03252nas a2200337   4500000000100000000000100001008004100002260001500043653001200058653001100070653002500081653001500106653002100121653000900142653002200151653001600173653003900189100002900228700002100257700002100278700001800299700002700317700002300344700002600367245009100393856008800484300000800572490000700580520231300587022001402900       2019                            d  c2019-07-1510aAnimals10aHumans10aPeriodicals as Topic10aPrediction10aPublication Bias10aRisk10aSystematic review10aTranslation10aTranslational Research, Biomedical1 aCathalijn H. C. Leenaars1 aCarien Kouwenaar1 aFrans R. Stafleu1 aAndré Bleich1 aMerel Ritskes-Hoitinga1 aRob B. M. De Vries1 aFranck L. B. Meijboom00aAnimal to human translation: a systematic scoping review of reported concordance rates  uhttps://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-1976-2  a2230 v173 aBACKGROUND: Drug development is currently hampered by high attrition rates; many developed treatments fail during clinical testing. Part of the attrition may be due to low animal-to-human translational success rates; so-called "translational failure". As far as we know, no systematic overview of published translational success rates exists.
SYSTEMATIC SCOPING REVIEW: The following research question was examined: "What is the observed range of the animal-to-human translational success (and failure) rates within the currently available empirical evidence?". We searched PubMed and Embase on 16 October 2017. We included reviews and all other types of "umbrella"-studies of meta-data quantitatively comparing the translational results of studies including at least two species with one being human. We supplemented our database searches with additional strategies. All abstracts and full-text papers were screened by two independent reviewers. Our scoping review comprises 121 references, with various units of measurement: compound or intervention (k = 104), study/experiment (k = 10), and symptom or event (k = 7). Diagnostic statistics corresponded with binary and continuous definitions of successful translation. Binary definitions comprise percentages below twofold error, percentages accurately predicted, and predictive values. Quantitative definitions comprise correlation/regression (r2) and meta-analyses (percentage overlap of 95% confidence intervals). Translational success rates ranged from 0 to 100%.
CONCLUSION: The wide range of translational success rates observed in our study might indicate that translational success is unpredictable; i.e. it might be unclear upfront if the results of primary animal studies will contribute to translational knowledge. However, the risk of bias of the included studies was high, and much of the included evidence is old, while newer models have become available. Therefore, the reliability of the cumulative evidence from current papers on this topic is insufficient. Further in-depth "umbrella"-studies of translational success rates are still warranted. These are needed to evaluate the probabilistic evidence for predictivity of animal studies for the human situation more reliably, and to determine which factors affect this process.  a1479-5876