Interspecies differences (e.g., different genes and proteins expressions, distribution and/or affinity of transmembrane receptors, immunogenic responses, disease susceptibility, etc.) |
- identification and usage of animal species that mimic the best the human conditions - validation of obtained results in several species and in multiple small and large animal models |
Inadequate animal models (e.g., different phenotypic features, pathophysiological mechanisms, doses, routes, and timings of drug administration, lengths of follow-up, endpoints, etc.) |
- utilization of more ‘humanized’ animal models - studies in animals of different species, ages, and genders, with different forms and phases of the disease, and clinically-relevant comorbidities and medications - administration of tested therapies using clinically-relevant doses, routes, and timings - evaluation of long-term, functional, clinically-relevant outcomes - close clinical-preclinical collaboration in animal model development - algorithms to help identify most clinically-relevant animal models |
Methodological rigor (e.g., lack of randomization and blinding, inadequate sample sizes, lack of model standardization, inappropriate statistical analyses, publication bias, etc.) |
- standardized experimental models - correct sample sizing - randomization and blinding - multicenter studies - adequate (including intention-to-treat) statistical analyses - correct and complete reporting of both positive and negative study results - pre-registration of animal studies (e.g., preclinicaltrials.eu) - performing multicenter, blind, randomized, controlled preclinical trials |
‘Sabotage’ by clinical trials (e.g., different study designs, populations characteristics, doses, routes, and timings of drug administration, different endpoints, assessment of drugs with unconvincing preclinical results, etc.) | Clinical trials:
- started only after completion of relevant preclinical studies - preceded by a correct and complete analysis of previous preclinical studies - testing only those strategies that provided convincing preclinical results |