Patient preferences do matter: a discrete choice experiment conducted with breast cancer patients in six European countries, with latent class analysis.

OBJECTIVES: The evolution of breast cancer (BC) treatments has resulted in tailored therapies for the different types and stages of BC. Each treatment has a profile of benefits and adverse effects which are taken into consideration when planning a treatment pathway. This study examines whether patients' preferences are in line with what is considered important from decision makers viewpoint. METHODS: An online discrete choice experiment was conducted in six European countries (France, Germany, Ireland, Poland, Spain, UK) with BC patients. Six attributes were included: overall survival (OS), hyperglycemia, rash, pain, functional well-being (FWB), and out-of-pocket payment (OOP). Sixteen choice sets with two hypothetical treatments and a "No treatment" option were presented. Data were analyzed with the use of heteroscedastic conditional, mixed logistic, and latent class models. Marginal rate of substitution (MRS) were estimated for OOP versus the rest of attributes to establish the ranking of preferences for each attribute. RESULTS: Two hundred and forty-seven patients with advanced or metastatic BC and 314 with early-stage BC responded. Forty-nine percent of patients were < 44 years old and 65 percent had completed university education. The MRS of the analysis demonstrated that "severe pain" is the highest dis-preferred attribute level, followed by "severe impairment in FWB" and OS. Four classes of patients as "decision makers" were identified. CONCLUSIONS: This study suggests that there is heterogeneity in treatment preferences of BC patients depending on their sociodemographic and disease-related characteristics. In combination with clinical guidelines, patient preferences can support the selection and tailoring of treatment options.

Treatment pathways and associated costs of metastatic colorectal cancer in Greece.

OBJECTIVES: Colorectal cancer (CRC) is the second leading cause of cancer in Europe, with 1.931.590 people newly diagnosed in 2020. The purpose of this study is the investigation of treatment options and healthcare resource metastatic CRC (mCRC) in Greece. METHODS: This study is based on the information collected in November 2020 by an expert panel comprising of 6 medical oncologists from major public and private centers around Greece. A 3-round survey was undertaken, according to Delphi method. The treatment phases studied were: pre-progression; disease progression and terminal care. Pharmaceutical costs and resource utilization data were considered from the perspective of the Greek National Services Organization (EOPYY). RESULTS: Experts agreed that the anticipated prevalence of RAS mutation in mCRC is 47% (30% RAS/BRAF WT Left, 17% RAS/BRAF WT Right); 8% BRAF while, MSI-H/dMMR are found in 5% of mCRC tumors. Based on mutational status, 74.8% of patients receive biological targeted therapies in combination with fluoropyrimidine/based combination chemotherapy, as 1st line treatment, and 25.2% combination chemotherapy alone. At 2nd line, 58.6% of patients receive biological targeted therapies in combination with chemotherapy, 25.4% immunotherapy, 11% combination chemotherapy and 5% biological targeted therapies. At 3rd line 56% of patients receive combination chemotherapy, 28% biological targeted therapies, 10% biological targeted therapies in combination with chemotherapy and 6% immunotherapy. The weighted annual cost (pharmaceuticals and resource use cost) in 1st line per mCRC patient was calculated at €28,407, in 2nd line €33,568, in 3rd line €25,550. The annual cost beyond 3rd line per patient regardless mutation was €19,501 per mCRC patient. CONCLUSIONS: mCRC is a societal challenge for healthcare systems as the treatment is more prolonged but expand patients' survival. Thus, reimbursement decisions should be based not just on the cost of the treatment, but on the magnitude of the benefit of its treatment on patients' survival and quality of life.

Patient preferences for breast cancer treatments: a discrete choice experiment in France, Ireland, Poland and Spain.

Aim: To understand breast cancer patients' trade-offs when choosing treatments and to identify the most important treatment attributes which drive decisions. Materials & methods: A discrete choice experiment was conducted in France, Ireland, Poland and Spain. Progression-free survival, febrile neutropenia, pain, functional well-being and out-of-pocket payment were the treatment attributes. Results: 371 patients were willing to pay €6896 per year for 1 additional year of progression-free survival, €17,288 per year for perfect functional well-being and €15,138 for one pain-free year. Patients are willing to trade off progression-free survival months for better functional abilities and less pain. Conclusion: Patient preferences should be considered by regulatory agencies, reimbursement bodies, payors and clinicians for best treatment choices for the individuals.

The authors wanted to explore what breast cancer patients want the most from their cancer treatments. For this purpose, their preferences were collected in four European countries via a discrete choice experiment. The study showed that patients prefer treatments that improve their ability to function well in their daily lives and reduce their levels of pain. Patients' preferences for treatment outcomes might differ from those of the treating clinicians or regulators. Hence, these aspects can be discussed with their clinicians to make a joint decision on the choice of treatments.

Lacosamide as a first-line treatment option in focal epilepsy: a cost-utility analysis for the Greek healthcare system.

BACKGROUND AND AIMS: Epilepsy is the most common serious neurological disorder worldwide. Approximately 40% of patients with focal epileptic seizures remain uncontrolled with antiepileptic drug (AED) monotherapy or polytherapy. Lacosamide has been recently approved by the European Medicines Agency as monotherapy for the treatment of focal seizures. The aim of this study was to estimate the cost-effectiveness of lacosamide compared with zonisamide as first-line treatment of focal epilepsy in patients with epilepsy aged ≥ 16 years to inform clinical decision-making in Greece. METHODS: A discrete event simulation model was adapted to reflect treatment pathways and resource use within the Greek national healthcare system, as specified by clinical experts. The model captures time-varying events and patient characteristics. Clinical inputs were sourced from pivotal trials and a network meta-analysis comparing lacosamide with other AEDs. The model predicts disease progression and seizures, relevant and most common adverse events, withdrawal due to lack of efficacy or adverse events, and epilepsy-specific and all-cause mortality over a 2-year time horizon. Unit costs were retrieved from published Greek sources. Health outcomes were measured as quality-adjusted life years (QALYs); secondary outcome was the cost per seizure avoided. Robustness of the results was tested with univariate and probabilistic sensitivity analyses. RESULTS: The lacosamide treatment pathway was associated with higher costs (i.e. €1,064) and an additional 0.119 QALYs when compared with zonisamide, resulting in an incremental cost-effectiveness ratio of €8,938 per QALY gained. The sensitivity analyses demonstrated that the results are most sensitive to the efficacy and utility estimates. LIMITATIONS: There are a number of limitations which stem from the process of model adaptation and lack of local real-world evidence. CONCLUSIONS: Lacosamide is a cost-effective option at a willingness-to-pay threshold of €30,000 per QALY, representing a valuable monotherapy treatment option for patients with focal epileptic seizures in the Greek setting.

A Cost-Effectiveness Analysis of Intradiscal Electrothermal Therapy Compared with Circumferential Lumbar Fusion.

STUDY DESIGN: Cost-effectiveness analysis. OBJECTIVE: To evaluate the cost-effectiveness of intradiscal electrothermal therapy (IDET) relative to circumferential lumbar fusion with femoral ring allograft (FRA) in the United Kingdom. SUMMARY OF BACKGROUND DATA: Circumferential lumbar fusion is an established treatment for discogenic low back pain. However, IDET could be a cost-effective treatment alternative as it can be carried out as a day case. METHODS: Patient-level data were available for patients with discogenic low back pain treated with FRA (n = 37) in a randomized trial of FRA vs. titanium cage, and for patients recruited to a separate study evaluating the use of IDET (n = 85). Both studies were carried out at a single institution in the United Kingdom. Patients were followed-up for 24 months, with data collected on low back disability (Oswestry Disability Index), back and leg pain (visual analog scale), quality of life (Short Form 36), radiographic evaluations, and U.K. National Health Service (NHS) resource use. Cost-effectiveness was measured by the incremental cost per quality-adjusted life year (QALY) gained. RESULTS: Both treatments produced statistically significant improvements in outcome at 24-month follow-up. NHS costs were significantly lower with IDET due to a shorter mean procedure time (377.4 minutes vs. 49.9 minutes) and length of stay (7 days vs. 1.2 days). At a threshold of £20,000 per QALY, the probability that IDET is cost effective is high. CONCLUSIONS: Both treatments led to significant improvements in patient outcomes that were sustained for at least 24 months. Costs were lower with IDET, and for appropriate patients IDET is an effective and cost-effective treatment alternative.

Identifying the primary outcome for a randomised controlled trial in rheumatoid arthritis: the role of a discrete choice experiment.

BACKGROUND: This study sought to establish the preferences of people with Rheumatoid Arthritis (RA) about the best outcome measure for a health and fitness intervention randomised controlled trial (RCT). The results of this study were used to inform the choice of the trial primary and secondary outcome measure. METHODS: A discrete choice experiment (DCE) was used to assess people's preferences regarding a number of outcomes (foot and ankle pain, fatigue, mobility, ability to perform daily activities, choice of footwear) as well as different schedules and frequency of delivery for the health and fitness intervention. The outcomes were chosen based on literature review, clinician recommendation and patients' focus groups. The DCE was constructed in SAS software using the D-efficiency criteria. It compared hypothetical scenarios with varying levels of outcomes severity and intervention schedule. Preference weights were estimated using appropriate econometric models. The partial log-likelihood method was used to assess the attribute importance. RESULTS: One hundred people with RA completed 18 choice sets. Overall, people selected foot and ankle pain as the most important outcome, with mobility being nearly as important. There was no evidence of differential preference between intervention schedules or frequency of delivery. CONCLUSIONS: Foot and ankle pain can be considered the patient choice for primary outcome of an RCT relating to a health and fitness intervention. This study demonstrated that, by using the DCE method, it is possible to incorporate patients' preferences at the design stage of a RCT. This approach ensures patient involvement at early stages of health care design.

Cost-effectiveness of the Family Nurse Partnership (FNP) programme in England: Evidence from the building blocks trial.

RATIONAL, AIMS, AND OBJECTIVES: The Family Nurse Partnership (FNP) is a licensed intensive home visiting intervention developed in the United States. It has been provided in England by the Department of Health since 2006. The Building Blocks trial assessed the effectiveness and cost-effectiveness of FNP in England. METHODS: We performed a cost-utility analysis (National Health Service (NHS) perspective) alongside the Building Blocks trial (over 2.5 y). The analysis was conducted in accordance with National Institute for Health and Clinical Excellence (NICE) reference case standards. Health-related quality of life was elicited from mothers using the EQ-5D-3L. Resource-use data were collected from self-reported questionnaires, Hospital Episode Statistics, general practitioner records and the central Department of Health FNP database. Costs and quality-adjusted life years (QALYs) were discounted at 3.5%. The base case analysis used an intention to treat approach on the imputed dataset using multiple imputation. RESULTS: The FNP intervention costs on average £1812 more per participant compared to usual care (95% confidence interval: -£2700; £5744). Incremental adjusted mean QALYs are marginally higher for FNP (mean difference 0.0036, 95% confidence interval: -0.017; 0.025). The probability of FNP being cost-effective is less than 20% given the current NICE willingness to pay threshold of £20 000 per additional QALY. The results were robust to sensitivity analyses. CONCLUSION: Given the absence of significant benefits of FNP in terms of the primary outcomes of the trial and only marginal maternal QALY gains, FNP does not represent a cost-effective intervention when compared with existing services already offered to young pregnant women.

Effectiveness of a nurse-led intensive home-visitation programme for first-time teenage mothers (Building Blocks): a pragmatic randomised controlled trial.

BACKGROUND: Many countries now offer support to teenage mothers to help them to achieve long-term socioeconomic stability and to give a successful start to their children. The Family Nurse Partnership (FNP) is a licensed intensive home-visiting intervention developed in the USA and introduced into practice in England that involves up to 64 structured home visits from early pregnancy until the child's second birthday by specially recruited and trained family nurses. We aimed to assess the effectiveness of giving the programme to teenage first-time mothers on infant and maternal outcomes up to 24 months after birth. METHODS: We did a pragmatic, non-blinded, randomised controlled, parallel-group trial in community midwifery settings at 18 partnerships between local authorities and primary and secondary care organisations in England. Eligible participants were nulliparous and aged 19 years or younger, and were recruited at less than 25 weeks' gestation. Field-based researchers randomly allocated mothers (1:1) via remote randomisation (telephone and web) to FNP plus usual care (publicly funded health and social care) or to usual care alone. Allocation was stratified by site and minimised by gestation (<16 weeks vs ≥16 weeks), smoking status (yes vs no), and preferred language of data collection (English vs non-English). Mothers and assessors (local researchers at baseline and 24 months' follow-up) were not masked to group allocation, but telephone interviewers were blinded. Primary endpoints were biomarker-calibrated self-reported tobacco use by the mother at late pregnancy, birthweight of the baby, the proportion of women with a second pregnancy within 24 months post-partum, and emergency attendances and hospital admissions for the child within 24 months post-partum. Analyses were by intention to treat. This trial is registered with ISRCTN, number ISRCTN23019866. FINDINGS: Between June 16, 2009, and July 28, 2010, we screened 3251 women. After enrolment, 823 women were randomly assigned to receive FNP and 822 to usual care. All follow-up data were retrieved by April 25, 2014. 304 (56%) of 547 women assigned to FNP and 306 (56%) of 545 assigned to usual care smoked at late pregnancy (adjusted odds ratio [AOR] 0·90, 97·5% CI 0·64-1·28). Mean birthweight of 742 babies with mothers assigned to FNP was 3217·4 g (SD 618·0), whereas birthweight of 768 babies assigned to usual care was 3197·5 g (SD 581·5; adjusted mean difference 20·75 g, 97·5% CI -47·73 to 89·23. 587 (81%) of 725 assessed children with mothers assigned to FNP and 577 (77%) of 753 assessed children assigned to usual care attended an emergency department or were admitted to hospital at least once before their second birthday (AOR 1·32, 97·5% CI 0·99-1·76). 426 (66%) of 643 assessed women assigned to FNP and 427 (66%) 646 assigned to usual care had a second pregnancy within 2 years (AOR 1·01, 0·77-1·33). At least one serious adverse event (mainly clinical events associated with pregnancy and infancy period) was reported for 310 (38%) of 808 participants (mother-child) in the usual care group and 357 (44%) of 810 in the FNP group, none of which were considered related to the intervention. INTERPRETATION: Adding FNP to the usually provided health and social care provided no additional short-term benefit to our primary outcomes. Programme continuation is not justified on the basis of available evidence, but could be reconsidered should supportive longer-term evidence emerge. FUNDING: Department of Health Policy Research Programme.

Systematic review of the economic evidence on home visitation programmes for vulnerable pregnant women.

INTRODUCTION: A systematic review of the economic evidence on home visitation programmes for young or vulnerable pregnant women was undertaken to provide a summary of the existing literature of these interventions. SOURCES OF DATA: Relevant studies were identified from a number of sources including large databases, free text search on Google Scholar as well as hand-searching of the obtained references. The search yielded a large number of papers, of which 12 were considered appropriate to be included in the review. These were either full or partial economic evaluations: four studies were cost-benefit analyses, three were cost-effectiveness analyses and the remaining were costing studies. AREAS OF AGREEMENT: The review highlighted the paucity of good quality economic evaluations in the area of home visiting programmes for young or vulnerable pregnant women. Methods varied substantially between the studies spanning from differing data sources (e.g. single randomized trials or meta-analyses) to different perspectives taken, cost items and outcomes included in the analysis. AREAS OF CONTROVERSY: It is difficult to establish a coherent body of economic evidence for these interventions and draw a firm conclusion on their value for money. GROWING POINTS: Home visiting programmes are complex interventions, with impact on the lives of mothers and their children. The funding of such interventions should be based on rigorous effectiveness and economic evidence. AREAS TIMELY FOR DEVELOPING RESEARCH: There is a need for well-designed economic evaluations which will follow the appropriate methodological guidelines and also take into account the complexity of such interventions. These analyses should preferably consider multiple perspectives and allow for the fact that the majority of the benefits accrue in the long-term future.

The effectiveness and cost-effectiveness of the Family Nurse Partnership home visiting programme for first time teenage mothers in England: a protocol for the Building Blocks randomised controlled trial.

BACKGROUND: The Nurse Family Partnership programme was developed in the USA where it is made available to pregnant young mothers in some socially deprived geographic areas. The related Family Nurse Partnership programme was introduced in England by the Department of Health in 2006 with the aim of improving outcomes for the health, wellbeing and social circumstances of young first-time mothers and their children. METHODS / DESIGN: This multi-centre individually randomised controlled trial will recruit 1600 participants from 18 Primary Care Trusts in England, United Kingdom. The trial will evaluate the effectiveness of Family Nurse Partnership programme and usual care versus usual care for nulliparous pregnant women aged 19 or under, recruited by 24 weeks gestation and followed until the child's second birthday. Data will be collected from participants at baseline, 34-36 weeks gestation, 6, 12, 18 and 24 months following birth. Routine clinical data will be collected from maternity, primary care and hospital episodes statistics. Four primary outcomes are to be reported from the trial: birth weight; prenatal tobacco use; child emergency attendances and/or admissions within two years of birth; second pregnancy within two years of first birth. DISCUSSION: This trial will evaluate the effectiveness and cost effectiveness of the Family Nurse Partnership in England. The findings will provide evidence on pregnancy and early childhood programme outcomes for policy makers, health professionals and potential recipients in three domains (pregnancy and birth, child health and development, and parental life course and self-sufficiency) up to the child's second birthday. TRIAL REGISTRATION: Trial registration number: ISRCTN23019866.

Cost-effectiveness of acupuncture for irritable bowel syndrome: findings from an economic evaluation conducted alongside a pragmatic randomised controlled trial in primary care.

BACKGROUND: There is insufficient evidence to determine whether acupuncture is a cost-effective treatment for irritable bowel syndrome. The objective of this study is to assess the cost-effectiveness of acupuncture as an adjunct to usual care versus usual care alone for the treatment of Irritable Bowel Syndrome (IBS). METHODS: Cost-utility analysis conducted alongside a pragmatic, multicentre, randomised controlled trial. 233 patients with irritable bowel syndrome were randomly allocated to either acupuncture plus usual care, or usual care alone. Cost-effectiveness outcomes are expressed in terms of incremental cost per quality adjusted life year (QALY) at one year after randomisation. Costs were estimated from the UK National Health Service perspective for a time horizon of one year. Cost-utility ratios were estimated based on complete case analysis for the base case analysis, where only patients with available EQ-5D and cost data were included. Sensitivity analyses comprised a multiple imputation approach for missing data and a subgroup analysis for the more severe cases of IBS. RESULTS: The base case analysis showed acupuncture to be marginally more effective than usual care (gain of 0.0035 QALYs, 95% CI: -0.00395 to 0.0465) and more expensive (incremental cost of £218 per patient (95% CI: 55.87 to 492.87) resulting in an incremental cost-effectiveness ratio of approximately £62,500. Sensitivity analysis using multiple imputation for missing data resulted in acupuncture appearing less effective and more costly than usual care, so usual care is dominant. Subgroup analysis selecting the most severe cases of IBS (Symptom Severity Score of over 300) suggested that acupuncture may be a cost-effective treatment option for this group, with a cost-per-QALY of £6,500. CONCLUSIONS: Acupuncture as an adjunct to usual care is not a cost-effective option for the whole IBS population; however it may be cost-effective for those with more severe irritable bowel syndrome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN08827905.

Cost-effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts: economic evaluation alongside a randomised controlled trial (EVerT trial).

BACKGROUND: Plantar warts (verrucae) are extremely common. Although many will spontaneously disappear without treatment, treatment may be sought for a variety of reasons such as discomfort. There are a number of different treatments for cutaneous warts, with salicylic acid and cryotherapy using liquid nitrogen being two of the most common forms of treatment. To date, no full economic evaluation of either salicylic acid or cryotherapy has been conducted based on the use of primary data in a pragmatic setting. This paper describes the cost-effectiveness analysis which was conducted alongside a pragmatic multicentre, randomised trial evaluating the clinical effectiveness of cryotherapy versus 50% salicylic acid of the treatment of plantar warts. METHODS: A cost-effectiveness analysis was undertaken alongside a pragmatic multicentre, randomised controlled trial assessing the clinical effectiveness of 50% salicylic acid and cryotherapy using liquid nitrogen at 12 weeks after randomisation of patients. Cost-effectiveness outcomes were expressed as the additional cost required to completely cure the plantar warts of one additional patient. A NHS perspective was taken for the analysis. RESULTS: Cryotherapy costs on average £101.17 (bias corrected and accelerated (BCA) 95% CI: 85.09-117.26) more per participant over the 12 week time-frame, while there is no additional benefit, in terms of proportion of patients healed compared with salicylic acid. CONCLUSIONS: Cryotherapy is more costly and no more effective than salicylic acid. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18994246 [controlled-trials.com] and National Research Register N0484189151.

Cryotherapy versus salicylic acid for the treatment of plantar warts (verrucae): a randomised controlled trial.

OBJECTIVE: To compare the clinical effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts. DESIGN: A multicentre, open, two arm randomised controlled trial. SETTING: University podiatry school clinics, NHS podiatry clinics, and primary care in England, Scotland, and Ireland. PARTICIPANTS: 240 patients aged 12 years and over, with a plantar wart that in the opinion of the healthcare professional was suitable for treatment with both cryotherapy and salicylic acid. INTERVENTIONS: Cryotherapy with liquid nitrogen delivered by a healthcare professional, up to four treatments two to three weeks apart. Patient self treatment with 50% salicylic acid (Verrugon) daily up to a maximum of eight weeks. MAIN OUTCOME MEASURES: Complete clearance of all plantar warts at 12 weeks. Secondary outcomes were (a) complete clearance of all plantar warts at 12 weeks controlling for age, whether the wart had been treated previously, and type of wart, (b) patient self reported clearance of plantar warts at six months, (c) time to clearance of plantar wart, (d) number of plantar warts at 12 weeks, and (e) patient satisfaction with the treatment. RESULTS: There was no evidence of a difference between the salicylic acid and cryotherapy groups in the proportions of participants with complete clearance of all plantar warts at 12 weeks (17/119 (14%) v 15/110 (14%), difference 0.65% (95% CI -8.33 to 9.63), P=0.89). The results did not change when the analysis was repeated but with adjustment for age, whether the wart had been treated previously, and type of plantar wart or for patients' preferences at baseline. There was no evidence of a difference between the salicylic acid and cryotherapy groups in self reported clearance of plantar warts at six months (29/95 (31%) v 33/98 (34%), difference -3.15% (-16.31 to 10.02), P=0.64) or in time to clearance (hazard ratio 0.80 (95% CI 0.51 to 1.25), P=0.33). There was also no evidence of a difference in the number of plantar warts at 12 weeks (incident rate ratio 1.08 (0.81 to 1.43), P=0.62). CONCLUSIONS: Salicylic acid and the cryotherapy were equally effective for clearance of plantar warts. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18994246, National Research Register N0484189151.

Health outcomes in economic evaluation: who should value health?

The valuation of health states is an integral part of economic evaluation studies. The source of these valuations (general public vs. patients) is surrounded by controversy. Health state values generated by the general public are often different compared with those of patients. General public values may not account for adaptation of the patients; patients' values potentially incorporate self-interest. Decisions on the appropriate source of health values ultimately depend on the specific decision-making context and objectives of the evaluation. Differences in valuations and implications for decision-making should be explicitly addressed. Further research should systematically identify circumstances in which public and patients' valuations diverge. There appears ground for development of methods that allow the simultaneous incorporation of patients and public preferences. Existing literature which discusses the issues around the health state valuation is summarized.

Acupuncture for irritable bowel syndrome: a protocol for a pragmatic randomised controlled trial.

BACKGROUND: There is insufficient evidence on the effectiveness of acupuncture for irritable bowel syndrome (IBS) for conclusions to be drawn. Given the current interest in acupuncture by patients, it is in the public interest to establish more rigorous evidence. Building on the positive findings from a pilot study, in this paper we present the protocol for a fully-powered trial designed to establish whether or not acupuncture is effective and cost-effective. METHODS/DESIGN: In this pragmatic randomised controlled trial we will randomise patients recruited directly from GP databases to either 10 sessions of acupuncture plus usual GP care or to usual GP care alone. The primary clinical outcome will be the IBS Symptom Severity Score (SSS) (maximum score 500) at three months, and at 12 month assessing whether there is an overall benefit. We estimate the sample size required to detect a minimum clinical difference at 90% power and 5% significance to be 188 patients. To allow for loss to follow up we will recruit 220 patients drawn from an estimated primary care population of 140 000. Analysis will be by intention-to-treat, and multiple imputation is to be used for missing data.In a nested qualitative study using in-depth interviews, we will explore how patients, acupuncturists, and GPs explain and subsequently understand acupuncture to work. We will use purposive sampling to identify patients and flexible topic guides for the interviews. The data analysis will lead to a thematic description of how patients and practitioners explain how acupuncture works, and whether or not the explanations influence treatment outcome and/or referrals.We will undertake a cost-effectiveness analysis at 12 months by comparing resource use in the two groups with any treatment benefit. We will use the EQ-5D to measure health-related quality of life and convert into quality adjusted life years (QALYs). We will generate cost effectiveness acceptability curves (CEACs) exploring the probability that acupuncture will produce an acceptable cost per QALY at different cost-effectiveness thresholds. DISCUSSION: The trial has received NHS ethics approval and recruited 233 patients between November 2008 and June 2009. Results are expected in 2011. TRIAL REGISTRATION: Current Controlled Trials ISRCTN08827905.

Cost-effectiveness of salmeterol xinafoate/fluticasone propionate combination inhaler in chronic asthma.

OBJECTIVE: To determine where in the treatment steps recommended by the British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN) Asthma Guideline it is cost-effective to use salmeterol xinafoate/fluticasone propionate combination inhaler (SFC) (Seretide) compared with other inhaled corticosteroid (ICS) containing regimens (with and without a long acting beta-2 agonist (LABA)) for chronic asthma in adults and children. RESEARCH DESIGN AND METHODS: Meta-analyses of percentage symptom-free days (%SFD) were used within a cost-effectiveness model. Time spent in two asthma control health states, 'symptom-free' and 'with-symptoms' was used as the measure of differential treatment effectiveness. SFC was compared with varying doses of fluticasone propionate (FP) and beclometasone dipropionate (BDP) with or without a separate salmeterol inhaler, and with the budesonide/formoterol combination inhaler (BUD/FORM) (Symbicort). Drug costs, non-drug costs and quality adjusted life years (QALY) were incorporated into the analyses. Results are presented as cost per QALY ratios and uncertainty explored using probabilistic sensitivity analysis. RESULTS: Compared with an increased dose of FP in adults, SFC either 'dominates' (i.e. cheaper and more effective) FP or the cost per QALY is 6852 pounds sterling. The cost per QALYs estimated in sensitivity analyses using BDP costs range from 5679 pounds sterling to 15,997 pounds sterling. For children the cost per QALY for SFC 50 Evohaler compared with an increased dose of FP is pound 15,739 pounds sterling. SFC is similarly clinically effective in improving %SFDs compared with FP plus salmeterol delivered in separate inhalers (mean differences for each dose comparison of -3.9 (low) (with a 95% confidence interval (CI): -12.96; 5.16); 4.10 (medium) (95% CI: -3.01; 11.21); -0.4 (high) (95% CI: -8.88; 8.08)) and BUD/FORM (mean difference of 0.40 (95% CI -3.69; 4.49)) in adults, and a cheaper SFC option is available at all doses (annual cost savings range from 18 pounds sterling-427 pounds sterling per patient). SFC was similarly effective compared with FP plus salmeterol in separate inhalers in children under 12 and also resulted in annual cost savings of between 47 pounds sterling and 77 pounds sterling. A number of other comparisons were also made and the results are available as electronic supplementary data. CONCLUSIONS: This is the first analysis to estimate the cost-effectiveness of SFC in chronic asthma compared with multiple comparators and based on a systematic identification of relevant trials and data on %SFDs. The findings suggest that for adults and children uncontrolled on BDP 400 microg/day or equivalent it is a cost-effective option to switch to SFC (at an equivalent ICS dose) compared with increasing the dose of ICS. For adults and children aged 12 years and over who have passed this point and are uncontrolled on BDP 800 microg/day or equivalent, switching to SFC remains a cost-effective approach. Where an adult or child requires an ICS and a LABA to be co-prescribed, SFC is a cost-effective option compared with FP or BDP plus salmeterol delivered in separate inhalers. In adults who require combination therapy, SFC is a cost-effective option compared with BUD/FORM.