Statistical review of animal trials—A guideline

Abstract

Any experiment involving living organisms requires justification of the need and moral defensibleness of the study. Statistical planning, design, and sample size calculation of the experiment are no less important review criteria than general medical and ethical points to consider. Errors made in the statistical planning and data evaluation phase can have severe consequences on both results and conclusions. They might proliferate and thus impact future trials-an unintended outcome of fundamental research with profound ethical consequences. Unified statistical standards are currently missing for animal review boards in Germany.In order to accompany, we developed a biometric form to be filled and handed in with the proposal at the concerned local authority on animal welfare. It addresses relevant points to consider for biostatistical planning of animal experiments and can help both the applicants and the reviewers in overseeing the entire experiment(s) planned. Furthermore, the form might also aid in meeting the current standards set by the 3+3R's principle of animal experimentation: Replacement, Reduction, Refinement as well as Robustness, Registration, and Reporting. The form has already been in use by the concerned local authority of animal welfare in Berlin, Germany. In addition, we provide reference to our user guide giving more detailed explanation and examples for each section of the biometric form. Unifying the set of biostatistical aspects will help both the applicants and the reviewers to equal standards and increase quality of preclinical research projects, also for translational, multicenter, or international studies.

Delivery of Indocyanine Green, a Photosensitizer, Into Balloon-Injured Atherosclerotic Plaque of Hyperlipidemic New Zealand Rabbits

“…Of course, for confirmatory trials (e.g., the proof PDT works in atherosclerosis) it is needed to collect more robust evidence [42]. Furthermore, we aim to respect the 3R's principle of animal experiments: Replacement, Reduction, Refinement [43]. In this perspective one rabbit to serve as control is justified.…”

Lost in Translation: Failure of Preclinical Studies to Accurately Predict the Effect of Regional Analgesia on Cancer Recurrence

“…37,38 Last, laboratory animal investigations should use adequate sample sizes and rigorous statistical methods, designs resembling those used routinely for clinical research to avoid type 1 and type 2 errors. 119,120 What We can learn from the Disconnect between preclinical results and Major trial evidence Preclinical research involves experiments on cells, tissues, animals, and other biologic materials and seeks to better understand diseases' biologic mechanisms and develop potential therapies. Disciplines include molecular biology, pharmacology, toxicology, and animal behavioral sciences.…”

“…37,38 Last, laboratory animal investigations should use adequate sample sizes and rigorous statistical methods, designs resembling those used routinely for clinical research to avoid type 1 and type 2 errors. 119,120…”

Modeling and drug discovery of clonal hematopoiesis of indeterminate potential (CHIP) - driven cardiovascular disease in self-organizing cardiac organoids (SCO)

“…Hence, our SCO platform potentially facilitates a reduction in animal use, which saves scientists a tremendous amount of time for ethical review and defense and reduces numerous research grants for purchasing or generating animal models. Furthermore, our lab-built SCO platform makes our experiment more humanitarian and environmentalfriendly, which fits The Three Rs principle (Replace, Reduce, and Refine), aiming to make it more effective and humane 32 .…”

“…Furthermore, TET2 deficiency worsens cardiac remodeling and function in mouse models of chronic ischemia and pressure overload hypertrophy 11,24 . However, using animal models for CHIP study not only costs scientists a tremendous amount of time for ethical review and defense, as well as countless research funding for purchasing or generating models but also goes against The Three Rs principle (Replace, Reduce, and Refine) aiming to make scientific research a more effective and humane process 32 .…”