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1.  Cost-Effectiveness of an Opportunistic Screening Programme and Brief Intervention for Excessive Alcohol Use in Primary Care 
PLoS ONE  2009;4(5):e5696.
Background
Effective prevention of excessive alcohol use has the potential to reduce the public burden of disease considerably. We investigated the cost-effectiveness of Screening and Brief Intervention (SBI) for excessive alcohol use in primary care in the Netherlands, which is targeted at early detection and treatment of ‘at-risk’ drinkers.
Methodology and Results
We compared a SBI scenario (opportunistic screening and brief intervention for ‘at-risk’ drinkers) in general practices with the current practice scenario (no SBI) in the Netherlands. We used the RIVM Chronic Disease Model (CDM) to extrapolate from decreased alcohol consumption to effects on health care costs and Quality Adjusted Life Years (QALYs) gained. Probabilistic sensitivity analysis was employed to study the effect of uncertainty in the model parameters. In total, 56,000 QALYs were gained at an additional cost of €298,000,000 due to providing alcohol SBI in the target population, resulting in a cost-effectiveness ratio of €5,400 per QALY gained.
Conclusion
Prevention of excessive alcohol use by implementing SBI for excessive alcohol use in primary care settings appears to be cost-effective.
doi:10.1371/journal.pone.0005696
PMCID: PMC2682644  PMID: 19479081
2.  Randomised controlled trial of Alexander technique lessons, exercise, and massage (ATEAM) for chronic and recurrent back pain: economic evaluation 
Objective An economic evaluation of therapeutic massage, exercise, and lessons in the Alexander technique for treating persistent back pain.
Design Cost consequences study and cost effectiveness analysis at 12 month follow-up of a factorial randomised controlled trial.
Participants 579 patients with chronic or recurrent low back pain recruited from primary care.
Interventions Normal care (control), massage, and six or 24 lessons in the Alexander technique. Half of each group were randomised to a prescription for exercise from a doctor plus behavioural counselling from a nurse.
Main outcome measures Costs to the NHS and to participants. Comparison of costs with Roland-Morris disability score (number of activities impaired by pain), days in pain, and quality adjusted life years (QALYs). Comparison of NHS costs with QALY gain, using incremental cost effectiveness ratios and cost effectiveness acceptability curves.
Results Intervention costs ranged from £30 for exercise prescription to £596 for 24 lessons in Alexander technique plus exercise. Cost of health services ranged from £50 for 24 lessons in Alexander technique to £124 for exercise. Incremental cost effectiveness analysis of single therapies showed that exercise offered best value (£61 per point on disability score, £9 per additional pain-free day, £2847 per QALY gain). For two-stage therapy, six lessons in Alexander technique combined with exercise was the best value (additional £64 per point on disability score, £43 per additional pain-free day, £5332 per QALY gain).
Conclusions An exercise prescription and six lessons in Alexander technique alone were both more than 85% likely to be cost effective at values above £20 000 per QALY, but the Alexander technique performed better than exercise on the full range of outcomes. A combination of six lessons in Alexander technique lessons followed by exercise was the most effective and cost effective option.
doi:10.1136/bmj.a2656
PMCID: PMC3272680  PMID: 19074232
3.  Adaptive Pacing, Cognitive Behaviour Therapy, Graded Exercise, and Specialist Medical Care for Chronic Fatigue Syndrome: A Cost-Effectiveness Analysis 
PLoS ONE  2012;7(8):e40808.
Background
The PACE trial compared the effectiveness of adding adaptive pacing therapy (APT), cognitive behaviour therapy (CBT), or graded exercise therapy (GET), to specialist medical care (SMC) for patients with chronic fatigue syndrome. This paper reports the relative cost-effectiveness of these treatments in terms of quality adjusted life years (QALYs) and improvements in fatigue and physical function.
Methods
Resource use was measured and costs calculated. Healthcare and societal costs (healthcare plus lost production and unpaid informal care) were combined with QALYs gained, and changes in fatigue and disability; incremental cost-effectiveness ratios (ICERs) were computed.
Results
SMC patients had significantly lower healthcare costs than those receiving APT, CBT and GET. If society is willing to value a QALY at £30,000 there is a 62.7% likelihood that CBT is the most cost-effective therapy, a 26.8% likelihood that GET is most cost effective, 2.6% that APT is most cost-effective and 7.9% that SMC alone is most cost-effective. Compared to SMC alone, the incremental healthcare cost per QALY was £18,374 for CBT, £23,615 for GET and £55,235 for APT. From a societal perspective CBT has a 59.5% likelihood of being the most cost-effective, GET 34.8%, APT 0.2% and SMC alone 5.5%. CBT and GET dominated SMC, while APT had a cost per QALY of £127,047. ICERs using reductions in fatigue and disability as outcomes largely mirrored these findings.
Conclusions
Comparing the four treatments using a health care perspective, CBT had the greatest probability of being the most cost-effective followed by GET. APT had a lower probability of being the most cost-effective option than SMC alone. The relative cost-effectiveness was even greater from a societal perspective as additional cost savings due to reduced need for informal care were likely.
doi:10.1371/journal.pone.0040808
PMCID: PMC3411573  PMID: 22870204
4.  Cost-Effectiveness of Lifestyle Counselling as Primary Prevention of Gestational Diabetes Mellitus: Findings from a Cluster-Randomised Trial 
PLoS ONE  2013;8(2):e56392.
Aims
The aim was to evaluate the cost-effectiveness of primary prevention of gestational diabetes mellitus (GDM) through intensified counselling on physical activity, diet, and appropriate weight gain among the risk group.
Materials and Methods
The cost-effectiveness analysis was based on data from a cluster-randomised controlled GDM prevention trial carried out in primary health-care maternity clinics in Finland. Women (n = 399) with at least one risk factor for GDM were included. The incremental cost-effectiveness ratio (ICER) was calculated in terms of birth weight, 15D, and perceived health as measured with a visual analogue scale (VAS). A bootstrap technique for cluster-randomised samples was used to estimate uncertainty around a cost-effectiveness acceptability curve.
Results
The mean total cost in the intervention group was €7,763 (standard deviation (SD): €4,511) and in the usual-care group was €6,994 (SD: €4,326, p = 0.14). The mean intervention cost was €141. The difference for costs in the birth-weight group was €753 (95% CI: −250 to 1,818) and in effects for birth weight was 115 g (95% CI: 15 to 222). The ICER for birth weight was almost €7, with 86.7% of bootstrap pairs located in the north-east quadrant, indicating that the intervention was more effective and more expensive in birth weight terms than the usual care was. The data show an 86.7% probability that each gram of birth weight avoided requires an additional cost of €7.
Conclusions
Intervention was effective for birth weight but was not cost-effective for birth weight, 15D, or VAS when compared to the usual care.
Trial Registration
ISRCTN 33885819.
doi:10.1371/journal.pone.0056392
PMCID: PMC3574155  PMID: 23457562
5.  Cost-Effectiveness of the Diabetes Care Protocol, a Multifaceted Computerized Decision Support Diabetes Management Intervention That Reduces Cardiovascular Risk 
Diabetes Care  2009;33(2):258-263.
OBJECTIVE
The Diabetes Care Protocol (DCP), a multifaceted computerized decision support diabetes management intervention, reduces cardiovascular risk of type 2 diabetic patients. We performed a cost-effectiveness analysis of DCP from a Dutch health care perspective.
RESEARCH DESIGN AND METHODS
A cluster randomized trial provided data of DCP versus usual care. The 1-year follow-up patient data were extrapolated using a modified Dutch microsimulation diabetes model, computing individual lifetime health-related costs, and health effects. Incremental costs and effectiveness (quality-adjusted life-years [QALYs]) were estimated using multivariate generalized estimating equations to correct for practice-level clustering and confounding. Incremental cost-effectiveness ratios (ICERs) were calculated and cost-effectiveness acceptability curves were created. Stroke costs were calculated separately. Subgroup analyses examined patients with and without cardiovascular disease (CVD+ or CVD− patients, respectively).
RESULTS
Excluding stroke, DCP patients lived longer (0.14 life-years, P = NS), experienced more QALYs (0.037, P = NS), and incurred higher total costs (€1,415, P = NS), resulting in an ICER of €38,243 per QALY gained. The likelihood of cost-effectiveness given a willingness-to-pay threshold of €20,000 per QALY gained is 30%. DCP had a more favorable effect on CVD+ patients (ICER = €14,814) than for CVD− patients (ICER = €121,285). Coronary heart disease costs were reduced (€−587, P < 0.05).
CONCLUSIONS
DCP reduces cardiovascular risk, resulting in only a slight improvement in QALYs, lower CVD costs, but higher total costs, with a high cost-effectiveness ratio. Cost-effective care can be achieved by focusing on cardiovascular risk factors in type 2 diabetic patients with a history of CVD.
doi:10.2337/dc09-1232
PMCID: PMC2809259  PMID: 19933991
6.  The Healthy Steps Study: A randomized controlled trial of a pedometer-based Green Prescription for older adults. Trial protocol 
BMC Public Health  2009;9:404.
Background
Graded health benefits of physical activity have been demonstrated for the reduction of coronary heart disease, some cancers, and type-2 diabetes, and for injury reduction and improvements in mental health. Older adults are particularly at risk of physical inactivity, and would greatly benefit from successful targeted physical activity interventions.
Methods/Design
The Healthy Steps study is a 12-month randomized controlled trial comparing the efficacy of a pedometer-based Green Prescription with the conventional time-based Green Prescription in increasing and maintaining physical activity levels in low-active adults over 65 years of age. The Green Prescription interventions involve a primary care physical activity prescription with 3 follow-up telephone counselling sessions delivered by trained physical activity counsellors over 3 months. Those in the pedometer group received a pedometer and counselling based around increasing steps that can be monitored on the pedometer, while those in the standard Green Prescription group received counselling using time-based goals. Baseline, 3 month (end of intervention), and 12 month measures were assessed in face-to-face home visits with outcomes measures being physical activity (Auckland Heart Study Physical Activity Questionnaire), quality of life (SF-36 and EQ-5D), depressive symptoms (Geriatric Depression Scale), blood pressure, weight status, functional status (gait speed, chair stands, and tandem balance test) and falls and adverse events (self-report). Utilisation of health services was assessed for the economic evaluation carried out alongside this trial. As well, a process evaluation of the interventions and an examination of barriers and motives for physical activity in the sample were conducted. The perceptions of primary care physicians in relation to delivering physical activity counselling were also assessed.
Discussion
The findings from the Healthy Steps trial are due in late 2009. If successful in improving physical activity in older adults, the pedometer-based Green Prescription could assist in reducing utilisation of health services and improve cardiovascular health and reduction of risk for a range of non-communicable lifestyles diseases.
Trial registration
Australian and New Zealand Clinical Trials Registry ACTRN012606000023550
doi:10.1186/1471-2458-9-404
PMCID: PMC2780414  PMID: 19878605
7.  Review of Australian health economic evaluation – 245 interventions: what can we say about cost effectiveness? 
Background
There is an increasing body of published cost-utility analyses of health interventions which we sought to draw together to inform research and policy.
Methods
To achieve consistency in costing base and policy context, study scope was limited to Australian-based cost-effectiveness analyses. Through a comprehensive literature review we identified 245 health care interventions that met our study criteria.
Results
The median cost-effectiveness ratio was A$18,100 (~US$13,000) per QALY/DALY/LY (quality adjusted life year gained or, disability adjusted life year averted or life year gained). Some modalities tended to perform worse, such as vaccinations and diagnostics (median cost/QALY $58,000 and $68,000 respectively), than others such as allied health, lifestyle, in-patient interventions (median cost/QALY/DALY/LY all at ~A$9,000~US$6,500). Interventions addressing some diseases such as diabetes and impaired glucose tolerance or alcohol and drug dependence tended to perform well (median cost/QALY/DALY/LY < A$3,700, < US$5,000). Interventions targeting younger persons < 25 years (median cost/QALY/DALY/LY < A$41,200) tended to perform less well than those targeting adults > 25 years (median cost/QALY/DALY/LY < A$16,000). However, there was also substantial variation in the cost effectiveness of individual interventions within and across all categories.
Conclusion
For any given condition, modality or setting there are likely to be examples of interventions that are cost effective and cost ineffective. It will be important for decision makers to make decisions based on the individual merits of an intervention rather than rely on broad generalisations. Further evaluation is warranted to address gaps in the literature and to ensure that evaluations are performed in areas with greatest potential benefit.
doi:10.1186/1478-7547-6-9
PMCID: PMC2413209  PMID: 18489788
8.  Cost effectiveness analysis of a randomised trial of acupuncture for chronic headache in primary care 
BMJ : British Medical Journal  2004;328(7442):747.
Objective To evaluate the cost effectiveness of acupuncture in the management of chronic headache.
Design Cost effectiveness analysis of a randomised controlled trial.
Setting General practices in England and Wales.
Participants 401 patients with chronic headache, predominantly migraine.
Interventions Patients were randomly allocated to receive up to 12 acupuncture treatments over three months from appropriately trained physiotherapists, or to usual care alone.
Main outcome measure Incremental cost per quality adjusted life year (QALY) gained.
Results Total costs during the one year period of the study were on average higher for the acupuncture group (£403; $768; €598) than for controls (£217) because of the acupuncture practitioners' costs. The mean health gain from acupuncture during the one year of the trial was 0.021 quality adjusted life years (QALYs), leading to a base case estimate of £9180 per QALY gained. This result was robust to sensitivity analysis. Cost per QALY dropped substantially when the analysis incorporated likely QALY differences for the years after the trial.
Conclusions Acupuncture for chronic headache improves health related quality of life at a small additional cost; it is relatively cost effective compared with a number of other interventions provided by the NHS.
doi:10.1136/bmj.38033.896505.EB
PMCID: PMC381327  PMID: 15023830
9.  Cost-Effectiveness of Treating Upper Limb Spasticity Due to Stroke with Botulinum Toxin Type A: Results from the Botulinum Toxin for the Upper Limb after Stroke (BoTULS) Trial  
Toxins  2012;4(12):1415-1426.
Stroke imposes significant burdens on health services and society, and as such there is a growing need to assess the cost-effectiveness of stroke treatment to ensure maximum benefit is derived from limited resources. This study compared the cost-effectiveness of treating post-stroke upper limb spasticity with botulinum toxin type A plus an upper limb therapy programme against the therapy programme alone. Data on resource use and health outcomes were prospectively collected for 333 patients with post-stroke upper limb spasticity taking part in a randomized trial and combined to estimate the incremental cost per quality adjusted life year (QALY) gained of botulinum toxin type A plus therapy relative to therapy alone. The base case incremental cost-effectiveness ratio (ICER) of botulinum toxin type A plus therapy was £93,500 per QALY gained. The probability of botulinum toxin type A plus therapy being cost-effective at the England and Wales cost-effectiveness threshold value of £20,000 per QALY was 0.36. The point estimates of the ICER remained above £20,000 per QALY for a range of sensitivity analyses, and the probability of botulinum toxin type A plus therapy being cost-effective at the threshold value did not exceed 0.39, regardless of the assumptions made.
doi:10.3390/toxins4121415
PMCID: PMC3528253  PMID: 23342679
botulinum toxin type A; stroke; upper limb spasticity; cost-effectiveness
10.  Cost-Effectiveness Analysis of a Community Health Worker Intervention for Low-Income Hispanic Adults with Diabetes 
Introduction
The objective of our study was to estimate the long-term cost-effectiveness of a lifestyle modification program led by community health workers (CHWs) for low-income Hispanic adults with type 2 diabetes.
Methods
We forecasted disease outcomes, quality-adjusted life years (QALYs) gained, and lifetime costs associated with attaining different hemoglobin A1c (A1c) levels. Outcomes were projected 20 years into the future and discounted at a 3.0% rate. Sensitivity analyses were conducted to assess the extent to which our results were dependent on assumptions related to program effectiveness, projected years, discount rates, and costs.
Results
The incremental cost-effectiveness ratio of the intervention ranged from $10,995 to $33,319 per QALY gained when compared with usual care. The intervention was particularly cost-effective for adults with high glycemic levels (A1c > 9%). The results are robust to changes in multiple parameters.
Conclusion
The CHW program was cost-effective. This study adds to the evidence that culturally sensitive lifestyle modification programs to control diabetes can be a cost-effective way to improve health among Hispanics with diabetes, particularly among those with high A1c levels.
doi:10.5888/pcd9.120074
PMCID: PMC3475531  PMID: 22916995
11.  Health economic assessment of ferric carboxymaltose in patients with iron deficiency and chronic heart failure based on the FAIR-HF trial: an analysis for the UK 
European Journal of Heart Failure  2012;14(7):782-790.
Aims
The purpose of this study was to evaluate the cost-effectiveness of iron repletion using intravenous (i.v.) ferric carboxymaltose (FCM) in chronic heart failure (CHF) patients with iron deficiency with or without anaemia. Cost-effectiveness was studied from the perspective of the National Health Service in the UK.
Methods and results
A model-based cost-effectiveness analysis was used to compare iron repletion with FCM with no iron treatment. Using data from the FAIR-HF trial and publicly available sources and publications, per patient costs and clinical effectiveness of FCM were estimated compared with placebo. Cost assessment was based on study drug and administration costs, cost of CHF treatment, and hospital length of stay. The incremental cost-effectiveness ratio (ICER) of FCM use was expressed as cost per quality-adjusted life year (QALY) gained, and sensitivity analyses were performed on the base case. The time horizon of the analysis was 24 weeks. Mean QALYs were higher in the FCM arm (difference 0.037 QALYs; bootstrap-based 95% confidence interval 0.017–0.060). The ICER of FCM compared with placebo was €4414 per QALY gained for the FAIR-HF dosing regimen. Sensitivity analyses confirmed the base case result to be robust.
Conclusion
From the UK payers’ perspective, managing iron deficiency in CHF patients using i.v. FCM was cost-effective in this analysis. The base case ICER was clearly below the threshold of €22 200–€33 300/QALY gained (£20 000–£30 000) typically used by the UK National Institute for Health and Clinical Excellence and proved to be robust in sensitivity analysis. Improved symptoms and better quality of life contributed to this result.
doi:10.1093/eurjhf/hfs083
PMCID: PMC3380546  PMID: 22689292
Chronic heart failure; Anaemia; Iron deficiency; Cost-effectiveness analysis; Healthcare costs
12.  The cost-effectiveness of telestroke in the treatment of acute ischemic stroke 
Neurology  2011;77(17):1590-1598.
Objective:
To conduct a cost-effectiveness analysis of telestroke—a 2-way, audiovisual technology that links stroke specialists to remote emergency department physicians and their stroke patients—compared to usual care (i.e., remote emergency departments without telestroke consultation or stroke experts).
Methods:
A decision-analytic model was developed for both 90-day and lifetime horizons. Model inputs were taken from published literature where available and supplemented with western states' telestroke experiences. Costs were gathered using a societal perspective and converted to 2008 US dollars. Quality-adjusted life-years (QALYs) gained were combined with costs to generate incremental cost-effectiveness ratios (ICERs). In the lifetime horizon model, both costs and QALYs were discounted at 3% annually. Both one-way sensitivity analyses and Monte Carlo simulations were performed.
Results:
In the base case analysis, compared to usual care, telestroke results in an ICER of $108,363/QALY in the 90-day horizon and $2,449/QALY in the lifetime horizon. For the 90-day and lifetime horizons, 37.5% and 99.7% of 10,000 Monte Carlo simulations yielded ICERs <$50,000/QALY, a ratio commonly considered acceptable in the United States.
Conclusion:
When a lifetime perspective is taken, telestroke appears cost-effective compared to usual care, since telestroke costs are upfront but benefits of improved stroke care are lifelong. If barriers to use such as low reimbursement rates and high equipment costs are reduced, telestroke has the potential to diminish the striking geographic disparities of acute stroke care in the United States.
doi:10.1212/WNL.0b013e318234332d
PMCID: PMC3198982  PMID: 21917781
13.  Cost Effectiveness of Facility-Based Care, Home-Based Care and Mobile Clinics for Provision of Antiretroviral Therapy in Uganda 
Pharmacoeconomics  2009;27(11):963-973.
Background
Stakeholders in HIV/AIDS care currently use different programmes for provision of antiretroviral therapy (ART) in Uganda. It is not known which of these represents the best value for money.
Objective
To compare the cost effectiveness of home-based care (HBC), facility-based care (FBC) and mobile clinic care (MCC) for provision of ART in Uganda.
Methods
Incremental cost-effectiveness analysis was performed using decision and Markov modeling of adult AIDS patients in WHO Clinical Stage 3 and 4 from the perspective of the Ugandan healthcare system. The main outcome measures were cost (year 2008 values), life expectancy in life-years (LY) and the incremental cost-effectiveness ratio (ICER) measured as cost per QALY or LY gained over 10 years.
Results
Ten-year mean undiscounted life expectancy was lowest for FBC (3.6 LY), followed by MCC (4.3 LY) and highest for HBC (5.3 LY), while the mean discounted QALYs were also lowest for FBC (2.3), followed by MCC (2.9) and highest for HBC (3.7). The 10-year mean costs per patient were lowest for FBC ($US3212), followed by MCC ($US4782) and highest for HBC ($US7033). The ICER was lower for MCC versus FBC ($US2241 per LY and $US2615 per QALY) than for HBC versus MCC ($US2251 per LY and $US2814 per QALY). FBC remained cost effective in univariate and probabilistic sensitivity analyses.
Conclusions
FBC appears to be the most cost-effective programme for provision of ART in Uganda. This analysis supports the implementation of FBC for scale-up and sustainability of ART in Uganda. HBC and MCC would be competitive only if there is increased access, increased adherence or reduced cost.
doi:10.2165/11318230-000000000-00000
PMCID: PMC3305803  PMID: 19888795
14.  Secondary prevention after PCI: the cost-effectiveness of statin therapy in the Netherlands 
Netherlands Heart Journal  2004;12(7-8):331-336.
Background
Little is known about the cost-effectiveness of secondary prevention after percutaneous coronary intervention (PCI). The aim of this study was to estimate the cost-effectiveness of statin therapy.
Methods
A cost-effectiveness analysis was performed using data from the Lescol Intervention Prevention Study (LIPS). In the LIPS trial, patients with normal-to-moderate hypercholesterolaemia who had undergone a first PCI were randomised to receive either fluvastatin 40 mg twice-daily plus dietary counselling or dietary counselling alone. A Markov model was used to estimate the incremental costs per quality-adjusted life year (QALY) and life year gained (LYG). Costs were based on prices and reimbursed charges, utility data were drawn from literature. Monte Carlo simulations and multivariate analysis were used to assess uncertainty.
Results
Routine statin treatment costs an additional €734 (SD €686) per patient over ten years compared with controls. It resulted in an additional 0.078 (0.047) QALYs or 0.082 (0.041) LYG. The incremental costs per QALY and LYG were €9312 (€14,648) and €8954 (€16,617) respectively. Anticipating a willingness to pay of €20,000 per QALY, there is a 75.1% chance that fluvastatin treatment is cost-effective.
Conclusion
Statin therapy with fluvastatin is economically efficient with regard to reducing heart disease in the Netherlands when given routinely to all patients following PCI.
PMCID: PMC2497147
cardiac events; cost-effectiveness; fluvastatin; secondary prevention; statins
15.  Treatment of Advanced or Recurrent Cervical Cancer with Cisplatin or Cisplatin Containing Regimens: A Cost Effective Analysis 
Journal of Cancer  2012;3:454-458.
Background: Trials have demonstrated improvements in survival with adding paclitaxel (P) or topotecan (T) to cisplatin (C) for the treatment of advanced cervical cancer. We sought to evaluate the cost effectiveness of these regimens.
Methods: A decision model was developed based on Gynecologic Oncology Group (GOG) protocols 169 and 179. Arm 1 is 6 cycles of cisplatin. Arm 2 is 6 cycles of CP while arm 3 is 6 cycles of CT. Parameters include overall survival (OS), cost and complications. Sensitivity analyses were performed.
Results: The incremental cost-effectiveness ratio (ICER) for C versus CP is $13,654/quality-adjusted life-year (QALY) gained. For CT compared to C, the ICER is $152,327/QALY. When compared simultaneously, CT is dominated. At a willingness to pay (WTP) threshold of $50,000/QALY, C is the preferred option but CP is acceptable. Sensitivity analyses suggest that CT would become the preferred option if it was to improve OS to 24 months (compared to 9.4 months).
Conclusions: In this model, CP is an acceptable alternative to cisplatin for the treatment of these patients with an increase in cost of only $13,654/QALY. The addition of topotecan did not increase survival enough to justify the increased cost.
doi:10.7150/jca.4807
PMCID: PMC3520020  PMID: 23236342
cervical cancer; chemotherapy; cisplatin; paclitaxel; topotecan.
16.  Cemented, cementless, and hybrid prostheses for total hip replacement: cost effectiveness analysis 
Objective To compare the cost effectiveness of the three most commonly chosen types of prosthesis for total hip replacement.
Design Lifetime cost effectiveness model with parameters estimated from individual patient data obtained from three large national databases.
Setting English National Health Service.
Participants Adults aged 55 to 84 undergoing primary total hip replacement for osteoarthritis.
Interventions Total hip replacement using either cemented, cementless, or hybrid prostheses.
Main outcome measures Cost (£), quality of life (EQ-5D-3L, where 0 represents death and 1 perfect health), quality adjusted life years (QALYs), incremental cost effectiveness ratios, and the probability that each prosthesis type is the most cost effective at alternative thresholds of willingness to pay for a QALY gain.
Results Lifetime costs were generally lowest with cemented prostheses, and postoperative quality of life and lifetime QALYs were highest with hybrid prostheses. For example, in women aged 70 mean costs were £6900 ($11 000; €8200) for cemented prostheses, £7800 for cementless prostheses, and £7500 for hybrid prostheses; mean postoperative EQ-5D scores were 0.78, 0.80, and 0.81, and the corresponding lifetime QALYs were 9.0, 9.2, and 9.3 years. The incremental cost per QALY for hybrid compared with cemented prostheses was £2500. If the threshold willingness to pay for a QALY gain exceeded £10 000, the probability that hybrid prostheses were most cost effective was about 70%. Hybrid prostheses have the highest probability of being the most cost effective in all subgroups, except in women aged 80, where cemented prostheses were most cost effective.
Conclusions Cemented prostheses were the least costly type for total hip replacement, but for most patient groups hybrid prostheses were the most cost effective. Cementless prostheses did not provide sufficient improvement in health outcomes to justify their additional costs.
doi:10.1136/bmj.f1026
PMCID: PMC3583598  PMID: 23447338
17.  The impact of healthcare costs in the last year of life and in all life years gained on the cost-effectiveness of cancer screening 
British Journal of Cancer  2009;100(8):1240-1244.
It is under debate whether healthcare costs related to death and in life years gained (LysG) due to life saving interventions should be included in economic evaluations. We estimated the impact of including these costs on cost-effectiveness of cancer screening. We obtained health insurance, home care, nursing homes, and mortality data for 2.1 million inhabitants in the Netherlands in 1998–1999. Costs related to death were approximated by the healthcare costs in the last year of life (LastYL), by cause and age of death. Costs in LYsG were estimated by calculating the healthcare costs in any life year. We calculated the change in cost-effectiveness ratios (CERs) if unrelated healthcare costs in the LastYL or in LYsG would be included. Costs in the LastYL were on average 33% higher for persons dying from cancer than from any cause. Including costs in LysG increased the CER by €4040 in women, and by €4100 in men. Of these, €660 in women, and €890 in men, were costs in the LastYL. Including unrelated healthcare costs in the LastYL or in LYsG will change the comparative cost-effectiveness of healthcare programmes. The CERs of cancer screening programmes will clearly increase, with approximately €4000. However, because of the favourable CER's, including unrelated healthcare costs will in general have limited policy implications.
doi:10.1038/sj.bjc.6605018
PMCID: PMC2676546  PMID: 19367281
cost-effectiveness; economic evaluation; screening
18.  Cost effectiveness analysis of population-based serology screening and 13C-Urea breath test for Helicobacter pylori to prevent gastric cancer: A markov model 
AIM: To compare the costs and effectiveness of no screening and no eradication therapy, the population-based Helicobacter pylori (H pylori) serology screening with eradication therapy and 13C-Urea breath test (UBT) with eradication therapy.
METHODS: A Markov model simulation was carried out in all 237 900 Chinese males with age between 35 and 44 from the perspective of the public healthcare provider in Singapore. The main outcome measures were the costs, number of gastric cancer cases prevented, life years saved, and quality-adjusted life years (QALYs) gained from screening age to death. The uncertainty surrounding the cost-effectiveness ratio was addressed by one-way sensitivity analyses.
RESULTS: Compared to no screening, the incremental cost-effectiveness ratio (ICER) was $16 166 per life year saved or $13 571 per QALY gained for the serology screening, and $38 792 per life year saved and $32 525 per QALY gained for the UBT. The ICER was $477 079 per life year saved or $390 337 per QALY gained for the UBT compared to the serology screening. The cost-effectiveness of serology screening over the UBT was robust to most parameters in the model.
CONCLUSION: The population-based serology screening for H pylori was more cost-effective than the UBT in prevention of gastric cancer in Singapore Chinese males.
doi:10.3748/wjg.14.3021
PMCID: PMC2712169  PMID: 18494053
Cost-effectiveness analysis; Gastric cancer; Helicobacter pylori; 13C-Urea breath test; Serology
19.  Lifestyle interventions for knee pain in overweight and obese adults aged ≥45: economic evaluation of randomised controlled trial 
Objective To estimate the cost effectiveness of four different lifestyle interventions for knee pain.
Design Cost utility analysis of randomised controlled trial.
Setting Five general practices in the United Kingdom.
Participants 389 adults aged ≥45 with self reported knee pain and body mass index (BMI) ≥28.
Interventions Dietary intervention plus quadriceps strengthening exercises, dietary intervention, quadriceps strengthening exercises, and leaflet provision. Participants received home visits over a two year period.
Main outcome measure Incremental cost per quality adjusted life year (QALY) gained over two years from a health service perspective.
Results Advice leaflet was associated with a mean change in cost of −£31, and a mean QALY gain of 0.085. Both strengthening exercises and dietary intervention were more effective (0.090 and 0.133 mean QALY gain, respectively) but were not cost effective. Dietary intervention plus strengthening exercises had a mean cost of £647 and a mean QALY gain of 0.147 and was estimated to have an incremental cost of £10 469 per QALY gain (relative to leaflet provision), and a 23.1% probability of being cost effective at a £20 000/QALY threshold.
Conclusion Dietary intervention plus strengthening exercises was estimated to be cost effective for individuals with knee pain, but with a large level of uncertainty.
Trial registration ISRCTN93206785.
doi:10.1136/bmj.b2273
PMCID: PMC2728802  PMID: 19690341
20.  Cost-effectiveness of cardiac resynchronisation therapy for patients with moderate-to-severe heart failure: a lifetime Markov model 
BMJ Open  2011;1(2):e000276.
Objective
To assess the cost-effectiveness of cardiac resynchronisation therapy (CRT) both with CRT-P (biventricular pacemaker only) and with CRT-D (biventricular pacemaker with defibrillator) in patients with New York Heart Association (NYHA) functional class III/IV from a Belgian healthcare-payer perspective.
Methods
A lifetime Markov model was designed to calculate the cost–utility of both interventions. In the reference case, the treatment effect was based on the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure trial. Costs were based on real-world data. Pharmacoeconomic guidelines were applied, including probabilistic modelling and sensitivity analyses.
Results
Compared with optimal medical treatment, on average 1.31 quality-adjusted life-years (QALY) are gained with CRT-P at an additional cost of €14 700, resulting in an incremental cost-effectiveness ratio (ICER) of about €11 200/QALY. As compared with CRT-P, CRT-D treatment adds on average an additional 0.55 QALYs at an extra cost of €30 900 resulting in an ICER of €57 000/QALY. This result was very sensitive to the incremental clinical benefit of the defibrillator function on top of CRT.
Conclusions
Based on efficiency arguments, CRT-P can be recommended for NYHA class III and IV patients if there is a willingness to pay more than €11 000/QALY. Even though CRT-D may offer a survival benefit over CRT-P, the incremental clinical benefit appears to be too marginal to warrant a threefold-higher device price for CRT-D. Further clinical research should focus on the added value of CRT-D over CRT-P.
Article summary
Article focus
To assess the cost-effectiveness of cardiac resynchronisation therapy (CRT) both with CRT-P (biventricular pacemaker only) and with CRT-D (biventricular pacemaker with defibrillator).
Key messages
CRT-P can be recommended for reimbursement for New York Heart Association class III and IV patients if there is a willingness to pay more than €11 000/quality-adjusted life-year.
Current evidence is insufficient to show the superiority of CRT-D over CRT-P. With a threefold-higher device cost, CRT-D's cost-effectiveness is questionable.
Strengths and limitations
Hospital billing data of 342 Belgian CRT implantations were at our disposal for cost calculations.
The results of the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure trial were used to model the treatment effect. This happens to be the only trial that compared CRT-P as well as CRT-D versus optimal pharmacological treatment, allowing an indirect comparison to be made between CRT-P and CRT-D.
Following health economic theory, CRT-D is compared with CRT-P, not with optimal pharmacological treatment (ie, working on the cost-efficiency frontier).
A direct estimate of the added value of CRT-D versus CRT-P in patients with moderate to severe heart failure is lacking. This may be an interesting topic for further research in a randomised controlled trial, especially because of the threefold higher price for a CRT-D device versus CRT-P.
Generic utility instruments to measure quality of life are not always used in clinical trials. To support economic evaluations, it would be useful to include more systematically a generic utility instrument in the study protocol.
doi:10.1136/bmjopen-2011-000276
PMCID: PMC3211050  PMID: 22021894
21.  Cost-Effectiveness of a Telephone-Delivered Intervention for Physical Activity and Diet 
PLoS ONE  2009;4(9):e7135.
Background
Given escalating rates of chronic disease, broad-reach and cost-effective interventions to increase physical activity and improve dietary intake are needed. The cost-effectiveness of a Telephone Counselling intervention to improve physical activity and diet, targeting adults with established chronic diseases in a low socio-economic area of a major Australian city was examined.
Methodology/Principal Findings
A cost-effectiveness modelling study using data collected between February 2005 and November 2007 from a cluster-randomised trial that compared Telephone Counselling with a “Usual Care” (brief intervention) alternative. Economic outcomes were assessed using a state-transition Markov model, which predicted the progress of participants through five health states relating to physical activity and dietary improvement, for ten years after recruitment. The costs and health benefits of Telephone Counselling, Usual Care and an existing practice (Real Control) group were compared. Telephone Counselling compared to Usual Care was not cost-effective ($78,489 per quality adjusted life year gained). However, the Usual Care group did not represent existing practice and is not a useful comparator for decision making. Comparing Telephone Counselling outcomes to existing practice (Real Control), the intervention was found to be cost-effective ($29,375 per quality adjusted life year gained). Usual Care (brief intervention) compared to existing practice (Real Control) was also cost-effective ($12,153 per quality adjusted life year gained).
Conclusions/Significance
This modelling study shows that a decision to adopt a Telephone Counselling program over existing practice (Real Control) is likely to be cost-effective. Choosing the ‘Usual Care’ brief intervention over existing practice (Real Control) shows a lower cost per quality adjusted life year, but the lack of supporting evidence for efficacy or sustainability is an important consideration for decision makers. The economics of behavioural approaches to improving health must be made explicit if decision makers are to be convinced that allocating resources toward such programs is worthwhile.
Trial Registration
This paper uses data collected in a previous clinical trial registered at the Australian Clinical Trials Registry, Australian New Zealand Clinical Trials Registry: Anzcrt.org.au ACTRN012607000195459
doi:10.1371/journal.pone.0007135
PMCID: PMC2744997  PMID: 19779611
22.  Cost effectiveness of an outpatient multidisciplinary pulmonary rehabilitation programme 
Thorax  2001;56(10):779-784.
BACKGROUND—Pulmonary rehabilitation programmes improve the health of patients disabled by lung disease but their cost effectiveness is unproved. We undertook a cost/utility analysis in conjunction with a randomised controlled clinical trial of pulmonary rehabilitation versus standard care.
METHODS—Two hundred patients, mainly with chronic obstructive pulmonary disease, were randomly assigned to either an 18 visit, 6 week rehabilitation programme or standard medical management. The difference between the mean cost of 12 months of care for patients in the rehabilitation and control groups (incremental cost) and the difference between the two groups in quality adjusted life years (QALYs) gained (incremental utility) were determined. The ratio between incremental cost and utility (incremental cost/utility ratio) was calculated.
RESULTS—Each rehabilitation programme for up to 20 patients cost £12 120. The mean incremental cost of adding rehabilitation to standard care was £ -152 (95% CI -881 to 577) per patient, p=NS. The incremental utility of adding rehabilitation was 0.030 (95% CI 0.002 to 0.058) QALYs per patient, p=0.03. The point estimate of the incremental cost/utility ratio was therefore negative. The bootstrapping technique was used to model the distribution of cost/utility estimates possible from the data. A high likelihood of generating QALYs at negative or relatively low cost was indicated. The probability of the cost per QALY generated being below £0 was 0.64.
CONCLUSIONS—This outpatient pulmonary rehabilitation programme produces cost per QALY ratios within bounds considered to be cost effective and is likely to result in financial benefits to the health service.


doi:10.1136/thorax.56.10.779
PMCID: PMC1745931  PMID: 11562517
23.  The psoriatic arthritis cost evaluation study: a cost-of-illness study on tumour necrosis factor inhibitors in psoriatic arthritis patients with inadequate response to conventional therapy 
Rheumatology (Oxford, England)  2008;47(11):1664-1670.
Objective. To evaluate costs, benefits and cost–effectiveness of anti-TNF agents in PsA patients with inadequate response to conventional treatment.
Methods. A total of 107 patients, from nine Italian rheumatology centres, with different forms of PsA were given anti-TNF treatment, mainly etanercept (87%). Information on resource use, health-related quality of life, disease activity, function and laboratory values were collected at baseline and through out the 12 months of therapy. Cost (expressed in euro 2007) and utility (measured by EuroQol) before and after anti-TNF therapy initiation were compared in order to estimate the incremental cost per quality-adjusted life year (QALY) gained, and cost–effectiveness acceptability curve was calculated.
Results. At the end of 12 months, there was a significant increase in direct cost due to an increase of drug cost caused by TNF inhibitors that was only partially offset by the decrease in indirect cost. In the last 6 months of therapy, the direct cost increased by €5052, the cost for the National Health System (NHS) by €5044 and the social cost by €4638. However, a gain of 0.12 QALY resulted in a cost per QALY gained of €40 876 for the NHS and of €37 591 for the society. The acceptability curve showed that there would be a 97% likelihood that anti-TNF therapy would be considered cost-effective at willingness-to-pay threshold of €60 000 per QALY gained.
Conclusion. Cost–effectiveness ratios are within the commonly accepted willingness-to-pay threshold. These results need to be confirmed in larger samples of patients.
doi:10.1093/rheumatology/ken320
PMCID: PMC2569134  PMID: 18725374
Psoriatic arthritis; Anti-tumour necrosis factor; Cost–effectiveness; Quality-adjusted life year
24.  Applying economic evaluation to public health interventions: the case of interventions to promote physical activity 
Background
This paper explores the application of alternative approaches to economic evaluation of public health interventions, using a worked example of exercise referral schemes (ERSs).
Methods
Cost-utility (CUA) and cost-consequence analyses (CCA) were used to assess the cost-effectiveness of ERSs. For the CUA, evidence was synthesized using a decision analytic model that adopts a lifetime horizon and NHS/Personal Social Services perspective. Outcomes were expressed as incremental cost per quality-adjusted life-year (QALY). CCA was conducted from a partial-societal perspective, including health and non-healthcare costs and benefits. Outcomes were reported in natural units, such as cases of strokes or CHD avoided.
Results
Compared with usual care, the incremental cost per QALY of ERS is £20 876. Based on a cohort of 100 000 individuals, CCA estimates cost of ERS at £22 million to the healthcare provider and £12 million to participants. The benefits of ERS include additional 3900 people becoming physically active, 51 cases of CHD avoided, 16 cases of stroke avoided, 86 cases of diabetes avoided and a gain of ∼800 QALYs.
Conclusions
CCA might provide greater transparency than CUA in reporting the outcomes of public health interventions and have greater resonance with stakeholders involved in commissioning these interventions.
doi:10.1093/pubmed/fds050
PMCID: PMC3580051  PMID: 22753453
cost-consequence analysis; cost-utility analysis; economic evaluation; physical activity; public health intervention
25.  Cost effectiveness of nurse led secondary prevention clinics for coronary heart disease in primary care: follow up of a randomised controlled trial 
BMJ : British Medical Journal  2005;330(7493):707.
Objective To establish the cost effectiveness of nurse led secondary prevention clinics for coronary heart disease based on four years' follow up of a randomised controlled trial.
Design Cost effectiveness analysis.
Setting 19 general practices in north east Scotland.
Participants 1343 patients (673 in intervention group and 670 in control group, as originally randomised) aged under 80 years with a diagnosis of coronary heart disease but without terminal illness or dementia and not housebound.
Intervention Nurse led clinics to promote medical and lifestyle components of secondary prevention.
Main outcome measures Costs of clinics; overall costs to health service; and cost per life year and per quality adjusted life year (QALY) gained, expressed as incremental gain in intervention group compared with control group.
Results The cost of the intervention (clinics and drugs) was £136 ($254; €195) per patient higher (1998-9 prices) in the intervention group, but the difference in other NHS costs, although lower for the intervention group, was not statistically significant. Overall, 28 fewer deaths occurred in the intervention group leading to a gain in mean life years per patient of 0.110 and of 0.124 QALYs. The incremental cost per life year saved was £1236 and that per QALY was £1097.
Conclusion Nurse led clinics for the secondary prevention of coronary heart disease in primary care seem to be cost effective compared with most interventions in health care, with the main gains in life years saved.
doi:10.1136/bmj.38342.665417.8F
PMCID: PMC555633  PMID: 15716289

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