Table 4 References on translational success in studies of adverse events and toxicology
From: Animal to human translation: a systematic scoping review of reported concordance rates
Study ID | Field of research | Summary of findings |
|---|---|---|
Alden_2011 | Carcinogenicity | Out of 287 registered drugs that were tested in rats and mice for carcinogenicity, results were concordant with humans for 146 |
Allen_1988 | Carcinogenicity | Correlation of carcinogenic dose between animals and humans ranged from 0.49 to 0.90 depending on the analysis |
Bailey_2013 | Safety | All likelihood ratios (LRs) are larger than 1, indicating predictive value of the experiments in dogs. Inverse negative LRs (iNLRs) are very small, indicating relatively limited predictive value of negative results in dogs for humans. Positive LRs (PLRs) for dogs are large; if toxicity is observed in dogs, it is likely to occur also in humans. There is no correlation between positive predictive values (PVVs) and PLRs |
Bailey_2014 | Safety | All LRs are larger than 1, indicating predictive value of the experiments in rats, mice and rabbits. iNLRs are very small, indicating relatively limited predictive value of negative results in these species for humans. PLRs for these species are large; if toxicity is observed in rats, mice or rabbits, it is likely to occur also in humans. Both PLR and iNLR depend on sample size |
Bailey_2015 | Safety | All LRs are larger than 1, indicating predictive value of the animal experiments. iNLRs are very small, indicating relatively limited predictive value of negative results in animals for humans. PLR for non-human primates (NHPs) is large; if toxicity is observed in NHP, it is likely to occur also in humans |
Brown_1983 | Teratogenicity | Correct positives: 30–97%; correct negatives: 35–80%; animal to human lowest effective dose ratio: 1.8–50 |
Claude_2007 | Adverse events | 70% of human adverse events was predicted by animal models. Predictivity is higher for non-rodents than rodents. Predictivity was highest for haematological and cardiovascular, and lowest for cutaneous and ophthalmological adverse events |
Crouch_1979 | Carcinogenicity | Data for carcinogenic potency correlated |
Davis_1998 | QT prolongation | Out of 9 noncardiac drugs that show QT prolongation in humans, literature on dog cardiac effects was found for 7; 6 showing QT prolongation, 1 showing increased mortality |
Ennever_2003 | Carcinogenicity | Sensitivity appears to be high, but the lifetime rodent bioassay lacks accuracy. Sensitivity decreases if only results that are positive in both rats and mice are considered positive. The LRB produces many false positives and false negatives |
Fletcher_1978 | Adverse events | Correlations between animal toxicity and human adverse events are considerably more frequent than discrepancies. Gastro-intestinal adverse events show the best correlation |
Fourches_2010A | Drug-induced liver injury | The concordance of liver effects between rodents and humans (44%) and between non-rodent species and humans (40%) was low |
Freireich_1966 | Toxic dose | Results in preclinical tests correlate remarkably well with results in man |
Goodman_1991 | Carcinogenicity | For 18 out of 20 examined chemicals with sufficient evidence, human and rodent evidence are consistent |
Hoffmann_2018 | Skin sensitization | Overall accuracy in skin sensitization prediction from animal to human was 74%, which decreased to 45% when considering five categories of potency |
Igarashi_1995 | Adverse events | Out of 31 pharmacological items tested after systemic administration, 17 showed a significant association with any clinical adverse reaction |
Litchfield_1961A | Adverse events | 18 out of the 53 physical signs observed in man were predicted correctly in rats; 29 out of the 53 in dogs |
Litchfield_1962 | Adverse events | Out of the 86 physical signs analysed in animals, 64 accurately reflected occurrence or absence in man |
Monticello_2017 | Adverse events | Excluding subjective adverse events, for rodents, PVV ranged from 0 to 54% and NPV ranged from 69 to 96%; for dogs, PVV ranged from 0 to 52% and NPV ranged from 76 to 96%; and for monkeys, PVV ranged from 0 to 91% and NPV ranged from 70 to 100% |
Olson_2000A | Adverse events | In any species tested, 71% of human adverse events was predicted. Predictivity is higher for non-rodents than rodents. Predictivity was highest for haematological, cardiovascular and gastrointestinal toxicities, and lowest for cutaneous toxicities |
Schein_1970 | Adverse events | For the prediction of certain adverse event in humans, administration of highly toxic dose levels to animals is needed |
Schein_1973a | Adverse events | For most organ systems, combining dog and monkey data reduces false negatives for prediction of human adverse events for anticancer drugs |
Schein_1973b | Adverse events | Correct predictions of anticancer drug-induced adverse events are accompanied by a high percentage of false positives |
Schein_1975 | Adverse events | Results from 13 additional drugs generally overlap with the preceding analysis |
Tamaki_2013 | Adverse events | 37% of adverse drug reactions in humans were predicted from animal studies |
VanMeer_2012 | Severe adverse reactions | Performed animal studies are not sensitive enough to predict post-marketing serious adverse reactions |
Weaver_2003 | Adverse events | No significant associations were observed between human and guinea pig data |
Wilbourn_1986 | Carcinogenicity | Sensitivity for the predictivity of animals for human carcinogenicity is high (84%), and there is good consistency between animals and humans in target organs |