Cost-effectiveness of statins in the prevention of coronary heart disease events in middle-aged Finnish men

ABSTRACT

Objective: This study evaluated the long-term cost-effectiveness of atorvastatin 20?mg, rosuvastatin 10?mg and simvastatin 40?mg in primary and secondary prevention of CHD in Finland.

Research design and methods: The effect of statin therapy on the incidence of CHD and the expected total costs of the disease were described using a Markov state transition model. Due to the limited amount of evidence concerning mortality and morbidity for rosuvastatin, the model was used to transmute the efficiency data of all statins (decrease in total cholesterol) into long-term endpoints (myocardial infarction, death) using risk functions of the FINRISK and 4S studies. The study followed a characterized cohort of 55-year-old Finnish men with an average 3.3–6.6?%?baseline risk of dying from cardiovascular disease within a 10-year period.

Main outcome measures: Incremental cost-effectiveness ratios (ICERs) for atorvastatin and rosuvastatin, compared with simvastatin, measured as cost of life years gained (€/LYG) and cost of quality adjusted life years gained (€/QALY).

Results: The use of rosuvastatin increased the life expectancy by 0.27 years on average (LYG) compared with simvastatin, producing additional 0.08 quality-adjusted life-years (QALYs). Compared with simvastatin, the cost of one LYG with rosuvastatin was €10 834 and the cost of one QALY gained was €36 548 (discount rate 5?%?per annum). Corresponding figures for atorvastatin were €31 286/LYG and €105 599/QALY.

Conclusions: If the decision makers’ willingness to pay for a QALY gained is around €40 000 there is a high probability (?>?50?%?) that rosuvastatin represents a cost-effective form of therapy in the prevention of CHD in middle-aged men with an average 3.3–6.6?%?risk of dying within 10 years from cardiovascular disease. However, the true clinical impact of these results needs confirmation from on-going clinical trials, as the role of rosuvastatin in reducing clinical events is pending, but for simvastatin and atorvastatin established.     

Cost–effectiveness analysis of sacral neuromodulation (SNM) with Interstim for fecal incontinence patients in Spain

ABSTRACT

Introduction: Fecal incontinence (FI) is a condition with a high impact on the psychological and social life of healthy people. Interstim, the sacral neuromodulation (SNM) therapy, has shown higher effectiveness and safety rates than surgical procedures like dynamic graciloplasty or artificial anal sphincter in patients with intact anal sphincter (IAS) and after sphincteroplasty in patients with structurally deficient anal sphincter (SDAS).

Objective: To assess the cost-effectiveness of FI management in two scenarios – with and without SNM – and to estimate the potential budget impact of its progressive introduction in the Spanish setting.

Methods: Two decision analytical models were developed (IAS and SDAS patients) representing the possible clinical paths for each of the scenarios (with and without SNM), as well as its clinical and economic consequences in the mid-to long term with a Markov model. Clinical and resource use data were retrieved from the literature and validated by a clinician expert panel. Effectiveness was measured with both QALYs and symptom-free years (SFY). A 3% discount rate was used for future costs and benefits (time horizon = 5 years). Prevalence figures were combined with Interstim sales forecasts to estimate the total number of patients to receive therapy over the next 5 years and the associated budget impact.

Results: The introduction of Interstim in the therapeutic management of FI has an associated cost-effectiveness of €16?181 (IAS patients) and €22?195 (SDAS patients) per QALY gained. The progressive introduction of Interstim in 75 to 100 patients/year will have an estimated budget impact of 0.1% of incremental costs in patients with FI.

Conclusions: Introducing Interstim in the management of FI in IAS and SDAS patients in the Spanish setting has shown to be an efficient measure with an incremental cost–effectiveness ratio below the accepted Spanish threshold (around €35?000/QALY), and with a relatively low additional cost for the Spanish NHS.     

The economic value of anti-IgE in severe persistent,IgE-mediated (allergic) asthma patients:adaptation of INNOVATE to Sweden

ABSTRACT

Background: Severe allergic asthma patients may not be controlled even with guideline recommended care, including inhaled corticosteroids, long-acting beta-2 agonists, theophylline, oral steroids and anti-leukotrienes. They experience exacerbations requiring intensive healthcare use and which may be fatal. Omalizumab, a new monoclonal antibody for use in IgE-mediated allergic diseases, reduces exacerbations and daily symptoms in this patient population. The aim of this study is to estimate the cost effectiveness of adding omalizumab to optimized standard therapy (ST) in patients with severe persistent IgE-mediated (allergic) asthma.

Methods: A Markov model comparing lifelong ST with a treatment period of omalizumab add-on therapy followed by ST, was developed based on efficacy data from the INNOVATE trial (28 weeks, N = 419) and Swedish life table and cost data. This model assumes that patients are at risk of having an exacerbation every 2 weeks and are at risk of dying from a clinically significant severe asthma exacerbation. Patients in a steady-state of having no exacerbations are defined to be in an ‘optimized asthma control’ state. Resource use data and utilities were obtained from INNOVATE and from a UK observational study. Costs from a societal perspective include estimates for drugs, routine care, exacerbations and costs in added years of life; benefits are expressed in QALYs. The response to omalizumab was evaluated after 16 weeks of trial, and non-responders stopped taking omalizumab for the remaining time.

Results: Total lifetime discounted costs and QALYs on ST were €52?702 and 11.60. Omalizumab add-on therapy cost an additional €42?754 for 0.76 additional QALYs, resulting in an incremental cost-effectiveness ratio of €56?091. A probabilistic sensitivity analysis indicates that the 95% CI around the ICER is [€31?328; €120?552]. One-way analyses indicate that the results are sensitive to the exacerbation-related mortality rate, the time horizon and the discount rates.

Conclusions: Based on the model and the assumptions used, our results suggest that omalizumab provides cost offsets, improves quality of life and may have an attractive ICER in treating the severe allergic asthma population.     

Economic evaluation of voriconazole in the treatment of invasive aspergillosis in the Netherlands

ABSTRACT

Objective: To asses the cost-effectiveness of voriconazole in comparison to conventional amphotericin B and itraconazole for the treatment of invasive aspergillosis in the Netherlands.

Methods: The cost-effectiveness of voriconazole in comparison to conventional amphotericin B or itraconazole was evaluated with a decision tree model followed by a life-time Markov model, focusing on long-term survival of patients treated for invasive aspergillosis. Efficacy after 12 weeks of treatment from clinical trials was used to estimate long-term effectiveness by extrapolating these short-term results over time. Information on medical resource consumption, treatment pathways and switch proportions were obtained from both the literature and Experts. Probabilistic analysis was used to compare the cost-effectiveness among the regimens.

Results: With voriconazole, the mean cost for treating invasive aspergillosis per patient was €32?651 (2.5th percentile and 97.5th of uncertainty distribution: €30?037; €36?859), compared to €33?616 (€30?920; €39?633) for conventional amphotericin B and €29?115 (€23?537; €61?414) for itraconazole. The mean survival of patients treated with voriconazole was 174.0 life weeks (160.1; 188.8), compared to 116.1 life weeks (104.8; 128.0) for conventional amphotericin B and 150.4 life weeks (109.1; 194.4) for itraconazole. The beneficial effects of voriconazole on both cost and effectiveness compared with conventional amphotericin B resulted in a probability of 69.8% that voriconazole was a dominant treatment (i.e. less costs and longer survival). The incremental cost-effectiveness ratio of voriconazole versus itraconazole was €150 per life week (i.e. 7800 euros per life-year gained). Depending on the willingness to pay (WTP) the probability of being cost-effective vs. itraconazole increased to a maximum probability of 70%.

Conclusion: In the treatment of invasive aspergillosis, voriconazole is dominant over amphotericin B and cost-effective in comparison to itraconazole.     

Cost-effectiveness in Italy of preventive treatment with ramipril in patients at high risk of cardiovascular events

ABSTRACT

Objectives: A cost-effectiveness analysis was conducted in Italy of preventive treatment with ramipril (an angiotensin converting enzyme [ACE] inhibitor) compared to no treatment in patients at high risk of cardiovascular death. The analysis was based on data extracted from the HOPE trial.

Methods: The current life table method was used in order to model a lifetime time horizon for outcomes and costs. The cohorts used were 1000 subjects on ramipril, and 1000 subjects on placebo enrolled in the HOPE trial. Kaplan–Meier curves at 5 years of the clinical study were fitted using an exponential model over a lifetime horizon, the outcome variables being myocardial infarction, stroke, revascularization and death. Total direct medical costs have been considered from a third-party payer's perspective – the Italian National Health Service. Resources involved in each event/activity were estimated using the modified Delphi technique with a panel of six clinicians. Types of resources reported included drug therapies, laboratory and imaging tests, physician visits, outpatient and inpatient rehabilitation, as well as medical and surgical hospital admissions. The incremental cost per life year gained was the main measure of the analysis.

Results: ICER (incremental cost-effectiveness ratio) decreases with the length of the treatment period. After the first year the ICER is €55?062 and subsequently decreases to about €12?770 at 5 years, €5945 at 10 years and €3726 at 20 years. The two ways sensitivity analysis showed that at 5 years ICERs range from a saving of €4059 to a cost of €22?929 (at 20 years they are €1814 and €4434), mainly depending on the cost of drug and cost of events. Previous analyses in other countries based on the HOPE study obtained ICER values which are comparable with our results, when taking into account the different cost structure of the health care systems.

Conclusions: On the basis of these results, the use of ramipril is likely to represent an efficient use of public health expenditure in the Italian healthcare system.     

Efficacy and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin in post-herpetic neuralgia and diabetic polyneuropathy

ABSTRACT

Objective: Neuropathic pain is often difficult to treat due to a complex pathophysiology. This study evaluated the efficacy, tolerability and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin for neuropathic pain in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN).

Methods: Patients completing 4-week monotherapy with 5% lidocaine medicated plaster or pregabalin were enrolled in an 8-week combination phase. Patients with adequate response to monotherapy (recalled average pain intensity of 4 or less on 11-point numeric rating scale in the previous 3 days [NRS-3 score]) continued their previous therapy, whereas those with insufficient response received combination therapy. Efficacy endpoints included change in NRS-3 from combination phase baseline, Patient and Clinical Global Impression of Change (PGIC/CGIC), and patient's satisfaction with treatment. Safety evaluation included adverse events (AEs), drug-related AEs (DRAEs), and withdrawal due to AEs.

Clinical trial registration: EudraCT No. 2006-003132-29.

Results: Of 229 patients in the per-protocol set (PPS: 68 PHN and 161 DPN), 71 received 5% lidocaine medicated plaster monotherapy, 57 had pregabalin added to 5% lidocaine medicated plaster, 57 pregabalin monotherapy and 44 received 5% lidocaine medicated plaster in addition to continued pregabalin treatment. There were no meaningful differences in demographic data between the treatment groups. Patients continuing on monotherapy demonstrated additional decreases in NRS-3 scores. Patients receiving combination therapy achieved clinically relevant reduction in NRS-3 values in addition to improvement achieved during the 4 weeks of monotherapy. Improvement was similar between the two combination therapy groups. Considerable improvements in patients’ treatment satisfaction were reported. Incidences of AEs were in line with previous reports for the two treatments and combination therapy was generally well tolerated.

Conclusions: In patients with PHN and painful DPN failing to respond to monotherapy, combination therapy with 5% lidocaine medicated plaster and pregabalin provides additional clinically relevant pain relief and is safe and well-tolerated.     

Reliability of the English version of the painDETECT questionnaire

Background: The painDETECT questionnaire (PD-Q) has been used widely for the identification of neuropathic pain (NeP); however, the reliability of the English version of the PD-Q has never been investigated.

Objective: This study aimed to determine the reliability of the PD-Q pre- (T0) and immediately post- (T1) clinical consultation and at one-week follow-up (T2).

Methods: We recruited 157 patients attending a Neurosurgery Spinal Clinic and Pain Management Department. Minor changes to PD-Q instructions were made to facilitate patient understanding; however, no changes to individual items or scoring were made. Intraclass correlation coefficients (ICCs) were used to assess the reliability of PD-Q total scores between T0–T1 and T0–T2; weighted kappa (κ) was used to assess the agreement of PD-Q classifications (unlikely NeP, ambiguous, likely NeP) between all time-points. To ensure stability of clinical pain, patients scoring ≤2 or ≥6 on the Patient Global Impression Scale (PGIC) at T2 were excluded from the T0–T2 analysis.

Results: Accounting for missing data and exclusions (change in PGIC score), data for 136 individuals (mean [SD] age: 56.8 [15.2]; 54% male) was available, of whom n?=?129 were included in the T0–T1 and n?=?69 in the T0–T2 comparisons. There was almost perfect agreement between the PD-Q total scores at T0–T1 time-points (ICC 0.911; 95% CI: 0.882–0.941) and substantial agreement at T0–T2 (ICC 0.792; 95% CI: 0.703–0.880). PD-Q classifications demonstrated substantial agreement for T0–T1 (weighted κ: 0.771; 95% CI: 0.683–0.858) and for T0–T2 (weighted κ: 0.691; 95% CI: 0.553–0.830). Missing data was accounted in 13% of our cohort and over 42% of our patients drew multiple pain areas on the PD-Q body chart.

Conclusion: The English version of the PD-Q is reliable as a screening tool for NeP. The validity of the questionnaire is still in question and has to be investigated in future studies.     

Cost-effectiveness analysis of escitalopram: a new SSRI in the first-line treatment of major depressive disorder in Austria

SUMMARY

Objectives: To compare the cost-effectiveness of escitalopram, a new selective serotonin reuptake inhibitor (SSRI), with (generic) citalopram in the first-line treatment of major depressive disorder (MDD) in Austria.

Methods: A two-path decision analytic model with a 6-month horizon was adapted to the Austrian setting using Austrian clinical guidelines. All patients (aged ≥ 18?years) started at the primary care path and were referred to specialist care in the secondary care path in case of insufficient response. Model inputs included drug-specific probabilities from head-to-head trial data, literature and expert opinion. The main outcome measure was success (i.e., remission defined as Montgomery–Åsberg Depression Rating Scale (MADRS) score ≤ 12) and costs of treatment (i.e., drug costs and medical care). The analysis was performed from the Austrian societal and Social Healthcare Insurance System (SHIS) perspectives. The Human Capital approach was used to estimate the societal costs of lost productivity.

Results: Treatment with escitalopram yielded lower expected cost and greater effectiveness compared with citalopram. The expected success rate was higher for escitalopram (64.5%) compared to citalopram (59.1%). From the SHIS perspective, the total expected cost per successfully treated patient was lower (€115) for escitalopram (€608) compared with citalopram (€723). From the societal perspective, these expected costs were €3034 and €3269 respectively. Sensitivity analyses on unit costs and probabilities demonstrated the robustness of the results. From the societal perspective, escitalopram remained the dominant treatment option, even at a cost of €0 for (generic) citalopram.

Conclusion: Escitalopram is a cost-effective alternative compared to (generic) citalopram in the first-line treatment of MDD in Austria.     

A cost-effectiveness analysis of immunotherapy with SQ allergen extract for patients with seasonal allergic rhinoconjunctivitis in selected European countries

ABSTRACT

Background: Seasonal allergic rhinoconjunctivitis can, for some people, reduce quality of life and the ability to cope with everyday tasks.

Scope: In this paper we investigate the cost-effective­ness of immunization therapy with Alutard SQ (ASQ) and compare the cost-effectiveness in countries where the therapy has been in use in order to assess the impact of national therapeutic practices on the results of health economic assessments. Data are obtained from a clinical trial carried out in 2001–2002. To evaluate the cost-effectiveness of immunization we have added data on resource use in Austria, Denmark, Finland, Germany, the Netherlands, and Sweden.

Findings: The computations result in cost-effectiveness ratios for allergen immunization between €10?000 and €20?000 per QALY even without provision for indirect costs, and achieving dominance in most countries where indirect costs have also been taken into account. The country comparisons show that the direct cost of administrating the up-dosing and maintenance differs considerably between countries, and that the cost of medical staff is substantial, constituting in most cases more than half of the direct costs of the immunization therapy.

Conclusion: The study shows that immunotherapy with SQ allergen extract is cost-effective in a wide range of national environments, and that cost-effectiveness differences by country are largely a result of different practices in the up-dosing phase.     

Efficacy and tolerability of twice-daily pregabalin for treating pain and related sleep interference in postherpetic neuralgia: a 13‐week,randomized trial

ABSTRACT

Objective: This trial evaluated the efficacy and safety of pregabalin dosed twice daily (BID) for relief of neuro-pathic pain associated with postherpetic neuralgia (PHN).

Research design and methods: The 13‐week, double-blind, placebo-controlled study randomized 370 patients with PHN to pregabalin (150, 300, or 600?mg/day BID) or placebo.

Main outcome measures: Primary efficacy measure was endpoint mean pain score from daily pain diaries. Secondary efficacy measures included endpoint mean sleep-interference score from daily sleep diaries and Patient Global Impression of Change (PGIC). Safety evaluations included adverse events (AEs), physical and neurologic examinations, 12-lead ECG, vital signs, and laboratory testing.

Results: Pregabalin provided significant, dose-proportional pain relief at endpoint: difference from placebo in mean pain score, 150?mg/day, –0.88, p = 0.0077; 300?mg/day, –1.07, p = 0.0016; 600?mg/day, –1.79, p = 0.0003. Weekly mean pain scores significantly improved as early as week 1. Sleep interference in all pregabalin groups was also significantly improved at endpoint, compared with placebo (?p < 0.001), beginning at week 1 (?p < 0.01). At study termination, patients in the 150 (p = 0.02) and 600?mg/day (p = 0.003) groups were more likely to report global improvement than were those in the placebo group.

Most AEs were mild or moderate. Among pregabalin-treated patients, 13.5% withdrew due to AEs, most commonly for dizziness (16 patients, 5.8%), somnolence (8, 2.9%), or ataxia (7, 2.5%).

Conclusions: Pregabalin, dosed BID, reduced neuropathic pain associated with PHN and was well tolerated. It also reduced the extent to which pain interfered with sleep. Pregabalin's effects were seen as early as week 1 and were sustained throughout the 13‐week study.     

Acute coronary syndromes in Europe: 1-year costs and outcomes

ABSTRACT

Objective: This study aims to estimate costs (including medications prescribed, intervention rates and hospital utilization) and health outcomes of acute coronary syndromes (ACS) during the first year following diagnosis.

Research design and methods: Treatment pathways for ACS patients were developed and country-specific resource use was multiplied by unit costs. Countries examined were the United Kingdom (UK), France, Germany, Italy and Spain. Patients with unstable angina and acute myocardial infarction (ST-segment elevation and non-ST-segment elevation with/without Q-wave) were considered. The study models the incidence of ACS, 1-year mortality, investigations, revascularisation, pharmaceutical use and medical management. Economic outcomes were direct healthcare costs (in 2004 Euros), including total cost, cost per patient with ACS and cost per capita.

Results: The estimated number of deaths in the first year following ACS diagnosis ranged from around 22?500 in Spain to over 90?000 in Germany. The largest contributors to total costs are hospital stay and revascularisation procedures. Pharmaceuticals were estimated at 14–25% of ACS total cost. The total cost of ACS in the UK is estimated around €1.9 billion, compared with €1.3 billion in France, €3.3 billion in Germany, €3.1 billion in Italy and €1.0 billion in Spain. The cost per ACS patient ranges from €7009 (in the UK) to €12?086 (Italy).

Conclusions: Countries with higher expenditure on ACS patients tended to have lower case-fatality rates, and countries with the lowest incidence of ACS also had the lowest cost per capita. The costs of ACS constitute a large proportion of total healthcare expenditure of Western European economies.     

Review of the cost of diabetes complications in Australia,Canada, France,Germany, Italy and Spain

ABSTRACT

Objectives: To provide a comprehensive source document on previously published cost data for diabetic complications in Australia, Canada, France, Germany, Italy and Spain for use in a peer-reviewed, validated diabetes model.

Methods: A search for published cost of diabetes complications data was performed in peer-reviewed journals listed in PubMed and health economic conference proceedings from 1994 to March 2005. Where country specific data were not available, we referred to government websites and local cost experts. All costs were inflated to 2003 Euros (€). Major complication costs are presented.

Results: First year costs of non-fatal myocardial infarction varied between €19?277 in Spain and €12?292 in Australia. In subsequent years of treatment, this range was €1226 (France) to €203 (Australia). Angina costs were similar across all four countries: €1716 in Australia; €2218 in Canada; €2613 in France; €3342 in Germany; €2297 in Italy; and €2207 in Spain. Event costs of non-fatal stroke were higher in Canada (€23?173) than in other countries (Australia €13?443; France €11?754; Germany €19?399; Italy €6583; Spain €4638). Event costs of end-stage renal disease varied depending on the type of dialysis: in Australia (€17?188–27?552); Canada (€33?811–58?159); France (€24?608–56?487); Germany (€46?296–68?175); Italy (€43?075–56?717); and Spain (€28?370–32?706). Lower extremity amputation costs were: €18?547 (Australia); €17?130 (Canada); €31?998 (France); €22?096 (Germany); €10?177 (Italy); and €14?787 (Spain).

Conclusions: Overall, our search showed costs are well documented in Australia, Canada, France and Germany, but revealed a paucity of data for Spain and Italy. Spanish costs, collected by contacting local experts and from government reports, generally appeared to be lower for treating cardiovascular complications than in other countries. Italian costs reported in the literature were primarily hospitalization costs derived from diagnosis-related groups, and therefore likely to misrepresent the cost of specific complications. Additional research is required to document complication costs in Spain and Italy. Australian and German values were collected primarily by referring to diagnostic related group (DRG) tariffs and, as a result, there may be a need for future economic evaluations measuring the accuracy of the costs and resource utilization in the reported values. These cost data are essential to create models of diabetes that are able to accurately simulate the cumulative costs associated with the progression of the disease and its complications.     

Economic analysis of a multicentre,randomised, phase III trial comparing FOLFOXIRI with FOLFIRI in patients with metastatic colorectal cancer in Greece

ABSTRACT

Introduction: An economic evaluation of the irinotecan, leucovorin, 5-fluorouracil (FOLFIRI) combination versus the irinotecan, oxaliplatin, leucovorin, 5-fluorouracil (FOLFOXIRI) regimen in patients with metastatic colorectal cancer was performed in the context of a randomised phase III study.

Methods: The trial did not find any differences in efficacy and, therefore, a cost-minimisation analysis was undertaken. Treatment cost accounts for the administration of first and second line chemotherapy, for concomitant medications, for laboratory and other examinations and hospitalisations due to treatment side effects. Unit prices used reflect 2006 and are common among NHS hospitals in Greece.

Results: The mean total cost of therapy in the FOLFOXIRI group (€18?344, 95% CI: €16?951–€19?776), was significantly higher than the FOLFIRI group (€12?201, 95% CI: €11?011–€13?427). Mean chemotherapy cost of the FOLFOXIRI group (€9016; 95% CI: €8338–€9669) was significantly higher than that of the FOLFIRI group (€4830; 95% CI: €4435–€5231). The next largest component of cost involves second line drugs, where the average cost per patient was €3306 (95% CI: €2479–€4237) in the FOLFIRI group and €3996 (95% CI: €3196–€4892) in the FOLFOXIRI group. The cost of hospitalisations was €1814 (95% CI: €1672–€1954) in the first group and €2663 (95% CI: €2469–€2859) in the second. The rest of the components represent a small part of the total cost and there are no differences in the two groups.

Conclusion: The combination of irinotecan, leucovorin, 5-fluorouracil has the same effectiveness as the combination of irinotecan, oxaliplatin, leucovorin, 5-fluorouracil in patients with metastatic colorectal cancer, nonetheless it is associated with a much lower overall treatment cost and it should be the preferred treatment regimen in this context.     

Economic evaluation of prolonged and enhanced ECG Holter monitoring in acute ischemic stroke patients

Objective: Atrial fibrillation (AF) is a major cause for recurrent stroke, has severe impact on a patient’s health and imposes a high economic burden for society. Current guidelines recommend 24?h ECG monitoring (standard-of-care, SoC) to detect AF after stroke to reduce the risk of future events. However, paroxysmal AF (PAF) is difficult to detect within this period as it occurs infrequently and unpredictably. In a randomized controlled trial (Find-AF_RANDOMISED), prolonged and enhanced Holter ECG monitoring (EPM) revealed a significantly higher detection rate of AF compared to SoC, although its cost-effectiveness has not yet been investigated.

Methods: Based on the data of FIND-AF_RANDOMISED, an economic evaluation was conducted. One group received EPM for 10?days after the event, and at 3 and 6?months; the other group received SoC. Healthcare resource use and quality of life (QoL) data were measured at baseline, and after 6 and 12?months. Incremental costs and quality-adjusted life years (QALYs) between both groups were compared. Non-parametric bootstrapping and one-way-sensitivity analyses were performed.

Results: A total of 281 patients with healthcare resource use and QoL data for all measurement points were considered in the economic evaluation (complete case analysis, CCA). The CCA yielded nonsignificant 315€ lower mean costs and 0.0013 less QALYs for patients receiving EPM with no statistically significant differences in any cost categories. Sensitivity analyses revealed robust results. Bootstrapping the results indicated moderate probability of cost-effectiveness.

Conclusions: EPM yielded reduced not significantly different costs without affecting QoL and may be a useful strategy to detect PAF in acute ischemic stroke patients in time.     

Modeling the economic and health consequences of managing chronic osteoarthritis pain with opioids in Germany: comparison of extended-release oxycodone and OROS hydromorphone

ABSTRACT

Objective: The Osmotic controlled-Release Oral delivery System (OROS) hydromorphone ensures continuous release of hydromorphone over 24 hours. It is anticipated that this will facilitate optimal pain relief, improve quality of sleep and compliance. This simulation compared managing chronic osteoarthritis pain with once-daily OROS hydromorphone with an equianalgesic dose of extended-release (ER) oxycodone administered two or three times a day.

Methods: This discrete event simulation follows patients for a year after initiating opioid treatment. Pairs of identical patients are created; one receives OROS hydromorphone the other ER oxycodone; undergo dose adjustments and after titration can be dissatisfied or satisfied, suffer adverse events, pain recurrence, or discontinue the opioid. Each is assigned an initial sleep problems score, and an improved score from a treatment dependent distribution at the end of titration; these are translated to a utility value. Utilities are assigned pre-treatment, updated until the patient reaches the optimal dose or is non-compliant or dissatisfied. The OROS hydromorphone and ER oxycodone doses are converted to equianalgesic morphine doses using the following ratios: hydromorphone to morphine ratio; 1:5, oxycodone to morphine ratio; 1:2. Sensitivity analyses explored uncertainty in the conversion ratios and other key parameters. Direct medical costs are in 2005 euros.

Results: Over 1 year on a mean daily morphine-equivalent dose of 90?mg, 14% were estimated to be dissatisfied with each opioid. OROS hydromorphone was predicted to yield 0.017 additional quality-adjusted life years (QALYs)/patient for a small additional annual cost (€141/patient), yielding an incremental cost-effectiveness ratio (ICER) of €8343/QALY gained. Changing the assumed conversion ratio for oxycodone:morphine to 1:1.5 led to lower net costs of €68 per patient, €3979/QALY, and for hydromorphone to 1:7.5 to savings.

Conclusion: Based on these analyses, OROS hydromorphone is expected to yield health benefits at reasonable cost in Germany.     

Targeting pain mediators induced by injured nerve-derived COX2 and PGE2 to treat neuropathic pain

Introduction: Neuropathic pain (NeP) is an intractable chronic pain condition which severely deteriorates the quality of life of 6% of the population. Caused by direct physical damage or diseases of the nervous system responsible for pain generation and transmission, NeP is manifested as spontaneous pain, hyperalgesia and allodynia. Its treatment is a challenging and unmet medical need. It is generally accepted that inflammatory mediators over-produced in injured nerves play a crucial role in the initiation and maintenance of NeP.

Areas covered: Among numerous inflammatory mediators, cyclooxygenase 2 (COX2) and its end product prostaglandin E2 (PGE2) are persistently up-regulated in infiltrating macrophages and Schwann cells in injured nerves and contribute to the development of NeP. In a NeP rat model and an ex vivo model of sensory ganglion explant culture, injured nerve-derived COX2 and PGE2 facilitate the synthesis of pain mediators including neuropeptides, ion channels, cytokines and neurotrophins in primary sensory neurons.

Expert Opinion: Stimulating the synthesis of pain mediators in primary sensory neurons is a novel mechanism underlying the contribution of injured nerve-derived COX2 and PGE2 to the genesis of NeP. Targeting COX2/PGE2/EP signaling in injured nerves through local administration could open a novel therapeutic avenue to treat this debilitating disease.     

The management of skin toxicity during erlotinib in advanced non-small cell lung cancer: how much does it cost?

Abstract

Introduction: The aim of this study is to estimate the costs for the foreseeable management of skin toxicity (papulo-pustular reactions) in patients treated with erlotinib for non-small cell lung cancer (NSCLC) in order to value the direct medical economical impact. No studies like the above have been published until now.

Materials and methods: We retrospectively analyzed all consecutive patients with NSCLC treated with erlotinib at Clinical Oncology Unit of University Hospital of Ferrara, Italy from June 2007 to May 2011. We evaluated severity and median duration of papulo-pustular reactions for each grade and we identified costs for the different therapeutic interventions.

Results: We evaluated 25 patients. Median time follow-up was 18.65 months (range 5.69–88.36). Finally, follow-up 7 patients (28.0%) were alive with metastases and 18 patients (72.0%) were deceased. Nineteen patients (76.0%) developed papulo-pustular reactions: 2 patients (10.5%) mild rash, 11 patients (57.9%) moderate rash and 6 patients (31.6%) severe rash; no case of hospitalization was observed. Median duration of mild rash was 97 days (costs-range: 157.7–452.2 €), median duration of moderate rash was 89 days (costs-range: 438.7–1035.6 €) and median duration of severe rash was 34 days (costs-range: 460.3–1057.2 €).

Conclusions: Our experience, though the analysis of not selected case study, showed that management of skin toxicities related to erlotinib is not so expensive, especially for low grade; therefore, we also recommended to give particular attention to low grade of toxicities for reducing progression to high grade and consequent risk of hospitalization, which really impact on costs.     

Short-term cost-effectiveness of insulin detemir and insulin aspart in people with type 1 diabetes who are prone to recurrent severe hypoglycemia

Objective: Based on the data of the HypoAna trial (ClinicalTrials.gov NCT00346996), a short-term cost–effectiveness analysis was conducted comparing an all insulin analogue regimen with an all human insulin regimen in people with type 1 diabetes who are prone to recurrent severe hypoglycemia.

Methods: Clinical data from the HypoAna trial and Danish cost data related to the treatment of severe hypoglycemia were used to populate a 1-year cost–effectiveness analysis. Hypoglycemia quality-of-life data were based on previously published utility values, used to calculate the quality-adjusted life-years (QALYs) gained. Sensitivity analyses were conducted to test the robustness of the analysis. The main outcome measure was the incremental cost–effectiveness ratio (ICER).

Results: The insulin analogue regimen was associated with greater total costs compared with the human insulin regimen (20,418 DKK [1972 GBP] vs. 18,558 DKK [1793 GBP], respectively), primarily driven by the difference in insulin costs. Total costs for corrective actions for hypoglycemic events, however, were lower in the insulin analogue group (927 DKK [89 GBP]) compared with the human insulin group (1311 DKK [127 GBP]), primarily due to a lower event rate. QALYs were higher with insulin analogues vs. human insulin (difference 0.0672). The resulting ICER was 27,685 DKK (2674 GBP) per QALY gained, which is well below the generally accepted cost–effectiveness threshold.

Conclusions: The analysis shows that treating people with type 1 diabetes who are prone to recurrent severe hypoglycemia with an insulin analogue regimen is cost-effective compared with a human insulin regimen.     

painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain

ABSTRACT

Objective: Nociceptive and neuropathic components both contribute to pain. Since these components require different pain management strategies, correct pain diagnosis before and during treatment is highly desirable. As low back pain (LBP) patients constitute an important subgroup of chronic pain patients, we addressed the following issues: (i) to establish a simple, validated screening tool to detect neuropathic pain (NeP) components in chronic LBP patients, (ii) to determine the prevalence of neuropathic pain components in LBP in a large-scale survey, and (iii) to determine whether LBP patients with an NeP component suffer from worse, or different, co-morbidities.

Methods: In co-operation with the German Research Network on Neuropathic Pain we developed and validated the painDETECT questionnaire (PD‐Q) in a prospective, multicentre study and subsequently applied it to approximately 8000 LBP patients.

Results: The PD‐Q is a reliable screening tool with high sensitivity, specificity and positive predictive accuracy; these were 84% in a palm-top computerised version and 85%, 80% and 83%, respectively, in a corresponding pencil-and-paper questionnaire. In an unselected cohort of chronic LBP patients, 37% were found to have predominantly neuropathic pain. Patients with NeP showed higher ratings of pain intensity, with more (and more severe) co‐morbidities such as depression, panic/anxiety and sleep disorders. This also affected functionality and use of health-care resources. On the basis of given prevalence of LBP in the general population, we calculated that 14.5% of all female and 11.4% of all male Germans suffer from LBP with a predominant neuropathic pain component.

Conclusion: Simple, patient-based, easy-to-use screening questionnaires can determine the prevalence of neuropathic pain components both in individual LBP patients and in heterogeneous cohorts of such patients. Since NeP correlates with more intense pain, more severe co‐morbidity and poorer quality of life, accurate diagnosis is a milestone in choosing appropriate therapy.