Quantification of translational success: rates of concordance between the results of animal experiments and human trials: A systematized review

Biomedical research aims to understand human disease on a mechanistic level,
in order to develop possible cures. Drug development is a lengthy and
expensive process, which relies on pre-clinical experiments (e.g. animal
experiments) and clinical trials (i.e. human experiments). However, candidate
drugs that are successful in animal experiments often fail in clinical trials,
which leads to a financial burden and even to potentially life-threatening
experiences for trial participants. To prevent unnecessary risks and expenses,
we need to understand why the outcomes from animal studies fail to translate
to humans in phase I-II clinical trials.

Quantitative assessment of the predictability of currently used animal models
allows for an ethical discourse of acceptability, and a statistical analysis of
predictive value. This systematized review will collect and describe the
available quantitative data from studies that assessed animal-to-human
translational success rate. We define successful translation as replication in a
randomized trial in humans (mainly phase I-II) of statistically significant
positive (or negative) results for the primary study outcome as described by
the authors in animal experiments. We do not expect to find clinical trial
publications after animal experiments with negative results. We prefer to focus
on early clinical trials over market access, as successful trials do not always
result in clinically available medication for reasons beyond animal-to-human
predictability. Besides studies explicitly addressing translational success rates,
we will include meta-analyses including both human and animal studies, as
they provide quantitative information on translation for individual
interventions