The methodological quality of animal research in critical care: the public face of science.

Meredith Bara,Ari R Joffe

doi:10.1186/s13613-014-0026-8

Abstract

BackgroundAnimal research (AR) findings often do not translate to humans; one potential reason is the poor methodological quality of AR. We aimed to determine this quality of AR reported in critical care journals.MethodsAll AR published from January to June 2012 in three high-impact critical care journals were reviewed. A case report form and instruction manual with clear definitions were created, based on published recommendations, including the ARRIVE guidelines. Data were analyzed with descriptive statistics.ResultsSeventy-seven AR publications were reviewed. Our primary outcome (animal strain, sex, and weight or age described) was reported in 52 (68%; 95% confidence interval, 56% to 77%). Of the 77 publications, 47 (61%) reported randomization; of these, 3 (6%) reported allocation concealment, and 1 (2%) the randomization procedure. Of the 77 publications, 31 (40%) reported some type of blinding; of these, disease induction (2, 7%), intervention (7, 23%), and/or subjective outcomes (17, 55%) were blinded. A sample size calculation was reported in 4/77 (5%). Animal numbers were missing in the Methods section in 16 (21%) publications; when stated, the median was 32 (range 6 to 320; interquartile range, 21 to 70). Extra animals used were mentioned in the Results section in 31 (40%) publications; this number was unclear in 23 (74%), and >100 for 12 (16%). When reporting most outcomes, numbers with denominators were given in 35 (45%), with no unaccounted numbers in 24 (31%), and no animals excluded from analysis in 20 (26%). Most (49, 64%) studies reported >40, and another 19 (25%) reported 21 to 40 statistical comparisons. Internal validity limitations were discussed in 7 (9%), and external validity (to humans) discussed in 71 (92%), most with no (30, 42%) or only a vague (9, 13%) limitation to this external validity mentioned.ConclusionsThe reported methodological quality of AR was poor. Unless the quality of AR significantly improves, the practice may be in serious jeopardy of losing public support.

Highlights

Animal research (AR) findings often do not translate to humans; one potential reason is the poor methodological quality of AR
We find that the reported methodological quality of AR published in three highimpact critical care journals during 6 months of the year 2012 was poor, potentially contributing to the poor translation rate to human medicine
We reviewed all consecutive AR published in three prominent critical care journals (Critical Care Medicine, Intensive Care Medicine, and American Journal of Respiratory and Critical Care Medicine) during 6 months of the year 2012 to determine the reporting of a priori-determined methodological quality factors

Summary

Introduction

Animal research (AR) findings often do not translate to humans; one potential reason is the poor methodological quality of AR. Translation of biomedical animal research (AR) findings to humans has been disappointing [1,2]. There are two main possible reasons for this. Animals are complex biological systems; their nonlinear dynamics and responses are extremely sensitive to initial conditions [3,4]. Despite superficial physiologic and genetic similarity between species, it may not be that responses to similar perturbations or disease will be relevantly similar. The methodological quality of AR may be poor, causing misleading results [5,6,7,8,9].

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