Effectiveness of CPAP vs. Noninvasive Ventilation Based on Disease Severity in Obesity Hypoventilation Syndrome and Concomitant Severe Obstructive Sleep Apnea.

RATIONALE: Obesity hypoventilation syndrome (OHS) with concomitant severe obstructive sleep apnea (OSA) is treated with CPAP or noninvasive ventilation (NIV) during sleep. NIV is costlier, but may be advantageous because it provides ventilatory support. However, there are no long-term trials comparing these treatment modalities based on OHS severity. OBJECTIVE: To determine if CPAP have similar effectiveness when compared to NIV according to OHS severity subgroups. METHODS: Post hoc analysis of the Pickwick randomized clinical trial in which 215 ambulatory patients with untreated OHS and concomitant severe OSA, defined as apnoea-hypopnea index (AHI)≥30events/h, were allocated to NIV or CPAP. In the present analysis, the Pickwick cohort was divided in severity subgroups based on the degree of baseline daytime hypercapnia (PaCO2 of 45-49.9 or ≥50mmHg). Repeated measures of PaCO2 and PaO2 during the subsequent 3 years were compared between CPAP and NIV in the two severity subgroups. Statistical analysis was performed using linear mixed-effects model. RESULTS: 204 patients, 97 in the NIV group and 107 in the CPAP group were analyzed. The longitudinal improvements of PaCO2 and PaO2 were similar between CPAP and NIV based on the PaCO2 severity subgroups. CONCLUSION: In ambulatory patients with OHS and concomitant severe OSA who were treated with NIV or CPAP, long-term NIV therapy was similar to CPAP in improving awake hypercapnia, regardless of the severity of baseline hypercapnia. Therefore, in this patient population, the decision to prescribe CPAP or NIV cannot be solely based on the presenting level of PaCO2.

Telemedicine Strategy to Rescue CPAP Therapy in Sleep Apnea Patients with Low Treatment Adherence: A Pilot Study.

Patients with sleep apnea are usually treated with continuous positive airway pressure (CPAP). This therapy is very effective if the patient's adherence is satisfactory. However, although CPAP adherence is usually acceptable during the first months of therapy, it progressively decreases, with a considerable number of patients accepting average treatment duration below the effectiveness threshold (4 h/night). Herein, our aim was to describe and evaluate a novel telemedicine strategy for rescuing CPAP treatment in patients with low adherence after several months/years of treatment. This two-week intervention includes (1) patient support using a smartphone application, phone and voice recorder messages to be answered by a nurse, and (2) daily transmission and analysis of signals from the CPAP device and potential variation of nasal pressure if required. On average, at the end of the intervention, median CPAP adherence considerably increased by 2.17 h/night (from 3.07 to 5.24 h/night). Interestingly, the procedure was able to markedly rescue CPAP adherence: the number of patients with poor adherence (<4 h/night) was considerably reduced from 38 to 7. After one month, adherence improvement was maintained (median 5.09 h/night), and only 13 patients had poor adherence (<4 h/night). This telemedicine intervention (103€ per included patient) is a cost-effective tool for substantially increasing the number of patients with CPAP adherence above the minimum threshold for achieving positive therapeutic effects.

Long-term Noninvasive Ventilation in Obesity Hypoventilation Syndrome Without Severe OSA: The Pickwick Randomized Controlled Trial.

BACKGROUND: Noninvasive ventilation (NIV) is an effective form of treatment in obesity hypoventilation syndrome (OHS) with severe OSA. However, there is paucity of evidence in patients with OHS without severe OSA phenotype. RESEARCH QUESTION: Is NIV effective in OHS without severe OSA phenotype? STUDY DESIGN AND METHODS: In this multicenter, open-label parallel group clinical trial performed at 16 sites in Spain, we randomly assigned 98 stable ambulatory patients with untreated OHS and apnea-hypopnea index < 30 events/h (ie, no severe OSA) to NIV or lifestyle modification (control group) using simple randomization through an electronic database. The primary end point was hospitalization days per year. Secondary end points included other hospital resource utilization, incident cardiovascular events, mortality, respiratory functional tests, BP, quality of life, sleepiness, and other clinical symptoms. Both investigators and patients were aware of the treatment allocation; however, treating physicians from the routine care team were not aware of patients' enrollment in the clinical trial. The study was stopped early in its eighth year because of difficulty identifying patients with OHS without severe OSA. The analysis was performed according to intention-to-treat and per-protocol principles and by adherence subgroups. RESULTS: Forty-nine patients in the NIV group and 49 in the control group were randomized, and 48 patients in each group were analyzed. During a median follow-up of 4.98 years (interquartile range, 2.98-6.62), the mean hospitalization days per year ± SD was 2.60 ± 5.31 in the control group and 2.71 ± 4.52 in the NIV group (adjusted rate ratio, 1.07; 95% CI, 0.44-2.59; P = .882). NIV therapy, in contrast with the control group, produced significant longitudinal improvement in Paco2, pH, bicarbonate, quality of life (Medical Outcome Survey Short Form 36 physical component), and daytime sleepiness. Moreover, per-protocol analysis showed a statistically significant difference for the time until the first ED visit favoring NIV. In the subgroup with high NIV adherence, the time until the first event of hospital admission, ED visit, and mortality was longer than in the low adherence subgroup. Adverse events were similar between arms. INTERPRETATION: In stable ambulatory patients with OHS without severe OSA, NIV and lifestyle modification had similar long-term hospitalization days per year. A more intensive program aimed at improving NIV adherence may lead to better outcomes. Larger studies are necessary to better determine the long-term benefit of NIV in this subgroup of OHS. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01405976; URL: www.clinicaltrials.gov.

Echocardiographic Changes with Positive Airway Pressure Therapy in Obesity Hypoventilation Syndrome. Long-Term Pickwick Randomized Controlled Clinical Trial.

Rationale: Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking.Objectives: In a prespecified secondary analysis of the largest multicenter randomized controlled trial of OHS (Pickwick Project; N = 221 patients with OHS and coexistent severe obstructive sleep apnea), we compared the effectiveness of three years of NIV and CPAP on structural and functional echocardiographic changes.Methods: At baseline and annually during three sequential years, patients underwent transthoracic two-dimensional and Doppler echocardiography. Echocardiographers at each site were blinded to the treatment allocation. Statistical analysis was performed using a linear mixed-effects model with a treatment group and repeated measures interaction to determine the differential effect between CPAP and NIV.Measurements and Main Results: A total of 196 patients were analyzed: 102 were treated with CPAP and 94 were treated with NIV. Systolic pulmonary artery pressure decreased from 40.5 ± 1.47 mm Hg at baseline to 35.3 ± 1.33 mm Hg at three years with CPAP, and from 41.5 ± 1.56 mm Hg to 35.5 ± 1.42 with NIV (P < 0.0001 for longitudinal intragroup changes for both treatment arms). However, there were no significant differences between groups. NIV and CPAP therapies similarly improved left ventricular diastolic dysfunction and reduced left atrial diameter. Both NIV and CPAP improved respiratory function and dyspnea.Conclusions: In patients with OHS who have concomitant severe obstructive sleep apnea, long-term treatment with NIV and CPAP led to similar degrees of improvement in pulmonary hypertension and left ventricular diastolic dysfunction.Clinical trial registered with www.clinicaltrials.gov (NCT01405976).

Trends in horizontal inequity in access to public health care services by immigrant condition in Spain (2006-2017).

BACKGROUND: The objective of this research is to analyse trends in horizontal inequity in access to public health services by immigration condition in Spain throughout the period 2006-2017. We focus on "economic immigrants" because they are potentially the most vulnerable group amongst immigrants. METHODS: Based on the National Health Surveys of 2006-07 (N = 29,478), 2011-12 (N = 20,884) and 2016-17 (N = 22,903), hierarchical logistic regressions with random effects in Spain's autonomous communities are estimated to explain the probability of using publicly-financed health care services by immigrant condition, controlling by health care need and other socioeconomic and demographic variables. RESULTS: Our results indicate that there are several horizontal inequities, though they changed throughout the decade studied. Regarding primary care services, the period starts (2006-07) with no global evidence of horizontal inequity in access (although the analysis by continent shows inequity that is detrimental to Eastern Europeans and Asians), giving way to inequity favouring economic immigrants (particularly Latin Americans and Africans) in 2011-12 and 2016-17. An opposite trend happens with specialist care, as the period starts (2006-07) with evidence of inequity that is detrimental to economic immigrants (particularly those from North of Africa) but this inequity disappears with the economic crisis and after it (with the only exception of Eastern Europeans in 2011-12, whose probability to visit a specialist is lower than for natives). Regarding emergency care, our evidence indicates horizontal inequity in access that favours economic immigrants (particularly Latin Americans and North Africans) that remains throughout the period. In general, there is no inequity in hospitalisations, with the exception of 2011-12, where inequity in favour of economic immigrants (particularly those from Latin America) takes place. CONCLUSIONS: The results obtained here may serve, firstly, to prevent alarm about negative discrimination of economic immigrants in their access to public health services, even after the implementation of the Royal Decree RD Law 16/2012. Conversely, our results suggest that the horizontal inequity in access to specialist care that was found to be detrimental to economic immigrants in 2006-07, disappeared in global terms in 2011-12 and also by continent of origin in 2016-17.

Comprehensive management of obstructive sleep apnea by telemedicine: Clinical improvement and cost-effectiveness of a Virtual Sleep Unit. A randomized controlled trial.

INTRODUCTION: Obstructive sleep apnea (OSA) is a prevalent disease associated with significant morbidity and high healthcare costs. Information and communication technology could offer cost-effective management options. OBJECTIVES: To evaluate an out-of-hospital Virtual Sleep Unit (VSU) based on telemedicine to manage all patients with suspected OSA, including those with and without continuous positive airway pressure (CPAP) therapy. METHODS: This was an open randomized controlled trial. Patients with suspected OSA were randomized to hospital routine (HR) or VSU groups to compare the clinical improvement and cost-effectiveness in a non-inferiority analysis. Improvement was assessed by changes in the Quebec Sleep Questionnaire (QSQ), EuroQol (EQ-5D and EQ-VAS), and Epworth Sleepiness Scale (ESS). The follow-up was 3 months. Cost-effectiveness was assessed by a Bayesian analysis based on quality-adjusted life-years (QALYs). RESULTS: The HR group (n: 92; 78% OSA, 57% CPAP) compared with the VSU group (n: 94; 83% OSA, 43% CPAP) showed: CPAP compliance was similar in both groups, the QSQ social interactions domain improved significantly more in the HR group whereas the EQ-VAS improved more in the VSU group. Total and OSA-related costs were lower in the VSU group than the HR. The Bayesian cost-effectiveness analysis showed that VSU was cost-effective for a wide range of willingness to pay for QALYs. CONCLUSIONS: The VSU offered a cost-effective means of improving QALYs than HR. However, the assessment of its clinical improvement was influenced by the choice of the questionnaire; hence, additional measurements of clinical improvement are needed. Our findings indicate that VSU could help with the management of many patients, irrespective of CPAP use.

Long-term clinical effectiveness of continuous positive airway pressure therapy versus non-invasive ventilation therapy in patients with obesity hypoventilation syndrome: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Obesity hypoventilation syndrome is commonly treated with continuous positive airway pressure or non-invasive ventilation during sleep. Non-invasive ventilation is more complex and costly than continuous positive airway pressure but might be advantageous because it provides ventilatory support. To date there have been no long-term trials comparing these treatment modalities. We therefore aimed to determine the long-term comparative effectiveness of both treatment modalities. METHODS: We did a multicentre, open-label, randomised controlled trial at 16 clinical sites in Spain. We included patients aged 15-80 years with untreated obesity hypoventilation syndrome and an apnoea-hypopnoea index of 30 or more events per h. We randomly assigned patients, using simple randomisation through an electronic database, to receive treatment with either non-invasive ventilation or continuous positive airway pressure. Both investigators and patients were aware of the treatment allocation. The research team was not involved in deciding hospital treatment, duration of treatment in the hospital, and adjustment of medications, as well as adjudicating cardiovascular events or cause of mortality. Treating clinicians from the routine care team were not aware of the treatment allocation. The primary outcome was the number of hospitalisation days per year. The analysis was done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01405976. FINDINGS: From May 4, 2009, to March 25, 2013, 100 patients were randomly assigned to the non-invasive ventilation group and 115 to the continuous positive airway pressure group, of which 97 patients in the non-invasive ventilation group and 107 in the continuous positive airway pressure group were included in the analysis. The median follow-up was 5·44 years (IQR 4·45-6·37) for all patients, 5·37 years (4·36-6·32) in the continuous positive airway pressure group, and 5·55 years (4·53-6·50) in the non-invasive ventilation group. The mean hospitalisation days per patient-year were 1·63 (SD 3·74) in the continuous positive airway pressure group and 1·44 (3·07) in the non-invasive ventilation group (adjusted rate ratio 0·78, 95% CI 0·34-1·77; p=0·561). Adverse events were similar between both groups. INTERPRETATION: In stable patients with obesity hypoventilation syndrome and severe obstructive sleep apnoea, non-invasive ventilation and continuous positive airway pressure have similar long-term effectiveness. Given that continuous positive airway pressure has lower complexity and cost, continuous positive airway pressure might be the preferred first-line positive airway pressure treatment modality until more studies become available. FUNDING: Instituto de Salud Carlos III, Spanish Respiratory Foundation, and Air Liquide Spain.

Impact of the Spanish smoke-free laws on cigarette sales, 2000-2015: partial bans on smoking in public places failed and only a total tobacco ban worked.

In January 2006, the Spanish government enacted a tobacco control law that banned smoking in bars and restaurants, with exceptions depending on the floor space of the premises. In January 2011, further legislation in this area was adopted, removing these exceptions. We analyse the effect produced on cigarette sales by these two bans. We approach this problem using an interrupted time series analysis while accounting for the potential effects of autocorrelation and seasonality. The data source used was the official data on legal sales of tobacco in Spain, from January 2000 to December 2015 (excluding the Canary Islands and the autonomous cities of Ceuta and Melilla). As confounder variables, we use the log-transformed average prices for manufactured and hand-rolled cigarettes (or the average minimum excise tax as a proxy), and log-transformed real-household disposable income. The implementation of a total smoke-free ban in Spain was associated with an immediate reduction in cigarette sales between 9% to 11%. In contrast, in the period immediately following the partial ban, no such reduction was detected, beyond the trend already present. Our results indicate that, in Spain, partial bans on smoking in public places failed, and that only a total tobacco ban worked.

Bayesian meta-analysis: The role of the between-sample heterogeneity.

The random effect approach for meta-analysis was motivated by a lack of consistent assessment of homogeneity of treatment effect before pooling. The random effect model assumes that the distribution of the treatment effect is fully heterogenous across the experiments. However, other models arising by grouping some of the experiments are plausible. We illustrate on simulated binary experiments that the fully heterogenous model gives a poor meta-inference when fully heterogeneity is not the true model and that the knowledge of the true cluster model considerably improves the inference. We propose the use of a Bayesian model selection procedure for estimating the true cluster model, and Bayesian model averaging to incorporate into the meta-analysis the clustering estimation. A well-known meta-analysis for six major multicentre trials to assess the efficacy of a given dose of aspirin in post-myocardial infarction patients is reanalysed.

Bayesian Solutions for Handling Uncertainty in Survival Extrapolation.

OBJECTIVE: Survival extrapolation using a single, best-fit model ignores 2 sources of model uncertainty: uncertainty in the true underlying distribution and uncertainty about the stability of the model parameters over time. Bayesian model averaging (BMA) has been used to account for the former, but it can also account for the latter. We investigated BMA using a published comparison of the Charnley and Spectron hip prostheses using the original 8-year follow-up registry data. METHODS: A wide variety of alternative distributions were fitted. Two additional distributions were used to address uncertainty about parameter stability: optimistic and skeptical. The optimistic (skeptical) model represented the model distribution with the highest (lowest) estimated probabilities of survival but reestimated using, as prior information, the most optimistic (skeptical) parameter estimated for intermediate follow-up periods. Distributions were then averaged assuming the same posterior probabilities for the optimistic, skeptical, and noninformative models. Cost-effectiveness was compared using both the original 8-year and extended 16-year follow-up data. RESULTS: We found that all models obtained similar revision-free years during the observed period. In contrast, there was variability over the decision time horizon. Over the observed period, we detected considerable uncertainty in the shape parameter for Spectron. After BMA, Spectron was cost-effective at a threshold of £20,000 with 93% probability, whereas the best-fit model was 100%; by contrast, with a 16-year follow-up, it was 0%. CONCLUSIONS: This case study casts doubt on the ability of the single best-fit model selected by information criteria statistics to adequately capture model uncertainty. Under this scenario, BMA weighted by posterior probabilities better addressed model uncertainty. However, there is still value in regularly updating health economic models, even where decision uncertainty is low.

A Bayesian cost-effectiveness analysis of a telemedicine-based strategy for the management of sleep apnoea: a multicentre randomised controlled trial.

BACKGROUND: Compliance with continuous positive airway pressure (CPAP) therapy is essential in patients with obstructive sleep apnoea (OSA), but adequate control is not always possible. This is clinically important because CPAP can reverse the morbidity and mortality associated with OSA. Telemedicine, with support provided via a web platform and video conferences, could represent a cost-effective alternative to standard care management. AIM: To assess the telemedicine impact on treatment compliance, cost-effectiveness and improvement in quality of life (QoL) when compared with traditional face-to-face follow-up. METHODS: A randomised controlled trial was performed to compare a telemedicine-based CPAP follow-up strategy with standard face-to-face management. Consecutive OSA patients requiring CPAP treatment, with sufficient internet skills and who agreed to participate, were enrolled. They were followed-up at 1, 3 and 6 months and answered surveys about sleep, CPAP side effects and lifestyle. We compared CPAP compliance, cost-effectiveness and QoL between the beginning and the end of the study. A Bayesian cost-effectiveness analysis with non-informative priors was performed. RESULTS: We randomised 139 patients. At 6 months, we found similar levels of CPAP compliance, and improved daytime sleepiness, QoL, side effects and degree of satisfaction in both groups. Despite requiring more visits, the telemedicine group was more cost-effective: costs were lower and differences in effectiveness were not relevant. CONCLUSIONS: A telemedicine-based strategy for the follow-up of CPAP treatment in patients with OSA was as effective as standard hospital-based care in terms of CPAP compliance and symptom improvement, with comparable side effects and satisfaction rates. The telemedicine-based strategy had lower total costs due to savings on transport and less lost productivity (indirect costs). TRIAL REGISTER NUMBER: NCT01716676.

A Bayesian sensitivity study of risk difference in the meta-analysis of binary outcomes from sparse data.

In most cases, including those of discrete random variables, statistical meta-analysis is carried out using the normal random effect model. The authors argue that normal approximation does not always properly reflect the underlying uncertainty of the original discrete data. Furthermore, in the presence of rare events the results from this approximation can be very poor. This review proposes a Bayesian meta-analysis to address binary outcomes from sparse data and also introduces a simple way to examine the sensitivity of the quantities of interest in the meta-analysis with respect to the structure dependence selected. The findings suggest that for binary outcomes data it is possible to develop a Bayesian procedure, which can be directly applied to sparse data without ad hoc corrections. By choosing a suitable class of linking distributions, the authors found that a Bayesian robustness study can be easily implemented. For illustrative purposes, an example with real data is analyzed using the proposed Bayesian meta-analysis for binomial sparse data.

Effectiveness of three sleep apnea management alternatives.

RATIONALE: Home respiratory polygraphy (HRP) may be a cost-effective alternative to polysomnography (PSG) for diagnosis and treatment election in patients with high clinical probability of obstructive sleep apnea (OSA), but there is conflicting evidence on its use for a wider spectrum of patients. OBJECTIVES: To determine the efficacy and cost of OSA management (diagnosis and therapeutic decision making) using (1) PSG for all patients (PSG arm); (2) HRP for all patients (HRP arm); and (3) HRP for a subsample of patients with high clinical probability of being treated with continuous positive airway pressure (CPAP) and PSG for the remainder (elective HRP arm). METHODS: Multicentric study of 366 patients with intermediate-high clinical probability of OSA, randomly subjected to HRP and PSG. We explored the diagnostic and therapeutic decision agreements between the PSG and both HRP arms for several HRP cutoff points and calculated costs for equal diagnostic and/or therapeutic decision efficacy. RESULTS: For equal diagnostic and therapeutic decision efficacy, PSG arm costs were 18% higher than HRP arm costs and 20% higher than elective HRP arm costs. HRP arm costs tended to be lower than elective HRP arm costs, and both tended to be lower than PSG arm costs if patient costs were omitted. CONCLUSION: Home respiratory polygraphy is a less costly alternative than polysomnography for the diagnosis and therapeutic decision making for patients with suspected obstructive sleep apnea. We found no advantage in cost terms, however, in using home respiratory polygraphy for all patients or home respiratory polygraphy for the most symptomatic patients and polysomnography for the rest.

Effectiveness of home respiratory polygraphy for the diagnosis of sleep apnoea and hypopnoea syndrome.

INTRODUCTION: Home respiratory polygraphy (HRP) may be a cost-effective alternative to polysomnography for the diagnosis of sleep apnoea-hypopnoea syndrome (SAHS), but stronger evidence is needed. Normally, patients transport HRP equipment from the hospital to home and back, which may create difficulties for some patients. OBJECTIVES: To determine both the diagnostic efficacy and cost of HRP (with and without a transportation service moving the device and telematic transmission of data) in a large sample compared with in-hospital polysomnography. METHODS: Patients suspected of having SAHS were included in a multicentre study (eight hospitals). They were assigned to home and hospital protocols in random order. Receiver operating characteristic curves were constructed for manual respiratory polygraphy scoring protocol and different polysomnographic cut-off points. Diagnostic efficacies for several polysomnographic cut-off points were explored and costs for two equally effective alternatives were calculated. RESULTS: Of 366 randomised patients, 348 completed the protocol. The best receiver operating characteristic curve was obtained with a polysomnographic cut-off of the apnoea-hypopnoea index (AHI)≥5. The sensitive HRP AHI cut-off point (<5) had a sensitivity of 96%, a specificity of 57% and a negative likelihood ratio (LR) of 0.07; the specific cut-off (>10) had a sensitivity of 87%, a specificity of 86% and a positive LR of 6.25. The cost of HRP was half that of polysomnography. Telematic transmission costs were similar if the patients' costs were taken in to account. CONCLUSION: HRP is an alternative to polysomnography in patients with suspected SAHS. Telematic procedures may help patients with limited mobility and those who live a long way from the sleep centre.

Bayesian variable selection in cost-effectiveness analysis.

Linear regression models are often used to represent the cost and effectiveness of medical treatment. The covariates used may include sociodemographic variables, such as age, gender or race; clinical variables, such as initial health status, years of treatment or the existence of concomitant illnesses; and a binary variable indicating the treatment received. However, most studies estimate only one model, which usually includes all the covariates. This procedure ignores the question of uncertainty in model selection. In this paper, we examine four alternative Bayesian variable selection methods that have been proposed. In this analysis, we estimate the inclusion probability of each covariate in the real model conditional on the data. Variable selection can be useful for estimating incremental effectiveness and incremental cost, through Bayesian model averaging, as well as for subgroup analysis.

Willingness to pay for alternative policies for patients with Alzheimer's Disease.

This paper focuses on eliciting the willingness to pay (WTP) for policy measures aimed at improving the health care offered to patients suffering from Alzheimer's disease (AD). We utilize a discrete choice experiment (DCE) approach for the elicitation of the preferences of the general population for three alternative policies: home care, day care centres, and medium or long-stay centres. The results show that these policies are significantly valued across the surveyed population. The monthly WTP per hour of home care is estimated as 4 euros per individual, while the monthly WTP values for full population coverage in day centres and medium-long-stay centres are estimated as 0.43 euros and 0.42 euros respectively. We compare the results of classical and Bayesian estimation methods, and conclude that the latter provide a better representation of the heterogeneity in the sample. The results are significant for health care, as they enable policymakers to identify the social demand for such services, as well as the relative economic values placed on the alternative policy measures.

Incorporating model uncertainty in cost-effectiveness analysis: a Bayesian model averaging approach.

Recently, several authors have proposed the use of linear regression models in cost-effectiveness analysis. In this paper, by modelling costs and outcomes using patient and Health Centre covariates, we seek to identify the part of the cost or outcome difference that is not attributable to the treatment itself, but to the patients' condition or to characteristics of the Centres. Selection of the covariates to be included as predictors of effectiveness and cost is usually assumed by the researcher. This behaviour ignores the uncertainty associated with model selection and leads to underestimation of the uncertainty about quantities of interest. We propose the use of Bayesian model averaging as a mechanism to account for such uncertainty about the model. Data from a clinical trial are used to analyze the effect of incorporating model uncertainty, by comparing two highly active antiretroviral treatments applied to asymptomatic HIV patients. The joint posterior density of incremental effectiveness and cost and cost-effectiveness acceptability curves are proposed as decision-making measures.

Bayesian cost-effectiveness analysis with two measures of effectiveness: the cost-effectiveness acceptability plane.

Cost-effectiveness analysis (CEA) compares the costs and outcomes of two or more technologies. However, there is no consensus about which measure of effectiveness should be used in each analysis. Clinical researchers have to select an appropriate outcome for their purpose, and this choice can have dramatic consequences on the conclusions of their analysis. In this paper we present a Bayesian cost-effectiveness framework to carry out CEA when more than one measure is considered. In particular, we analyse the case in which two measures of effectiveness, one binary and the other continuous, are considered. Decision-making measures, such as the incremental cost-effectiveness ratio, incremental net-benefit and cost-effectiveness acceptability curves, are used to compare costs and one measure of outcome. We propose an extension of cost-acceptability curves, namely the cost-effectiveness acceptability plane, as a suitable measure for decision taking. The models were validated using data from two clinical trials. In the first one, we compared four highly active antiretroviral treatments applied to asymptomatic HIV patients. As measures of effectiveness, we considered the percentage of patients with undetectable levels of viral load, and changes in quality of life, measured according to EuroQol. In the second clinical trial we compared three methadone maintenance programmes for opioid-addicted patients. In this case, the measures of effectiveness considered were quality of life, according to the Nottingham Health Profile, and adherence to the treatment, measured as the percentage of patients who participated in the whole treatment programme.

Self-perceived health status of schizophrenic patients in Spain: analysis of geographic differences.

This report explores the use of regression models for estimating health status of schizophrenic patients from a Bayesian perspective. The aims are: to obtain a set of values of health states of the EQ-5D based on self-assessed health from a sample of schizophrenic patients; and to analyze the differences in the health status and in patients' perceptions of their health status between four mental health districts in Spain. The authors develop two linear models with dummy variables. The first model seeks to obtain an index of the health status of the patients using a visual analog scale as a dependent variable and the different dimensions of EQ-5D as regressors. The second model enables analysis of the differences between the self-assessed health status in the different geographic areas and also the differences between the patients' self-assessed health states, irrespective of their actual health state, in the different geographic areas. The analysis is done using a Bayesian approach with Gibbs sampling (computer program WinBUGS 1.4). Data concerning self-assessed EQ-5D with visual analog scale from four geographic areas of schizophrenic patients were obtained for the purposes of this analysis. The health status index for this sample was obtained and the differences for this index between the four geographic areas were analyzed. The study reveals variables that explain the differences in patients' health status and health state assessment. Four possible scenarios are considered.