BackgroundRomiplostim, a thrombopoietin receptor agonist (TPOra), is a second-line medical treatment option for adults with chronic immune thrombocytopenia (ITP). Clinical trials have shown that romiplostim increases platelet counts, while reducing the risk of bleeding and, in turn, the need for costly rescue medications.AimsThe objective of this study was to assess the cost effectiveness of romiplostim in the treatment of adult ITP in Ireland, in comparison with eltrombopag and the medical standard of care (SoC).MethodsA lifetime treatment-sequence cost-utility Markov model with embedded decision tree was developed from an Irish healthcare perspective to compare romiplostim with eltrombopag and SoC. The model was driven by platelet response (platelet count ≥50 × 109/L), which determined effectiveness and progression along the treatment pathway, need for rescue therapy (e.g. intravenous immunoglobulin [IVIg] and steroids) and risk of bleeding. Probability of response, mean treatment duration, average time to initial response and utilities were derived from clinical trials and other published evidence. Treatment sequences and healthcare utilization practice were validated by Irish clinical experts. Costs were assessed in € for 2011 and included drug acquisition costs and costs associated with monitoring patients and management of bleeding, as available from published Irish reimbursement lists and other relevant sources. Deterministic and probabilistic sensitivity analyses were conducted.ResultsRomiplostim treatment resulted in an average of 20.2 fewer administrations of rescue medication (IVIg or intravenous steroids) over a patient lifetime than eltrombopag, and 29.3 fewer rescue medication administrations than SoC. Romiplostim was dominant, with cost savings of €13,258 and €22,673 and gains of 0.76 and 1.17 quality-adjusted life-years (QALYs), compared with eltrombopag and SoC, respectively. Romiplostim remained cost effective throughout a variety of potential scenarios, including short-term TPOra treatment duration (1 year). One-way sensitivity analysis showed that the model was most sensitive to variation in the cost of IVIg and use of romiplostim and IVIg. Probabilistic sensitivity analysis showed that romiplostim was likely to be cost effective in over 90 % of cases compared with eltrombopag, and 96 % compared with SoC at a willingness-to-pay threshold of €30,000 per QALY.ConclusionsUse of romiplostim in the ITP treatment pathway, compared with eltrombopag or SoC, is likely to be cost effective in Ireland. Romiplostim improves clinical outcomes by increasing platelet counts, reducing bleeding events and the use of IVIg and steroids, resulting in both cost savings and additional QALYs when compared with current treatment practices.Electronic supplementary materialThe online version of this article (doi:10.1007/s40258-013-0044-y) contains supplementary material, which is available to authorized users.

IntroductionOpioid treatment for chronic pain is a known risk factor for falls and/or fractures in elderly patients. The latter cause a significant cost to the National Health Service and the Personal Social Services in the UK. Tramadol has a higher risk of fractures than some other opioid analgesics used to treat moderate-to-severe pain and, in the model described here, we investigate the cost effectiveness of transdermal buprenorphine treatment compared with tramadol in a high-risk population.MethodsA model was developed to assess the cost effectiveness of tramadol compared with transdermal buprenorphine over a 1-year time horizon and a patient population of high-risk patients (female patients age 75 or older). To estimate the total cost and quality-adjusted life years (QALYs) of treatment, published odds ratios are used in combination with the published incidence rates of four types of fracture: hip, wrist, humerus and other.ResultsThe model shows tramadol to be associated with 1,058 more fractures per 100,000 patients per year compared with transdermal buprenorphine, resulting in transdermal buprenorphine being cost-effective with an incremental cost-effectiveness ratio of less than £7,000 compared with tramadol. Sensitivity analysis found this result to be robust.LimitationsIn the UK data, there is uncertainty regarding the transdermal buprenorphine odds ratios for fractures. Odds ratios published in Danish and Swedish studies show similar point estimates but are associated with less uncertainty.ConclusionTransdermal buprenorphine is cost-effective compared to tramadol at a willingness-to-pay threshold of £20,000 per QALY.

An automated spectrophotometric assay for serum a-hydroxybutyrate dehydrogenase (SHBD) activity has been developed. This utilizes the change in absorbance at 340 nm. consequent upon oxidation of NADH. Determinations are made at 380C. at a rate of 6o per hour, and measurement of test and blank requirzs only I5 plitre serum. Sera of known SHBD activity assayed by a manual kinetic spectrophotometric technique at 25sC. are used as standards. The normal range determined for 648 subjects was 40-200 mIU/ml. There was no difference between the sexes, and in both, SHBD activity increased significantly with age. Sera from 528 patients suspected of having sustained myocardial infarction were assayed. Of 197 patients in whom infarctimn was established on clinical and electrocardiographic criteria, iSo had raised SHBD activity. Of 286 patients in whom infarction was ultimately excluded, 67 had raised SHBD activity. The accuracy of SHBD activity in confirming the diagnosis of myocardial infarction was comparable with that of aspartate aminotransferase activity as determined spectrophotometrically in the same subjects, and there were advantages in carrying out both procedures. Storage of sera at-20°C. resulted in a I5 per cent increase in SHBD activity, whereas a fall of 5 per cent occurred after 7 days at 40C. Human serum contains an enzyme catalysing the reversible reduction of ac-oxobutyrate according to the following equation: ce-oxobutyrate + NADH2 ce-hydroxybutyrate + NAD The enzyme concerned has been named serum hydroxybutyrate dehydrogenase (SHBD), but its activity is a function of the lactate dehydrogenase isoenzymes (Rosalki and Wilkinson, i960). These are composed of two molecular subgroups, and it is the faster-moving isoenzymes rich in the B sub-grQup that mainly account for SHBD activity (Latner and Skillen, i968). The role of SHBD determinations as an aid to the diagnosis of myocardial infarction has been established (Elliott and Wilkinson,

No abstract

International Kidney and Monoclonal research Group (IKMG) recommendations for screening for acute kidney injury (AKI) secondary to multiple myeloma (MM) include the assessment of patients with the serum free light chain test (sFLC). Here we compare the economic impact of following this recommendation compared to standard serum and urine electrophoretic techniques. An economic model was constructed using published UK data and centre specific clinician advice. The model compared the following scenarios: (i) serum protein electrophoresis (SPEP) + sFLC (IKMG recommendation), (ii) SPEP alone, (iii) SPEP + urine electrophoresis (SPEP + UPE), with a positive test in scenarios (i)—(iii) proceeding to immunofixation electrophoresis (IFE); (iv) all electrophoretic methods run in parallel (SPEP + UPE + sIFE + uIFE). The key economic drivers in the model were length of in-patient stay and dialysis costs. The incremental costs per QALY gained were modelled over a 365d time horizon. The economic model utilized a decision tree structure to the time of diagnosis and a Markov model including the health states: dialysis dependence, renal function recovery, other cause of AKI and death. The model structure and assumptions were validated through clinician consultation. Survival in the diagnostic pathway was estimated using hazard ratios applied to survival of MM based on the stage of AKI, obtained from a retrospective observational study (Han, et al., 2013). Survival within the Markov model post-diagnosis was based on UK data stratified for cast nephropathy patients who had or had not recovered renal function. Post-diagnosis, a probability of renal recovery based on the duration of AKI prior to diagnosis was applied. Utility values in the decision tree structure were estimated using the Modification of Diet in Renal Disease equation. The Markov model employed previously published utility values in MM with a decrement applied for dialysis dependence. Costs for medical resource use, medical management, dialysis, adverse events associated with dialysis and terminal care were derived from the 2012-2013 NHS Reference Cost and British National Formulary. Key user defined values for the comparison included a presenting patient distribution of 10% stage 2 AKI, 45% stage 3 AKI (dialysis independent) and 45% stage 3 AKI (dialysis dependent), 1% incidence of cast nephropathy as a cause of AKI, and a 20% incidence of renal biopsy following a positive diagnostic result. User amendable fields ensure the model is amenable to refinement as new data on assay performance and patient pathways become available. The incremental costs and QALYs for each comparator are shown in Table 1. The model predicts the pathway with SPEP + sFLC to be dominant; SPEP + sFLC accrues the most QALYs and the least costs. The savings in the diagnostic decision tree (£7, £31, -£5, respectively) are driven by reduced dialysis and in-patient bed stay costs. In the treatment pathway savings (£34, £37, £41, respectively) are driven by reduced dialysis costs. Probabilistic sensitivity analysis showed the model results to be robust - the probability of SPEP + sFLC being cost-effective at a £20,000 per QALY willingness to pay threshold was 98.6%, 93.8%, 92.6%, respectively. Table 1 - Base Case Cost-Effectiveness Results Model Results SPEP + sFLC SPEP Difference Total Cost (GBP) £427 £467 -£40 Total QALYs 0.6245 0.6235 0.00099 ICER=Incremental Cost/ Incremental QALY Dominant Model Results SPEP + sFLC SPEP Difference Total Cost (GBP) £427 £495 -£68 Total QALYs 0.6245 0.6231 0.00133 ICER=Incremental Cost/ Incremental QALY Dominant Model Results SPEP + sFLC SPEP Difference Total Cost (GBP) £427 £463 -£36 Total QALYs 0.6245 0.6239 0.00055 ICER=Incremental Cost/ Incremental QALY Dominant This model supports the recommended international guidelines for screening for AKI secondary to MM. Inclusion of the sFLC assay improves the probability of renal recovery and survival by reducing time to diagnosis and treatment. Cost savings and QALY gains are found in both the diagnostic stage and treatment stage of the patient pathway. The SPEP + sFLC pathway is therefore cost-effective at a willingness to pay threshold of £20,000 per QALY with a high probability of cost-effectiveness against all comparator pathways from probabilistic sensitivity analysis. The model template may be used in future health economic models to assess the contribution of new assays into diagnostic algorithms. Disclosures No relevant conflicts of interest to declare.