Improving the speed and quality of an Adverse Event cluster analysis with Stepwise Expectation Maximization and Community Detection

Adverse drug reactions are unwanted effects alongside the intended benefit of a drug and might be responsible for 3-7\% of hospitalizations. Finding such reactions is partly done by analysing individual case safety reports (ICSR) of adverse events. The reports consist of categorical terms that describe the event.Data-driven identification of suspected adverse drug reactions using this data typically considers single adverse event terms, one at a time. This single term approach narrows the identification of reports and information in the reports is ignored during the search. If one instead assumes that each report is connected to a topic, then by creating a cluster of the reports that are connected to the topic more reports would be identified. More context would also be provided by virtue of the topics. This thesis takes place at Uppsala Monitoring Centre which has implemented a probabilistic model of how an ICSR, and its topic, is assumed to be generated. The parameters of the model are estimated with expectation maximization (EM), which also assigns the reports to clusters. The clusters are improved with Consensus Clustering that identify groups of reports that tend to be grouped together by several runs of EM. Additionally, in order to not cluster outlying reports all clusters below a certain size are excluded. The objective of the thesis is to improve the algorithm in terms of computational efficiency and quality, as measured by stability and clinical coherence. The convergence of EM is improved using stepwise EM, which resulted in a speed up of at least 1.4, and a decrease of the computational complexity. With all the speed improvements the speed up factor of the entire algorithm can reach 2 but is constrained by the size of the data. In order to improve the clusters' quality, the community detection algorithm Leiden is used. It is able to improve the stability with the added benefit of increasing the number of clustered reports. The clinical coherence score performs worse with Leiden. There are good reasons to further investigate the benefits of Leiden as there were suggestions that community detection identified clusters with greater resolution that still appeared clinically coherent in a posthoc analysis