Caseecrossover design: An alternative strategy for detecting drug-induced liver injury

Objective: Our observational study was conducted to assess if the caseecrossover design could be applied to detect the risk of hepatoxic drugs on liver injury in the automated databases. Study Design and Setting: The study was conducted on approximately 22 million people enrolled in Taiwan's National Health Insurance database from 1997 to 2004. We applied caseecrossover and caseecontrol designs to assess the estimated risks of liver injury related to well-known hepatoxic drugs, including isoniazid, rifampicin, erythromycin, and diclofenac. Using caseecrossover and caseecontrol designs, we analyzed to explore the association between hospitalization and our target drugs through a conditional logistic regression model. Results: The adjusted odds ratios (ORs) of isoniazid, rifampicin, erythromycin, and diclofenac showed 24.4 (confidence interval [CI] = 10.7-55.5), 30.8 (CI = 14.1-67.1), 2.1 (CI = 1.4-3.1), and 2.9 (CI = 2.4-3.5) among 4,413 hospitalized liver injury patients during the 30-day exposure window by the caseecrossover designs. Most adjusted ORs by caseecrossover design were more conservative than ORs by caseecontrol design. Conclusions: In addition to a caseecontrol design, the caseecrossover design is a suitable method, for detecting the potential hepa-totoxicity of drugs.