Comparison of treatment effects between animal experiments and clinical trials: systematic review

Abstract

Objective To examine concordance between treatment effects in animal experiments and clinical trials. Study design Systematic review. Data sources Medline, Embase, SIGLE, NTIS, Science Citation Index, CAB, BIOSIS. Study selection Animal studies for interventions with unambiguous evidence of a treatment effect (benefit or harm) in clinical trials: head injury, antifibrinolytics in haemorrhage, thrombolysis in acute ischaemic stroke, tirilazad in acute ischaemic stroke, antenatal corticosteroids to prevent neonatal respiratory distress syndrome, and bisphosphonates to treat osteoporosis. Review methods Data were extracted on study design, allocation concealment, number of randomised animals, type of model, intervention, and outcome. Results Corticosteroids did not show any benefit in clinical trials of treatment for head injury but did show a benefit in animal models (pooled odds ratio for adverse functional outcome 0.58, 95% confidence interval 0.41 to 0.83). Antifibrinolytics reduced bleeding in clinical trials but the data were inconclusive in animal models. Thrombolysis improved outcome in patients with ischaemic stroke. In animal models, tissue plasminogen activator reduced infarct volume by 24% (95% confidence interval 20% to 28%) and improved neurobehavioural scores by 23% (17% to 29%). Tirilazad was associated with a worse outcome in patients with ischaemic stroke. In animal models, tirilazad reduced infarct volume by 29% (21% to 37%) and improved neurobehavioural scores by 48% (29% to 67%). Antenatal corticosteroids reduced respiratory distress and mortality in neonates whereas in animal models respiratory distress was reduced but the effect on mortality was inconclusive (odds ratio 4.2, 95% confidence interval 0.85 to 20.9). Bisphosphonates increased bone mineral density in patients with osteoporosis. In animal models the bisphosphonate alendronate increased bone mineral density compared with placebo by 11.0% (95% confidence interval 9.2% to 12.9%) in the combined results for the hip region. The corresponding treatment effect in the lumbar spine was 8.5% (5.8% to 11.2%) and in the combined results for the forearms (baboons only) was 1.7% ( − 1.4% to 4.7%). Conclusions Discordance between animal and human studies may be due to bias or to the failure of animal models to mimic clinical disease adequately.

The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

“…Major discrepancies between drug effects in animal models and in human trials have recently been pointed out, which may be due to design of the models, assessment tools for determination of drug efficacy, and timing of drug application (Perel et al, 2007). These facts have to be taken into consideration, especially for long term drug intervention studies.…”

Interleukin-1 Receptor Antagonist in Animal Models of Stroke: A Fair Summing Up?

“…This compares favorably to the 24% reduction reported in a meta-analysis of preclinical data for tissue plasminogen activator. 2 In contrast to other similar meta-analyses, 3,4 in which the efficacy detected in individual studies declined with higher ''quality scores,'' the reported efficacy of IL-1RA increases when more of the 10 ''quality items'' are reported in the study's methods. We welcome the authors' thorough analysis of much of the current knowledge regarding the efficacy of IL-1RA in animal models of stroke, and agree that there is room for improvements in the conduct of preclinical studies in stroke.…”

Effects of simvastatin on bleomycin-induced pulmonary fibrosis in female rats

“…It is well known that discrepancies exist between animal and human data and that a drug that is active in the animal may be useless in the human (Perel et al, 2007). Such an occurrence is often due to inappropriate translation of the drug dose from one animal species to another.…”