcomes included QALYs, perforations, ulcers, or bleeds, cardiovascular events, and costs.

Results: Etoricoxib was cost-effective compared to nsNSAIDs in terms of cost per QALY saved (£5611). Probabilistic sensitivity analysis found a 77% probability of the incremental cost per QALY saved being within a threshold for cost-effectiveness of £20?000. The expected direct costs over the 52-week period were £1.23 (95% uncertainty distribution £1.10; £1.39) and £1.13 per day (£0.78; £1.55) for patients starting with etoricoxib and nsNSAIDs, respectively. When costs related to absenteeism were taken into account, the cost per QALY saved was £281.

Conclusions: Given the underlying assumptions and data used, this economic evaluation demonstrated that, compared to nsNSAIDs, etoricoxib is a cost-effective therapy for AS patients in the UK.     

Post-traumatic stress disorder in UK police officers

ABSTRACT

Objective: To assess the long term cost effectiveness of clopidogrel monotherapy compared with acetylsalicylic acid (aspirin; ASA) monotherapy in patients at risk of secondary occlusive vascular events (OVEs) in the UK.

Design: Cost utility analysis based on clinical data from CAPRIE (a multicentre randomised controlled trial, involving 19?185 patients); long-term effects were extrapolated beyond the trial period using a Markov model populated with data from UK observational studies. Health economic evaluation carried out from the perspective of the UK National Health Service.

Participants: A representative cohort of 1000 UK patients aged 60?years (approximate mean age of the CAPRIE population), with the qualifying diagnoses of myocardial infarction, ischaemic stroke and peripheral arterial disease, who are at risk of secondary OVEs (non-fatal myocardial infarction, non-fatal stroke or vascular death).

Interventions: Patients were assumed to receive treatment with either clopidogrel (75?mg/day) for 2?years followed by ASA (325?mg/day, average) for their remaining lifetime, or ASA alone (325?mg/day, average) for life.

Main outcome measures: Incremental cost per life year gained and incremental cost per quality-adjusted life year (QALY) gained.

Results: In the base case, the incremental cost effectiveness of clopidogrel versus ASA in this population is estimated at £18?888 per life year gained and £21?489 per QALY gained. Multiple deterministic and probabilistic sensitivity analyses suggest the model is robust to variations in a wide range of input parameters.

Conclusion: Two years of treatment with clopidogrel can be considered a cost effective intervention in patients at risk of secondary OVEs in the UK.     

What are the dangers of biological therapy discontinuation or dose reduction strategies when treating rheumatoid arthritis?

Introduction: Treatment with biological DMARDs (bDMARDs) has meant that remission or low disease activity (LDA) is now a realistic goal for patients with rheumatoid arthritis (RA). However, as in the case of all long-term therapies, potential side-effects give rise to concern. The main reasons for withdrawing or tapering bDMARDs are safety and the sustainability of national healthcare systems. Given these data our review has been focused on important question: whether conventional, including steroids, or bDMARDs can be reduced or even stopped in patients with stable established RA or early RA.

Areas covered: The studies included in the evaluation had to be RCTs, observational studies, systematic reviews evaluating the withdrawing or tapering bDMARDs in RA patients who have been on long-term treatment and have achieved remission or LDA. A search was made in the MEDLINE and EMBASE databases from 1980 to May 2016.

Expert commentary: There is curently no standardised way of identifying the patients for whom reducing bDMARD therapy is appropriate. Clinical experience and data from de-escalation studies suggest that patients with RA in sustained remission are the best target population for studying drug-tapering regimens, and that LDA should not be considered an adequate indication for bDMARD de-escalation because it could hide a persistent amount of inflammation.     

Cost-effectiveness of levodopa/carbidopa/entacapone (Stalevo) compared to standard care in UK Parkinson's disease patients with wearing-off

ABSTRACT

Background and methods: A Markov model was developed to evaluate the cost-effectiveness of levodopa/carbidopa/entacapone (LCE;Stalevo*), in the treatment of patients with Parkinson's disease (PD) and end-of-dose motor fluctuations (wearing-off). LCE, with or without other antiparkinsonian medications, was compared to UK standard care, comprising traditional levodopa/dopa-decarboxylase inhibitor (DDCI) with other antiparkinsonian medications (e.g. selegiline or dopamine agonists) added as needed. The costs and outcomes of both treatments were projected over a period of 10 years from the perspective (a) of society as a whole and (b) of the UK National Health Service (NHS). Sensitivity analyses, including second-order Monte Carlo simulations, were performed to assess the confidence level of the primary results.

Results: Treatment with LCE produced an average gain of +1.04 quality-adjusted life-years (QALYs) per patient (2.57 vs. 1.53) in the base-case analysis (discount rate 3.5%). This gain was accompanied by a reduction in the total 10-year direct cost of care to society of £10?198 per patient (~ ¤14?800). From the societal perspective, therefore, LCE was dominant, producing better clinical outcomes with lower costs. This dominance was reiterated in all sensitivity analyses of society-focused analysis, including a shortening of the time-frame to 5 years.

Although treatment with LCE resulted in an increase in direct costs per patient of £3239 (£25?756 versus £22?517) to the NHS over the 10-year period analysed, the incremental cost-effectiveness ratio (ICER) of LCE was only £3105 per QALY gained (~ ¤4500). All ICERs to the NHS remained below £3800 per QALY gained in univariate sensitivity analyses applying different discount rates. When a shorter, 5-year, time-horizon was analysed, the NHS-related ICER for LCE was £6526 per QALY gained. All these ICERs are within the range usually considered to indicate acceptable or highly acceptable cost effectiveness (defined as < £30?000 per QALY gained).

The results of the Monte Carlo simulations indicated that the likelihood of LCE being either ‘dominant’ or more effective at an ‘acceptable cost’ from either the societal or the NHS perspective was high, exceeding 96% in the base-case sensitivity analysis, and was 93% even when all the uncertainties associated with the model were taken into consideration simultaneously. In particular, compared to standard care, the probability that LCE would provide better outcomes at a lower cost to society as a whole was 77% in the base-case sensitivity analysis and 72% in the scenario involving the highest degree of uncertainty.

Conclusions: In the UK the use of LCE to treat PD patients with wearing-off is beneficial to individual patients and likely to offer money savings to society as a whole, compared with UK standard therapy. The added cost of the medication itself is exceeded by the savings made in other direct costs of PD, mainly those relating to social care or PD-related private expenditures.     

A cost-utility analysis of once daily solifenacin compared to tolterodine in the treatment of overactive bladder syndrome

ABSTRACT

Objective: To evaluate the cost-utility of solifenacin, a new generation antimuscarinic, compared with tolterodine in the treatment of overactive bladder syndrome (OAB), from the perspective of the UK National Health Service (NHS).

Research design and methods: A 1-year Markov model was constructed using data from a 12-week, randomised, double-blind study that compared flexible dosing with solifenacin (5?mg and 10?mg) with tolterodine (IR 2?mg bd/ER 4?mg) in adults with OAB. The model incorporated five discrete health states that were based on disease severity (micturitions/day and incontinence episodes/day). A ‘drop out’ state was also used in the model to account for patients that discontinued treatment in the first year. UK-specific costs for drug treatment and pad use as well as utilities were assigned to each health state.

Results: Solifenacin was a less costly and more effective treatment strategy compared with tolterodine. During the course of 1 year, the estimated cost per patient was £509 for patients treated with solifenacin and £526 for those given tolterodine, a cost saving of £17 per patient. Treatment with solifenacin was also associated with a small incremental gain of 0.004 quality-adjusted-life-years (QALYs) over tolterodine. Sensitivity analysis suggests that the incremental cost effectiveness of solifenacin relative to tolterodine does not appear to exceed £30?000/QALY with even large variations in key model parameters.

Conclusion: Flexible dosing with solifenacin is likely to be cost-effective versus tolterodine in the treatment of OAB. Further studies are needed to confirm these results.     

Modelling the economic and health consequences of cardiac resynchronization therapy in the UK

ABSTRACT

Objective: Clinical evidence supports the use of cardiac resynchronization therapy (CRT) in advanced heart failure, but its cost-effectiveness is still unclear. This analysis assessed the economic and health consequences in the UK of implanting a CRT in patients with NYHA class III-IV heart failure.

Methods: A discrete event simulation of heart failure was used to compare the course over 5 years of 1000 identical pairs of patients – one receiving both CRT and optimum pharmacologic treatment (OPT), the other OPT alone. All inputs were obtained from the data collected in the CArdiac REsynchronization in Heart Failure (CARE-HF) trial and a hospital in the UK. Direct medical costs (in 2004 £) from the perspective of the National Health Service were considered. Both costs and benefits were discounted at 3.5%. Sensitivity analyses addressed all model inputs and multivariate analyses were performed by varying key parameters simultaneously.

Results: The model predicted 471 deaths and 2263 hospitalizations over 5 years with OPT alone and 348 deaths and 1764 hospitalizations with CRT, equivalent to a 26% reduction in mortality and 22% in hospitalizations, at a discounted cost of £11?423 per patient with CRT vs. £4900 with OPT alone. CRT was predicted to increase quality-adjusted survival by 0.43 QALYs per patient, resulting in an incremental cost-effectiveness ratio of £15?247 per QALY gained (range: £12?531–£23?184). Sensitivity analyses revealed that this outcome was most sensitive to time horizon and cost of implantation.

Conclusion: Based on these 5‐year analyses, CRT is expected to yield substantial health benefits at a reasonable cost.     

An economic assessment of analogue basal–bolus insulin versus human basal–bolus insulin in subjects with type 1 diabetes in the UK

ABSTRACT

Background: A recent study demonstrated that treatment of type 1 diabetes with an analogue basal–bolus insulin regimen was associated with improved glycaemic control (HbA_1c –0.22% points, p < 0.001), reduced risk of hypo­glycaemic events (–21%, p = 0.036) and reduction in body mass index (–0.30?kg/m², p < 0.001) compared to a human basal–bolus regimen after 18 weeks.

Methods: A published and validated computer simulation model was used to project long-term economic and clinical outcomes in a simulated cohort of type 1 diabetes patients treated with either insulin detemir plus insulin aspart (analogue) or Neutral Protamine Hagedorn plus human soluble insulin (human), in a UK setting. Probabilities of complications and HbA_1c-dependent adjustments were derived from major clinical and epidemiological studies. Complication and treatment costs were projected over patient lifetimes from a National Health Service perspective. Costs and clinical benefits were discounted at 3.5% annually.

Results: Quality-adjusted life expectancy (QALE) was 0.66 quality-adjusted life years (QALY) higher in the analogue insulin versus the human insulin group (mean ± SD) (7.65 ± 0.09 versus 6.99 ± 0.08). Direct lifetime costs were £1654 greater with analogue versus human insulin treatment (£40?876 ± 1119 versus £39?222 ± 1141), producing an incremental cost effectiveness ratio (ICER) of £2500 per QALY gained. Sensitivity analyses showed the results were robust under a range of plausible scenarios.

Conclusions: Treatment with analogue insulin was associated with a decreased incidence of long-term complications and improved QALE, but slightly higher treatment costs compared to human insulin therapy. Analogue insulin treatment had an ICER within the range generally considered to represent good value for money in the UK.     

The safety of emerging biosimilar drugs for the treatment of rheumatoid arthritis

Introduction: Biological disease-modifying anti-rheumatic drugs (bDMARDs), often administered in combination with methotrexate, target specific inflammatory mediators and have transformed the treatment of rheumatic diseases, especially rheumatoid arthritis (RA) but also the spondyloarthritides. However, the high cost of these drugs in many countries restricts patient access. As many bDMARDs have reached or are near to patent expiration, numerous biosimilar drugs are in development and some have already been approved. Biosimilars are generally priced lower than their reference products (RPs), or bio-originators, and as prices come down it is hoped that patient access to these drugs will increase, making the safety of these drugs an area of major interest.

Areas covered: This article reviews publicly available safety data on biosimilars in RA.

Expert opinion: Most available data for biosimilars in RA relate to tumor necrosis factor inhibitors (TNFi) and rituximab (an anti-CD20 monoclonal antibody). As biosimilar use around the world increases, evidence supporting the clinical safety of the biosimilars compared with their RPs also grows. To date, no new safety concerns have been raised in studies with TNFi or rituximab biosimilars for the treatment of RA; safety profiles have been consistent with those of their RPs. However, careful post-marketing pharmacovigilance remains necessary.     

Cost-effectiveness of ziconotide in intrathecal pain management for severe chronic pain patients in the UK

ABSTRACT

Objective: To examine the cost-effectiveness of using intrathecal ziconotide in the treatment of severe chronic pain compared to best supportive care for patients with intractable chronic pain in the United Kingdom.

Methods: Using a simulation model, the analysis evaluated the cost and health economic consequences of using ziconotide as a treatment for severe chronic pain. The modelled population and clinical data were based on a randomised controlled trial in which the main outcome was reduction in pain as measured by the visual analogue scale of pain intensity (VASPI). Resource use data were elicited using a modified Delphi panel and costed using published sources. Utility values were derived from a separate research study. The main outcome measure was the cost per quality-adjusted life-year (QALY). Extensive scenario analysis was conducted to evaluate parameter uncertainty.

Results: Overall, findings were robust to most assumptions. The cost-effectiveness of ziconotide compared to best supportive care (BSC) was £27?443 per QALY (95% CI £18?304–38?504). Scenarios were investigated in which discount rates, the time horizon, the threshold for qualifying as a responder, pump-related assumptions, utilities, ziconotide drug dose, and the patient discontinuation rate with ziconotide were varied. The most sensitive parameter was the dosage of ziconotide: using the lower and upper bounds of the average ziconotide dosage observed in the long-term open-label study changed the incremental cost-effectiveness ratio (ICER) to £15?500 [£8206–25?405] and £44?700 [£30?541–62?670].

Conclusions: Ziconotide may offer an economically feasible alternative solution for patients for whom current treatment is inappropriate or ineffective. The main study limitation is that some model inputs, mainly related to resource use, are based on assumptions or expert interviews.     

Cost-effectiveness of detemir-based basal/bolus therapy versus NPH-based basal/bolus therapy for type 1 diabetes in a UK setting: an economic analysis based on meta-analysis results of four clinical trials

SUMMARY

Background: A meta-analysis of results from four clinical trials in type 1 diabetes patients showed that insulin detemir (IDet)-based basal/bolus treatment of type 1 diabetes led to improved HbA1c (0.15%-points lower), reduced risk of major hypoglycaemic events (by 2%) and reduction in body mass index (BMI) (0.26kg/m²) compared to protamine Hagedorn human (NPH) insulin-based basal/bolus therapy in type 1 patients.

Methods: A published, validated, peer-reviewed Markov simulation model (the CORE Diabetes Model) projected short-term results obtained from the fixed-effects (weighted average) meta-analysis to long-term incidence of complications, improvements in quality-adjusted life years (QALY), long-term costs and the cost-effectiveness for IDet combinations versus NPH combinations in type 1 diabetes patients. Probabilities of complications and HbA1c-dependent adjustments were derived from the DCCT and other studies. Costs of treating complications in the UK were retrieved from published sources. Total direct costs (complications?+?treatment costs) for each arm were projected over patient lifetimes from a UK National Heath Service perspective. Both costs and clinical outcomes were discounted at 3.5% annually.

Results: Improved glycaemic control, decreased hypoglycaemic events and BMI with IDet-based basal/bolus therapy led to fewer diabetes-related complications, an increase in quality-adjusted life expectancy of 0.09 years, increased total lifetime costs/patient of £1707 and an incremental cost-effectiveness ratio of £19,285 per QALY gained. Results were stable under a wide range of reasonable assumptions.

Conclusions: Short-term improvements seen with IDet combinations versus NPH combinations led to decreased complications, improvements in QALYs and reductions in complication costs, which partially offset the additional costs of detemir, leading to a cost-effectiveness ratio which fell within a range considered to represent excellent value for money (< £35,000/QALY gained).     

Modelling the cost-effectiveness of tofacitinib for the treatment of rheumatoid arthritis in the United States

Background and objectives: Rheumatoid arthritis (RA) is a chronic, debilitating disease affecting an estimated 1.5 million patients in the US. The condition is associated with a substantial health and economic burden. An economic model was developed to evaluate the cost-effectiveness of tofacitinib (a novel oral Janus kinase inhibitor) versus biologic therapies commonly prescribed in the US for the treatment of RA.

Methods: A cost–utility model was developed whereby sequences of treatments were evaluated. Response to treatment was modeled by HAQ change, and informed by a network meta-analysis. Mortality, resource use and quality of life were captured in the model using published regression analyses based on HAQ score. Treatment discontinuation was linked to response to treatment and to adverse events. Patients were modeled as having had an inadequate response to methotrexate (MTX-IR), or to a first biologic therapy (TNFi-IR).

Results: The tofacitinib strategy was associated with cost savings compared with alternative treatment sequences across all modeled scenarios (i.e. in both the MTX-IR and TNFi-IR scenarios), with lifetime cost savings per patient ranging from $65,205 to $93,959 (2015 costs). Cost savings arose due to improved functioning and the resulting savings in healthcare expenditure, and lower drug and administration costs. The tofacitinib strategies all resulted in an increase in quality-adjusted life years (QALYs), with additional QALYs per patient ranging from 0.01 to 0.22.

Conclusions: Tofacitinib as a second-line therapy following methotrexate failure and as a third-line therapy following a biologic failure produces lower costs and improved quality of life compared with the current pathway of care.     

Cost-utility analysis in a UK setting of self-monitoring of blood glucose in patients with type 2 diabetes

ABSTRACT

Background: Self-monitoring of blood glucose (SMBG) in type 2 diabetes patients has been shown in meta-analyses of randomized trials to improve HbA_1c by ～0.4% when compared to no SMBG. However, the cost of testing supplies is high, improvements in health utility due to improved glycaemic control may be possible and cost-effectiveness has not been evaluated.

Methods: A peer-reviewed validated model projected improvements in lifetime quality-adjusted life years (QALYs), long-term costs and cost-effectiveness of SMBG versus no SMBG. Markov/Monte Carlo modelling simulated the progression of complications (cardiovascular, neuropathy, renal and eye disease). Transition probabilities and HbA_1c-dependent adjustments came from the United Kingdom Prospective Diabetes Study (UKPDS) and other major studies. Effects of SMBG on HbA_1c came from clinical studies, meta-analyses and population studies, but can only be considered ‘moderate’ levels of evidence. Costs of complications were retrieved from published sources. Direct costs of diabetes complications and SMBG were projected over patient lifetimes from a UK National Health Service perspective. Outcomes were discounted at 3.5% annually. Extensive sensitivity analyses were performed.

Results: Depending on the type of diabetes treatment (diet and exercise/oral medications/insulin), improvements in glycaemic control with SMBG improved discounted QALYs anywhere from 0.165 to 0.255 years, with increased total costs of £1013–£2564/patient, giving incremental cost-effectiveness ratios of £4508:£15?515/QALY gained, well within current UK willingness-to-pay limits. Results were robust under a wide range of plausible assumptions.

Conclusions: Based on the moderate level of clinical evidence available to date, improvements in glycaemic control with interventions, including SMBG, can improve patient outcomes, with acceptable cost-effectiveness ratios in the UK setting.     

Clinical utility of therapeutic drug monitoring in biological disease modifying anti-rheumatic drug treatment of rheumatic disorders: a systematic narrative review

Introduction: Biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) have improved the treatment outcomes of inflammatory rheumatic diseases including Rheumatoid Arthritis and spondyloarthropathies. Inter-individual variation exists in (maintenance of) response to bDMARDs. Therapeutic Drug Monitoring (TDM) of bDMARDs could potentially help in optimizing treatment for the individual patient.

Areas covered: Evidence of clinical utility of TDM in bDMARD treatment is reviewed. Different clinical scenarios will be discussed, including: prediction of response after start of treatment, prediction of response to a next bDMARD in case of treatment failure of the first, prediction of successful dose reduction or discontinuation in case of low disease activity, prediction of response to dose-escalation in case of active disease and prediction of response to bDMARD in case of flare in disease activity.

Expert opinion: The limited available evidence does often not report important outcomes for diagnostic studies, such as sensitivity and specificity. In most clinical relevant scenarios, predictive value of serum (anti-) drug levels is absent, therefore the use of TDM of bDMARDs cannot be advocated. Well-designed prospective studies should be done to further investigate the promising scenarios to determine the place of TDM in clinical practice.     

Cost-effectiveness of macrogol 4000 compared to lactulose in the treatment of chronic functional constipation in the UK

ABSTRACT

Objective: To estimate the cost-effectiveness of macrogol 4000 compared to lactulose in the treatment of chronic functional constipation, from the perspective of the National Health Service (NHS) in the UK.

Methods: A decision model depicting the management of chronic functional constipation was constructed using clinical outcomes and resource use values derived from patients suffering from chronic functional constipation in The Health Improvement Network (THIN) Database. The model was used to estimate the cost-effectiveness of a general practitioner (GP) prescribing macrogol 4000 relative to lactulose to treat adults ≥18 years of age suffering from chronic functional constipation.

Results: Forty-two per cent (95% confidence interval [CI]: 38%; 46%) of macrogol 4000-treated patients are expected to be successfully treated within 3 months after starting treatment, compared to 31% (95% CI: 27%; 37%) of lactulose-treated patients. Patients' health status at 3 months was estimated to be 0.213 (95% CI: 0.200; 0.223) and 0.210 (95% CI: 0.197; 0.220) quality-adjusted life years (QALYs) in the macrogol 4000 and lactulose groups, respectively. The total 3-monthly NHS cost of treating patients with macrogol 4000 or lactulose was estimated to be £115 (95% CI: £98; £132) and £102 (95% CI: £86; £119), respectively. Hence, the cost per QALY gained with macrogol 4000 was estimated to be £4333.

Conclusion: Within the limitations of the model, treatment with macrogol 4000 relative to lactulose is expected to increase the probability of being successfully treated by 35% at 3 months (p < 0.0001), although this yields only a 1% improvement in health gain. Nevertheless, macrogol 4000 affords a cost-effective addition to the range of laxatives available for this potentially resource-intensive condition, since it is clinically more effective than lactulose and the cost-effective strategy from the perspective of the NHS.     

A cost-effectiveness model of smoking cessation based on a randomised controlled trial of varenicline versus placebo in patients with chronic obstructive pulmonary disease

Objectives: Smoking is an important risk factor in chronic obstructive pulmonary disease (COPD). A recent clinical trial demonstrated the efficacy of varenicline versus placebo as an aid to smoking cessation in patients with COPD. This study examines the cost-effectiveness of varenicline from the perspective of the healthcare systems of Spain (base case), the UK, France, Germany, Greece and Italy.

Methods: A Markov model was developed to determine the cost-effectiveness of varenicline as an aid to smoking cessation, compared to a placebo, in a COPD population. Cost-effectiveness was determined by the incremental cost per quality-adjusted life year (QALY) gained.

Results: In the Spanish base case varenicline had an incremental cost of €1021/person for an average of 0.24 life years (0.17 QALYs), gained over the lifetime of a cohort of COPD patients, resulting in an incremental cost-effectiveness ratio (ICER) of €5,566. In the other European countries, the ICER varied between €4,519 (UK) and €10,167 (Italy). Probabilistic sensitivity analysis suggested varenicline had a high probability (>95%) of being cost-effective at a threshold of €30,000/QALY.

Conclusions: Varenicline is expected to be a cost-effective aid to smoking cessation in COPD patients in all of the countries studied.     

Cost-effectiveness comparison of current proton-pump inhibitors to treat gastro-oesophageal reflux disease in the UK

ABSTRACT

Objective: Gastro-oesophageal reflux disease (GORD) is a recurring condition with many patients requiring long-term maintenance therapy. Therefore initial choice of treatment has long-term cost implications. The aim was to compare the costs and effectiveness of treatment of GORD (unconfirmed by endoscopy) with seven proton pump inhibitors (PPIs: esomeprazole, lansoprazole (capsules and oro-dispersible tablets), omeprazole (generic and branded), pantoprazole and rabeprazole), over one year.

Design and methods: A treatment model was developed of 13 interconnected Markov models incorporating acute treatment of symptoms, long-term therapy and subsequent decisions to undertake endoscopy to confirm diagnosis. Patients were allowed to stop treatment or to receive maintenance treatment either continuously or on-demand depending on response to therapy. Long-term dosing schedule (high dose or step-down dose) was based on current market data. Efficacy of treatments was based on clinical trials and follow-up studies, while resource use patterns were determined by a panel of physicians.

Main outcome measures: The model predicts total expected annual costs, number of symptom-free days and quality-adjusted life-years (QALY).

Results: Generic omeprazole and rabeprazole dominated (i.e. cost less and resulted in more symptom-free days and higher QALY gains) the other PPIs. Rabeprazole had a favourable cost-effectiveness ratio of £3.42 per symptom-free day and £8308/quality-adjusted life-year gained when compared with generic omeprazole. Rabeprazole remained cost-effective independent of choice of maintenance treatment (i.e. proportion of patients remaining on continuous treatment versus on-demand treatment).

Conclusions: Economic models provide a useful framework to evaluate PPIs in realistic clinical scenarios. Our findings show that rabeprazole is cost-effective for the treatment of GORD.