Dissociation between Animal and Clinical Studies. Where Do We Go Wrong?
Article Category: Editorial
Pubblicato online: 05 mag 2022
Pagine: 497 - 500
DOI: https://doi.org/10.47803/rjc.2021.31.3.497
© 2021 Alina Scridon, published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.
Main problems explaining the gap between clinical and preclinical research and their potential solutions.
| 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 |