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Uwe Aickelin
Publication date
2014
fields
Informatics Engineering
and research's language is
English
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The pharmaceutical industry is plagued by the problem of side effects that can occur anytime a prescribed medication is ingested. There has been a recent interest in using the vast quantities of medical data available in longitudinal observational databases to identify causal relationships between drugs and medical events. Unfortunately the majority of existing post marketing surveillance algorithms measure how dependant or associated an event is on the presence of a drug rather than measuring causality. In this paper we investigate potential attributes that can be used in causal inference to identify side effects based on the Bradford-Hill causality criteria. Potential attributes are developed by considering five of the causality criteria and feature selection is applied to identify the most suitable of these attributes for detecting side effects. We found that attributes based on the specificity criterion may improve side effect signalling algorithms but the experiment and dosage criteria attributes investigated in this paper did not offer sufficient additional information.
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Longitudinal observational databases have become a recent interest in the post marketing drug surveillance community due to their ability of presenting a new perspective for detecting negative side effects. Algorithms mining longitudinal observation databases are not restricted by many of the limitations associated with the more conventional methods that have been developed for spontaneous reporting system databases. In this paper we investigate the robustness of four recently developed algorithms that mine longitudinal observational databases by applying them to The Health Improvement Network (THIN) for six drugs with well document known negative side effects. Our results show that none of the existing algorithms was able to consistently identify known adverse drug reactions above events related to the cause of the drug and no algorithm was superior.
A standard assumption for causal inference about the joint effects of time-varying treatment is that one has measured sufficient covariates to ensure that within covariate strata, subjects are exchangeable across observed treatment values, also known as sequential randomization assumption (SRA). SRA is often criticized as it requires one to accurately measure all confounders. Realistically, measured covariates can rarely capture all confounders with certainty. Often covariate measurements are at best proxies of confounders, thus invalidating inferences under SRA. In this paper, we extend the proximal causal inference (PCI) framework of Miao et al. (2018) to the longitudinal setting under a semiparametric marginal structural mean model (MSMM). PCI offers an opportunity to learn about joint causal effects in settings where SRA based on measured time-varying covariates fails, by formally accounting for the covariate measurements as imperfect proxies of underlying confounding mechanisms. We establish nonparametric identification with a pair of time-varying proxies and provide a corresponding characterization of regular and asymptotically linear estimators of the parameter indexing the MSMM, including a rich class of doubly robust estimators, and establish the corresponding semiparametric efficiency bound for the MSMM. Extensive simulation studies and a data application illustrate the finite sample behavior of proposed methods.
Causal effect sizes may vary among individuals and they can even be of opposite directions. When there exists serious effect heterogeneity, the population average causal effect (ACE) is not very informative. It is well-known that individual causal effects (ICEs) cannot be determined in cross-sectional studies, but we will show that ICEs can be retrieved from longitudinal data under certain conditions. We will present a general framework for individual causality where we will view effect heterogeneity as an individual-specific effect modification that can be parameterized with a latent variable, the receptiveness factor. The distribution of the receptiveness factor can be retrieved, and it will enable us to study the contrast of the potential outcomes of an individual under stationarity assumptions. Within the framework, we will study the joint distribution of the individuals potential outcomes conditioned on all individuals factual data and subsequently the distribution of the cross-world causal effect (CWCE). We discuss conditions such that the latter converges to a degenerated distribution, in which case the ICE can be estimated consistently. To demonstrate the use of this general framework, we present examples in which the outcome process can be parameterized as a (generalized) linear mixed model.
We introduce computational causal inference as an interdisciplinary field across causal inference, algorithms design and numerical computing. The field aims to develop software specializing in causal inference that can analyze massive datasets with a variety of causal effects, in a performant, general, and robust way. The focus on software improves research agility, and enables causal inference to be easily integrated into large engineering systems. In particular, we use computational causal inference to deepen the relationship between causal inference, online experimentation, and algorithmic decision making. This paper describes the new field, the demand, opportunities for scalability, open challenges, and begins the discussion for how the community can unite to solve challenges for scaling causal inference and decision making.
Weighting methods are a common tool to de-bias estimates of causal effects. And though there are an increasing number of seemingly disparate methods, many of them can be folded into one unifying regime: causal optimal transport. This new method directly targets distributional balance by minimizing optimal transport distances between treatment and control groups or, more generally, between a source and target population. Our approach is model-free but can also incorporate moments or any other important functions of covariates that the researcher desires to balance. We find that the causal optimal transport outperforms competitor methods when both the propensity score and outcome models are misspecified, indicating it is a robust alternative to common weighting methods. Finally, we demonstrate the utility of our method in an external control study examining the effect of misoprostol versus oxytocin for treatment of post-partum hemorrhage.
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