Background/Aims: Drug Induced Liver Injury (DILI) is a major cause of liver failure in the US and the leading reason for failure of investigational drugs in clinical trials, lack of drug approval, and postmarket withdrawal of approved drugs. Recent genome-wide association studies have identified variations within the major histocompatibility complex in Caucasians to be linked with flucloxacillin and lumiracoxib-related liver injury. The need for replication of these findings and extension of these investigations to other drug exposures and other ethnic groups will require substantial case numbers with supporting medical record documentation. With support from The Serious Adverse Event Consortium, an international consortium led by the pharmaceutical industry in conjunction with the FDA, we conducted a feasibility study to evaluate the potential for using electronic clinical and administrative data from two HMORN sites to identify provisional DILI cases.
Methods: Building upon previous research, we developed data specifications for electronic searches of ICD-9 codes with time proximate laboratory results indicative of liver-related disease. Electronic criteria were used to ‘rule out’ other liver diseases and other co-morbid conditions indicative of systematic liver-related effects. For feasibility testing, two methods of population identification were incorporated: the VDW and EMR reporting. All records from 1/1/00-8/1/09 that were identified as ‘potential DILI cases’ were reviewed manually, and selected data were abstracted, including suspected implicated drug(s).
Results: Records for 1,123,173 individuals were screened for potential case status; 29,893 records with one or more diagnoses of interest were identified. After application of the “rule out’ exclusion criteria, 584 potential DILI cases were reviewed and 99 ultimately met provisional case status. Drugs commonly associated with provisional DILI cases were sulfa-containing antibiotics, anticonvulsants, isoniazid, and statins. Roughly one-half of provisional DILI cases were associated with a single implicated drug.
Conclusions: Electronic infrastructures currently available within many highly integrated health care delivery systems can be efficiently leveraged to support identification of provisional DILI events. Systems that have comprehensive episodic, historic and post-event data, including lab, diagnostic, treatment, imaging, and medication records that can be accessed electronically should be considered primary systems for expanding DILI case accumulation efforts.