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 da
tabases 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.
Drugs are frequently prescribed to patients with the aim of improving each patients medical state, but an unfortunate consequence of most prescription drugs is the occurrence of undesirable side effects. Side effects that occur in more than one in a
thousand patients are likely to be signalled efficiently by current drug surveillance methods, however, these same methods may take decades before generating signals for rarer side effects, risking medical morbidity or mortality in patients prescribed the drug while the rare side effect is undiscovered. In this paper we propose a novel computational meta-analysis framework for signalling rare side effects that integrates existing methods, knowledge from the web, metric learning and semi-supervised clustering. The novel framework was able to signal many known rare and serious side effects for the selection of drugs investigated, such as tendon rupture when prescribed Ciprofloxacin or Levofloxacin, renal failure with Naproxen and depression associated with Rimonabant. Furthermore, for the majority of the drug investigated it generated signals for rare side effects at a more stringent signalling threshold than existing methods and shows the potential to become a fundamental part of post marketing surveillance to detect rare side effects.
The electronic healthcare databases are starting to become more readily available and are thought to have excellent potential for generating adverse drug reaction signals. The Health Improvement Network (THIN) database is an electronic healthcare dat
abase containing medical information on over 11 million patients that has excellent potential for detecting ADRs. In this paper we apply four existing electronic healthcare database signal detecting algorithms (MUTARA, HUNT, Temporal Pattern Discovery and modified ROR) on the THIN database for a selection of drugs from six chosen drug families. This is the first comparison of ADR signalling algorithms that includes MUTARA and HUNT and enabled us to set a benchmark for the adverse drug reaction signalling ability of the THIN database. The drugs were selectively chosen to enable a comparison with previous work and for variety. It was found that no algorithm was generally superior and the algorithms natural thresholds act at variable stringencies. Furthermore, none of the algorithms perform well at detecting rare ADRs.
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.
The wealth of computerised medical information becoming readily available presents the opportunity to examine patterns of illnesses, therapies and responses. These patterns may be able to predict illnesses that a patient is likely to develop, allowin
g the implementation of preventative actions. In this paper sequential rule mining is applied to a General Practice database to find rules involving a patients age, gender and medical history. By incorporating these rules into current health-care a patient can be highlighted as susceptible to a future illness based on past or current illnesses, gender and year of birth. This knowledge has the ability to greatly improve health-care and reduce health-care costs.
Data-mining techniques have frequently been developed for Spontaneous reporting databases. These techniques aim to find adverse drug events accurately and efficiently. Spontaneous reporting databases are prone to missing information, under reporting
and incorrect entries. This often results in a detection lag or prevents the detection of some adverse drug events. These limitations do not occur in electronic health-care databases. In this paper, existing methods developed for spontaneous reporting databases are implemented on both a spontaneous reporting database and a general practice electronic health-care database and compared. The results suggests that the application of existing methods to the general practice database may help find signals that have gone undetected when using the spontaneous reporting system database. In addition the general practice database provides far more supplementary information, that if incorporated in analysis could provide a wealth of information for identifying adverse events more accurately.
