Model-based Economic Evaluation Research Articles

Sedative-hypnotic medicines and falls in community-dwelling older adults: a cost-effectiveness (decision-tree) analysis from a US Medicare perspective.

Both the 2012 Beers list and the American Geriatric Society 'Choosing Wisely' campaign suggest restraint in the use of sedative-hypnotics for the treatment of insomnia in older people. Sedative hypnotic agents continue to be widely prescribed even though their use in the elderly is associated with an increased risk of falls, fractures, and emergency hospitalizations. The aim of this study was to estimate the cost effectiveness of cognitive behavioral therapy (CBT) compared with sedative-hypnotics and no treatment for insomnia in the US Medicare population, adjusting for the risk of falls and related consequences. A model-based economic evaluation (decision tree) using the US Medicare perspective and a conservative annual temporal framework was conducted. Simulations were performed in a hypothetical cohort of Medicare beneficiaries suffering from insomnia. The main outcome measure was the incremental cost per quality-adjusted life year (QALY) gained. Sensitivity analyses assessed the robustness of the base-case analysis. On an annual basis, CBT showed a dominance (cost: US$19,442; QALYs: 0.594) over sedative hypnotics (cost: US$32,452; QALYs: 0.552) and no treatment (cost: US$33,853; QALYs: 0.517). Assuming a willingness to pay of US$50,000, the net monetary benefit was positive for CBT (US$10,287) and negative for sedative hypnotics (-US$4,851) and no treatment (-US$7,993). CBT had a 95% chance of being the dominant strategy, with results most sensitive to an older adult's baseline risk of falling. Failure to consider drug harms such as drug-induced falls and hospitalization represents a growing public health concern, significantly underestimating the cost of sedative-hypnotic therapy and loss in quality of life for the elderly. Public payers should reconsider reimbursement of sedative-hypnotic drugs as first-line treatment for insomnia in older adults.

Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes—individual patient data (IPD) meta-analysis and health economic evaluation

BackgroundPregnant women who gain excess weight are at risk of complications during pregnancy and in the long term. Interventions based on diet and physical activity minimise gestational weight gain with varied effect on clinical outcomes. The effect of interventions on varied groups of women based on body mass index, age, ethnicity, socioeconomic status, parity, and underlying medical conditions is not clear. Our individual patient data (IPD) meta-analysis of randomised trials will assess the differential effect of diet- and physical activity-based interventions on maternal weight gain and pregnancy outcomes in clinically relevant subgroups of women.Methods/designRandomised trials on diet and physical activity in pregnancy will be identified by searching the following databases: MEDLINE, EMBASE, BIOSIS, LILACS, Pascal, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of s of Reviews of Effects, and Health Technology Assessment Database. Primary researchers of the identified trials are invited to join the International Weight Management in Pregnancy Collaborative Network and share their individual patient data. We will reanalyse each study separately and confirm the findings with the original authors. Then, for each intervention type and outcome, we will perform as appropriate either a one-step or a two-step IPD meta-analysis to obtain summary estimates of effects and 95% confidence intervals, for all women combined and for each subgroup of interest. The primary outcomes are gestational weight gain and composite adverse maternal and fetal outcomes. The difference in effects between subgroups will be estimated and between-study heterogeneity suitably quantified and explored. The potential for publication bias and availability bias in the IPD obtained will be investigated. We will conduct a model-based economic evaluation to assess the cost effectiveness of the interventions to manage weight gain in pregnancy and undertake a value of information analysis to inform future research.Systematic review registrationPROSPERO 2013: CRD42013003804

Markov Model-Based Economic Evaluation of Combination Therapy with Ezetimibe and Statin Monotherapy.

Markov Model-Based Economic Evaluation of Combination Therapy with Ezetimibe and Statin Monotherapy.

Is diabetes and hypertension screening worthwhile in resource-limited settings? An economic evaluation based on a pilot of a Package of Essential Non-communicable disease interventions in Bhutan.

In response to a lack of cost-effective data on screening and early treatment of diabetes and hypertension in resource-limited settings, a model-based economic evaluation was performed on the World Health Organization (WHO)'s Package of Essential Non-communicable (PEN) disease interventions for primary health care in Bhutan. Both local and international data were applied in the model in order to derive lifetime costs and outcomes resulting from the early treatment of diabetes and hypertension. The results indicate that the current screening option (where people who are overweight, obese or aged 40 years or older who visit primary care facilities are screened for diabetes and hypertension) represents good value for money compared to 'no screening'. The study findings also indicate that expanding opportunistic screening (70% coverage of the target population) to universal screening (where 100% of the target population are screened), is likely to be even more cost-effective. From the sensitivity analysis, the value of the screening options remains the same when disease prevalence varies. Therefore, applying this model to other healthcare settings is warranted, since disease prevalence is one of the major factors in affecting the cost-effectiveness results of screening programs.

PRM73 - Survival modeling for the estimation of transition probabilities in model-based economic evaluations in the absence of individual patient data: A tutorial

Survival modeling techniques are increasingly being used as part of decision modeling for health economic evaluations. As many models are available, it is imperative for interested readers to know about the steps in selecting and using the most suitable ones. The objective of this paper is to propose a tutorial for the application of appropriate survival modeling techniques to estimate transition probabilities, for use in model-based economic evaluations, in the absence of individual patient data (IPD). An illustration of the use of the tutorial is provided based on the final progression-free survival (PFS) analysis of the BOLERO-2 trial in metastatic breast cancer (mBC). An algorithm was adopted from Guyot and colleagues, and was then run in the statistical package R to reconstruct IPD, based on the final PFS analysis of the BOLERO-2 trial. It should be emphasized that the reconstructed IPD represent an approximation of the original data. Afterwards, we fitted parametric models to the reconstructed IPD in the statistical package Stata. Both statistical and graphical tests were conducted to verify the relative and absolute validity of the findings. Finally, the equations for transition probabilities were derived using the general equation for transition probabilities used in model-based economic evaluations, and the parameters were estimated from fitted distributions. The results of the application of the tutorial suggest that the log-logistic model best fits the reconstructed data from the latest published Kaplan–Meier (KM) curves of the BOLERO-2 trial. Results from the regression analyses were confirmed graphically. An equation for transition probabilities was obtained for each arm of the BOLERO-2 trial. In this paper, a tutorial was proposed and used to estimate the transition probabilities for model-based economic evaluation, based on the results of the final PFS analysis of the BOLERO-2 trial in mBC. The results of our study can serve as a basis for any model (Markov) that needs the parameterization of transition probabilities, and only has summary KM plots available.

Cost-effectiveness of diagnostic strategies for the management of abnormal uterine bleeding (heavy menstrual bleeding and post-menopausal bleeding): a decision analysis.

Heavy menstrual bleeding (HMB) and post-menopausal bleeding (PMB) together constitute the commonest gynaecological presentation in secondary care and impose substantial demands on health service resources. Accurate diagnosis is of key importance to realising effective treatment, reducing morbidity and, in the case of PMB, reducing mortality. There are many tests available, including transvaginal scan (TVS), endometrial biopsy (EBx), saline infusion sonography and outpatient hysteroscopy (OPH); however, optimal diagnostic work-up is unclear. To determine the most cost-effective diagnostic testing strategy for the diagnosis and treatment of (i) HMB and (ii) PMB. Parameter inputs were derived from systematic quantitative reviews, individual patient data (IPD) from existing data sets and focused searches for specific data. In the absence of data estimates, the consensus view of an expert clinical panel was obtained. Two clinically informed decision-analytic models were constructed to reflect current service provision for the diagnostic work-up of women presenting with HMB and PMB. The model-based economic evaluation took the form of a cost-effectiveness analysis from the perspective of the NHS in a contemporary, 'one-stop' secondary care clinical setting, where all indicated testing modalities would be available during a single visit. Two potentially cost-effective testing strategies for the initial investigation of women with HMB were identified: OPH alone or in combination with EBx. Although a combination testing strategy of OPH + EBx was marginally more effective, the incremental cost-effectiveness ratio (ICER) was approximately £21,000 to gain one more satisfied patient, whereas for OPH it was just £360 when compared with treatment with the levonorgestrel intrauterine system (LNG-IUS) without investigation. Initial testing with OPH was the most cost-effective testing approach for women wishing to preserve fertility and for women with symptoms refractory to empirical treatment with a LNG-IUS. For the investigation of PMB, selective use of TVS based on historical risk prediction for the diagnostic work-up of women presenting with PMB generated an ICER compared with our reference strategy of 'no initial work-up' of £129,000 per extra woman surviving 5 years. The ICERs for the two other non-dominated testing strategies, combining history and TVS or combining OPH and TVS, were over £2M each. In the absence of IPD, estimates of accuracy for test combinations presented some uncertainty where test results were modelled as being discordant. For initial investigation of women presenting to secondary care with HMB who do not require preservation of their fertility, our research suggests a choice between OPH alone or a combination of OPH and EBx. From our investigation, OPH appears to be the optimal first-line diagnostic test used for the investigation of women presenting to secondary care with HMB wishing to preserve their fertility or refractory to previous medical treatment with the LNG-IUS. We would suggest that the current recommendation of basing the initial investigation of women with PMB on the universal TVS measurement of endometrial thickness at a 5-mm threshold may need to be replaced by a strategy of restricting TVS to women with risk factors (e.g. increasing age-raised body mass index, diabetes or nulliparity), obtained from the preceding clinical assessment. The National Institute for Health Research Health Technology Assessment programme.

Conservative management, surgery and radiosurgery for treatment of vestibular schwannomas: a model‐based approach to cost‐effectiveness

To undertake a cost-effectiveness analysis comparing conservative management, surgery and radiosurgery for treating small-to-medium (1-20 mm)-sized vestibular schwannomas. Model-based economic evaluation using individual-level data from a Birmingham-based longitudinal patient database and from published sources. Both a decision tree and state-transition (Markov) model were developed, from an National Health Service (NHS) perspective. Sensitivity analyses were also carried out. Secondary care treatment for patients with small-to-medium-sized vestibular schwannomas. Three hypothetical cohorts of adult patients receiving conservative management, radiosurgery or surgery treatment, aged 58 years as starting age within model. Cost-effectiveness based on cost per quality-adjusted life year (QALY). Conservative management is the preferred strategy for the treatment of small-to-medium-sized vestibular schwannomas. Conservative management is both cheaper (-£ 722 and -£ 2764) and more effective (0.136 and 0.554 quality-adjusted life years) than both radiosurgery and surgery, respectively. A conservative strategy can therefore be considered as highly cost-effective. This result is sensitive to the assumed quality-of-life parameters in the model. Sensitivity analysis suggests that the probability of a conservative strategy being the most cost-effective approach compared with surgery and radiosurgery at a willingness to pay of £ 20 000/quality-adjusted life year gained is 80% and 55%, respectively. A conservative approach is the preferred strategy for treatment of small-to-medium vestibular schwannomas. This result is sensitive to quality-of-life values used in the analysis. More research is required to assess the impact of treatment upon patients' health-related quality of life over time.

Survival Modeling for the Estimation of Transition Probabilities in Model-Based Economic Evaluations in the Absence of Individual Patient Data: A Tutorial

Survival modeling techniques are increasingly being used as part of decision modeling for health economic evaluations. As many models are available, it is imperative for interested readers to know about the steps in selecting and using the most suitable ones. The objective of this paper is to propose a tutorial for the application of appropriate survival modeling techniques to estimate transition probabilities, for use in model-based economic evaluations, in the absence of individual patient data (IPD). An illustration of the use of the tutorial is provided based on the final progression-free survival (PFS) analysis of the BOLERO-2 trial in metastatic breast cancer (mBC). An algorithm was adopted from Guyot and colleagues, and was then run in the statistical package R to reconstruct IPD, based on the final PFS analysis of the BOLERO-2 trial. It should be emphasized that the reconstructed IPD represent an approximation of the original data. Afterwards, we fitted parametric models to the reconstructed IPD in the statistical package Stata. Both statistical and graphical tests were conducted to verify the relative and absolute validity of the findings. Finally, the equations for transition probabilities were derived using the general equation for transition probabilities used in model-based economic evaluations, and the parameters were estimated from fitted distributions. The results of the application of the tutorial suggest that the log-logistic model best fits the reconstructed data from the latest published Kaplan-Meier (KM) curves of the BOLERO-2 trial. Results from the regression analyses were confirmed graphically. An equation for transition probabilities was obtained for each arm of the BOLERO-2 trial. In this paper, a tutorial was proposed and used to estimate the transition probabilities for model-based economic evaluation, based on the results of the final PFS analysis of the BOLERO-2 trial in mBC. The results of our study can serve as a basis for any model (Markov) that needs the parameterization of transition probabilities, and only has summary KM plots available.

Evaluating PET–CT in routine surveillance and follow‐up after treatment for cervical cancer: a cost‐effectiveness analysis

To undertake a cost-effectiveness analysis that compares positron emission tomography - computed tomography (PET-CT) imaging plus standard practice with standard practice alone in the diagnosis of recurrent or persistent cervical cancer during routine surveillance and follow-up of women who have previously been diagnosed and treated. Model-based economic evaluation using data from a systematic review, supplemented with data from other sources, and taking a UK National Health Service (NHS) perspective. Secondary Care in England. Women at least 3months after the completion of treatment, with either recurrent or persistent cervical cancer. A state transition (Markov) model was developed using TreeAgePro2011. The structure of the model was informed by the reviews of the trials and clinical input. In the model, two diagnostic strategies were examined. A one-way sensitivity analysis, probabilistic sensitivity analysis, and a value of information analysis were also carried out. Cost-effectiveness based on incremental cost per quality-adjusted life year (QALY). Adding PET-CT to the current treatment strategy of clinical examination and scanning [magnetic resonance imaging (MRI) and/or CT scan] during the routine surveillance and follow-up of women with recurrent or persistent cervical cancer is significantly more costly, with only a minimal increase in effectiveness. The incremental cost-effectiveness ratio (ICER) for the strategy of PET-CT as an adjunct to the standard treatment strategy that included clinical examination, MRI, and/or CT scan, compared with the usual treatment alone, was over £1million per QALY. The results of the current analysis suggest that use of PET-CT in the diagnosis of recurrent or persistent cervical cancer is not cost-effective. Current guidelines recommending imaging using PET-CT as a diagnostic or surveillance tool need to be reconsidered in light of these results. This study did not specifically investigate the use of PET-CT in women with symptoms and radiological suspicion of recurrence where exenteration was considered. More research in that specific area is required.

Sentinel lymph node status in vulval cancer: systematic reviews of test accuracy and decision-analytic model-based economic evaluation

Vulval cancer causes 3-5% of all gynaecological malignancies and requires surgical removal and inguinofemoral lymphadenectomy (IFL). Complications affect > 50% of patients, including groin wound infection, lymphoedema and cellulitis. A sentinel lymph node (SLN) is the first groin node with the highest probability of malignancy. SLN biopsy would be useful if it could accurately identify patients in whom cancer has spread to the groin, without removing all groin nodes. SLNs can be identified by isosulfan blue dye and/or technetium-99 ((99m)Tc) radioactive tracer during lymphoscintigraphy. The blue dye/(99m)Tc procedure only detects SLN, not metastases - this requires histological examination, which can include ultrastaging and staining with conventional haematoxylin and eosin (H&E) or immunohistochemistry. To determine the test accuracy and cost-effectiveness of the SLN biopsy with (99m)Tc and/or blue dye compared with IFL or clinical follow-up for test negatives in vulval cancer, through systematic reviews and economic evaluation. Standard medical databases, including MEDLINE, EMBASE, Science Citation Index and The Cochrane Library, medical search gateways, reference lists of review articles and included studies were searched to January 2011. For accuracy and effectiveness, standard methods were used and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were to January 2011, with no language restrictions. Meta-analyses were carried out with Meta-Disc version 1.4 (Javier Zamora, Madrid, Spain) for accuracy; none was appropriate for effectiveness. The economic evaluation from a NHS perspective used a decision-tree model in DATA TreeAge Pro Healthcare 2001 (TreeAge Software, Inc., Williamstown, MA, USA). Six options (blue dye with H&E, blue dye with ultrastaging, (99m)Tc with H&E, (99m)Tc with ultrastaging, blue dye/(99m)Tc with H&E, blue dye/(99m)Tc with ultrastaging) were compared with IFL. Deterministic and probabilistic sensitivity analyses were conducted. For accuracy, of the 26 included studies, most evaluated (99m)Tc/blue dye combined. Four studies had clinical follow-up only for test negatives and five had clinical follow-up for all and IFL for test negatives. Numbers with no SLN found were difficult to distinguish from those with negative SLN biopsies. The largest group of 11 studies using (99m)Tc/blue dye, ultrastaging and immunohistochemistry had a pooled sensitivity of 95.6% [95% confidence interval (CI) 91.5% to 98.1%] and a specificity of 100% (95% CI 99.0% to 100%). Mean SLN detection rates were 94.6% for (99m)Tc, 68.7% for blue dye and 97.7% for both. One study measured global health status quality of life (QoL) and found no difference between SLN biopsy and IFL. One patient preference evaluation showed that 66% preferred IFL rather than a 5% false-negative rate from SLN biopsy. For effectiveness, of 14,038 references, one randomised controlled trial, three case-control studies and 13 case series were found. Approximately 50% died from vulval cancer and 50% from other causes during follow-ups. Recurrences were in the ratio of approximately 4 : 2 : 1 vulval, groin and distant, with more recurrences in node-positive patients. No studies reported QoL. For cost per death averted, IFL was less costly and more effective than strategies using SLN biopsy. For morbidity-free survival and long-term morbidity-free survival, (99m)Tc with ultrastaging was most cost-effective. Strategies with blue dye only and H&E only were never cost-effective. The incremental cost-effectiveness ratio for (99m)Tc with ultrastaging compared with IFL was £4300 per case of morbidity-free survival and £7100 per long-term morbidity-free survival. The main limitations of this study include the lack of good-quality evidence on accuracy, effectiveness and QoL. A large project such as this takes time to publish, so the most recent studies are not included. A sensitive and specific combined metastatic SLN detection test and information on generic QoL in vulval cancer is urgently required. The National Institute for Health Research Health Technology Assessment programme.

A Model-Based Economic Evaluation of Improved Primary Care Management of Patients with Type 2 Diabetes in Australia

There are few studies investigating the economic value of the Australian practice nurse workforce on the management of chronic conditions. This is particularly important in Australia, where the government needs evidence to inform decisions on whether to maintain or redirect current financial incentives that encourage practices to recruit practice nurses. The objective of this study was to estimate the lifetime costs and quality-adjusted life-years (QALYs) associated with two models of practice nurse involvement in clinical-based activities (high and low level) in the management of type 2 diabetes within the primary care setting. A previously validated state transition model (the United Kingdom Prospective Diabetes Study Outcomes Model) was adapted, which uses baseline prognostic factors (e.g. gender, haemoglobin A1c [HbA1c]) to predict the risk of occurrence of diabetes-related complications (e.g. stroke). The model was populated by data from Australian and UK observational studies. Costs and utility values associated with complications were summed over patients' lifetimes to estimate costs and QALY gains from the perspective of the health care system. All costs were expressed in 2011 Australian dollars (AU$). The base-case analysis assumed a 40-year time horizon with an annual discount rate of 5 %. Relative to low-level involvement of practice nurses in the provision of clinical-based activities, the high-level model was associated with lower mean lifetime costs of management of complications (-AU$8,738; 95 % confidence interval [CI] -AU$12,522 to -AU$4,954), and a greater average gain in QALYs (0.3; 95 % CI 0.2-0.4). A range of sensitivity analyses were performed, in which the high-level model was dominant in all cases. Our results suggest that the high-level model is a dominant management strategy over the low-level model in all modelled scenarios. These findings indicate the need for effective primary care-based incentives to encourage general practices not only to employ practice nurses, but to better integrate them into the provision of clinical services.

A systematic review of models used in cost-effectiveness analyses of preventing osteoporotic fractures

This review was aimed at the evolution of health economic models used in evaluations of clinical approaches aimed at preventing osteoporotic fractures. Models have improved, with medical continuance becoming increasingly recognized as a contributor to health and economic outcomes, as well as advancements in epidemiological data. Model-based health economic evaluation studies are increasingly used to investigate the cost-effectiveness of osteoporotic fracture preventions and treatments. The objective of this study was to carry out a systematic review of the evolution of health economic models used in the evaluation of osteoporotic fracture preventions. Electronic searches within MEDLINE and EMBASE were carried out using a predefined search strategy. Inclusion and exclusion criteria were used to select relevant studies. References listed of included studies were searched to identify any potential study that was not captured in our electronic search. Data on country, interventions, type of fracture prevention, evaluation perspective, type of model, time horizon, fracture sites, expressed costs, types of costs included, and effectiveness measurement were extracted. Seventy-four models were described in 104 publications, of which 69% were European. Earlier models focused mainly on hip, vertebral, and wrist fracture, but later models included multiple fracture sites (humerus, pelvis, tibia, and other fractures). Modeling techniques have evolved from simple decision trees, through deterministic Markov processes to individual patient simulation models accounting for uncertainty in multiple parameters. Treatment continuance has been increasingly taken into account in the models in the last decade. Models have evolved in their complexity and emphasis, with medical continuance becoming increasingly recognized as a contributor to health and economic outcomes. This evolution may be driven in part by the desire to capture all the important differentiating characteristics of medications under scrutiny, as well as the advancement in epidemiological data relevant to osteoporosis fractures.

Cost-effectiveness of sentinel lymph node biopsy vs inguinofemoral lymphadenectomy in women with vulval cancer

Background:This study examines the cost-effectiveness of sentinel lymph node biopsy, a potentially less morbid procedure, compared with inguinofemoral lymphadenectomy (IFL) among women with stage I and stage II vulval squamous cell carcinoma.Methods:A model-based economic evaluation was undertaken based on clinical evidence from a systematic review of published sources. A decision tree model was developed with the structure being informed by clinical input, taking the perspective of the health-care provider.Results:For overall survival for 2 years, IFL was found to be the most cost-effective option and dominated all other strategies, being the least costly and most effective. For morbidity-free related outcomes for 2 years, sentinel lymph node (SLN) biopsy with 99mTc and blue dye and haematoxylin & eosin (H&E) histopathology, with ultrastaging and immunohistochemistry reserved for those that test negative following H&E is likely to be the most effective approach.Conclusion:SLN biopsy using 99mTc and blue dye with ultrastaging may be considered the most cost-effective strategy based on the outcome of survival free of morbidity for 2 years. The findings here also indicate that using blue dye and H&E for the identification of the SLN and the identification of metastasis, respectively, are not sensitive enough to be used on their own.

Review of economic evidence in the prevention and early detection of colorectal cancer.

This paper aims to systematically review the cost-effectiveness evidence, and to provide a critical appraisal of the methods used in the model-based economic evaluation of CRC screening and subsequent surveillance. A search strategy was developed to capture relevant evidence published 1999-November 2012. Databases searched were MEDLINE, EMBASE, National Health Service Economic Evaluation (NHS EED), EconLit, and HTA. Full economic evaluations that considered costs and health outcomes of relevant intervention were included. Sixty-eight studies which used either cohort simulation or individual-level simulation were included. Follow-up strategies were mostly embedded in the screening model. Approximately 195 comparisons were made across different modalities; however, strategies modelled were often simplified due to insufficient evidence and comparators chosen insufficiently reflected current practice/recommendations. Studies used up-to-date evidence on the diagnostic test performance combined with outdated information on CRC treatments. Quality of life relating to follow-up surveillance is rare. Quality of life relating to CRC disease states was largely taken from a single study. Some studies omitted to say how identified adenomas or CRC were managed. Besides deterministic sensitivity analysis, probabilistic sensitivity analysis (PSA) was undertaken in some studies, but the distributions used for PSA were rarely reported or justified. The cost-effectiveness of follow-up strategies among people with confirmed adenomas are warranted in aiding evidence-informed decision making in response to the rapidly evolving technologies and rising expectations.

Cost-effectiveness of transcatheter aortic valve implantation (TAVI) for aortic stenosis in patients who are high risk or contraindicated for surgery: a model-based economic evaluation

Calcific aortic stenosis (AS) is a common valvular heart disease. Patients with severe symptomatic AS typically survive less than 3 years. In such patients, intervention with surgical aortic valve replacement (SAVR) may increase survival. However, in some patients SAVR is associated with a high operative risk and medical management is considered appropriate. Transcatheter aortic valve implantation (TAVI) is a relatively recent technique to avoid the invasiveness of open surgery. This procedure has been used for the treatment of patients with severe AS who are unsuitable for SAVR (because it is too high risk and/or for other reasons such as suffering from porcelain aorta) and is increasingly being considered for other patients. To determine the cost-effectiveness of TAVI being made available for patients who are high risk or contraindicated for SAVR through a review of existing economic evaluations and development of a model. Bibliographic databases [MEDLINE, EMBASE, The Cochrane Library, Health Technology Assessment (HTA), Database of Abstracts of Reviews of Effects (DARE) and NHS Economic Evaluation Database (EED), Centre for Reviews and Dissemination HTA, DARE and NHS EED], guideline resources, current trials registers, websites/grey literature and manufacturers' websites, and consultation with clinical experts were used to identify studies for the review and information for the model. Databases were searched from 2007 to November 2010. A model was built to assess the cost-effectiveness of TAVI separately in patients suitable and unsuitable for SAVR, together with overall results for the effect of making TAVI available. Substantial deterministic sensitivity analysis was carried out together with probabilistic sensitivity analysis. No fully published cost-effectiveness studies were found. Modelling patients not suitable for SAVR, the base-case results show TAVI as more costly but more effective than medical management, with an incremental cost-effectiveness ratio (ICER) of £12,900 per quality-adjusted life-year (QALY). The ICER was below £20,000 per QALY for over 99% of model runs in the probabilistic sensitivity analysis. For patients suitable for SAVR, the comparator with TAVI is a mixture of SAVR and medical management. TAVI is both more costly and less effective than this comparator assuming that most patients would receive SAVR in the absence of TAVI. This is robust to a number of assumption changes about the effects of treatment, but sensitive to assumptions about the proportion of patients receiving SAVR in the comparator. If the use of TAVI is extended to include more patients suitable for SAVR, the overall results from the model become less favourable for TAVI. The modelling involves extrapolation of short-term data and the comparison between TAVI and SAVR is not based on randomised data. More trial data on the latter have been published since the modelling was undertaken. The results for TAVI compared with medical management in patients unsuitable for surgery are reasonably robust and suggest that TAVI is likely to be cost-effective. For patients suitable for SAVR, TAVI could be both more costly and less effective than SAVR. The overall results suggest that, if a very substantial majority of TAVI patients are those unsuitable for SAVR, the cost-effectiveness of a broad policy of introducing TAVI may fall below £20,000 per QALY. Future work required includes the incorporation of new data made available after completion of this work. The National Institute for Health Research Health Technology Assessment programme.

Cost-effectiveness of a nurse-based intervention (AIMS) to improve adherence among HIV-infected patients: design of a multi-centre randomised controlled trial

BackgroundNon-adherence to HIV-treatment can have a negative impact on patients’ treatment success rates, quality of life, infectiousness, and life expectancy. Few adherence interventions have shown positive effects on adherence and/or virologic outcomes. The theory- and evidence-based Adherence Improving self-Management Strategy (AIMS) is an intervention that has been demonstrated to improve adherence and viral suppression rates in a randomised controlled trial. However, evidence of its cost-effectiveness is lacking. Following a recent review suggesting that cost-effectiveness evaluations of adherence interventions for chronic diseases are rare, and that the methodology of such evaluations is poorly described in the literature, this manuscript presents the study protocol for a multi-centre trial evaluating the effectiveness and cost-effectiveness of AIMS among a heterogeneous sample of patients.Methods/designThe study uses a multi-centre randomised controlled trial design to compare the AIMS intervention to usual care from a societal perspective. Embedded in this RCT is a trial-based and model-based economic evaluation. A planned number of 230 HIV-infected patients are randomised to receive either AIMS or usual care. The relevant outcomes include changes in adherence, plasma viral load, quality of life, and societal costs. The time horizon for the trial-based economic evaluation is 12–15 months. Costs and effects are extrapolated to a lifetime horizon for the model-based economic evaluation.DiscussionThe present multicentre RCT is designed to provide sound methodological evidence regarding the effectiveness and cost-effectiveness of a nurse-based counselling intervention (AIMS) to support treatment adherence among a large and heterogeneous sample of HIV-infected patients in the Netherlands. The objective of the current paper is to describe the trial protocol in sufficient detail to allow full evaluation of the quality of the study design. It is anticipated that, if proven cost-effective, AIMS can contribute to improved evidence-based counselling guidelines for HIV-nurses and other health care professionals.Trial registrationThe study has been registered on clinicaltrials.gov (Identifier: NCT01429142).

Model-based economic evaluation for medical decision making: learn from the past and prepare for the future.

In July 2012 issue of Annals of Cardiothoracic Surgery, Gada and colleagues (1) presented an economic evaluation for transapical aortic valve implantation (TAVI) in high risk patients with aortic stenosis. A Markov model was developed to compare mortality, costs and quality-adjusted life years (QALYs) of TAVI with aortic valve replacement (AVR) and medical management from a payer’s perspective over a life time horizon. In the reference case, the incremental cost effectiveness ratios (ICERs) were $44,384/QALY for TAVI and $42,637/QALY for AVR when compared with the medical management, while TAVI was dominated by AVR (i.e. TAVI gained fewer QALYs at higher costs). The ICERs were sensitive to post-surgery mortality, health utilities, and the cost of TAVI.

Cetuximab in first line treatment of metastatic colorectal cancer

The present health technology assessment report evaluates the clinical and economic profile of cetuximab in first-line metastatic colorectal cancer (mCRC) in Italy. The first part of the report addresses the epidemiological, clinical, social and economic impact of mCRC. In the second part, evidence of efficacy, safety and cost-effectiveness of cetuximab and its available alternatives is shown. Finally, a model-based economic evaluation aimed at comparing cetuximab-based re­gimens vs. alternative therapeutic strategies indicated in mCRC in Italy is presented. The model estimates the incremental cost-effectiveness of adding cetuximab to FOLFOX-4 or FOLFIRI based on KRAS status, vs. adding bevacizumab to FOLFOX-4 or vs. FOLFOX-4 or FOLFIRI alone. A theoretical analysis vs. panitumumab has also been performed, despite panitumumab is not yet reimbursed in Italy in first-line mCRC. Survival outcomes, quality of life and costs of patient ma­nagement are estimated through a Markov model, using the Italian National Healthcare Service (NHS) perspective, over a 10 year period, taking into account KRAS status of patients. The results of the pharmaco-economic analysis show that cetuximab + FOLFOX-4 and cetuximab + FOLFIRI are associated with increased survival, increased cost and increased quality adjusted survival, compared to all other treatments currently indicated and reimbursed in Italy. Adding cetuximab to FOLFOX-4 or FOLFIRI, based on KRAS status shows favorable incremental cost-effectiveness ratio (ICER) vs. adding bevacizumab to FOLFIRI or vs. FOLFOX-4 or FOLFIRI alone. ICER of cetuximab (in combination with FOLFOX-4 or FOLFIRI), compared to currently reimbursed alternatives, is estimated between 6 and 13 thousand Euros per QALY gai­ned, depending on alternative treatment. These estimates are robust in extensive sensitivity analyses. As a final result, both clinical and economic evidence analyzed in this health technology assessment leads to recommend cetuximab as preferred option for the first-line treatment of mCRC KRAS wild-type patients in Italy.

The clinical effectiveness and cost-effectiveness of exercise referral schemes: a systematic review and economic evaluation

Exercise referral schemes (ERS) aim to identify inactive adults in the primary-care setting. The GP or health-care professional then 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 individual. To assess the clinical effectiveness and cost-effectiveness of ERS for people with a diagnosed medical condition known to benefit from physical activity (PA). The scope of this report was broadened to consider individuals without a diagnosed condition who are sedentary. MEDLINE; EMBASE; PsycINFO; The Cochrane Library, ISI Web of Science; SPORTDiscus and ongoing trial registries were searched (from 1990 to October 2009) and included study references were checked. Systematic reviews: the effectiveness of ERS, predictors of ERS uptake and adherence, and the cost-effectiveness of ERS; and the development of a decision-analytic economic model to assess cost-effectiveness of ERS. Seven randomised controlled trials (UK, n = 5; non-UK, n = 2) met the effectiveness inclusion criteria, five comparing ERS with usual care, two compared ERS with an alternative PA intervention, and one to an ERS plus a self-determination theory (SDT) intervention. In intention-to-treat analysis, compared with usual care, there was weak evidence of an increase in the number of ERS participants who achieved a self-reported 90-150 minutes of at least moderate-intensity PA per week at 6-12 months' follow-up [pooled relative risk (RR) 1.11, 95% confidence interval 0.99 to 1.25]. There was no consistent evidence of a difference between ERS and usual care in the duration of moderate/vigorous intensity and total PA or other outcomes, for example physical fitness, serum lipids, health-related quality of life (HRQoL). There was no between-group difference in outcomes between ERS and alternative PA interventions or ERS plus a SDT intervention. None of the included trials separately reported outcomes in individuals with medical diagnoses. Fourteen observational studies and five randomised controlled trials provided a numerical assessment of ERS uptake and adherence (UK, n = 16; non-UK, n = 3). Women and older people were more likely to take up ERS but women, when compared with men, were less likely to adhere. The four previous economic evaluations identified suggest ERS to be a cost-effective intervention. Indicative incremental cost per quality-adjusted life-year (QALY) estimates for ERS for various scenarios were based on a de novo model-based economic evaluation. Compared with usual care, the mean incremental cost for ERS was £169 and the mean incremental QALY was 0.008, with the base-case incremental cost-effectiveness ratio at £20,876 per QALY in sedentary people without a medical condition and a cost per QALY of £14,618 in sedentary obese individuals, £12,834 in sedentary hypertensive patients, and £8414 for sedentary individuals with depression. Estimates of cost-effectiveness were highly sensitive to plausible variations in the RR for change in PA and cost of ERS. We found very limited evidence of the effectiveness of ERS. The estimates of the cost-effectiveness of ERS are based on a simple analytical framework. The economic evaluation reports small differences in costs and effects, and findings highlight the wide range of uncertainty associated with the estimates of effectiveness and the impact of effectiveness on HRQoL. No data were identified as part of the effectiveness review to allow for adjustment of the effect of ERS in different populations. There remains considerable uncertainty as to the effectiveness of ERS for increasing activity, fitness or health indicators or whether they are an efficient use of resources in sedentary people without a medical diagnosis. We failed to identify any trial-based evidence of the effectiveness of ERS in those with a medical diagnosis. Future work should include randomised controlled trials assessing the cinical effectiveness and cost-effectivenesss of ERS in disease groups that may benefit from PA. The National Institute for Health Research Health Technology Assessment programme.

Addressing the Challenge for Well Informed and Consistent Reimbursement Decisions

In the context of ever-increasing healthcare expenditures and resource-limited health services, the comparative analysis of costs and benefits of competing healthcare technologies (e.g. pharmaceuticals) is essential to support public funding decisions. Australia has been at the forefront of the integration of economic evidence with reimbursement decisions to fund new pharmaceutical products through a national-level body, the Pharmaceutical Benefits Advisory Committee (PBAC). Pharmaceutical companies submit applications to have their products considered for reimbursement. The PBAC recommendations form the basis of Australian Government decisions about public funding and listing of medicines on the Pharmaceutical Benefits Scheme. The UK National Institute for Health and Clinical Excellence (NICE), amongst others, has adopted guidelines to use economic evidence for reimbursement decision processes. Decision analytic models are an expected framework for the economic evaluation of healthcare technologies submitted to national regulatory bodies such as the PBAC and NICE for public funding. They provide an explicit process for synthesising data from a variety of sources, linking intermediate outcomes to final endpoints (e.g. QALYs), extrapolating beyond the data observed in a clinical trial, and allowing for the appropriate handling and representation of uncertainty around outputs. It is now well accepted that uncertainty is inherent within any model-based economic evaluation and needs to be handled appropriately so that policy makers can have confidence in themodel’s results and/ormake decisions regarding the need for additional information. In model-based evaluations, the sources of uncertainty have been classified into three broad categories. Parameter uncertainty concerns models’ input values (e.g. probabilities of moving between states, resource use estimates) and the fact that the true values of most parameters are unknown. A further source of uncertainty, methodological, relates to the choice of analytic methods such as the perspective taken (e.g. society, government). Structural uncertainty arises from the assumptions imposed by the modelling framework and refers to the structure of the chosen model, i.e. the choice of clinical events represented in a model, and the possible transitions between them. Issues around parameter and methodological uncertainties are generally well understood and continually refined in guidelines developed by the national reimbursement bodies such as the PBAC and NICE (e.g. sensitivity analysis to address parameter uncertainty and using a ‘reference case’ to deal withmethodological uncertainty). Although concerns have been raised regarding the impact of assumptions incorporated in model structures on the quality of models, and conjecture that structural uncertainty may have a greater impact on the model’s results than other sources of uncertainty, relatively little guidance has been EDITORIAL Pharmacoeconomics 2011; doi: 10.2165/11593000-000000000-0000