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1.  Cost-Effectiveness of Interventions to Promote Physical Activity: A Modelling Study 
PLoS Medicine  2009;6(7):e1000110.
Linda Cobiac and colleagues model the costs and health outcomes associated with interventions to improve physical activity in the population, and identify specific interventions that are likely to be cost-saving.
Physical inactivity is a key risk factor for chronic disease, but a growing number of people are not achieving the recommended levels of physical activity necessary for good health. Australians are no exception; despite Australia's image as a sporting nation, with success at the elite level, the majority of Australians do not get enough physical activity. There are many options for intervention, from individually tailored advice, such as counselling from a general practitioner, to population-wide approaches, such as mass media campaigns, but the most cost-effective mix of interventions is unknown. In this study we evaluate the cost-effectiveness of interventions to promote physical activity.
Methods and Findings
From evidence of intervention efficacy in the physical activity literature and evaluation of the health sector costs of intervention and disease treatment, we model the cost impacts and health outcomes of six physical activity interventions, over the lifetime of the Australian population. We then determine cost-effectiveness of each intervention against current practice for physical activity intervention in Australia and derive the optimal pathway for implementation. Based on current evidence of intervention effectiveness, the intervention programs that encourage use of pedometers (Dominant) and mass media-based community campaigns (Dominant) are the most cost-effective strategies to implement and are very likely to be cost-saving. The internet-based intervention program (AUS$3,000/DALY), the GP physical activity prescription program (AUS$12,000/DALY), and the program to encourage more active transport (AUS$20,000/DALY), although less likely to be cost-saving, have a high probability of being under a AUS$50,000 per DALY threshold. GP referral to an exercise physiologist (AUS$79,000/DALY) is the least cost-effective option if high time and travel costs for patients in screening and consulting an exercise physiologist are considered.
Intervention to promote physical activity is recommended as a public health measure. Despite substantial variability in the quantity and quality of evidence on intervention effectiveness, and uncertainty about the long-term sustainability of behavioural changes, it is highly likely that as a package, all six interventions could lead to substantial improvement in population health at a cost saving to the health sector.
Please see later in the article for Editors' Summary
Editors' Summary
The human body needs regular physical activity throughout life to stay healthy. Physical activity—any bodily movement produced by skeletal muscles that uses energy—helps to maintain a healthy body weight and to prevent or delay heart disease, stroke, type 2 diabetes, colon cancer, and breast cancer. In addition, physically active people feel better and live longer than physically inactive people. For an adult, 30 minutes of moderate physical activity—walking briskly, gardening, swimming, or cycling—at least five times a week is sufficient to promote and maintain health. But at least 60% of the world's population does not do even this modest amount of physical activity. The daily lives of people in both developed and developing countries are becoming increasingly sedentary. People are sitting at desks all day instead of doing manual labor; they are driving to work in cars instead of walking or cycling; and they are participating less in physical activities during their leisure time.
Why Was This Study Done?
In many countries, the chronic diseases that are associated with physical inactivity are now a major public-health problem; globally, physical inactivity causes 1.9 million deaths per year. Clearly, something has to be done about this situation. Luckily, there is no shortage of interventions designed to promote physical activity, ranging from individual counseling from general practitioners to mass-media campaigns. But which intervention or package of interventions will produce the optimal population health benefits relative to cost? Although some studies have examined the cost-effectiveness of individual interventions, different settings for analysis and use of different methods and assumptions make it difficult to compare results and identify which intervention approaches should be give priority by policy makers. Furthermore, little is known about the cost-effectiveness of packages of interventions. In this study, the researchers investigate the cost-effectiveness in Australia (where physical inactivity contributes to 10% of deaths) of a package of interventions designed to promote physical activity in adults using a standardized approach (ACE-Prevention) to the assessment of the cost-effectiveness of health-care interventions.
What Did the Researchers Do and Find?
The researchers selected six interventions for their study: general practitioner “prescription” of physical activity; general practitioner referral to an exercise physiologist; a mass-media campaign to promote physical activity; the TravelSmart car use reduction program; a campaign to encourage the use of pedometers to increase physical activity; and an internet-based program. Using published data on the effects of physical activity on the amount of illness and death caused by breast and colon cancer, heart disease, stroke, and type 2 diabetes and on the effectiveness of each intervention, the researchers calculated the health outcomes of each intervention in disability-adjusted life years (DALY; a year of healthy life lost because of premature death or disability) averted over the lifetime of the Australian population. They also calculated the costs associated with each intervention offset by the costs associated with the five conditions listed above. These analyses showed that the pedometer program and the mass-media campaign were likely to be the most cost-effective interventions. These interventions were also most likely to be cost-saving. Referral to an exercise physiologist was the least cost-effective intervention. The other three interventions, though unlikely to be cost-saving, were likely to be cost-effective. Finally, a package of all six interventions would be cost-effective and would avert 61,000 DALYs, a third of what could be achieved if every Australian did 30 minutes of physical activity five times a week.
What Do These Findings Mean?
As in all modeling studies, these findings depend on the quality of the data and on the assumptions included by the researchers in their calculations. Unfortunately, there was substantial variability in the quantity and quality of evidence on the effectiveness of each intervention and uncertainty about the long-term effects of each intervention. Nevertheless, the findings presented in this study suggest that the assessment of the cost-effectiveness of a combination of interventions designed to promote physical activity might provide policy makers with some guidance about the best way to reduce the burden of disease caused by physical inactivity. More specifically, for Australia, these findings suggest that the package of the six interventions considered here is likely to provide a cost-effective way to substantially improve the health of the nation.
Additional Information
Please access these Web sites via the online version of this summary at
The World Health Organization provides information about physical activity and health (in several languages); it also provides an explanation of DALYs
The US Centers for Disease Control and Prevention provides information on physical activity for different age groups and for health professionals
The UK National Health Service information source Choices also explains the benefits of regular physical activity
MedlinePlus has links to other resources about exercise and physical fitness (in English and Spanish)
The University of Queensland Web site has more information on ACE-Prevention (Assessing Cost-Effectiveness Prevention)
PMCID: PMC2700960  PMID: 19597537
2.  Estimating the cost-effectiveness of lifestyle intervention programmes to prevent diabetes based on an example from Germany: Markov modelling 
Type 2 diabetes mellitus (T2D) poses a large worldwide burden for health care systems. One possible tool to decrease this burden is primary prevention. As it is unethical to wait until perfect data are available to conclude whether T2D primary prevention intervention programmes are cost-effective, we need a model that simulates the effect of prevention initiatives. Thus, the aim of this study is to investigate the long-term cost-effectiveness of lifestyle intervention programmes for the prevention of T2D using a Markov model. As decision makers often face difficulties in applying health economic results, we visualise our results with health economic tools.
We use four-state Markov modelling with a probabilistic cohort analysis to calculate the cost per quality-adjusted life year (QALY) gained. A one-year cycle length and a lifetime time horizon are applied. Best available evidence supplies the model with data on transition probabilities between glycaemic states, mortality risks, utility weights, and disease costs. The costs are calculated from a societal perspective. A 3% discount rate is used for costs and QALYs. Cost-effectiveness acceptability curves are presented to assist decision makers.
The model indicates that diabetes prevention interventions have the potential to be cost-effective, but the outcome reveals a high level of uncertainty. Incremental cost-effectiveness ratios (ICERs) were negative for the intervention, ie, the intervention leads to a cost reduction for men and women aged 30 or 50 years at initiation of the intervention. For men and women aged 70 at initiation of the intervention, the ICER was EUR27,546/QALY gained and EUR19,433/QALY gained, respectively. In all cases, the QALYs gained were low. Cost-effectiveness acceptability curves show that the higher the willingness-to-pay threshold value, the higher the probability that the intervention is cost-effective. Nonetheless, all curves are flat. The threshold value of EUR50,000/QALY gained has a 30-55% probability that the intervention is cost-effective.
Lifestyle interventions for primary prevention of type 2 diabetes are cost-saving for men and women aged 30 or 50 years at the start of the intervention, and cost-effective for men and women aged 70 years. However, there is a high degree of uncertainty around the ICERs. With the conservative approach adopted for this model, the long-term effectiveness of the intervention could be underestimated.
PMCID: PMC3256095  PMID: 22099547
Diabetes mellitus; health care costs; health care economics and organisations; primary prevention; life style; early intervention; decision making
3.  Cost-effectiveness and cost-utility of a Web-based or print-delivered tailored intervention to promote physical activity among adults aged over fifty: an economic evaluation of the Active Plus intervention 
The adverse health effects of insufficient physical activity (PA) result in high costs to society. The economic burden of insufficient PA, which increases in our aging population, stresses the urgency for cost-effective interventions to promote PA among older adults. The current study provides insight in the cost-effectiveness and cost-utility of different versions of a tailored PA intervention (Active Plus) among adults aged over fifty.
The intervention conditions (i.e. print-delivered basic (PB; N = 439), print-delivered environmental (PE; N = 435), Web-based basic (WB; N = 423), Web-based environmental (WE; N = 432)) and a waiting-list control group were studied in a clustered randomized controlled trial. Intervention costs were registered during the trial. Health care costs, participant costs and productivity losses were identified and compared with the intervention effects on PA (in MET-hours per week) and quality-adjusted life years (QALYs) 12 months after the start of the intervention. Cost-effectiveness ratios (ICERs) and cost-utility ratios (ICURs) were calculated per intervention condition. Non-parametric bootstrapping techniques and sensitivity analyses were performed to account for uncertainty.
As a whole (i.e. the four intervention conditions together) the Active Plus intervention was found to be cost-effective. The PB-intervention (ICER = €-55/MET-hour), PE-intervention (ICER = €-94/MET-hour) and the WE-intervention (ICER = €-139/MET-hour) all resulted in higher effects on PA and lower societal costs than the control group. With regard to QALYs, the PB-intervention (ICUR = €38,120/QALY), the PE-intervention (ICUR = €405,892/QALY) and the WE-intervention (ICUR = €-47,293/QALY) were found to be cost-effective when considering a willingness-to-pay threshold of €20,000/QALY. In most cases PE had the highest probability to be cost-effective.
The Active Plus intervention was found to be a cost-effective manner to increase PA in a population aged over fifty when compared to no-intervention. The tailored Active Plus intervention delivered through printed material and with additional environmental information (PE) turned out to be the most cost-effective intervention condition as confirmed by the different sensitivity analyses. By increasing PA at relatively low costs, the Active Plus intervention can contribute to a better public health.
Trial registration
Dutch Trial Register: NTR2297
Electronic supplementary material
The online version of this article (doi:10.1186/s12966-014-0122-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4189727  PMID: 25262435
Tailored intervention; Older adults; Physical activity; Cost-effectiveness; Cost-utility; Quality of life
4.  Cryptococcal Meningitis Treatment Strategies in Resource-Limited Settings: A Cost-Effectiveness Analysis 
PLoS Medicine  2012;9(9):e1001316.
David Boulware and colleagues assess the cost effectiveness of different treatment strategies in low- and middle-income countries for cryptococcal meningitis, one of the most common opportunistic infections of people with HIV.
Cryptococcal meningitis (CM) is the most common form of meningitis in Africa. World Health Organization guidelines recommend 14-d amphotericin-based induction therapy; however, this is impractical for many resource-limited settings due to cost and intensive monitoring needs. A cost-effectiveness analysis was performed to guide stakeholders with respect to optimal CM treatment within resource limitations.
Methods and Findings:
We conducted a decision analysis to estimate the incremental cost-effectiveness ratio (ICER) of six CM induction regimens: fluconazole (800–1,200 mg/d) monotherapy, fluconazole + flucytosine (5FC), short-course amphotericin (7-d) + fluconazole, 14-d of amphotericin alone, amphotericin + fluconazole, and amphotericin + 5FC. We computed actual 2012 healthcare costs in Uganda for medications, supplies, and personnel, and average laboratory costs for three African countries. A systematic review of cryptococcal treatment trials in resource-limited areas summarized 10-wk survival outcomes. We modeled one-year survival based on South African, Ugandan, and Thai CM outcome data, and survival beyond one-year on Ugandan and Thai data. Quality-adjusted life years (QALYs) were determined and used to calculate the cost-effectiveness ratio and ICER. The cost of hospital care ranged from $154 for fluconazole monotherapy to $467 for 14 d of amphotericin + 5FC. Based on 18 studies investigating outcomes for HIV-infected individuals with CM in resource-limited settings, the estimated mean one-year survival was lowest for fluconazole monotherapy, at 40%. The cost-effectiveness ratio ranged from $20 to $44 per QALY. Overall, amphotericin-based regimens had higher costs but better survival. Short-course amphotericin (1 mg/kg/d for 7 d) with fluconazole (1,200 mg/d for14 d) had the best one-year survival (66%) and the most favorable cost-effectiveness ratio, at $20.24/QALY, with an ICER of $15.11 per additional QALY over fluconazole monotherapy. The main limitation of this study is the pooled nature of a systematic review, with a paucity of outcome data with direct comparisons between regimens.
Short-course (7-d) amphotericin induction therapy coupled with high-dose (1,200 mg/d) fluconazole is “very cost effective” per World Health Organization criteria and may be a worthy investment for policy-makers seeking cost-effective clinical outcomes. More head-to-head clinical trials are needed on treatments for this neglected tropical disease.
Please see later in the article for the Editors' Summary.
Editors' Summary
Cryptococcal meningitis, a fungal infection of the membranes around the brain and spinal cord, affects about a million people every year (most of them living in sub-Saharan Africa and Southeast Asia) and kills about 640,000 people annually. People become infected with Cryptococcus neoformans, the fungus that causes cryptococcal meningitis and which is found in soil and dirt, by breathing it in. In healthy individuals, infection rarely causes disease. But in people living with AIDS, whose immune system has been damaged by HIV infection, and in people whose immune system is compromised for other reasons, the fungus can invade and damage many organs, including the brain. Cryptococcal meningitis, the symptoms of which include fever, stiff neck, headache, and vomiting, is diagnosed by looking for the fungus in fluid taken from the spinal cord in a procedure called a lumbar puncture. Cryptococcal meningitis is treated with antifungal drugs such as amphotericin, fluconazole, and flucytosine (induction therapy); recurrence of the infection is prevented by taking fluconazole daily for life or until the immune system recovers.
Why Was This Study Done?
The World Health Organization (WHO) recommends a 14-day regimen of intravenous (injected) amphotericin and oral flucytosine or fluconazole for induction therapy of cryptococcal meningitis. Unfortunately, this regimen is impractical in many resource-limited settings because of the cost of the drugs and hospital care and the need for intensive monitoring—amphotericin is extremely toxic. Consequently, high-dose fluconazole monotherapy is the usual treatment for cryptococcal meningitis in resource-limited countries, although this regimen is much less effective. Another regimen that has improved survival in trials is flucytosine with fluconazole for two weeks. However, flucytosine is very expensive and is not licensed in most sub-Saharan African countries. Stakeholders in developing countries badly need guidance, therefore, on which induction treatment for cryptococcal meningitis they should recommend to optimize outcomes in their particular countries. In this cost-effectiveness analysis (a study that compares the costs and health effects of different interventions), the researchers use costs in Uganda to estimate the survival, cost, and cost per benefit associated with various induction treatments for cryptococcal meningitis in HIV-infected patients.
What Did the Researchers Do and Find?
The researchers calculated the overall cost of six induction treatments using 2012 healthcare costs in Uganda for medications, supplies, and hospital care, and average laboratory costs for monitoring treatment from three African countries. They used data from published trials of cryptococcal meningitis treatment in resource-limited areas to estimate ten-week and one-year survival, life expectancy, and quality-adjusted life years (QALYs, the number of years of life added by an intervention, adjusted for the quality of life) for each intervention. Finally, they calculated the cost-effectiveness ratio (cost per QALY gained) and the incremental cost effectiveness ratio (ICER, the additional cost of a treatment strategy compared to fluconazole monotherapy divided by the incremental improvement in QALYs) for each intervention. The estimated costs per person for each induction treatment strategy ranged from US$154 for 14 days of fluconazole monotherapy to US$467 for 14 days of amphotericin plus flucytosine. Estimated average one-year survival was lowest for fluconazole (40%) and highest for short-course (seven days) amphotericin plus 14 days of fluconazole (66%), similar to other amphotericin-based treatments. Cost-effectiveness ratios ranged from US$20 per QALY for short-course amphotericin plus fluconazole to US$44 per QALY for 14 days of amphotericin plus flucytosine. Short-course amphotericin plus fluconazole had the lowest ICER (US$15.11 per additional QALY over fluconazole monotherapy).
What Do These Findings Mean?
These findings suggest that, among the treatments investigated, a seven-day course of amphotericin with high-dose fluconazole for at least two weeks is the most cost-effective induction treatment for cryptococcal meningitis in Uganda. Although this result should be generalizable to other African countries, it needs to be treated with caution because very few trials have actually looked at the clinical effectiveness of this particular regimen. While short short-course amphotericin appears to be substantially more effective than fluconazole monotherapy, large-scale trials comparing short-course amphotericin regimens with more traditional 14-day regimens in resource-limited countries must be undertaken before short-course amphotericin-based treatments are adopted. Notably, however, if these trials confirm that survival with short-course amphotericin with fluconazole is about 30% better than with fluconazole alone, the researchers calculate that moving to short-course amphotericin could save about 150,000 lives every year in sub-Saharan Africa at a cost of US$220 per life saved.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLOS Medicine Perspective by Andrew Farlow provides a clearinghouse for updated guidelines for cryptococcal diagnosis and treatment.
The US Centers for Disease Control and Prevention provides information on Cryptococcus neoformans and a training manual called the Cryptococcal Screening Program Training Manual for Healthcare Providers
NAM/aidsmap provides information about all aspects of infection with Cryptococcus neoformans, including a personal story about cryptococcal meningitis
AIDS InfoNet has a fact sheet on cryptococcal meningitis (in several languages)
The not-for-profit organization Project Inform, which provides information, inspiration, and advocacy for people with HIV/AIDS and hepatitis C (in English and Spanish), has a fact sheet on cryptococcal meningitis
The MedlinePlus encyclopedia has a page on cryptococcal meningitis (in English and Spanish)
PMCID: PMC3463510  PMID: 23055838
5.  Economic Appraisal of Ontario's Universal Influenza Immunization Program: A Cost-Utility Analysis 
PLoS Medicine  2010;7(4):e1000256.
Beate Sander and colleagues assess the cost-effectiveness of the program that provides free seasonal influenza vaccines to the entire population of Ontario, Canada.
In July 2000, the province of Ontario, Canada, initiated a universal influenza immunization program (UIIP) to provide free seasonal influenza vaccines for the entire population. This is the first large-scale program of its kind worldwide. The objective of this study was to conduct an economic appraisal of Ontario's UIIP compared to a targeted influenza immunization program (TIIP).
Methods and Findings
A cost-utility analysis using Ontario health administrative data was performed. The study was informed by a companion ecological study comparing physician visits, emergency department visits, hospitalizations, and deaths between 1997 and 2004 in Ontario and nine other Canadian provinces offering targeted immunization programs. The relative change estimates from pre-2000 to post-2000 as observed in other provinces were applied to pre-UIIP Ontario event rates to calculate the expected number of events had Ontario continued to offer targeted immunization. Main outcome measures were quality-adjusted life years (QALYs), costs in 2006 Canadian dollars, and incremental cost-utility ratios (incremental cost per QALY gained). Program and other costs were drawn from Ontario sources. Utility weights were obtained from the literature. The incremental cost of the program per QALY gained was calculated from the health care payer perspective. Ontario's UIIP costs approximately twice as much as a targeted program but reduces influenza cases by 61% and mortality by 28%, saving an estimated 1,134 QALYs per season overall. Reducing influenza cases decreases health care services cost by 52%. Most cost savings can be attributed to hospitalizations avoided. The incremental cost-effectiveness ratio is Can$10,797/QALY gained. Results are most sensitive to immunization cost and number of deaths averted.
Universal immunization against seasonal influenza was estimated to be an economically attractive intervention.
Please see later in the article for the Editors' Summary
Editors' Summary
Annual outbreaks (epidemics) of influenza—a viral disease of the nose, throat, and airways—make millions of people ill and kill about 500,000 individuals every year. In doing so, they impose a considerable economic burden on society in terms of health care costs and lost productivity. Influenza epidemics occur because small but frequent changes in the viral proteins to which the immune system responds mean that an immune response produced one year by exposure to an influenza virus provides only partial protection against influenza the next year. Annual immunization with a vaccine that contains killed influenza viruses of the major circulating strains can boost this natural immunity and greatly reduce a person's chances of catching influenza. Consequently, many countries run seasonal influenza vaccine programs. These programs usually target people at high risk of complications from influenza and individuals likely to come into close contact with them, and people who provide essential community services. So, for example, in most Canadian provinces, targeted influenza immunization programs (TIIPs) offer free influenza vaccinations to people aged 65 years or older, to people with chronic medical conditions, and to health care workers.
Why Was This Study Done?
Some experts argue, however, that universal vaccination might provide populations with better protection from influenza. In 2000, the province of Ontario in Canada decided, therefore, to introduce a universal influenza immunization program (UIIP) to provide free influenza vaccination to everyone older than 6 months, the first large program of this kind in the world. A study published in 2008 showed that, following the introduction of the UIIP, vaccination rates in Ontario increased more than in other Canadian provinces. In addition, deaths from influenza and influenza-related use of health care facilities decreased more in Ontario than in provinces that continued to offer a TIIP. But is universal influenza vaccination good value for money? In this study, the researchers evaluate the cost-effectiveness of the Ontario UIIP by comparing the health outcomes and costs associated with its introduction with the health outcomes and costs associated with a hypothetical continuation of targeted influenza immunization.
What Did the Researchers Do and Find?
The researchers used data on TIIP and UIIP vaccine uptake, physician visits, emergency department visits, hospitalizations for influenza, and deaths from influenza between 1997 and 2004 in Ontario and in nine Canadian states offering TIIPs, and Ontario cost data, in their “cost-utility” analysis. This type of analysis estimates the additional cost required to generate a year of perfect health (a quality-adjusted life-year or QALY) through the introduction of an intervention. QALYs are calculated by multiplying the time spent in a certain health state by a measure of the quality of that health state. The researchers report that the cost of Ontario's UIIP was about twice as much as the cost of a TIIP for the province. However, the introduction of the UIIP reduced the number of influenza cases by nearly two-thirds and reduced deaths from influenza by more than a quarter compared with what would have been expected had the province continued to offer a TIIP, an overall saving of 1,134 QALYs. Furthermore, the reduction in influenza cases halved influenza-related health care costs, mainly because of reductions in hospitalization. Overall, this means that the additional cost to Ontario of saving one QALY through the introduction of the UIIP was Can$10,797, an “incremental cost-effectiveness ratio” of $10,797 per QALY gained.
What Do These Findings Mean?
In Canada, an intervention is considered cost-effective from the point of view of a health care purchaser if it costs less than Canadian $50,000 to gain one QALY. These findings indicate, therefore, that for Ontario the introduction of the UIIP is economically attractive. Indeed, the researchers calculate that even if the costs of the UIIP were to double, the additional cost of saving one QALY by introducing universal immunization would remain below $50,000. Other “sensitivity” analyses undertaken by the researchers also indicate that universal immunization is likely to be effective and cost-effective in Ontario if other key assumptions and/or data included in the calculations are varied within reasonable limits. Given these findings, the researchers suggest that a UIIP might be an appealing intervention in other Canadian provinces and in other high-income countries where influenza transmission and health-care costs are broadly similar to those in Ontario.
Additional Information
Please access these Web sites via the online version of this summary at
A PLoS Medicine Research Article by Kwong and colleagues describes how the introduction of universal influenza immunization in Ontario altered influenza-related health care use and deaths in the province
Wikipedia pages are available on QALYs and on cost-utility analysis (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Bandolier, an independent online journal about evidence-based health-care, provides information about QALYs and their use in cost-utility analysis
The UK National Institute for Health and Clinical Excellence has a webpage on Measuring effectiveness and cost-effectiveness: the QALY
PMCID: PMC2850382  PMID: 20386727
6.  Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease (COPD) Using an Ontario Policy Model 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at:
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-Term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at:
For more information on the economic analysis, please visit the PATH website:
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website:
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation throughout the airways, parenchyma, and pulmonary vasculature. The inflammation causes repeated cycles of injury and repair in the airway wall— inflammatory cells release a variety of chemicals and lead to cellular damage. The inflammation process also contributes to the loss of elastic recoil pressure in the lung, thereby reducing the driving pressure for expiratory flow through narrowed and poorly supported airways, in which airflow resistance is significantly increased. Expiratory flow limitation is the pathophysiological hallmark of COPD.
Exacerbations of COPD contribute considerably to morbidity and mortality, and impose a burden on the health care system. They are a leading cause of emergency room visits and hospitalizations, particularly in the winter. In Canada, the reported average cost for treating a moderate exacerbation is $641; for a major exacerbation, the cost is $10,086.
The objective of this study was to evaluate the cost-effectiveness and budget impact of the following interventions in moderate to very severe COPD, investigated in the Medical Advisory Secretariat Chronic Obstructive Pulmonary Disease Mega-Analysis Series:
smoking cessation programs in moderate COPD in an outpatient setting:
– intensive counselling (IC) versus usual care (UC)
– nicotine replacement therapy (NRT) versus UC
– IC + NRT versus placebo
– bupropion versus placebo
multidisciplinary care (MDC) teams versus UC in moderate to severe COPD in an outpatient setting
pulmonary rehabilitation (PR) versus UC following acute exacerbations in moderate to severe COPD
long-term oxygen therapy (LTOT) versus UC in severe hypoxemia in COPD in an outpatient setting
– noninvasive positive pressure ventilation (NPPV) + usual medical care versus usual medical care in acute respiratory failure due to an acute exacerbation in severe COPD in an inpatient setting
– weaning with NPPV versus weaning with invasive mechanical ventilation in acute respiratory failure due to an acute exacerbation in very severe COPD in an inpatient setting
A cost-utility analysis was conducted using a Markov probabilistic model. The model consists of different health states based on the Global Initiative for Chronic Obstructive Lung Disease COPD severity classification. Patients were assigned different costs and utilities depending on their severity health state during each model cycle. In addition to moving between health states, patients were at risk of acute exacerbations of COPD in each model cycle. During each cycle, patients could have no acute exacerbation, a minor acute exacerbation, or a major exacerbation. For the purposes of the model, a major exacerbation was defined as one that required hospitalization. Patients were assigned different costs and utilities in each model cycle, depending on whether they experienced an exacerbation, and its severity.
Starting cohorts reflected the various patient populations from the trials analyzed. Incremental cost-effectiveness ratios (ICERs)—that is, costs per quality-adjusted life-year (QALY)—were estimated for each intervention using clinical parameters and summary estimates of relative risks of (re)hospitalization, as well as mortality and abstinence rates, from the COPD mega-analysis evidence-based analyses.
A budget impact analysis was also conducted to project incremental costs already being incurred or resources already in use in Ontario. Using provincial data, medical literature, and expert opinion, health system impacts were calculated for the strategies investigated.
All costs are reported in Canadian dollars.
All smoking cessation programs were dominant (i.e., less expensive and more effective overall). Assuming a base case cost of $1,041 and $1,527 per patient for MDC and PR, the ICER was calculated to be $14,123 per QALY and $17,938 per QALY, respectively. When the costs of MDC and PR were varied in a 1-way sensitivity analysis to reflect variation in resource utilization reported in the literature, the ICER increased to $55,322 per QALY and $56,270 per QALY, respectively. Assuming a base case cost of $2,261 per year per patient for LTOT as reported by data from the Ontario provincial program, the ICER was calculated to be $38,993 per QALY. Ventilation strategies were dominant (i.e., cheaper and more effective), as reflected by the clinical evidence of significant in-hospital days avoided in the study group.
Ontario currently pays for IC through physician billing (translating to a current burden of $8 million) and bupropion through the Ontario Drug Benefit program (translating to a current burden of almost $2 million). The burden of NRT was projected to be $10 million, with future expenditures of up to $1 million in Years 1 to 3 for incident cases.
Ontario currently pays for some chronic disease management programs. Based on the most recent Family Health Team data, the costs of MDC programs to manage COPD were estimated at $85 million in fiscal year 2010, with projected future expenditures of up to $51 million for incident cases, assuming the base case cost of the program. However, this estimate does not accurately reflect the current costs to the province because of lack of report by Family Health Teams, lack of capture of programs outside this model of care by any data set in the province, and because the resource utilization and frequency of visits/follow-up phone calls were based on the findings in the literature rather than the actual Family Health Team COPD management programs in place in Ontario. Therefore, MDC resources being utilized in the province are unknown and difficult to measure.
Data on COPD-related hospitalizations were pulled from Ontario administrative data sets and based on consultation with experts. Half of hospitalized patients will access PR resources at least once, and half of these will repeat the therapy, translating to a potential burden of $17 million to $32 million, depending on the cost of the program. These resources are currently being absorbed, but since utilization is not being captured by any data set in the province, it is difficult to quantify and estimate. Provincial programs may be under-resourced, and patients may not be accessing these services effectively.
Data from the LTOT provincial program (based on fiscal year 2006 information) suggested that the burden was $65 million, with potential expenditures of up to $0.2 million in Years 1 to 3 for incident cases.
From the clinical evidence on ventilation (i.e., reduction in length of stay in hospital), there were potential cost savings to the hospitals of $42 million and $12 million for NPPV and weaning with NPPV, respectively, if the study intervention were adopted. Future cost savings were projected to be up to $4 million and $1 million, respectively, for incident cases.
Currently, costs for most of these interventions are being absorbed by provider services, the Ontario Drug Benefit Program, the Assistive Devices Program, and the hospital global budget. The most cost-effective intervention for COPD will depend on decision-makers’ willingness to pay. Lack of provincial data sets capturing resource utilization for the various interventions poses a challenge for estimating current burden and future expenditures.
PMCID: PMC3384363  PMID: 23074422
7.  Long-term health outcomes and cost-effectiveness of a computer-tailored physical activity intervention among people aged over fifty: modelling the results of a randomized controlled trial 
BMC Public Health  2014;14(1):1099.
Physical inactivity is a significant predictor of several chronic diseases, becoming more prevalent as people age. Since the aging population increases demands on healthcare budgets, effectively stimulating physical activity (PA) against acceptable costs is of major relevance. This study provides insight into long-term health outcomes and cost-effectiveness of a tailored PA intervention among adults aged over fifty.
Intervention participants (N = 1729) received tailored advice three times within four months, targeting the psychosocial determinants of PA. The intervention was delivered in different conditions (i.e. print-delivered versus Web-based, and with or without additional information on local PA opportunities). In a clustered RCT, the effects of the different intervention conditions were compared to each other and to a control group. Effects on weekly Metabolic Equivalents (MET)-hours of PA obtained one year after the intervention started were extrapolated to long-term outcomes (5-year, 10-year and lifetime horizons) in terms of health effects and quality-adjusted life years (QALYs) and its effect on healthcare costs, using a computer simulation model. Combining the model outcomes with intervention cost estimates, this study provides insight into the long-term cost-effectiveness of the intervention. Incremental cost-effectiveness ratios (ICERs) were calculated.
For all extrapolated time horizons, the printed and the Web-based intervention resulted in decreased incidence numbers for diabetes, colon cancer, breast cancer, acute myocardial infarctions, and stroke and increased QALYs as a result of increased PA. Considering a societal Willingness-to-Pay of €20,000/QALY, on a lifetime horizon the printed (ICER = €7,500/QALY) as well as the Web-based interventions (ICER = €10,100/QALY) were cost-effective. On a 5-year time horizon, the Web-based intervention was preferred over the printed intervention. On a 10-year and lifetime horizon, the printed intervention was the preferred intervention condition, since the monetary savings of the Web-based intervention did no longer outweigh its lower effects. Adding environmental information resulted in a lower cost-effectiveness.
A tailored PA intervention in a printed delivery mode, without environmental information, has the most potential for being cost-effective in adults aged over 50.
Trial registration
The current study was registered at the Dutch Trial Register (NTR2297; April 26th 2010).
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2458-14-1099) contains supplementary material, which is available to authorized users.
PMCID: PMC4221676  PMID: 25342517
Cost-effectiveness; Modelling; Quality of life; Disease incidence; Physical activity; Tailored intervention; Print-delivered; Web-based
8.  Effectiveness and Cost Effectiveness of Expanding Harm Reduction and Antiretroviral Therapy in a Mixed HIV Epidemic: A Modeling Analysis for Ukraine 
PLoS Medicine  2011;8(3):e1000423.
A cost-effectiveness study by Sabina Alistar and colleagues evaluates the effectiveness and cost effectiveness of different levels of investment in methadone, ART, or both, in the mixed HIV epidemic in Ukraine.
Injection drug use (IDU) and heterosexual virus transmission both contribute to the growing mixed HIV epidemics in Eastern Europe and Central Asia. In Ukraine—chosen in this study as a representative country—IDU-related risk behaviors cause half of new infections, but few injection drug users (IDUs) receive methadone substitution therapy. Only 10% of eligible individuals receive antiretroviral therapy (ART). The appropriate resource allocation between these programs has not been studied. We estimated the effectiveness and cost-effectiveness of strategies for expanding methadone substitution therapy programs and ART in mixed HIV epidemics, using Ukraine as a case study.
Methods and Findings
We developed a dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs using opiates, and IDUs on methadone substitution therapy, stratified by HIV status, and populated it with data from the Ukraine. We considered interventions expanding methadone substitution therapy, increasing access to ART, or both. We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, infections averted, and incremental cost-effectiveness. Without incremental interventions, HIV prevalence reached 67.2% (IDUs) and 0.88% (non-IDUs) after 20 years. Offering methadone substitution therapy to 25% of IDUs reduced prevalence most effectively (to 53.1% IDUs, 0.80% non-IDUs), and was most cost-effective, averting 4,700 infections and adding 76,000 QALYs compared with no intervention at US$530/QALY gained. Expanding both ART (80% coverage of those eligible for ART according to WHO criteria) and methadone substitution therapy (25% coverage) was the next most cost-effective strategy, adding 105,000 QALYs at US$1,120/QALY gained versus the methadone substitution therapy-only strategy and averting 8,300 infections versus no intervention. Expanding only ART (80% coverage) added 38,000 QALYs at US$2,240/QALY gained versus the methadone substitution therapy-only strategy, and averted 4,080 infections versus no intervention. Offering ART to 80% of non-IDUs eligible for treatment by WHO criteria, but only 10% of IDUs, averted only 1,800 infections versus no intervention and was not cost effective.
Methadone substitution therapy is a highly cost-effective option for the growing mixed HIV epidemic in Ukraine. A strategy that expands both methadone substitution therapy and ART to high levels is the most effective intervention, and is very cost effective by WHO criteria. When expanding ART, access to methadone substitution therapy provides additional benefit in infections averted. Our findings are potentially relevant to other settings with mixed HIV epidemics.
Please see later in the article for the Editors' Summary
Editors' Summary
HIV epidemics in Eastern Europe and Central Asia are mainly driven by increasing use of injection drugs combined with heterosexual transmission. In the Ukraine, in 2007, there were 82,000 officially registered people living with HIV—three times the number registered in 1999—and an estimated 395,000 HIV infected adults. The epidemic in Ukraine, like other countries in the region, is concentrated in at-risk populations, particularly people who inject drugs: in 2007, an estimated 390,000 Ukrainians were injecting drugs, an increase in drug use over the previous decade, not only in Ukraine, but in other former USSR states, owing to the easy availability of precursors for injection drugs in a climate of economic collapse.
The common practices of people who inject drugs in Ukraine and in other countries in the region, such as social injecting, syringe sharing, and using common containers, increase the risk of transmitting HIV. Public health interventions such as needle exchange can limit these risk factors and have been gradually implemented in these countries. In 2007, Ukraine approved the use of methadone substitution therapy and the current target is for 11,000 people who inject drugs to be enrolled in substitution therapy by 2011. Furthermore, since treatment for HIV-infected individuals is also necessary, national HIV control plans included a target of 90% antiretroviral therapy (ART) coverage by 2010 but in 2007 less than 10% of the 91,000 eligible people received treatment. Although the number of people who inject drugs and who receive ART is unknown, physicians are often reluctant to treat people who inject drugs using ART owing to alleged poor compliance.
Why Was This Study Done?
As resources for HIV interventions in the region are limited, it is important to investigate the appropriate balance between investments in methadone substitution therapy and ART in order to maximize benefits to public health. Several studies have analyzed the cost effectiveness of methadone substitution therapy in similar settings but have not considered tradeoffs between ART and methadone substitution therapy. Therefore, to provide insights into the appropriate public health investment in methadone substitution therapy and ART in Ukraine, the researchers evaluated the public health effectiveness and cost effectiveness of different strategies for scaling up methadone substitution therapy and/or expanding ART.
What Did the Researchers Do and Find?
The researchers developed a model to accommodate different population groups: people who inject drugs on substitution therapy with methadone; people who inject opiates and do not take any substitution therapy; and people who do not inject any drugs, hence do not need substitution therapy. The researchers inputted Ukraine country-level data into this model and used current HIV trends in Ukraine to make rational assumptions on possible future trends and scenarios. They considered scenarios expanding methadone substitution therapy availability, increasing acces to ART, or both. Then, the researchers measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, infections averted, and incremental cost effectiveness for the different scenarios. They found that after 20 years, HIV prevalence reached 67.2% in people who inject drugs and 0.88% in people who do not inject drugs without further interventions. Offering methadone substitution therapy to 25% of people who inject drugs was the most effective strategy in reducing prevalence of HIV and was also the most cost effective, averting 4,700 infections and adding 75,700 QALYs versus the status quo at $530/QALY gained. Expanding both methadone substitution therapy and ART was also a highly cost effective option, adding 105,000 QALYs at US$1,120/QALY gained versus the methadone substitution therapy-only strategy. Offering ART to 80% of eligible people who did not inject drugs, and 10% of people who injected drugs averted only 1,800 infections, and added 76,400 QALYs at $1,330/QALY gained.
What Do These Findings Mean?
The results show that methadone substitution-focused therapeutic scenarios are the most cost effective, and that benefits increase with the scale of the project, even among people who do not inject drugs. This makes a methadone substitution strategy a highly cost-effective option for addressing the growing HIV epidemic in Ukraine. Therefore, if it is not feasible to invest in large-scale methadone substitution programs for any reason, political circumstances for example, providing as much methadone substitution as is acceptable is still desirable. While substitution therapy appears to avert the most HIV infections, expanded ART provides the largest total increase in QALYs. Thus, methadone substitution therapy and ART offer complementary benefits. Because the HIV epidemic in Ukraine is representative of the HIV epidemic in Eastern Europe and Central Asia, the cost-effective strategies that the researchers have identified may help inform all decision makers faced with a mixed HIV epidemic.
Additional Information
Please access these Web sites via the online version of this summary at
Alliance provides information on its work supporting community action on AIDS in Ukraine
USAID provides an HIV/AIDS Health Profile for Ukraine
UNICEF provides information about its activities to help Ukraine fight rising HIV/AIDS infection rates
International Harm Reduction Association provides information about the status of harm reduction interventions such as methadone substitution therapy around the world
PMCID: PMC3046988  PMID: 21390264
9.  The cost-effectiveness of exercise referral schemes 
BMC Public Health  2011;11:954.
Exercise referral schemes (ERS) aim to identify inactive adults in the primary care setting. The primary care professional refers the patient to a third party service, with this service taking responsibility for prescribing and monitoring an exercise programme tailored to the needs of the patient. This paper examines the cost-effectiveness of ERS in promoting physical activity compared with usual care in primary care setting.
A decision analytic model was developed to estimate the cost-effectiveness of ERS from a UK NHS perspective. The costs and outcomes of ERS were modelled over the patient's lifetime. Data were derived from a systematic review of the literature on the clinical and cost-effectiveness of ERS, and on parameter inputs in the modelling framework. Outcomes were expressed as incremental cost per quality-adjusted life-year (QALY). Deterministic and probabilistic sensitivity analyses investigated the impact of varying ERS cost and effectiveness assumptions. Sub-group analyses explored the cost-effectiveness of ERS in sedentary people with an underlying condition.
Compared with usual care, the mean incremental lifetime cost per patient for ERS was £169 and the mean incremental QALY was 0.008, generating a base-case incremental cost-effectiveness ratio (ICER) for ERS at £20,876 per QALY in sedentary individuals without a diagnosed medical condition. There was a 51% probability that ERS was cost-effective at £20,000 per QALY and 88% probability that ERS was cost-effective at £30,000 per QALY. In sub-group analyses, cost per QALY for ERS in sedentary obese individuals was £14,618, and in sedentary hypertensives and sedentary individuals with depression the estimated cost per QALY was £12,834 and £8,414 respectively. Incremental lifetime costs and benefits associated with ERS were small, reflecting the preventative public health context of the intervention, with this resulting in estimates of cost-effectiveness that are sensitive to variations in the relative risk of becoming physically active and cost of ERS.
ERS is associated with modest increase in lifetime costs and benefits. The cost-effectiveness of ERS is highly sensitive to small changes in the effectiveness and cost of ERS and is subject to some significant uncertainty mainly due to limitations in the clinical effectiveness evidence base.
PMCID: PMC3268756  PMID: 22200193
10.  Cost-Effectiveness of Pooled Nucleic Acid Amplification Testing for Acute HIV Infection after Third-Generation HIV Antibody Screening and Rapid Testing in the United States: A Comparison of Three Public Health Settings 
PLoS Medicine  2010;7(9):e1000342.
Angela Hutchinson and colleagues conducted a cost-effectiveness analysis of pooled nucleic acid amplification testing following HIV testing and show that it is not cost-effective at recommended antibody testing intervals for high-risk persons except in very high-incidence settings.
Detection of acute HIV infection (AHI) with pooled nucleic acid amplification testing (NAAT) following HIV testing is feasible. However, cost-effectiveness analyses to guide policy around AHI screening are lacking; particularly after more sensitive third-generation antibody screening and rapid testing.
Methods and Findings
We conducted a cost-effectiveness analysis of pooled NAAT screening that assessed the prevention benefits of identification and notification of persons with AHI and cases averted compared with repeat antibody testing at different intervals. Effectiveness data were derived from a Centers for Disease Control and Prevention AHI study conducted in three settings: municipal sexually transmitted disease (STD) clinics, a community clinic serving a population of men who have sex with men, and HIV counseling and testing sites. Our analysis included a micro-costing study of NAAT and a mathematical model of HIV transmission. Cost-effectiveness ratios are reported as costs per quality-adjusted life year (QALY) gained in US dollars from the societal perspective. Sensitivity analyses were conducted on key variables, including AHI positivity rates, antibody testing frequency, symptomatic detection of AHI, and costs. Pooled NAAT for AHI screening following annual antibody testing had cost-effectiveness ratios exceeding US$200,000 per QALY gained for the municipal STD clinics and HIV counseling and testing sites and was cost saving for the community clinic. Cost-effectiveness ratios increased substantially if the antibody testing interval decreased to every 6 months and decreased to cost-saving if the testing interval increased to every 5 years. NAAT was cost saving in the community clinic in all situations. Results were particularly sensitive to AHI screening yield.
Pooled NAAT screening for AHI following negative third-generation antibody or rapid tests is not cost-effective at recommended antibody testing intervals for high-risk persons except in very high-incidence settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Since 1981, acquired immunodeficiency syndrome (AIDS) has killed about 25 million people and about 30 million people are now infected with the human immunodeficiency virus (HIV), which causes AIDS. HIV, which is most often transmitted through unprotected sex with an infected partner or injection drug use, infects and kills immune system cells, leaving infected individuals susceptible to other infectious diseases. The first, often undiagnosed stage of HIV infection—acute HIV infection (AHI)—lasts a few weeks and sometimes involves a flu-like illness. During AHI, the immune system responds to HIV by beginning to make antibodies that recognize the virus but seroconversion—the appearance of detectable amounts of antibody in the blood—takes 6–12 weeks. During the second, symptom-free stage of HIV infection, which can last many years, the virus gradually destroys the immune system so that by the third stage of infection unusual infections (for example, persistent yeast infections) begin to occur. The final stage of infection (AIDS) is characterized by multiple severe infections and by the development of unusual cancers.
Why Was This Study Done?
Antiretroviral drugs control HIV infections but don't cure them. It is very important, therefore, to prevent HIV transmission by avoiding HIV risk behaviors that increase the risk of HIV infection such as having sex without a condom or with many partners. Individuals with AHI in particular need to avoid high-risk behaviors because these people are extremely infectious. However, routine tests for HIV infection that measure antibodies in the blood often give false-negative results in people with AHI because of the time lag between infection and seroconversion. Nucleic acid amplification testing (NAAT), which detects HIV genetic material in the blood, is a more accurate way to diagnose AHI but is expensive. In this study, the researchers investigate whether pooled NAAT screening (specimens are pooled before testing to reduce costs) for AHI in clinic settings after third-generation antibody testing is a cost-effective HIV prevention strategy. That is, does the gain in quality-adjusted life years (QALY, a measure of the quantity and quality of life generated by healthcare interventions) achieved by averting new HIV infections outweigh the costs of pooled NAAT screening?
What Did the Researchers Do and Find?
The researchers combined effectiveness data from a US study in which AHI was detected using pooled NAAT in three settings (sexually transmitted disease [STD] clinics, a community clinic serving men who have sex with men [MSM], and HIV counseling/testing sites) with a “micro-costing” study of NAAT and a mathematical model of HIV transmission. They then calculated the costs per QALY gained (the cost-effectiveness ratio) as a result of HIV prevention by identification and notification of people with AHI through pooled NAAT screening compared with repeat antibody testing. Pooled NAAT for AHI screening following annual antibody testing (the recommended testing interval for high-risk individuals), they estimate, would cost US$372,300 and US$484,400 per QALY gained for the counseling/testing sites and STD clinics, respectively, whereas pooled NAAT for AHI screening was cost-saving for the community clinic serving MSM. The cost-effectiveness ratio increased for the counseling/testing sites and STD clinics when the antibody testing interval was decreased to 6 months but remained cost-saving for the community clinic. With an antibody testing interval of 5 years, pooled NAAT was cost-saving in all three settings.
What Do These Findings Mean?
Cost-effectiveness ratios of US$100,000–US$200,000 are considered acceptable in the US. These results suggest therefore, that the cost of pooled NAAT screening for AHI following negative third-generation antibody testing is not acceptable at the recommended testing interval for high-risk individuals except in settings where HIV infection is very common such as clinics serving MSM. The researchers reach a similar conclusion in a separate cost-effectiveness analysis of pooled NAAT screening following a negative rapid HIV test. Although the accuracy of these results depends on numerous assumptions made in the cost-effectiveness analyses (for example, the degree to which awareness of HIV status affects the behavior of people with AHI), sensitivity analyses (investigations of the effect of altering key assumptions) show that these findings are not greatly affected by changes in many of these assumptions. Thus, the researchers conclude, NAAT screening should be reserved for settings that serve populations in which there are very high levels of new HIV infection.
Additional Information
Please access these Web sites via the online version of this summary at
The US Centers for Disease Control and Prevention provides information on HIV infection and AIDS and on HIV testing and diagnosis
HIV InSite has information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS nonprofit organization on many aspects of HIV/AIDS, including HIV testing (in English and Spanish)
MedlinePlus has links to further resources on AIDS (in English and Spanish)
The UK National Institute of Health and Clinical Excellence has a page on measuring effectiveness and cost-effectiveness
PMCID: PMC2946951  PMID: 20927354
11.  Cost Effectiveness of New Oral Anticoagulants for Stroke Prevention in Patients with Atrial Fibrillation in Two Different European Healthcare Settings 
Our objectives were to investigate the cost effectiveness of apixaban, rivaroxaban, and dabigatran compared with coumarin derivatives for stroke prevention in patients with atrial fibrillation in a country with specialized anticoagulation clinics (the Netherlands) and in a country without these clinics (the UK).
A decision-analytic Markov model was used to analyse the cost effectiveness of apixaban, rivaroxaban, and dabigatran compared with coumarin derivatives in the Netherlands and the UK over a lifetime horizon.
In the Netherlands, the use of rivaroxaban, apixaban, or dabigatran increased health by 0.166, 0.365, and 0.374 quality-adjusted life-years (QALYs) compared with coumarin derivatives, but also increased costs by €5,681, €4,754, and €5,465, respectively. The incremental cost-effectiveness ratios (ICERs) were €34,248, €13,024, and €14,626 per QALY gained. In the UK, health was increased by 0.302, 0.455, and 0.461 QALYs, and the incremental costs were similar for all three new oral anticoagulants (€5,118–5,217). The ICERs varied from €11,172 to 16,949 per QALY gained. In the Netherlands, apixaban had the highest chance (37 %) of being cost effective at a threshold of €20,000; in the UK, this chance was 41 % for dabigatran. The quality of care, reflected in time in therapeutic range, had an important influence on the ICER.
Apixaban, rivaroxaban, and dabigatran are cost-effective alternatives to coumarin derivatives in the UK, while in the Netherlands, only apixaban and dabigatran could be considered cost effective. The cost effectiveness of the new oral anticoagulants is largely dependent on the setting and quality of local anticoagulant care facilities.
Electronic supplementary material
The online version of this article (doi:10.1007/s40256-014-0092-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4250561  PMID: 25326294
12.  Cost-effectiveness of ticagrelor versus clopidogrel for the prevention of atherothrombotic events in adult patients with acute coronary syndrome in Germany 
The aim of this health economic analysis was to compare the cost-effectiveness of ticagrelor versus clopidogrel within the German health care system. A two-part decision model was adapted to compare treatment with ticagrelor or clopidogrel in a low-dose acetylsalicylic acid (ASA) cohort (≤150 mg) for all ACS patients and subtypes NSTEMI/IA and STEMI. A decision-tree approach was chosen for the first year after initial hospitalization based on trial observations from a subgroup of the PLATO study. Subsequent years were estimated by a Markov model. Following a macro-costing approach, costs were based on official tariffs and published literature. Extensive sensitivity analyses were performed to test the robustness of the model. One-year treatment with ticagrelor is associated with an estimated 0.1796 life-years gained (LYG) and gained 0.1570 quality-adjusted life-years (QALY), respectively, over the lifetime horizon. Overall average cost with ticagrelor is estimated to be EUR 11,815 vs. EUR 11,387 with generic clopidogrel over a lifetime horizon. The incremental cost-effectiveness ratio (ICER) was EUR 2,385 per LYG (EUR 2,728 per QALY). Comparing ticagrelor with Plavix® or the lowest priced generic clopidogrel, ICER ranges from dominant to EUR 3,118 per LYG (EUR 3,567 per QALY). These findings are robust under various additional sensitivity analyses. Hence, 12 months of ACS treatment using ticagrelor/ASA instead of clopidogrel/ASA may offer a cost-effective therapeutic option, even when the generic price for clopidogrel is employed.
Electronic supplementary material
The online version of this article (doi:10.1007/s00392-013-0552-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4269206  PMID: 23474908
Cost-effectiveness; Ticagrelor; Acute coronary syndrome; Prevention; Long-term impact; Germany
13.  Cost-Effectiveness Analysis of Acupuncture, Counselling and Usual Care in Treating Patients with Depression: The Results of the ACUDep Trial 
PLoS ONE  2014;9(11):e113726.
New evidence on the clinical effectiveness of acupuncture plus usual care (acupuncture) and counselling plus usual care (counselling) for patients with depression suggests the need to investigate the health-related quality of life and costs of these treatments to understand whether they should be considered a good use of limited health resources.
Methods and Findings
The cost-effectiveness analyses are based on the Acupuncture, Counselling or Usual care for Depression (ACUDep) trial results. Statistical analyses demonstrate a difference in mean quality adjusted life years (QALYs) and suggest differences in mean costs which are mainly due to the price of the interventions. Probabilistic sensitivity analysis is used to express decision uncertainty. Acupuncture and counselling are found to have higher mean QALYs and costs than usual care. In the base case analysis acupuncture has an incremental cost-effectiveness ratio (ICER) of £4,560 per additional QALY and is cost-effective with a probability of 0.62 at a cost-effectiveness threshold of £20,000 per QALY. Counselling compared with acupuncture is more effective and more costly with an ICER of £71,757 and a probability of being cost-effective of 0.36. A scenario analysis of counselling versus usual care, excluding acupuncture as a comparator, results in an ICER of £7,935 and a probability of 0.91.
Acupuncture is cost-effective compared with counselling or usual care alone, although the ranking of counselling and acupuncture depends on the relative cost of delivering these interventions. For patients in whom acupuncture is unavailable or perhaps inappropriate, counselling has an ICER less than most cost-effectiveness thresholds. However, further research is needed to determine the most cost-effective treatment pathways for depressed patients when the full range of available interventions is considered.
PMCID: PMC4245224  PMID: 25426637
14.  Economic savings versus health losses: The cost-effectiveness of generic antiretroviral therapy in the United States 
Annals of internal medicine  2013;158(2):84-92.
US HIV treatment guidelines recommend branded once-daily, one-pill efavirenz/emtricitabine/tenofovir as preferred first-line antiretroviral treatment (ART). With the anticipated approval of generic efavirenz in 2012 in the US, the cost of a once-daily, three-pill alternative (generic efavirenz, generic lamivudine, tenofovir) will decrease, but adherence and virologic suppression may be reduced.
To assess the clinical impact, costs, and cost-effectiveness of the generic-based three-pill regimen compared to the branded, co-formulated regimen. To project the potential national savings in the first year of a switch to generic-based ART.
Mathematical simulation of HIV disease.
Data Sources
Published data from US clinical trials and observational cohorts.
Target Population
HIV-infected patients eligible to start on or switch to an efavirenz-based generic ART regimen.
Time Horizon
Lifetime, One-year
US health system
No ART (for comparison), Three-pill Generic ART, and Branded ART
Outcome Measures
Quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICER, $/quality-adjusted life expectancy [QALY]).
Results of Base-Case Analysis
Compared to No ART, Generic ART has an ICER of $21,100/QALY. Compared to Generic ART, Branded ART increases lifetime costs by $42,500, and per-person survival gains by 0.37 QALYs, for an ICER of $114,800/QALY. Estimated first-year savings, if all eligible US patients start on or switch to Generic ART, are $920 million.
Results of Sensitivity Analysis
Most plausible assumptions about Generic ART efficacy and costs lead to Branded ART ICERs >$100,000/QALY.
The efficacy and price reduction associated with generics are unknown; estimates are intended to be conservative.
Compared to a slightly less effective generic-based regimen, the cost-effectiveness of first-line Branded ART exceeds $100,000/QALY. Generic-based ART in the US could yield substantial budgetary savings to HIV programs.
PMCID: PMC3664029  PMID: 23318310
15.  Is brief advice in primary care a cost-effective way to promote physical activity? 
This study models the cost-effectiveness of brief advice (BA) in primary care for physical activity (PA) addressing the limitations in the current limited economic literature through the use of a time-based modelling approach.
A Markov model was used to compare the lifetime costs and outcomes of a cohort of 100 000 people exposed to BA versus usual care. Health outcomes were expressed in terms of quality-adjusted life years (QALYs). Costs were assessed from a health provider perspective (£2010/11 prices). Data to populate the model were derived from systematic literature reviews and the literature searches of economic evaluations that were conducted for national guidelines. Deterministic and probability sensitivity analyses explored the uncertainty in parameter estimates including short-term mental health gains associated with PA.
Compared with usual care, BA is more expensive, incurring additional costs of £806 809 but it is more effective leading to 466 QALYs gained in the total cohort, a QALY gain of 0.0047/person. The incremental cost per QALY of BA is £1730 (including mental health gains) and thus can be considered cost-effective at a threshold of £20 000/QALY. Most changes in assumptions resulted in the incremental cost-effectiveness ratio (ICER) falling at or below £12 000/QALY gained. However, when short-term mental health gains were excluded the ICER was £27 000/QALY gained. The probabilistic sensitivity analysis showed that, at a threshold of £20 000/QALY, there was a 99.9% chance that BA would be cost-effective.
BA is a cost-effective way to improve PA among adults, provided short-term mental health gains are considered. Further research is required to provide more accurate evidence on factors contributing to the cost-effectiveness of BA.
PMCID: PMC3913207  PMID: 24352807
Health promotion through physical activity
16.  A lesson in business: cost-effectiveness analysis of a novel financial incentive intervention for increasing physical activity in the workplace 
BMC Public Health  2013;13:953.
Recently both the UK and US governments have advocated the use of financial incentives to encourage healthier lifestyle choices but evidence for the cost-effectiveness of such interventions is lacking. Our aim was to perform a cost-effectiveness analysis (CEA) of a quasi-experimental trial, exploring the use of financial incentives to increase employee physical activity levels, from a healthcare and employer’s perspective.
Employees used a 'loyalty card’ to objectively monitor their physical activity at work over 12 weeks. The Incentive Group (n=199) collected points and received rewards for minutes of physical activity completed. The No Incentive Group (n=207) self-monitored their physical activity only. Quality of life (QOL) and absenteeism were assessed at baseline and 6 months follow-up. QOL scores were also converted into productivity estimates using a validated algorithm. The additional costs of the Incentive Group were divided by the additional quality adjusted life years (QALYs) or productivity gained to calculate incremental cost effectiveness ratios (ICERs). Cost-effectiveness acceptability curves (CEACs) and population expected value of perfect information (EVPI) was used to characterize and value the uncertainty in our estimates.
The Incentive Group performed more physical activity over 12 weeks and by 6 months had achieved greater gains in QOL and productivity, although these mean differences were not statistically significant. The ICERs were £2,900/QALY and £2,700 per percentage increase in overall employee productivity. Whilst the confidence intervals surrounding these ICERs were wide, CEACs showed a high chance of the intervention being cost-effective at low willingness-to-pay (WTP) thresholds.
The Physical Activity Loyalty card (PAL) scheme is potentially cost-effective from both a healthcare and employer’s perspective but further research is warranted to reduce uncertainty in our results. It is based on a sustainable “business model” which should become more cost-effective as it is delivered to more participants and can be adapted to suit other health behaviors and settings. This comes at a time when both UK and US governments are encouraging business involvement in tackling public health challenges.
PMCID: PMC3852549  PMID: 24112295
Physical activity; Cost-effectiveness analysis; Financial incentives; Workplace intervention
17.  Economic evaluation of the artificial liver support system MARS in patients with acute-on-chronic liver failure 
Acute-on-chronic liver failure (ACLF) is a life threatening acute decompensation of a pre-existing chronic liver disease. The artificial liver support system MARS is a new emerging therapeutic option possible to be implemented in routine care of these patients. The medical efficacy of MARS has been demonstrated in first clinical studies, but economic aspects have so far not been investigated. Objective of this study was to estimate the cost-effectiveness of MARS.
In a clinical cohort trial with a prospective follow-up of 3 years 33 ACLF-patients treated with MARS were compared to 46 controls. Survival, health-related quality of life as well as direct medical costs for in- and outpatient treatment from a health care system perspective were determined. Based on the differences in outcome and indirect costs the cost-effectiveness of MARS expressed as incremental costs per life year gained and incremental costs per QALY gained was estimated.
The average initial intervention costs for MARS were 14600 EUR per patient treated. Direct medical costs over 3 years follow up were overall 40000 EUR per patient treated with MARS respectively 12700 EUR in controls. The 3 year survival rate after MARS was 52% compared to 17% in controls. Kaplan-Meier analysis of cumulated survival probability showed a highly significant difference in favour of MARS. Incremental costs per life-year gained were 31400 EUR; incremental costs per QALY gained were 47200 EUR.
The results after 3 years follow-up of the first economic evaluation study of MARS based on empirical patient data are presented. Although high initial treatment costs for MARS occur the significantly better survival seen in this study led to reasonable costs per live year gained. Further randomized controlled trials investigating the medical efficacy and the cost-effectiveness are recommended.
PMCID: PMC1601969  PMID: 17022815
18.  Targeted rotavirus vaccination of high-risk infants; a low cost and highly cost-effective alternative to universal vaccination 
BMC Medicine  2013;11:112.
The cost-effectiveness of universal rotavirus (RV) vaccination is controversial in developed countries. As a result, RV vaccination programs do not currently exist in most European countries. Hospitalization is the main driver of RV disease costs, and prematurity, low birth weight (LBW) and underlying medical conditions have been associated with RV hospitalization and complications. We investigated the cost-effectiveness of targeted RV vaccination of high-risk infants and universal RV vaccination versus no vaccination.
Disease burden, mortality and healthcare costs of RV hospitalization for children with and without prematurity, LBW and congenital pathology were quantified in two hospital-based observational studies in the Netherlands. Cost-effectiveness analysis was based on an age-structured stochastic multi-cohort model of the Dutch population comparing universal RV vaccination and targeted vaccination of high-risk infants to no vaccination. The primary endpoint was the incremental cost-effectiveness ratio (ICER), with a threshold of €35,000/quality-adjusted life year (QALY) from the healthcare provider perspective. Sensitivity analyses included vaccine price and coverage, herd-immunity and QALY losses.
A total of 936 children with RV infection were included. Prematurity, LBW and congenital pathology were associated with increased risks of RV hospitalization (relative risks (RR) ranging from 1.6 to 4.4), ICU admission (RR ranging from 4.2 to 7.9), prolonged hospital stay (1.5 to 3.0 excess days) and higher healthcare costs (€648 to €1,533 excess costs). Seven children succumbed due to RV complications, all belonging to the high-risk population. Targeted RV vaccination was highly cost-effective and potentially cost-saving from the healthcare provider perspective with ICERs below €20,000/QALY in all scenarios with total (undiscounted) annual healthcare costs between -€0.1 and €0.5 million/year. Results were most sensitive to mortality rates, but targeted vaccination remained highly cost-effective up to reductions of 90% compared to observed mortality. Universal RV vaccination was not considered cost-effective (mean ICER: €60,200/QALY) unless herd-immunity and caretaker QALY losses were included and vaccine prices were €60 at most (mean ICER: €21,309/QALY).
We recommend targeted RV vaccination for high-risk infants in developed countries.
PMCID: PMC3665442  PMID: 23622110
Rotavirus vaccination; Cost-effectiveness; Cost-utility; High-risk population; Targeted prevention; Hospitalization; Nosocomial infection; Mortality
19.  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.
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.
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).
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).
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.
PMCID: PMC2809259  PMID: 19933991
20.  Cost-Effectiveness of Lifestyle Modification in Diabetic Patients 
Diabetes Care  2009;32(8):1453-1458.
To explore the potential long-term health and economic consequences of lifestyle interventions for diabetic patients.
A literature search was performed to identify interventions for diabetic patients in which lifestyle issues were addressed. We selected recent (2003–2008), randomized controlled trials with a minimum follow-up of 12 months. The long-term outcomes for these interventions, if implemented in the Dutch diabetic population, were simulated with a computer-based model. Costs and effects were discounted at, respectively, 4 and 1.5% annually. A lifelong time horizon was applied. Probabilistic sensitivity analyses were performed, taking account of variability in intervention costs and (long-term) treatment effects.
Seven trials with 147–5,145 participants met our predefined criteria. All interventions improved cardiovascular risk factors at ≥1 year follow-up and were projected to reduce cardiovascular morbidity over lifetime. The interventions resulted in an average gain of 0.01–0.14 quality-adjusted life-years (QALYs) per participant. Health benefits were generally achieved at reasonable costs (≤€50,000/QALY). A self-management education program (X-PERT) and physical activity counseling achieved the best results with ≥0.10 QALYs gained and ≥99% probability to be very cost-effective (≤€20,000/QALY).
Implementation of lifestyle interventions would probably yield important health benefits at reasonable costs. However, essential evidence for long-term maintenance of health benefits was limited. Future research should be focused on long-term effectiveness and multiple treatment strategies should be compared to determine incremental costs and benefits of one over the other.
PMCID: PMC2713648  PMID: 19435958
21.  Economic evaluation of first-line and maintenance treatments for advanced non-small cell lung cancer: a systematic review 
During these last years, there have been an increased number of new drugs for non-small cell lung cancer (NSCLC), with a growing financial effect on patients and society. The purpose of this article was to review the economics of first-line and maintenance NSCLC treatments. We reviewed economic analyses of NSCLC therapies published between 2004 and 2014. In first-line settings, in unselected patients with advanced NSCLC, the cisplatin gemcitabine doublet appears to be cost-saving compared with other platinum doublets. In patients with nonsquamous NSCLC, the incremental cost-effectiveness ratios (ICERs) per life-year gained (LYG) were $83,537, $178,613, and more than $300,000 for cisplatin-pemetrexed compared with, respectively, cisplatin-gemcitabine, cisplatin-carboplatin-paclitaxel, and carboplatin-paclitaxel-bevacizumab. For all primary chemotherapy agents, use of carboplatin is associated with slightly higher costs than cisplatin. In all the analysis, bevacizumab had an ICER greater than $150,000 per quality-adjusted life-year (QALY). In epidermal growth factor receptor mutated advanced NSCLC, compared with carboplatin-paclitaxel doublet, targeted therapy based on testing available tissue yielded an ICER of $110,644 per QALY, and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Compared with the triplet carboplatin-paclitaxel-bevacizumab, testing and rebiopsy strategies had ICERs of $25,547 and $44,036 per QALY, respectively. In an indirect comparison, ICERs per LYG and QALY of erlotinib versus gefitinib were $39,431 and $62,419, respectively. In anaplastic lymphoma kinase-positive nonsquamous advanced NSCLC, the ICER of first-line crizotinib compared with that of chemotherapy was $255,970 per QALY. For maintenance therapy, gefitinib had an ICER of $19,214 per QALY, erlotinib had an ICER of $127,343 per LYG, and pemetrexed had an ICER varying between $183,589 and $205,597 per LYG. Most recent NSCLC strategies are based on apparently no cost-effective strategies if we consider an ICER below $50,000 per QALY an acceptable threshold. We need, probably on a countrywide level, to have a debate involving public health organizations and pharmaceutical companies, as well as clinicians and patients, to challenge the rising costs of managing lung cancer.
PMCID: PMC4271788  PMID: 25548525
lung cancer; costs; economics; cost-effectiveness; evaluation
22.  Cost-effectiveness and cost utility analysis of three pneumococcal conjugate vaccines in children of Peru 
BMC Public Health  2013;13:1025.
The clinical and economic burden associated with invasive and non-invasive pneumococcal and non-typeable Haemophilus influenzae (NTHi) diseases is substantial in the Latin America and Caribbean region, where pneumococcal vaccines have only been introduced to a few countries. This study analyzed the cost-effectiveness and cost utility of three different pneumococcal conjugate vaccines (PCVs) for Peru.
A Markov model that simulated the disease processes in a birth cohort over a lifetime, within 1,128 month cycles was used to evaluate the cost-effectiveness of 10-valent pneumococcal NTHi protein D conjugate vaccine (PHiD-CV) and 7- and 13-valent PCVs (PCV-7 and PCV-13). Expected quality-adjusted life years (QALYs), cost-savings and incremental cost-effectiveness ratios (ICERs) were calculated.
Without vaccination, pneumonia was associated with the greatest health economic burden (90% of QALYs lost and 63% of lifetime direct medical costs); while acute otitis media (AOM) was responsible for 1% of QALYs lost and 25% of direct medical costs. All vaccines were predicted to be cost-effective for Peru, with PHiD-CV being most cost-effective. PHiD-CV was predicted to generate 50 more QALYs gained and required a reduced investment (−US$ 3.4 million) versus PCV-13 (discounted data), and was therefore dominant and cost saving. The probabilistic sensitivity analysis showed that PHiD-CV generated more QALYs gained at a reduced cost than PCV-13 in 84% of the simulations and less QALYs gains at a reduced cost in 16%. Additional scenarios using different assumptions on vaccine efficacies based on previous evidence were explored, but no significant change in the overall cost-effective results were observed.
The results of this modeling study predict that PCVs are likely to be a cost-effective strategy to help relieve the epidemiological and economic burden associated with pediatric pneumococcal and NTHi diseases for Peru. PHiD-CV is likely to be a dominant (better health gains at a reduced net cost) intervention compared to PCV-13 or PCV-7. The most significant drivers for these results are the better health and economic profile of PHiD-CV against AOM and its reduced cost per dose available through the PAHO Revolving Fund in the LAC region.
PMCID: PMC4228443  PMID: 24171921
Pneumococcal disease; Pneumococcal vaccines; Cost-effectiveness; Acute otitis media; Non-typeable Haemophilus influenzae; Peru
23.  Cost-effectiveness of tipranavir versus comparator protease inhibitor regimens in HIV infected patients previously exposed to antiretroviral therapy in the Netherlands 
This study compares the costs and effects of a regimen with ritonavir-boosted tipranavir (TPV/r) to a physician-selected genotypically-defined standard-of-care comparator protease inhibitor regimen boosted with ritonavir (CPI/r) in HIV infected patients that were previously exposed to antiretroviral therapy in the Netherlands.
We compared the projected lifetime costs and effects of two theoretical groups of 1000 patients, one receiving a standard of care regimen with TPV/r as a component and the other receiving a standard of care regimen with CPI/r. A 3-stage Markov model was formulated to represent three different consecutive HAART regimens. The model uses 12 health states based on viral load and CD4+ count to simulate disease progression. The transition probabilities for the Markov model were derived from a United States cohort of treatment experienced HIV patients. Furthermore, the study design was based on 48-week data from the RESIST-2 clinical trial and local Dutch costing data. Cost and health effects were discounted at 4% and 1.5% respectively according to the Dutch guideline. The analysis was conducted from the Dutch healthcare perspective using 2006 unit cost prices.
Our model projects an accumulated discounted cost to the Dutch healthcare system per patient receiving the TPV/r regimen of €167,200 compared to €145,400 for the CPI/r regimen. This results in an incremental cost of €21,800 per patient. The accumulated discounted effect is 7.43 life years or 6.31 quality adjusted life years (QALYs) per patient receiving TPV/r, compared to 6.91 life years or 5.80 QALYs per patient receiving CPI/r. This translates into an incremental effect of TPV/r over CPI/r of 0.52 life years gained (LYG) or 0.51 QALYs gained. The corresponding incremental cost effectiveness ratios (iCERs) are €41,600 per LYG and €42,500 per QALY.
We estimated the iCER for TPV/r compared to CPI/r at approximately €40,000 in treatment experienced HIV-1 infected patients in the Netherlands. This ratio may well be in range of what is acceptable and warrants reimbursement for new drug treatments in the Netherlands, in particular in therapeutic areas as end-stage oncology and HIV and other last-resort health-care interventions.
PMCID: PMC2211743  PMID: 18034881
24.  Heterogeneity in cost-effectiveness of lifestyle counseling for metabolic syndrome risk groups -primary care patients in Sweden 
Clinical trials have indicated that lifestyle interventions for patients with lifestyle-related cardiovascular and diabetes risk factors (the metabolic syndrome) are cost-effective. However, patient characteristics in primary care practice vary considerably, i.e. they exhibit heterogeneity in risk factors. The cost-effectiveness of lifestyle interventions is likely to differ over heterogeneous patient groups.
Patients (62 men, 80 women) in the Kalmar Metabolic Syndrome Program (KMSP) in primary care (Kalmar regional healthcare area, Sweden) were divided into three groups reflecting different profiles of metabolic risk factors (low, middle and high risk) and gender. A Markov model was used to predict future cardiovascular disease and diabetes, including complications (until age 85 years or death), with health effects measured as QALYs and costs from a societal perspective in Euro (EUR) 2012, discounted 3%. Simulations with risk factor levels at start and at 12 months follow-up were performed for each group, with an assumed 4-year sustainability of intervention effects.
The program was estimated cost-saving for middle and high risk men, while the incremental cost vs. do-nothing varied between EUR 3,500 – 18,000 per QALY for other groups. There is heterogeneity in the cost-effectiveness over the risk groups but this does not affect the overall conclusion on the cost-effectiveness of the KMSP. Even the highest ICER (for high risk women) is considered moderately cost-effective in Sweden. The base case result was not sensitive to alternative data and methodology but considerably affected by sustainability assumptions. Alternative risk stratifications did not change the overall conclusion that KMSP is cost-effective. However, simple grouping with average risk factor levels over gender groups overestimate the cost-effectiveness.
Lifestyle counseling to prevent metabolic diseases is cost-effective in Swedish standard primary care settings. The use of risk stratification in the cost-effectiveness analysis established that the program was cost-effective for all patient groups, even for those with very high levels of lifestyle-related risk factors for the metabolic syndrome diseases. Heterogeneity in the cost-effectiveness of lifestyle interventions in primary care patients is expected, and should be considered in health policy decisions.
PMCID: PMC3765778  PMID: 23984906
Cost-effectiveness; Markov model; Metabolic syndrome; Lifestyle counseling; Primary care
25.  Cost-effectiveness analysis of mechanical thrombectomy in acute ischemic stroke 
Journal of neurosurgery  2009;110(3):508-513.
Mechanical thrombectomy is increasingly being used for the treatment of large-vessel ischemic stroke in patients who arrive outside of the 3-hour tissue plasminogen activator time window. In this study, the authors evaluated the cost and effectiveness of mechanical thrombectomy compared with standard medical therapy in patients who are ineligible to receive tissue plasminogen activator.
Clinical outcomes of an open-label study of mechanical thrombectomy were compared with a hypothetical control group with a lower recanalization rate (18 vs 60%) and a lower rate of symptomatic intracranial hemorrhage (0.6 vs 7.8%) than the active treatment group. A Markov cost-effectiveness model was built to compare the health benefits and costs associated with mechanical thrombectomy compared with standard medical therapy. All probabilities, quality-of-life factors, and costs were estimated from the published literature. Univariate sensitivity analyses were performed to assess how variations in model parameters affect health and economic outcomes.
Treatment of acute ischemic stroke with mechanical thrombectomy increased survival time by 0.54 quality-adjusted life years (QALYs), compared with standard medical therapy (2.37 vs 1.83 QALYs), at an increased cost of $6600. This yielded an incremental cost-effectiveness ratio (ICER) of $12,120 per QALY gained, a value generally considered cost-effective. Sensitivity analysis showed that mechanical thrombectomy remained cost-effective (ICER < $50,000 per QALY gained) for all model inputs varied over a reasonable range, except for age at stroke treatment. For patients older than 82 years of age, the treatment was only borderline cost-effective (ICER of $50,000-100,000 per QALY gained).
The treatment of large-vessel ischemic stroke with mechanical thrombectomy appears to be cost-effective. These results require validation when data from a randomized, controlled trial of mechanical thrombectomy become available.
PMCID: PMC2669322  PMID: 19025358
cost-benefit analysis; cost-effectiveness; mechanical thrombectomy; stroke

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