Publication Bias in Reports of Animal Stroke Studies Leads to Major Overstatement of Efficacy

Publication bias confounds attempts to use systematic reviews to assess the efficacy of various interventions tested in experiments modelling acute ischaemic stroke, leading to a 30% overstatement of efficacy of interventions tested in animals.The consolidation of scientific knowledge proceeds through the interpretation and then distillation of data presented in research reports, first in review articles and then in textbooks and undergraduate courses, until truths become accepted as such both amongst “experts” and in the public understanding. Where data are collected but remain unpublished, they cannot contribute to this distillation of knowledge. If these unpublished data differ substantially from published work, conclusions may not reflect adequately the underlying biological effects being described. The existence and any impact of such “publication bias” in the laboratory sciences have not been described. Using the CAMARADES (Collaborative Approach to Meta-analysis and Review of Animal Data in Experimental Studies) database we identified 16 systematic reviews of interventions tested in animal studies of acute ischaemic stroke involving 525 unique publications. Only ten publications (2%) reported no significant effects on infarct volume and only six (1.2%) did not report at least one significant finding. Egger regression and trim-and-fill analysis suggested that publication bias was highly prevalent (present in the literature for 16 and ten interventions, respectively) in animal studies modelling stroke. Trim-and-fill analysis suggested that publication bias might account for around one-third of the efficacy reported in systematic reviews, with reported efficacy falling from 31.3% to 23.8% after adjustment for publication bias. We estimate that a further 214 experiments (in addition to the 1,359 identified through rigorous systematic review; non publication rate 14%) have been conducted but not reported. It is probable that publication bias has an important impact in other animal disease models, and more broadly in the life sciences.Author Summary: Publication bias is known to be a major problem in thereporting of clinical trials, but its impact in basic researchhas not previously been quantified. Here we show thatpublication bias is prevalent in reports of laboratory-basedresearch in animal models of stroke, such that data from asmany as one in seven experiments remain unpublished.The result of this bias is that systematic reviews of thepublished results of interventions in animal models ofstroke overstate their efficacy by around one third.Nonpublication of data raises ethical concerns, firstbecause the animals used have not contributed to thesum of human knowledge, and second because participantsin clinical trials may be put at unnecessary risk ifefficacy in animals has been overstated. It is unlikely thatthis publication bias in the basic sciences is restricted tothe area we have studied, the preclinical modelling ofthe efficacy of candidate drugs for stroke. A related articlein PLoS Medicine (van der Worp et al., doi:10.1371/journal.pmed.1000245) discusses the controversies andpossibilities of translating the results of animal experimentsinto human clinical trials.