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InferBERT: A Transformer-Based Causal Inference Framework for Enhancing Pharmacovigilance.

ABSTRACT: Background: T ransformer-based language models have delivered clear improvements in a wide range of natural language processing (NLP) tasks. However, those models have a significant limitation; specifically, they cannot infer causality, a prerequisite for deployment in pharmacovigilance, and health care. Therefore, these transformer-based language models should be developed to infer causality to address the key question of the cause of a clinical outcome. Results: In this study, we propose an innovative causal inference model-InferBERT, by integrating the A Lite Bidirectional Encoder Representations from Transformers (ALBERT) and Judea Pearl's Do-calculus to establish potential causality in pharmacovigilance. Two FDA Adverse Event Reporting System case studies, including Analgesics-related acute liver failure and Tramadol-related mortalities, were employed to evaluate the proposed InferBERT model. The InferBERT model yielded accuracies of 0.78 and 0.95 for identifying Analgesics-related acute liver failure and Tramadol-related death cases, respectively. Meanwhile, the inferred causes of the two clinical outcomes, (i.e. acute liver failure and death) were highly consistent with clinical knowledge. Furthermore, inferred causes were organized into a causal tree using the proposed recursive do-calculus algorithm to improve the model's understanding of causality. Moreover, the high reproducibility of the proposed InferBERT model was demonstrated by a robustness assessment. Conclusion: The empirical results demonstrated that the proposed InferBERT approach is able to both predict clinical events and to infer their causes. Overall, the proposed InferBERT model is a promising approach to establish causal effects behind text-based observational data to enhance our understanding of intrinsic causality. Availability and implementation: The InferBERT model and preprocessed FAERS data sets are available on GitHub at https://github.com/XingqiaoWang/DeepCausalPV-master.

SUBMITTER: Wang X

PROVIDER: S-EPMC8202286 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Often, a community becomes alarmed when high rates of cancer are noticed, and residents suspect that the cancer cases could be caused by a known source of hazard. In response, the US Centers for Disease Control and Prevention recommend that departments of health perform a standardized incidence ratio (SIR) analysis to determine whether the observed cancer incidence is higher than expected. This approach has several limitations that are well documented in the existing literature. In this paper we propose a novel causal inference framework for cancer cluster investigations, rooted in the potential outcomes framework. Assuming that a source of hazard representing a potential cause of increased cancer rates in the community is identified a priori, we focus our approach on a causal inference estimand which we call the causal SIR (cSIR). The cSIR is a ratio defined as the expected cancer incidence in the exposed population divided by the expected cancer incidence for the same population under the (counterfactual) scenario of no exposure. To estimate the cSIR we need to overcome two main challenges: 1) identify unexposed populations that are as similar as possible to the exposed one to inform estimation of the expected cancer incidence under the counterfactual scenario of no exposure, and 2) publicly available data on cancer incidence for these unexposed populations are often available at a much higher level of spatial aggregation (e.g. county) than what is desired (e.g. census block group). We overcome the first challenge by relying on matching. We overcome the second challenge by building a Bayesian hierarchical model that borrows information from other sources to impute cancer incidence at the desired level of spatial aggregation. In simulations, our statistical approach was shown to provide dramatically improved results, i.e., less bias and better coverage, than the current approach to SIR analyses. We apply our proposed approach to investigate whether trichloroethylene vapor exposure has caused increased cancer incidence in Endicott, New York.

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InferBERT: A Transformer-Based Causal Inference Framework for Enhancing Pharmacovigilance.

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