Methods for Population Adjustment with Limited Access to Individual Patient Data: A Review and Simulation Study

Population-adjusted indirect comparisons estimate treatment effects when access to individual patient data is limited and there are cross-trial differences in effect modifiers. Popular methods include matching-adjusted indirect comparison (MAIC) and simulated treatment comparison (STC). There is limited formal evaluation of these methods and whether they can be used to accurately compare treatments. Thus, we undertake a comprehensive simulation study to compare standard unadjusted indirect comparisons, MAIC and STC across 162 scenarios. This simulation study assumes that the trials are investigating survival outcomes and measure continuous covariates, with the log hazard ratio as the measure of effect. MAIC yields unbiased treatment effect estimates under no failures of assumptions. The typical usage of STC produces bias because it targets a conditional treatment effect where the target estimand should be a marginal treatment effect. The incompatibility of estimates in the indirect comparison leads to bias as the measure of effect is non-collapsible. Standard indirect comparisons are systematically biased, particularly under stronger covariate imbalance and interaction effects. Standard errors and coverage rates are often valid in MAIC but the robust sandwich variance estimator underestimates variability where effective sample sizes are small. Interval estimates for the standard indirect comparison are too narrow and STC suffers from bias-induced undercoverage. MAIC provides the most accurate estimates and, with lower degrees of covariate overlap, its bias reduction outweighs the loss in effective sample size and precision under no failures of assumptions. An important future objective is the development of an alternative formulation to STC that targets a marginal treatment effect.Comment: 73 pages (34 are supplementary appendices and references), 8 figures, 2 tables. Full article (following Round 4 of minor revisions). arXiv admin note: text overlap with arXiv:2008.0595

Towards the Delimitation of a Conceptual Theoretical Framework for Evaluation Research

Los distintos enfoques aplicados a la evaluación de las políticas públicas se sitúan generalmente, en un marco conceptual de carácter técnico. Esto ha significado que las políticas públicas son entendidas como procesos secuenciales que deben ser analizados por etapas y en función de definiciones unificadoras de problemas de intervención. Tales enfoques, sin embargo, simplifican y limitan el análisis de estos complejos procesos de toma de decisiones. Al trabajar a partir de los conceptos de coordinación descentralizada y diferenciación contextual, es posible identificar distintas dimensiones involucradas en los procesos de intervención pública a la vez que las formas como estas se vinculan y coordinan en su implementación. Entender las políticas públicas más allá de su dimensión política y reconociendo la contraposición de intereses y expectativas como factores determinantes de sus resultados, obliga a repensar la investigación y evaluación de las políticas públicas, alejándose de las estrategias más tradicionales que se centran en enfoques de carácter técnico.The different approaches to public policy evaluation are usually situated in a framework of a technical nature. This has meant that public policies are understood as sequential processes that must be ana­lyzed in stages and in function of unifying definitions of the intervention problems. Such analysis ap­proaches, however, simplify and limit the analysis of these complex decision making processes. By working from the concepts of decentralized coordination and contextual differentiation, we can identify different dimensions involved in the processes of public intervention, as well as the ways on which these are linked and coordinated in its implementation. Understanding public policies beyond their po­litical dimension and recognizing the conflict of interests and expectations as determinants of outcomes; force us to rethink the research and evaluation of public policies, moving away from more traditional strategies focused on technical approaches.&nbsp

Religión y Libertad en la Independencia de los Estados Unidos de Norteamérica: desde la Emancipación Reformada a la Emancipación Ilustrada

The main characteristic of the so called "American Dream" lies in the fact of being strongly rooted in historical consciousness as the basis of identity and, therefore, as germ of custom and culture. Consequently, to fully understand the history of the United States, it is essential to refer to its origins, specifically with regard to the central role played by religion in the process of independence of the thirteen colonies. Does the history of the United States represent a unique and original event in universal history? Can it be said that the religious factor played a catalytic role in the political, social and economic development? To what extent religion granted unity and identity to the formation process of American culture, paving the way for the subsequent birth of a new political ideology

La democracia tocquevilliana: entre el dualismo y la dialéctica de la libertad

For Alexis de Tocqueville, a faithful son of the Enlightenment, the priority given to the individual in the pursuit of truth represents the starting point of an inexorable march of equality towards individual autonomy. In other words, in agreement with the historicist movements of the 19th Century, Tocqueville interprets history as a dialectical progress: History understood as progress in the Hegelian sense, whose becoming unfolds in virtue of a steady and unalterable progress towards a better society-civilization as a creation of the illustrated man. However, while for Hegel progress obeys a reason understood as self-knowledge, Tocqueville understands it as a balance between antagonisms: liberty-individual-democracy. In other words, the Tocquevillian dualism, expressed in the permanent tension between antagonisms equality vs. freedom, the individual vs the citizen–, leads towards a new class of dialectics of liberty. In this sense, the aforementioned triad represents, precisely, the tension that reveals itself as problematic, given that, ultimately, the elements that compose it arise antithetically

Transportability of model-based estimands in evidence synthesis

In evidence synthesis, effect modifiers are typically described as variables that induce treatment effect heterogeneity at the individual level, through treatment-covariate interactions in an outcome model parametrized at such level. As such, effect modification is defined with respect to a conditional measure, but marginal effect estimates are required for population-level decisions in health technology assessment. For non-collapsible measures, purely prognostic variables that are not determinants of treatment response at the individual level may modify marginal effects, even where there is individual-level treatment effect homogeneity. With heterogeneity, marginal effects for measures that are not directly collapsible cannot be expressed in terms of marginal covariate moments, and generally depend on the joint distribution of conditional effect measure modifiers and purely prognostic variables. There are implications for recommended practices in evidence synthesis. Unadjusted anchored indirect comparisons can be biased in the absence of individual-level treatment effect heterogeneity, or when marginal covariate moments are balanced across studies. Covariate adjustment may be necessary to account for cross-study imbalances in joint covariate distributions involving purely prognostic variables. In the absence of individual patient data for the target, covariate adjustment approaches are inherently limited in their ability to remove bias for measures that are not directly collapsible. Directly collapsible measures would facilitate the transportability of marginal effects between studies by: (1) reducing dependence on model-based covariate adjustment where there is individual-level treatment effect homogeneity and marginal covariate moments are balanced; and (2) facilitating the selection of baseline covariates for adjustment where there is individual-level treatment effect heterogeneity.Comment: 33 pages, 3 figures. Re-submitted to Statistics in Medicine after revision

Population-Adjusted Indirect Treatment Comparisons with Limited Access to Patient-Level Data

Health technology assessment systems base their decision-making on health-economic evaluations. These require accurate relative treatment effect estimates for specific patient populations. In an ideal scenario, a head-to-head randomized controlled trial, directly comparing the interventions of interest, would be available. Indirect treatment comparisons are necessary to contrast treatments which have not been analyzed in the same trial. Population-adjusted indirect comparisons estimate treatment effects where there are: no head-to-head trials between the interventions of interest, limited access to patient-level data, and cross-trial differences in effect measure modifiers. Health technology assessment agencies are increasingly accepting evaluations that use these methods across a diverse range of therapeutic areas. Popular approaches include matching-adjusted indirect comparison (MAIC), based on propensity score weighting, and simulated treatment comparison (STC), based on outcome regression. There is limited formal evaluation of these methods and whether they can be used to accurately compare treatments. Thus, I undertake a review and a simulation study that compares the standard unadjusted indirect comparisons, MAIC and STC across 162 scenarios. This simulation study assumes that the trials are investigating survival outcomes and measure continuous covariates, with the log hazard ratio as the measure of effect — one of the most widely used setups in health technology assessment applications. MAIC yields unbiased treatment effect estimates under no failures of assumptions. The typical usage of STC produces bias because it targets a conditional treatment effect where the target estimand should be a marginal treatment effect. The incompatibility of estimates in the indirect comparison leads to bias as the measure of effect is non-collapsible. When adjusting for covariates, one must integrate or average the conditional model over the population of interest to recover a compatible marginal treatment effect. I propose a marginalization method based on parametric G-computation that can be easily applied where the outcome regression is a generalized linear model or a Cox model. In addition, I introduce a novel general-purpose method based on the ideas underlying multiple imputation, which is termed multiple imputation marginalization (MIM) and is applicable to a wide range of models, including parametric survival models. The approaches view the covariate adjustment regression as a nuisance model and separate its estimation from the evaluation of the marginal treatment effect of interest. Both methods can accommodate a Bayesian statistical framework, which naturally integrates the analysis into a probabilistic framework, typically required for health technology assessment. Another simulation study provides proof-of-principle for the methods and benchmarks their performance against MAIC and the conventional STC. The simulations are based on scenarios with binary outcomes and continuous covariates, with the log-odds ratio as the measure of effect. The marginalized outcome regression approaches achieve more precise and more accurate estimates than MAIC, particularly when covariate overlap is poor, and yield unbiased marginal treatment effect estimates under no failures of assumptions. Furthermore, regressionadjusted estimates of the marginal effect provide greater precision and accuracy than the conditional estimates produced by the conventional STC, which are systematically biased because the log-odds ratio is a non-collapsible measure of effect. The marginalization methods outlined in this thesis are necessary and important for health technology assessment more generally, because marginal treatment effects should be the preferred inferential target for reimbursement decisions at the population level. Treatment effectiveness inputs in health economic models are often informed by the treatment coefficient of a multivariable regression. An often overlooked issue is that this has a conditional interpretation, and that the coefficients of the regression must be marginalized over the target population of interest to produce a relevant estimate for reimbursement decisions at the population level

Paradigmatic Tendencies in Cartography: A Synthesis of the Scientific-Empirical, Critical and Post-Representational Perspectives

Maps have been important elements of visual representation in the development of different societies, and for this reason they have mainly been considered from a practical and utilitarian point of view. This means that cartographers or mapmakers have largely focused on the technical aspects of the cartographic products, and cartography has given little attention to both its theoretical component and to its philosophical and epistemological aspects. The current study is dedicated to consider these views. In this study the main trends, thoughts and different directions in cartography during positivism/empiricism, neo-positivism and post-structuralism are reviewed; and cartography is analysed under the modernism and post-modernism periods. Some of the arguments proposed by philosophers such as Ludwig Wittgenstein and Karl Popper are examined as important contributions in our understanding of the development of cartography and mapping. This study also incorporates the idea or concept of paradigm, which has been taken from the field of the epistemology of sciences. The aforementioned opens a space to analyse cartography in terms of a paradigm shift. In the analysis of each trend within contemporary cartography – from the second half of the twentieth century until today – it is necessary to keep in mind the theoretical scheme of a scientific discipline (object of study, research aims, methods and approaches, and results). This helps to determine the body of knowledge in cartography. It is also important to consider the epistemological context in which the tendencies are developed: positivism/empiricism, realism/structuralism and idealism/hermeneutic. In this way, by considering three epistemological levels - essentialist/ontical (scientific), deconstructive (sociological), and ontological (emergent) - some paradigmatic tendencies are postulated. The first level results in tendencies such as cartographic communication, cartographic semiotics, analytical cartography and cartographic visualisation - all of these belong to the scientific-empirical perspective. In the second level, we have critical cartography, belonging to the critical perspective and that confronts the scientific stances. Finally, in the third level the so-called post-representational cartography arises in open opposition to the traditional representational cartography.Im Entwicklungsprozess verschiedener Gesellschaften sind Karten immer wichtige Elemente visueller Darstellung gewesen. Karten wurden meist aus einer praktischen und utilitaristischen Sicht betrachtet. Das heißt, dass sich Kartographen oder Kartenmacher gezielt auf die technischen Aspekte kartographischer Produkte fokussiert haben, und Kartographie sich nur wenig mit den theoretischen Komponenten und philosophischen oder epistemologischen Aspekten auseinandergesetzt hat. Diese Arbeit verfolgt das Ziel, diese Sichten zu analysieren. Diese Studie untersucht die verschiedenen kartographischen Denkrichtungen, die während des Positivismus/Empirismus, des Neo-Positivismus und der Post-Strukturalismusperioden entstanden sind und analysiert Kartographie der Moderne und post-moderner Perioden. Argumente von Philosophen wie Ludwig Wittgenstein und Karl Popper werden untersucht als wichtige Beiträge zu unserem Verständnis der Entwicklung der Kartographie. Diese Arbeit berücksichtigt auch das Konzept des Paradigmas, welches aus dem Gebiet der wissenschaftlichen Epistemologie adaptiert wurde. Dies eröffnet die Möglichkeit, Kartographie hinsichtlich eines Paradigmenwechsels analysieren zu können. Wenn man die Tendenzen der zeitgenössischen Kartographie – von der zweiten Hälfte des zwanzigsten Jahrhunderts bis heute – studiert, muss der theoretische Rahmen einer wissenschaftlichen Disziplin (Forschungsobjekt, Forschungsziel, Arbeitsmethodik und Ergebnisse) berücksichtigt werden. Dies erlaubt es, das gesammelte Wissen der Kartographie zu ermitteln. Ebenfalls wichtig ist die Berücksichtigung des epistemologischen Kontexts, in dem diese Tendenzen entstanden: Positivismus/Empirismus, Realismus/Strukturalismus und Idealismus/Hermeneutik. Unter Berücksichtigung dreier epistemologischer Ebenen – Essenzialisten/ontisch (wissenschaftlich), dekonstructiv (soziologisch) und ontologisch (emergent) – werden ausgewählte paradigmatische Tendenzen postuliert. Die erste Ebene ergibt Tendenzen wie die kartographische Kommunikation, die kartographische Semiotik, die analytische Kartographie und die kartographische Visualisierung, die alle zu der wissenschaftlich-empirischen Perspektive gehören. Zur zweiten Ebene gehört die kritische Kartographie, welche der kritischen Perspektive zugeordnet ist und die wissenschaftliche Standpunkte konfrontiert. Die so genannte post-repräsentative Kartographie entsteht aus der dritten Ebene im offenen Widerstand zur traditionellen repräsentativen Kartographie

Limitaciones al derecho de huelga en Chile: los servicios esenciales, el reemplazo de trabajadores y los servicios mínimos en el contexto de la reforma laboral

The right to strike is a fundamental right. The purpose is to ensure that there is sufficient protection for organizations that want to organize, especially with the possibility that eventually workers can negotiate on equal conditions with their employers. However, like any right recognized in law, it should merge and interact in the legal system with various rights, since in a pluralistic and democratic systems, limited rights do not exist. Thus, the right to strike is subject to limits and restrictions, these limits & restrictions can take affect only before extraordinary and authorized situations. For example in a serious national crisis or in the case of public service or essential services, in the strict sense term, limits can occur.No cabe duda que el derecho de huelga es un derecho fundamental, cuyo propósito es garantizar una adecuada protección al ejercicio del derecho de organización que gozan los trabajadores, y sobre todo a la posibilidad que finalmente los trabajadores puedan negociar en un plano de igualdad de condiciones con sus empleadores. Sin embargo, al igual que cualquier derecho reconocido en el ordenamiento jurídico, éste debe confluir e interactuar en el sistema jurídico con diversos derechos, puesto que en un sistema pluralista y democrático no existen derechos absolutos e ilimitados. De esta forma, el derecho de huelga se encuentra afecto a límites y restricciones, mismos que sólo debiesen proceder ante situaciones excepcionales y calificadas, como lo es ante una situación de crisis nacional aguda, o bien cuando se trate de una función pública o de servicios esenciales en el sentido estricto del término

Conflating marginal and conditional treatment effects: Comments on 'Assessing the performance of population adjustment methods for anchored indirect comparisons: A simulation study'

In this commentary, we highlight the importance of: (1) carefully considering and clarifying whether a marginal or conditional treatment effect is of interest in a population-adjusted indirect treatment comparison; and (2) developing distinct methodologies for estimating the different measures of effect. The appropriateness of each methodology depends on the preferred target of inference.Comment: 6 pages, submitted to Statistics in Medicine. Response to `Assessing the performance of population adjustment methods for anchored indirect comparisons: A simulation study' by Phillippo, Dias, Ades and Welton, published in Statistics in Medicine (2020). Updated after Ph.D. proposal defense/transfer viva comment

Prevalencia de vaginitis en mujeres que asisten al Consultorio Norte Dr. Jose Astaburuaga de la Ciudad de Talca

56 p.Las infecciones vaginales provocan uno de los más importantes gastos en Salud en la mayoría de los países. Es por esto que el estudio de tratamientos más efectivos es uno de los principales esfuerzos que realizan los profesionales de la Salud. El objetivo de este trabajo es determinar la prevalencia de vaginitis en las mujeres que asisten al consultorio Dr José Astaburuaga de la cuidad de Talca, a su vez observar la prevalencia que presenta cada microorganismo entre la población de estudio. Las muestras serán analizadas por medios de cultivos simples de laboratorio, examen directo, gram, Test de Aminas y en caso de necesitar se realizará susceptibilidad antimirobiana. Una vez terminado todo el proceso se emitirá un informe, el cual será entregado a la obstetra encargada. Dentro de los principales hallazgos con un total de 413 pacientes, a 10 pacientes se les pidió nueva muestra, 184 pacientes presentaron cultivos negativos, 10 presentaron Trichomonas vaginalis, 56 Candida albicans, 115 Gardnerella vaginalis, el resto de las pacientes presentaron otros microorganismos etiológicos