sensitivity analysis for certain permutation inferences in matched observational studies summary in observational studies treatments are not randomly assigned to experimental units so that randomization tests and their associated interval estimates are not generally applicable in an effort to compensate for the lack of randomization treated and control units are often matched on the basis of observed covariates however the possibility remains of bias due to residual imbalances in unobserved covariates a general though simple method is proposed for displaying the sensitivity of permutation inferences to a range of assumptions about unobserved covariates in matched observational studies the sensitivity analysis is applicable to wilcoxon s signed rank test to the mcnemar cox test for paired binary responses and to some matching problems with a variable number of controls

optimal matching with minimal deviation from fine balance in a study of obesity and surgical outcomes in multivariate matching fine balance constrains the marginal distributions of a nominal variable in treated and matched control groups to be identical without constraining who is matched to whom in this way a fine balance constraint can balance a nominal variable with many levels while focusing efforts on other more important variables when pairing individuals to minimize the total covariate distance within pairs fine balance is not always possible that is it is a constraint on an optimization problem but the constraint is not always feasible we propose a new algorithm which returns a minimum distance finely balanced match when one is feasible and otherwise minimizes the total distance among all matched samples that minimize the deviation from fine balance perhaps we can come very close to fine balance when fine balance is not attainable moreover in any event because our algorithm is guaranteed to come as close as possible to fine balance the investigator may perform one match and on that basis judge whether the best attainable balance is adequate or not we also show how to incorporate an additional constraint the algorithm is implemented in two similar ways first as an optimal assignment problem with an augmented distance matrix second as a minimum cost flow problem in a network the case of knee surgery in the obesity and surgical outcomes study motivated the development of this algorithm and is used as an illustration in that example two of 47 hospitals had too few nonobese patients to permit fine balance for the nominal variable with 47 levels representing the hospital but our new algorithm came very close to fine balance moreover in that example there was a shortage of nonobese diabetic patients and incorporation of an additional constraint forced the match to include all of these nonobese diabetic patients thereby coming as close as possible to balance for this important but recalcitrant covariate

resampling based multiple testing methods with covariate adjustment application to investigation of antiretroviral drug susceptibility identifying genetic mutations that cause clinical resistance to antiretroviral drugs requires adjustment for potential confounders such as the number of active drugs in a hiv infected patient s regimen other than the one of interest motivated by this problem we investigated resampling based methods to test equal mean response across multiple groups defined by hiv genotype after adjustment for covariates we consider construction of test statistics and their null distributions under two types of model parametric and semiparametric the covariate function is explicitly specified in the parametric but not in the semiparametric approach the parametric approach is more precise when models are correctly specified but suffer from bias when they are not the semiparametric approach is more robust to model misspecification but may be less efficient to help preserve type i error while also improving power in both approaches we propose resampling approaches based on matching of observations with similar covariate values matching reduces the impact of model misspecification as well as imprecision in estimation these methods are evaluated via simulation studies and applied to a data set that combines results from a variety of clinical studies of salvage regimens our focus is on relating hiv genotype to viral susceptibility to abacavir after adjustment for the number of active antiretroviral drugs excluding abacavir in the patient s regimen

using mixed integer programming for matching in an observational study of kidney failure after surgery this article presents a new method for optimal matching in observational studies based on mixed integer programming unlike widely used matching methods based on network algorithms which attempt to achieve covariate balance by minimizing the total sum of distances between treated units and matched controls this new method achieves covariate balance directly either by minimizing both the total sum of distances and a weighted sum of specific measures of covariate imbalance or by minimizing the total sum of distances while constraining the measures of imbalance to be less than or equal to certain tolerances the inclusion of these extra terms in the objective function or the use of these additional constraints explicitly optimizes or constrains the criteria that will be used to evaluate the quality of the match for example the method minimizes or constrains differences in univariate moments such as means variances and skewness differences in multivariate moments such as correlations between covari

substantial gains in bias reduction from matching with a variable number of controls summary in observational studies that match several controls to each treated subject substantially greater bias reduction is possible if the number of controls is not fixed but rather is allowed to vary from one matched set to another in certain cases matching with a fixed number of controls may remove only 50 of the bias in a covariate whereas matching with a variable number of controls may remove 90 of the bias even though both control groups have the same number of controls in total an example of matching in a study of surgical mortality is discussed in detail

optimal multilevel matching in clustered observational studies a case study of the effectiveness of private schools under a large scale voucher system abstracta distinctive feature of a clustered observational study is its multilevel or nested data structure arising from the assignment of treatment in a nonrandom manner to groups or clusters of units or individuals examples are ubiquitous in the health and social sciences including patients in hospitals employees in firms and students in schools what is the optimal matching strategy in a clustered observational study at first thought one might start by matching clusters of individuals and then within matched clusters continue by matching individuals but as we discuss in this article the optimal strategy is the opposite in typical applications where the intracluster correlation is not one it is best to first match individuals and once all possible combinations of matched individuals are known then match clusters in this article we use dynamic and integer programming to implement this strategy and extend optimal matching methods to hierarchical and multilevel settings among other match

combining propensity score matching with additional adjustments for prognostic covariates abstract propensity score matching refers to a class of multivariate methods used in comparative studies to construct treated and matched control samples that have similar distributions on many covariates this matching is the observational study analog of randomization in ideal experiments but is far less complete as it can only balance the distribution of observed covariates whereas randomization balances the distribution of all covariates both observed and unobserved an important feature of propensity score matching is that it can be easily combined with model based regression adjustments or with matching on a subset of special prognostic covariates or combinations of prognostic covariates that have been identified as being especially predictive of the outcome variables we extend earlier results by developing approximations for the distributions of covariates in matched samples created with linear propensity score methods for the practically important situation where matching uses both the estimat

matching and weighting with functions of error prone covariates for causal inference abstractmatching estimators are commonly used to estimate causal effects in nonexperimental settings covariate measurement error can be problematic for matching estimators when observational treatment groups differ on latent quantities observed only through error prone surrogates we establish necessary and sufficient conditions for matching and weighting with functions of observed covariates to yield unconfounded causal effect estimators generalizing results from the standard i e no measurement error case we establish that in common covariate measurement error settings including continuous variables with continuous measurement error discrete variables with misclassification and factor and item response theory models no single function of the observed covariates computed for all units in a study is appropriate for matching however we demonstrate that in some circumstances it is possible to create different functions of the observed covariates for treatment and control units to construct a va

facilitating score and causal inference trees for large observational studies assessing treatment effects in observational studies is a multifaceted problem that not only involves heterogeneous mechanisms of how the treatment or cause is exposed to subjects known as propensity but also differential causal effects across sub populations we introduce a concept termed the facilitating score to account for both the confounding and interacting impacts of covariates on the treatment effect several approaches for estimating the facilitating score are discussed in particular we put forward a machine learning method called causal inference tree cit to provide a piecewise constant approximation of the facilitating score with interpretable rules cit splits data in such a way that both the propensity and the treatment effect become more homogeneous within each resultant partition causal inference at different levels can be made on the basis of cit together with an aggregated grouping procedure cit stratifies data into strata where causal effects can be conveniently assessed within each besides a feasible way of predicting individual causal effects ice is made available by aggregating ensemble cit models both the stratified results and the estimated ice provide an assessment of heterogeneity of causal effects and can be integrated for estimating the average causal effect ace mean square consistency of cit is also established we evaluate the performance of proposed methods with simulations and illustrate their use with the nsw data in dehejia and wahba 1999 where the objective is to assess the impact of a labor training program the national supportedwork nsw demonstration on post intervention earnings

the central role of the propensity score in observational studies for causal effects abstract the results of observational studies are often disputed because of nonrandom treatment assignment for example patients at greater risk may be overrepresented in some treatment group this paper discusses the central role of propensity scores and balancing scores in the analysis of observational studies the propensity score is the estimated conditional probability of assignment to a particular treatment given a vector of observed covariates both large and small sample theory show that adjustment for the scalar propensity score is sufficient to remove bias due to all observed covariates applications include matched sampling on the univariate propensity score which is equal percent bias reducing under more general conditions than required for discriminant matching multivariate adjustment by subclassification on balancing scores where the same subclasses are used to estimate treatment effects for all outcome variables and in all subpopulations and visual representation of multivariate adjustment by a two dimensional plot author

a characterization of optimal designs for observational studies summary an empirical investigation of the effects of a treatment is an observational study if it involves the comparison of treated and control groups that were not formed by randomization in such studies treated and control groups may differ systematically with respect to pretreatment measures or covariates and addressing these pre treatment differences is a central concern matching and subclassification are two standard methods of adjusting for observed pretreatment differences they may be used alone e g cochran 1968 or in conjunction with analytical or model based adjustments e g rubin 1973 1979 holford 1978 rosenbaum and rubin 1984 section 3 3 and rosenbaum 1987 1988a in particular rubin s simulation studies suggest that model based adjustments applied to matched or subclassified samples are more robust than model based adjustments applied to unmatched samples the purpose of this paper is to identify the structure of an optimal subclassification i e one in which the treated and control subjects in the same subclass are on average as similar as possible with respect to observed covariates it turns out that this structure is simple and intuitive while adjustments may control imbalances in observed covariates they cannot

evaluation of subset matching methods and forms of covariate balance this paper conducts a monte carlo simulation study to evaluate the performance of multivariate matching methods that select a subset of treatment and control observations the matching methods studied are the widely used nearest neighbor matching with propensity score calipers and the more recently proposed methods optimal matching of an optimally chosen subset and optimal cardinality matching the main findings are i covariate balance as measured by differences in means variance ratios kolmogorov smirnov distances and cross match test statistics is better with cardinality matching because by construction it satisfies balance requirements ii for given levels of covariate balance the matched samples are larger with cardinality matching than with the other methods iii in terms of covariate distances optimal subset matching performs best iv treatment effect estimates from cardinality matching have lower root mean square errors provided strong requirements for balance specifically fine balance or strength k balance plus close mean balance in standard practice a matched sample is considered to be balanced if the absolute differences in means of the covariates across treatment groups are smaller than 0 1 standard deviations however the simulation results suggest that stronger forms of balance should be pursued in order to remove systematic biases due to observed covariates when a difference in means treatment effect estimator is used in particular if the true outcome model is additive then marginal distributions should be balanced and if the true outcome model is additive with interactions then low dimensional joints should be balanced copyright 2016 john wiley sons ltd

fibonacci heaps and their uses in improved network optimization algorithms in this paper we develop a new data structure for implementing heaps priority queues our structure fibonacci heaps abbreviated f heaps extends the binomial queues proposed by vuillemin and studied further by brown f heaps support arbitrary deletion from an n item heap in o log n amortized time and all other standard heap operations in o 1 amortized time using f heaps we are able to obtain improved running times for several network optimization algorithms in particular we obtain the following worst case bounds where n is the number of vertices and m the number of edges in the problem graph o n log n m for the single source shortest path problem with nonnegative edge lengths improved from o m log m n 2 n o n 2 log n nm for the all pairs shortest path problem improved from o nm log m n 2 n o n 2 log n nm for the assignment problem weighted bipartite matching improved from o nm log m n 2 n o m m n for the minimum spanning tree problem improved from o m log log m n 2 n where m n min i u log i n m n note that m n log n if m n of these results the improved bound for minimum spanning trees is the most striking although all the results give asymptotic improvements for graphs of appropriate densities

a two step bayesian approach for propensity score analysis simulations and case study a two step bayesian propensity score approach is introduced that incorporates prior information in the propensity score equation and outcome equation without the problems associated with simultaneous bayesian propensity score approaches the corresponding variance estimators are also provided the two step bayesian propensity score is provided for three methods of implementation propensity score stratification weighting and optimal full matching three simulation studies and one case study are presented to elaborate the proposed two step bayesian propensity score approach results of the simulation studies reveal that greater precision in the propensity score equation yields better recovery of the frequentist based treatment effect a slight advantage is shown for the bayesian approach in small samples results also reveal that greater precision around the wrong treatment effect can lead to seriously distorted results however greater precision around the correct treatment effect parameter yields quite good results with slight improvement seen with greater precision in the propensity score equation a comparison of coverage rates for the conventional frequentist approach and proposed bayesian approach is also provided the case study reveals that credible intervals are wider than frequentist confidence intervals when priors are non informative

dealing with limited overlap in estimation of average treatment effects summary estimation of average treatment effects under unconfounded or ignorable treatment assignment is often hampered by lack of overlap in the covariate distributions between treatment groups this lack of overlap can lead to imprecise estimates and can make commonly used estimators sensitive to the choice of specification in such cases researchers have often used ad hoc methods for trimming the sample we develop a systematic approach to addressing lack of overlap we characterize optimal subsamples for which the average treatment effect can be estimated most precisely under some conditions the optimal selection rules depend solely on the propensity score for a wide range of distributions a good approximation to the optimal rule is provided by the simple rule of thumb to discard all units with estimated propensity scores outside the range 0 1 0 9

finite element approximation of spectral acoustic problems on curved domains this paper deals with the finite element approximation of the displacement formulation of the spectral acoustic problem on a curved non convex two dimensional domain convergence and error estimates are proved for raviart thomas elements on a discrete polygonal domain h inline equation in the framework of the abstract spectral approximation theory similar results have been previously proved only for polygonal domains numerical tests confirming the theoretical results are reported

optimal matching for observational studies abstract matching is a common method of adjustment in observational studies currently matched samples are constructed using greedy heuristics or stepwise procedures that produce in general suboptimal matchings with respect to a particular criterion a matched sample is suboptimal if it could be improved by changing the controls assigned to specific treated units that is if it could be improved with the data at hand here optimal matched samples are obtained using network flow theory in addition to providing optimal matched pair samples this approach yields optimal constructions for several statistical matching problems that have not been studied previously including the construction of matched samples with multiple controls with a variable number of controls and the construction of balanced matched samples that combine features of pair matching and frequency matching computational efficiency is discussed extensive use is made of ideas from two essentially disjoint literatures namely st

using empirical bayes methods in biopharmaceutical research a compound sampling model where a unit specific parameter is sampled from a prior distribution and then observed are generated by a sampling distribution depending on the parameter underlies a wide variety of biopharmaceutical data for example in a multi centre clinical trial the true treatment effect varies from centre to centre observed treatment effects deviate from these true effects through sampling variation knowledge of the prior distribution allows use of bayesian analysis to compute the posterior distribution of clinic specific treatment effects frequently summarized by the posterior mean and variance more commonly with the prior not completely specified observed data can be used to estimate the prior and use it to produce the posterior distribution an empirical bayes or variance component analysis in the empirical bayes model the estimated prior mean gives the typical treatment effect and the estimated prior standard deviation indicates the heterogeneity of treatment effects in both the bayes and empirical bayes approaches estimated clinic effects are shrunken towards a common value from estimates based on single clinics this shrinkage produces more efficient estimates in addition the compound model helps structure approaches to ranking and selection provides adjustments for multiplicity allows estimation of the histogram of clinic specific effects and structures incorporation of external information this paper outlines the empirical bayes approach coverage will include development and comparison of approaches based on parametric priors for example a gaussian prior with unknown mean and variance and non parametric priors discussion of the importance of accounting for uncertainty in the estimated prior comparison of the output and interpretation of fixed and random effects approaches to estimating population values estimating histograms and identification of key considerations in the use and interpretation of empirical bayes methods

improving massive experiments with threshold blocking inferences from randomized experiments can be improved by blocking assigning treatment in fixed proportions within groups of similar units however the use of the method is limited by the difficulty in deriving these groups current blocking methods are restricted to special cases or run in exponential time are not sensitive to clustering of data points and are often heuristic providing an unsatisfactory solution in many common instances we present an algorithm that implements a widely applicable class of blocking threshold blocking that solves these problems given a minimum required group size and a distance metric we study the blocking problem of minimizing the maximum distance between any two units within the same group we prove this is a nondeterministic polynomial time hard problem and derive an approximation algorithm that yields a blocking where the maximum distance is guaranteed to be at most four times the optimal value this algorithm runs in o n log n time with o n space complexity this makes it to our knowledge the first blocking method with an ensured level of performance that works in massive experiments whereas many commonly used algorithms form pairs of units our algorithm constructs the groups flexibly for any chosen minimum size this facilitates complex experiments with several treatment arms and clustered data a simulation study demonstrates the efficiency and efficacy of the algorithm tens of millions of units can be blocked using a desktop computer in a few minutes

the bias due to incomplete matching observational studies comparing groups of treated and control units are often used to estimate the effects caused by treatments matching is a method for sampling a large reservoir of potential controls to produce a control group of modest size that is ostensibly similar to the treated group in practice there is a trade off between the desires to find matches for all treated units and to obtain matched treated control pairs that are extremely similar to each other we derive expressions for the bias in the average matched pair difference due to the failure to match all treated units incomplete matching and the failure to obtain exact matches inexact matching a practical example shows that the bias due to incomplete matching can be severe and moreover can be avoided entirely by using an appropriate multivariate nearest available matching algorithm which in the example leaves only a small residual bias due to inexact matching