Challenges and common weaknesses in case-control studies on drug use and road traffic injury based on drug testing of biological samples

To determine and discuss common weaknesses and errors in case-control studies on the association between drug use and road traffic crash injury among drivers and recommend improvements for future studies. A search for case-control studies published between 2000 and 2016 was performed using PubMed and other databases in addition to manual search. The used methodologies were compared with requirements and recommendations for case-control studies as well as current knowledge on the interpretation of drug concentrations in biological samples. Seventeen studies were identified. The major difficulties in the studies were related to likely selection bias, information bias, and confounding. In some studies, the definition of drug exposure was different for controls than for cases, generating potentially serious errors in the odds ratio estimations. Other weaknesses include lacking explanation of the assessment of drug exposure, missing covariates, lacking description of statistical methods, and lack of discussion of bias and confounding. Many of the observed challenges and weaknesses can be overcome or reduced. Recommendations for future studies are presented.