Related Experiment Video
Updated: May 23, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Case-crossover design: an alternative strategy for detecting drug-induced liver injury
Chang-Hsing Lee1, Jung-Der Wang, Pau-Chung Chen
1Department of Public Health, Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Room 733, 17 Syujhou Road, Taipei, Taiwan.
Objective:
Our observational study was conducted to assess if the case--crossover 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 case--crossover and case--control designs to assess the estimated risks of liver injury related to well-known hepatoxic drugs, including isoniazid, rifampicin, erythromycin, and diclofenac. Using case--crossover and case--control 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 case--crossover designs. Most adjusted ORs by case--crossover design were more conservative than ORs by case--control design.
Conclusions:
In addition to a case--control design, the case--crossover design is a suitable method, for detecting the potential hepatotoxicity of drugs.
Related Concept Videos
Crossover Experiments
Crossover designs are performed even with smaller sample sizes since the samples can act as their controls. These are better than simple randomized trials since patients are exposed to all the treatments.
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
Bioavailability Study Design: Single Versus Multiple Dose Studies
Bioequivalence Experimental Study Designs: Repeated Measures, Cross-Over, Carry-Over, and Latin Square Designs
Drug toxicity: Idiosyncratic Reactions
