★ Drug registration files remove bias in assessing non-clinical predictiveness. ★ Animal studies could detect 1:3 SARs at a target organ level. ★ Animal studies could detect 1:5 SARs as a true positive. ★ Animal studies only have retrospective value in pharmacovigilance activities. ★ Animal studies of products in all stages of development should be investigated.
The value of animal studies to assess drug safety is unclear because many such studies are biased and have methodological shortcomings. We studied whether post-marketing serious adverse reactions to small molecule drugs could have been detected on the basis of animal study data included in drug registration files. Of 93 serious adverse reactions related to 43 small molecule drugs, only 19% were identified in animal studies as a true positive outcome, which suggests that data from animal studies are of limited value to pharmacovigilance activities. Our study shows that drug registration files can be used to study the predictive value of animal studies and that the value of animal studies in all stages of the drug development should be investigated in a collaborative endeavour between regulatory authorities, industry, and academia.