Miguel A. Negrín

Methodological aspects in the assessment of treatment effects in observational health outcomes studies

Prospective observational studies, which provide information on the effectiveness of interventions in natural settings, may complement results from randomised clinical trials in the evaluation of health technologies. However, observational studies are subject to a number of potential methodological weaknesses, mainly selection and observer bias. This paper reviews and applies various methods to control for selection bias in the estimation of treatment effects and proposes novel ways to assess the presence of observer bias. We also address the issues of estimation and inference in a multilevel setting. We describe and compare the use of regression methods, propensity score matching, fixed-effects models incorporating investigator characteristics, and a multilevel, hierarchical model using Bayesian estimation techniques in the control of selection bias. We also propose to assess the existence of observer bias in observational studies by comparing patient- and investigator-reported outcomes. To illustrate these methods, we have used data from the SOHO (Schizophrenia Outpatient Health Outcomes) study, a large, prospective, observational study of health outcomes associated with the treatment of schizophrenia.The methods used to adjust for differences between treatment groups that could cause selection bias yielded comparable results, reinforcing the validity of the findings. Also, the assessment of observer bias did not show that it existed in the SOHO study. Observational studies, when properly conducted and when using adequate statistical methods, can provide valid information on the evaluation of health technologies.

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.

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.

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 Alzheimers 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.

Gaceta Sanitaria en 2015

A lo largo de 2015 se han recibido 416 manuscritos (además de os artículos del monográfico de lesiones que quedaban pendientes 10 del Informe SESPAS 2016), que representan una disminución e 22 manuscritos respecto a 2014 (fig. 1). Probablemente esto se eba al hecho de que es el primer año completo en que las/los autoas/es que han enviado manuscritos deben pagar parte de los gastos e producción. Al igual que el año anterior, hemos analizado algunas caracteísticas de los manuscritos. De los 416 recibidos, el Comité Editorial a rechazado sin pasar a revisión externa un 54,3% (61,6% en 2014). l motivo más frecuente de rechazo de entrada por parte de la irección fue que el manuscrito no era adecuado para la revista cuatro de cada 10 rechazos). Al analizar las principales caracteísticas asociadas a un menor rechazo de entrada, destacan los anuscritos escritos en inglés, las notas metodológicas y las cartas además de los editoriales y los debates, que suelen ser encargos), aquellos sobre algún tema de epidemiología social o de promoión de la salud. También fueron menos rechazados los manuscritos n que el/la primer/a autor/a pertenecía a un organismo público e investigación o de la Administración sanitaria y procedía de as comunidades autónomas de Aragón, Baleares, Cataluña, Comuidad Valenciana y País Vasco (aunque los números de algunas omunidades autónomas son muy reducidos). Los artículos cuaitativos y los firmados por autores/as de España fueron también enos rechazados de entrada. Las decisiones tomadas por el Comité Editorial en 2015 han mplicado un tiempo de respuesta de 3,1 días de media para el echazo sin revisión externa, y de 37,2 días (o 5,31 semanas) en el aso de rechazo tras la evaluación por personas revisoras externas. l porcentaje total de rechazo de manuscritos (de entrada y desués de ir a evaluación externa) ha sido del 67,4%; en las decisiones e 2014, el rechazo total fue del 68,7%. En la tabla 1 se presentan las 120 contribuciones publicadas en os seis números de 2015 de Gaceta Sanitaria. Para estos manusritos, la mediana entre su recepción y su aceptación definitiva ha ido de 11 semanas (igual que en 2014), y el tiempo entre la recepión y la asignación de volumen y número ha sido de 28 semanas e mediana, lo que supone una reducción a prácticamente la mitad n 2 años (50 semanas en 2013 y 36 en 2014), en parte debido a la isminución del número de manuscritos aceptados pendientes de ublicación. El tiempo hasta la publicación de los trabajos en avance n-line ha sido de 6 semanas de mediana (7 semanas en 2014). En la tabla 2 se muestran otras características de los trabajos ublicados. La mediana de autores por artículo ha sido de cuatro cinco en los originales). El 53,3% de los artículos tiene una mujer

Bayesian regression models for cost-effectiveness analysis.

Recent studies have shown how cost-effectiveness analysis can be undertaken in a regression framework. This contribution explores the use of practical regression models for estimating cost-effectiveness from a Bayesian perspective. Two different Bayesian models are described. The first considers the outcome measure to be a quantitative variable. In the second model the individual outcome measure is a binary variable with value 1 if any objective has been achieved. We describe the implementation of the model using data from a trial that compares two highly active antiretroviral therapies in HIV asymptomatic patients. Data on direct cost and data effectiveness (percentage of patients with undetectable viral load and quality of life) were recorded. If we consider the quality of life as an effectiveness measure, the new treatment is preferred for a willingness to pay more than 142.3 € for an increase in the quality of life. For illustrative purposes, if we compare the results with an analogous model that does not include covariates, the critical value becomes 247.4 €. For the binary measure of effectiveness the control treatment dominates the new treatment.

Optimal healthcare decisions: The importance of the covariates in cost–effectiveness analysis

This paper deals with the decision problem of choosing an optimal medical treatment, among M possible candidates, when the states of nature are the net benefit of the treatments, and regression models for the treatment cost and effectiveness are assumed. In this setting a crucial step in the analysis is the construction of the population subgroups sharing characteristics specified by the covariates, so that optimal decisions are now not for the whole population of patients but for patient population subgroups.

Utilización y tiempos de espera: dos vertientes inseparables del análisis de la equidad en el acceso al sistema sanitario público

El objetivo de esta investigacion consiste en analizar si existe equidad en el acceso a los servicios sanitarios publicos por niveles socioeconomicos. Se analiza conjuntamente la probabilidad de utilizar los servicios sanitarios y los tiempos de espera hasta ser atendidos, corrigiendose asi el sesgo de seleccion que se derivaria de su estudio separado, tal y como se evidencia en esta investigacion. Se propone una aproximacion bayesiana y se hace uso de la informacion a nivel individual sobre la utilizacion sanitaria, tiempos de espera, nivel socioeconomico, necesidad sanitaria y otras variables sociodemograficas contenidas en la En-cuesta nacional de salud (2006). Los resultados muestran que hay inequidad en el acceso a los servicios especializados y hospitalarios (tanto en utilizacion como en tiempos de espera) que perjudica a los niveles socioeconomicos inferiores. En los servicios de medicina general, si bien la utilizacion beneficia relativa-mente mas a los grupos de menor nivel socioeconomico, los tiempos de espera perjudican a los de menor nivel educativo.

Objective Bayesian meta-analysis for sparse discrete data.

This paper presents a Bayesian model for meta-analysis of sparse discrete binomial data, which are out of the scope of the usual hierarchical normal random-effect models. Treatment effectiveness data are often of this type. The crucial linking distribution between the effectiveness conditional on the healthcare center and the unconditional effectiveness is constructed from specific bivariate classes of distributions with given marginals. This assures coherency between the marginal and conditional prior distributions utilized in the analysis. Further, we impose a bivariate class of priors that is able to accommodate a wide range of heterogeneity degrees between the multicenter clinical trials involved. Applications to real multicenter data are given and compared with previous meta-analysis.

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.