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Objective: The objective of this analysis was to evaluate the cost-effectiveness of duloxetine when considered as an additional treatment option for UK-based patients suffering from diabetic peripheral neuropathic pain.Research Design and Methods: A decision-analytic model was used to represent the sequential management of patients with diabetic peripheral neuropathic pain. The standard UK treatment strategy was defined as first-line tricyclic antidepressants (amitriptyline), second-line anticonvulsants (gabapentin) and lastly an opioid-related treatment. The cost-effectiveness of duloxetine was evaluated as an additional first, second, third or fourth-line therapy over a 6-month treatment period for a cohort of 1000 patients. Treatment response was modelled based on changes from baseline pain severity using a standard 11-point pain scale (0-10); full response (>or= 50% change), partial response (30-49%) and no response (< 30%). The model was populated with efficacy and discontinuation data using indirect comparisons of treatment efficacy based on relative effects to a common placebo comparator.Results: The second-line use of duloxetine resulted in cost savings of pound 77,071 for every 1000 treated patients, with an additional 29 patients achieving a full pain response when compared to standard UK treatment. Additional quality-adjusted life years (QALYs) were achieved at 1.88 QALYs per 1000 patients.Conclusions: This UK-based economic model suggests that second-line use of duloxetine is a beneficial and cost-effective treatment strategy for diabetic peripheral neuropathic pain. [ABSTRACT FROM AUTHOR]

After fertilization, rapid changes of the Caenorhabditis elegans cytoskeleton occur in the transition from meiosis to mitosis, requiring precise regulation. The MEI-1/MEI-2 katanin microtubule-severing complex is essential for meiotic spindle formation but must be quickly inactivated to allow for proper formation of the mitotic spindle. MEI-1/MEI-2 inactivation is dependent on multiple redundant pathways. The primary pathway employs the MEL-26 substrate adaptor for the CUL-3/cullin-based E3 ubiquitin ligase, which targets MEI-1 for proteosomal degradation. Here, we used quantitative antibody staining to measure MEI-1 levels to determine how other genes implicated in MEI-1 regulation act relative to CUL-3/MEL-26 The anaphase-promoting complex/cyclosome, APC/C, the DYRK (Dual-specificity tyrosine-regulated kinase), MBK-2, and the CUL-2-based E3 ubiquitin ligase act together to degrade MEI-1, in parallel to MEL-26/CUL-3 CUL-2 is known to keep MEL-26 low during meiosis, so CUL-2 apparently changes its target from MEL-26 in meiosis to MEI-1 in mitosis. RFL-1, an activator of cullin E3 ubiquitin ligases, activates CUL-2 but not CUL-3 for MEI-1 elimination. HECD-1 (HECT/Homologous to the E6AP carboxyl terminus domain) E3 ligase acts as a MEI-1 activator in meiosis but functions as an inhibitor during mitosis, without affecting levels of MEI-1 or MEI-2 Our results highlight the multiple layers of MEI-1 regulation that are required during the switch from the meiotic to mitotic modes of cell division., (Copyright © 2016 Beard et al.)

Background: An economic analysis from the perspective of the UK National Health Service (NHS) evaluated the cost effectiveness of lisdexamfetamine dimesylate (LDX) compared with atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder who have had an inadequate response to methylphenidate., Methods: A 1-year decision-analytic model was constructed, with the health outcomes "response", "nonresponse", and "unable to tolerate". Clinical data were taken from a head-to-head, randomized controlled trial in inadequate responders to methylphenidate. Response to treatment was defined as a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement subscale. Tolerability was assessed by discontinuation rates owing to adverse events. Utility weights were identified via a systematic literature review. Healthcare resource use estimates were obtained via a survey of clinicians. Daily drug costs were derived from British National Formulary 2012 costs and mean doses reported in the trial. One-way and probabilistic sensitivity analyses (PSAs) were performed., Results: The comparison of LDX with atomoxetine resulted in an estimate of an incremental cost-effectiveness ratio of £1802 per quality-adjusted life-year (QALY). The result was robust in a wide range of sensitivity analyses; results were most sensitive to changes in drug costs and efficacy. In the PSA, assuming a maximum willingness to pay of £20,000 per QALY, LDX versus atomoxetine had an 86 % probability of being cost effective. In 38 % of PSA runs, LDX was more effective and less costly than atomoxetine., Conclusions: From the perspective of the UK NHS, LDX provides a cost-effective treatment option for children and adolescents who are inadequate responders to methylphenidate., Competing Interests: Compliance with Ethical Standards Ethical standards This was a non-interventional cost-utility analysis; therefore, institutional review board approval and informed consent were deemed unnecessary. This article does not contain any studies with human participants/animals performed by any of the authors. Funding This study was funded by Shire Development LLC. Funding was provided to RTI Health Solutions to develop the model. Open access was funded by Shire International GmbH. Conflict of interest EAZ and JAM are employees of RTI Health Solutions. MB is an employee of Shire. PH and JS were employees of Shire when this work was conducted. SMB was an employee of RTI when this work was conducted and is now employed by BresMed Health Solutions, Sheffield, UK.

Background: Left atrial appendage closure (LAAC) and nonwarfarin oral anticoagulants (NOACs) have emerged as safe and effective alternatives to warfarin for stroke prophylaxis in patients with nonvalvular atrial fibrillation (AF)., Objectives: This analysis assessed the cost-effectiveness of warfarin, NOACs, and LAAC with the Watchman device (Boston Scientific, Marlborough, Massachusetts) for stroke risk reduction in patients with nonvalvular AF at multiple time points over a lifetime horizon., Methods: A Markov model was developed to assess the cost-effectiveness of LAAC, NOACs, and warfarin from the perspective of the Centers for Medicare & Medicaid Services over a lifetime (20-year) horizon. Patients were 70 years of age and at moderate risk for stroke and bleeding. Clinical event rates, stroke outcomes, and quality of life information were drawn predominantly from PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) 4-year data and meta-analyses of warfarin and NOACs. Costs for stroke risk reduction therapies, treatment of associated acute events, and long-term care following disabling stroke were presented in 2015 U.S. dollars., Results: Relative to warfarin, LAAC was cost-effective at 7 years ($42,994/quality-adjusted life-years [QALY]), and NOACs were cost-effective at 16 years ($48,446/QALY). LAAC was dominant over NOACs by year 5 and warfarin by year 10. At 10 years, LAAC provided more QALYs than warfarin and NOACs (5.855 vs. 5.601 vs. 5.751, respectively). In sensitivity analyses, LAAC remained cost-effective relative to warfarin ($41,470/QALY at 11 years) and NOACs ($21,964/QALY at 10 years), even if procedure costs were doubled., Conclusions: Both NOACs and LAAC with the Watchman device were cost-effective relative to warfarin, but LAAC was also found to be cost-effective and to offer better value relative to NOACs. The results of this analysis should be considered when formulating policy and practice guidelines for stroke prevention in AF., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Gout is a chronic and inflammatory form of arthritis that is often overlooked despite the associated pain caused by acute flares and associated joint damage caused by the development of debilitating tophi. The increasing burden of gout, due to an aging population and the increased prevalence of known risk factors for hyperuricaemia, means that there is a continued need for new and effective urate-lowering treatments. The evaluation of these treatments will require a comprehensive and comparative evidence base describing the economic and humanistic burden of gout, taken from the perspective of patients, the healthcare system, and wider society., Objective: The objective of this study is to review and summarise the current evidence of the disease burden related to chronic gout, assessed in terms of both cost and health-related quality of life (HRQL), and to identify key factors correlated with an increased burden. The overall aim is to support the economic evaluation of new treatments for gout, and to highlight key data gaps that may need further study and exploration., Methods: Relevant literature dating from January 2000 to July 2014 was sourced through searches of the MEDLINE database via PubMed and The Cochrane Library. Articles published in English and reporting either the economic burden (cost) or the humanistic burden (HRQL/utility) of gout were identified, and key data were extracted and summarised, with key themes and data gaps identified and discussed., Results: Of the 323 studies identified, 39 met the inclusion criteria, of which 17 and 26 were relevant to the economic and humanistic burden, respectively. The economic burden of gout varied according to numerous factors, most notably serum urate acid levels and number of flares and tophi, resulting in higher healthcare resource use most often attributed to hospitalisation and inpatient stay. The incremental direct cost of gout has been suggested in the range of US$3165 to US$5515 (2004 and 2005 values, respectively) climbing to US$10,222 to US$21,467 (2008 values) per annum where patients are experiencing regular acute flares and have tophi present. The humanistic burden of gout was largely due to physical disability and pain resulting from chronic clinical manifestations. Short Form 6 dimensions (SF-6D) assessed utility weights are estimated at 0.53 for a patient with severe gout (≥3 flares/year and tophi) compared with 0.73 for an asymptomatic gout patient with serum acid levels <6 mg/dl., Conclusions: The evidence confirms that gout has a growing overall prevalence and represents a significant burden in terms of both direct healthcare cost and HRQL outcomes. In light of this, effective urate-lowering treatments are likely to be valued if they can be clearly demonstrated to be both clinically effective and cost effective. Published data to support healthcare decision making in non-US countries with regards to treatments for gout are currently limited, which is a key limitation of the current evidence base. More research is also required to extend our understanding of the impact of gout on indirect costs, and a need also exists to develop a more comprehensive set of comparative HRQL utility assessments.

Our objective was to evaluate data on the cost-effectiveness of febuxostat compared with standard clinical practice with allopurinol in patients with gout that was presented to the Scottish Medicines Consortium (SMC) in 2010. A Markov health-state model estimated the direct health-related costs and clinical benefits expressed as quality-adjusted life-years (QALYs). Adults with chronic gout and established hyperuricaemia received treatment sequences of daily doses of allopurinol 300 mg alone or allopurinol 300 mg followed by febuxostat 80 mg/120 mg. The proportion of patients achieving the target serum uric acid (sUA) level of less than 6 mg/dl (0.36 mmol/l) was linked to the utility per sUA level to generate an incremental cost-effectiveness ratio (ICER). Second-line therapy with febuxostat 80 mg/120 mg versus with allopurinol alone resulted in an ICER of £3,578 per QALY over a 5-year time horizon. Additional univariate analyses showed that ICER values were robust and ranged from £2,550 to £7,165 per QALY when different parameters (e.g., low- and high-dose allopurinol titrations and variations in treatment-induced flare rates) were varied. Febuxostat reduces sUA below the European League Against Rheumatism target of 0.36 mmol/l (6 mg/dl) in significantly more patients with gout than allopurinol in its most frequently prescribed dose of 300 mg per day. The SMC accepted febuxostat as cost-effective as a suitable second-line option for urate-lowering therapy for the treatment of patients with chronic hyperuricaemia in conditions where urate deposition has already occurred (including a history or presence of tophus and/or gouty arthritis) when treatment with allopurinol was inadequate, not tolerated, or contraindicated.

Aims: To report the complete lifetime direct healthcare costs of glaucoma treatment in a database of 1136 patients attending the Glaucoma Clinic at Glasgow Royal Infirmary, Glasgow, UK., Method: The database was interrogated to identify all patients who had initiated treatment at the Glaucoma Clinic at Glasgow Royal Infirmary, and who had subsequently died of natural causes. The healthcare resource use based cost assessment was based on two aspects of the direct National Health Service cost: drug costs (prescribed medications) and non-drug costs (inpatient or outpatient/and surgical or procedure costs)., Results: 106 patients (53 men, 53 women) were identified for whom there were lifetime treatment data. The mean lifespan of the patients was 80.5 years, and the mean number of years attending the glaucoma clinic was 7.05 years (range 1-22 years). The mean cost of glaucoma treatment over the lifetime of the patients was £3001, with an annual mean cost per patient of £475. Non-drug and drug costs made up 66% and 34% respectively, of the lifetime costs., Conclusions: This is the only study to directly assess the lifetime treatment costs of glaucoma. Awareness of the costs of glaucoma treatment may be of increased importance in these financially challenging times.

Objective: This meta-analysis compared efficacy (pain response) of drugs that are licensed or commonly used in the treatment of fibromyalgia. A meta-analysis of safety measured via discontinuation because of adverse events was also performed., Methods: We conducted a meta-analysis of 21 clinical trials to estimate treatment differences vs. placebo, separately, for duloxetine, fluoxetine, gabapentin, milnacipran, pramipexole, pregabalin, either of two tricyclic antidepressants, and tramadol plus paracetamol. Indirect treatment comparisons using mixed treatment comparisons methodology were conducted for all pairwise comparisons. Pain response was analyzed as improvement of at least 30%, and separately of 50%, from baseline., Results: When compared with placebo, statistically significant pain responses (improvement of 30% and 50%) were observed for patients treated with duloxetine, milnacipran 200 mg/day, pregabalin 300 or 450 mg/day, and tramadol plus paracetamol. Treatment with fluoxetine, gabapentin, or milnacipran 100 mg/day resulted in significant findings for the 30% improvement in pain response. The meta-analysis showed a statistically increased risk of discontinuation because of adverse events for milnacipran 100 and 200 mg/day (both P < 0.001), and pregabalin 300 and 450 mg/day (P = 0.009 and P < 0.001, respectively). All other treatments, except fluoxetine, showed numerically increased risk over placebo for discontinuation because of adverse events. In the indirect comparisons, no pairwise comparison of active treatments reached statistical significance for either pain response end point., Conclusion: All eight active treatments displayed evidence suggesting improvement over placebo in the treatment of pain in patients suffering from fibromyalgia. Indirect comparison of active treatments found no strong differences., (© 2011 RTI Health Solutions. Pain Practice © 2011 World Institute of Pain.)

Summary: The cost-effectiveness of Fracture Liaison Services (FLSs) for prevention of secondary fracture in osteoporosis patients in the United Kingdom (UK), and the cost associated with their widespread adoption, were evaluated. An estimated 18 fractures were prevented and £21,000 saved per 1,000 patients. Setup across the UK would cost an estimated £9.7 million., Introduction: Only 11% to 28% of patients with a fragility fracture receive osteoporosis treatment in the UK. FLSs provide an efficient means to identify patients and are endorsed by the Department of Health but have not been widely adopted. The objective of this study was to evaluate the cost-effectiveness of FLSs in the UK and the cost associated with their widespread adoption., Methods: A cost-effectiveness and budget-impact model was developed, utilising detailed audit data collected by the West Glasgow FLS., Results: For a hypothetical cohort of 1,000 fragility-fracture patients (740 requiring treatment), 686 received treatment in the FLS compared with 193 in usual care. Assessments and osteoporosis treatments cost an additional £83,598 and £206,544, respectively, in the FLS; 18 fractures (including 11 hip fractures) were prevented, giving an overall saving of £21,000. Setup costs for widespread adoption of FLSs across the UK were estimated at £9.7 million., Conclusions: FLSs are cost-effective for the prevention of further fractures in fragility-fracture patients. The cost of widespread adoption of FLS across the UK is small in comparison with other service provision and would be expected to result in important benefits in fractures avoided and reduced hospital bed occupancy.

Rationale: This review aims to examine economic evaluations of varenicline, to compare the reported cost-effectiveness of varenicline with that of treatments for major smoking-related diseases and to evaluate the findings for decision making., Methods: A literature search was performed to identify published articles in English indexed in MEDLINE and the Cochrane Library (Issue 1, 2009), which includes the Economic Evaluation Database. Additional sources also were searched to identify unpublished varenicline studies, including conference abstracts. The search for varenicline studies was limited from 2006 to October 2009; searches for all other types of studies were limited from 1990 to October 2009., Results: The search yielded a total of 20 relevant economic evaluations of varenicline. In addition, 37 reviews of economic evaluations in chronic obstructive pulmonary disease, non-small cell lung cancer and cardiovascular disease, as well as studies evaluating the impact of economic rewarding were considered in this review. From these identified economic evaluations, the incremental cost-effectiveness ratios for varenicline ranged from dominance (more effective and cost saving) to €18,582 per quality-adjusted life-year (including indirect costs). These estimates appeared substantially lower when compared with incremental cost-effectiveness ratios reported for secondary prevention of smoking-related diseases, which in some cases were as high as €66,218 per quality-adjusted life-year., Conclusions: Varenicline appears to be cost-effective from the perspective of both health care payers and employers, because of reduced health care consumption and costs. The cost-effectiveness of varenicline also compares favourably to that of interventions recommended for the treatment and prevention of smoking-related diseases., (© 2010 Blackwell Publishing Ltd.)

This study systematically collated clinical evidence on refractory generalized anxiety disorder (GAD). Refractory GAD patients are those who have failed to respond adequately to at least one earlier treatment for GAD. MEDLINE, EMBASE, The Cochrane Library and conference proceedings were searched to identify trials. Four placebo-controlled trials (pregabalin, olanzapine, quetiapine, risperidone) and four single-arm studies (aripiprazole, risperidone, quetiapine, ziprasidone) evaluated the add-ons to initial treatment(s) or switch of treatment(s) because of inadequate efficacy. The most robust trial was the pregabalin study, with a study duration of 8 weeks and a largest sample size that consists of 356 patients. A significant reduction in the Hamilton Anxiety Scale (HAM-A) score was found for pregabalin and risperidone augmentation compared with placebo. Olanzapine augmentation resulted in a significantly higher proportion of responders (using HAM-A scores) compared with placebo. Quetiapine augmentation did not result in significantly greater mean reductions in the HAM-Ascores compared with placebo. There is a need for effective and safe augmentation treatments for patient's refractory to initial treatments for GAD. This study has located one large robust trial assessing the add-on to pregabalin. All other trials were small and unpowered studies with less than 50 patients. Further high-quality trials of augmentation treatment on refractory GAD are required.

Objective: To evaluate the cost effectiveness of duloxetine when considered as an alternative treatment for patients in the United States (US) being treated for fibromyalgia pain., Research Design and Methods: A Markov model was used to evaluate the economic and clinical advantages of duloxetine in controlling fibromyalgia pain symptoms over a 2-year time horizon. A base-case treatment sequence was adopted from clinical guidelines, based on tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, anticonvulsants, and opioids. Treatment response was modeled using changes from baseline in pain severity, and response thresholds: full response (at least a 50% change), response (30-49% change), and no response (less than a 30% change). Clinical efficacy and discontinuation data were taken from placebo- and active-controlled trials identified in a systematic literature review and mixed-treatment comparison. Utility data were based on EQ-5D data., Main Outcome Measures: Additional symptom-control months (SCMs), defined as the amount of time at a response level of 30% or less, and quality-adjusted life-years (QALYs) over a 2-year time horizon., Results: For every 1000 patients, first-line duloxetine resulted in an additional 665 SCMs and 12.3 QALYs, at a cost of $582,911 (equivalent to incremental cost-effectiveness ratios [ICERs] of $877 per SCM and $47,560 per QALY). Second-line duloxetine resulted in an additional 460 SCMs and 8.7 QALYs, at a cost of $143,752 (equivalent to ICERs of $312 per SMC and $16,565 per QALY)., Limitations: Response data for TCAs are limited to 30% improvement levels, reported trials are small, and have low placebo response rates. The model necessarily assumes that response rates are independent of placement in the treatment sequence., Conclusions: The results suggest that the introduction of duloxetine into the standard treatment sequence for fibromyalgia not only provides additional patient benefits, reflected by time spent in pain control, but also is cost effective when compared with commonly adopted thresholds.

Objective: This was an evaluation of the cost-effectiveness of oral dabigatran etexilate compared with subcutaneous low-molecular-weight heparin (enoxaparin) for the prevention of venous thromboembolism (VTE) after total knee replacement (TKR) and total hip replacement (THR) surgery from the perspective of the UK National Health Service., Methods: Dabigatran etexilate (220 mg once daily) was compared with enoxaparin (40 mg once daily) in patients undergoing TKR (duration of prophylaxis, 6-10 days) and THR (duration of prophylaxis, 28-35 days). The 10-week acute postsurgical phase was modeled using a decision tree. A Markov process (1-year cycle length) was used to model long-term events (recurrent VTE, postthrombotic syndrome, and consequences of intracranial hemorrhage) for patients' remaining lifetimes. Relative risks for VTE and bleeding events were derived from 2 Phase III studies that compared dabigatran etexilate with enoxaparin 40 mg once daily. The probabilities of long-term events were estimated using data from published longitudinal studies., Results: Rates of VTE and bleeding events did not differ significantly between dabigatran etexilate and enoxaparin. Dabigatran etexilate was less costly than enoxaparin in TKR and substantially less costly in THR, primarily due to differences in administration costs. The cost of prophylaxis for THR patients, including drugs and administration costs, was estimated at pound 137 for dabigatran etexilate and pound 237 for enoxaparin ( pound 7 for nursing time during the hospital stay, pound 91 for nurse home visits for administration after hospital discharge, and an additional pound 2 in drug costs). At a willingness-to-pay threshold of pound 20,000 per quality-adjusted life-year, the probability of cost-effectiveness for dabigatran etexilate was 75% in TKR and 97% in THR. These results were robust across a range of sensitivity analyses., Conclusion: From the perspective of the UK National Health Service, thromboprophylaxis with dabigatran etexilate was cost-saving compared with enoxaparin 40 mg once daily, with comparable efficacy and safety profiles.

Second-generation atypical antipsychotics such as clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amisulpride and ariprazole offer the potential to reduce the significant health care resource demands in the treatment of schizophrenia through improved levels of initial clinical response and reduced levels of long-term acute relapse. However, the optimal sequencing of these drugs remains unclear. To consider this issue from a health economic viewpoint a decision model approach was used comparing healthcare costs and clinical outcomes when treating patients with alternative sequences of atypical antipsychotic treatment. Treated patients were assumed to be in a current acute episode with at least a 10-year history of disease and to be naive to previous atypical treatments. Treatment strategies were based on either first-line olanzapine or risperidone with switching to the alternative drug as second-line treatment following an inadequate clinical response to first-line drug therapy. Clinical response data were derived from a pivotal published comparative study of both olanzapine and risperidone. Published data on the long-term use of antipsychotic drugs where used wherever possible to populate the model for relapse rates during the maintenance phase. Health care resource data were defined for Germany based on expert clinical opinion. A treatment strategy of first-line olanzapine was shown to be cost saving over a 1-year period, with additional clinical benefits in the form of avoided relapses. The model suggests that over the first year of treatment a strategy of first-line olanzapine is associated with lower risk of additional relapse (0.33 fewer acute relapses per 100 patients per year) and with cost savings (euro 35,306 per 100 patients per year). There is a need for longer term direct in-trial comparisons of atypical antipsychotics to confirm these indicative results.

Prophylaxis-based antiviral treatment and intensive monitoring followed by pre-emptive antiviral treatment are both commonly used management strategies to reduce risk of cytomegalovirus (CMV) infection following renal transplantation. This study employed a decision-model approach using published efficacy data and information from a recent survey of French clinical practice to consider the relative costs and outcomes associated with CMV prevention strategies for high-risk patient groups. The cost per case of treating tissue invasive and symptomatic CMV disease was estimated at euro 15,431 and euro 10,852, respectively. In the highest infection-risk patient group (positive donor with no previous CMV history) prophylactic oral valaciclovir was shown to avoid the greatest number of CMV disease cases (35 cases per 100 transplanted patients) and reduced the overall CMV-related costs per transplanted patient by around 14% over a'wait-and-treat' baseline strategy. In contrast, intensive monitoring and preemptive treatment resulted in a much higher cost per transplanted patient. This analysis suggests that prophylactic treatment remains the most cost-effective approach to the management of CMV in renal-transplanted patients. Further comparative studies between prophylactic and pre-emptive treatment would be a valuable addition to the current evidence based on CMV prevention.

High-intermediate grade non-Hodgkin's lymphoma (NHL) is an aggressive form of the disease, which can respond well to combination chemotherapy, with long-term survival seen in 40-50% of patients. When NHL relapses following standard treatment, high-dose chemotherapy with peripheral blood stem cell or bone marrow support may still cure a significant proportion of patients. Despite a significant rise in the incidence of NHL over recent years, there remains only limited published economic study concerning the overall lifetime cost of treatment, the cost effectiveness of specific treatments or the overall societal cost burden of the disease. The majority of studies identified for the purposes of this review considered the cost of alternative forms of chemotherapy and bone marrow support strategies for patients with advanced disease. Data from these studies suggest that there is a definite trend towards reduced costs for high-dose therapy, possibly reflecting increasing technical experience and improved bone marrow recovery through the use of stem cell transplantation and growth factors. The limited number of cost-effectiveness evaluations suggest that high-dose therapy, following a chemosensitive relapse, is likely to be considered favourable against commonly quoted cost-effectiveness thresholds. Cost effectiveness is becoming an increasingly important factor to consider in the formal assessment of new interventions conducted by groups such as the UK National Institute for Clinical Excellence. In light of the increasing incidence of NHL and the extended use of high-dose treatments in other subgroups of patients, there is a need for increased research into the economics of new interventions for NHL.

The cost-effectiveness of high-dose chemotherapy in multiple myeloma was considered as part of a UK National Health Service Executive regional evidence-based appraisal process. The use of high-dose chemotherapy supported by autologous stem cell transplantation in patients under 65 years of age was shown to provide a marginal benefit of 0.7 life-years over conventional chemotherapy. This corresponded to an incremental cost 'per life-year gained' figure of approximately pound15 000, based upon initial treatment costs and trial-period data only. The use of high-dose chemotherapy in the first-line treatment of advanced multiple myeloma improves event-free and overall survival and appears to be a cost-effective treatment option.

Objectives: to inform the debate on whether seriously head-injured adult patients should be transported directly to the regional neurosurgical unit or indirectly after evaluation and stabilisation at the nearest hospital., Design: a simulation model was constructed to compare triage strategies and to identify those that predicted the maximum survivors. In each strategy, an estimate of the patient's condition in the field was used to determine the receiving hospital. The model used data from previous publications and local ambulance service and hospital databases. In the absence of valid data, expert clinical estimates were made and subjected to sensitivity analyses., Setting: an area in the North West Midlands of UK, covered by six acute hospitals including one with a regional neurosurgical unit., Outcome Measure: the number of survivors predicted by each triage strategy., Results: five strategies were identified which consistently predicted the highest number of survivors. Compared with current policy it was predicted that in the North West Midlands, ten lives per year could be saved (6 per million total population per year). The results from sensitivity analyses did not alter these successful policies., Conclusion: the successful strategies should be considered as potential improvements to be introduced into clinical practice.

Objective: To analyze the cost-effectiveness of resection for liver metastases compared with standard nonsurgical cytotoxic treatment., Summary Background Data: The efficacy of hepatic resection for metastases from colorectal cancer has been debated, despite reported 5-year survival rates of 20% to 40%. Resection is confined to specialized centers and is not widely available, perhaps because of lack of appropriate expertise, resources, or awareness of its efficacy. The cost-effectiveness of resection is important from the perspective of managed care in the United States and for the commissioning of health services in the United Kingdom., Methods: A simple decision-based model was developed to evaluate the marginal costs and health benefits of hepatic resection. Estimates of resectability for liver metastases were taken from UK-reported case series data. The results of 100 hepatic resections conducted in Sheffield from 1997 to 1999 were used for the cost calculation of liver resection. Survival data from published series of resections were compiled to estimate the incremental cost per life-year gained (LYG) because of the short period of follow-up in the Sheffield series., Results: Hepatic resection for colorectal liver metastases provides an estimated marginal benefit of 1.6 life-years (undiscounted) at a marginal cost of 6,742 pound sterling++. If 17% of patients have only palliative resections, the overall cost per LYG is approximately 5,236 pound sterling (5,985 pound sterling with discounted benefits). If potential benefits are extended to include 20-year survival rates, these figures fall to approximately 1,821 pound sterling (2,793 pound sterling with discounted benefits). Further univariate sensitivity analysis of key model parameters showed the cost per LYG to be consistently less than 15,000 pound sterling., Conclusion: In this model, hepatic resection appears highly cost-effective compared with nonsurgical treatments for colorectal-related liver metastases.

Pertussis infection is associated with significant morbidity in younger children (<4 years), which can include pneumonia, seizures and encephalopathy. Around one in 250 cases of pertussis in infants under the age of 6 months lead to death or severe brain damage. In the United Kingdom the control of pertussis infection has been based on a three-dose schedule of combined diphtheria, tetanus, whole-cell pertussis vaccine (DTPw) during the first 4 months of life. Coverage rates for primary vaccination are currently at high levels of over 90 per cent and infection rates are relatively low (approximately 1.2 per 100,000). However, there are concerns over the potential under-reporting of pertussis and clear shifts in the age pattern of notified cases are evident, with surveillance data suggesting a possible upward trend in the absolute numbers of infections in those at most risk (i.e. infants <3 months old). The addition of childhood booster dose(s) of pertussis vaccine to the standard schedule has potential clinical benefits and may be cost-effective. Selective adult booster immunization may also have a role to play in controlling the circulation of pertussis.

As part of an NHS Executive Trent regional initiative we considered the role and cost-effectiveness of high dose chemotherapy in the treatment of relapsed Hodgkin's disease and non-Hodgkin's lymphoma. The key trials and case series show an additional patient benefit of 0.8-1.1 life years over standard chemotherapy. We estimate incremental cost per life year gained of 12 800 pound silver-17 600 pound silver, which reduces further if long-term benefits are considered. High dose chemotherapy in these conditions is both life-saving and cost-effective.