The reliability of experimental findings depends on the rigour of experimental design. Here we show limited reporting of measures to reduce the risk of bias in a random sample of life sciences publications, significantly lower reporting of randomisation in work published in journals of high impact, and very limited reporting of measures to reduce the risk of bias in publications from leading United Kingdom institutions. Ascertainment of differences between institutions might serve both as a measure of research quality and as a tool for institutional efforts to improve research quality.

BackgroundExpression of various long noncoding RNAs (lncRNAs) may affect cancer prognosis. Here, we aim to gather and examine all evidence on the potential role of lncRNAs as novel predictors of survival in human cancer.MethodsWe systematically searched through PubMed, to identify all published studies reporting on the association between any individual lncRNA or group of lncRNAs with prognosis in human cancer (death or other clinical outcomes). Where appropriate, we then performed quantitative synthesis of those results using meta-analytic methods to identify the true effect size of lncRNAs on cancer prognosis. The reliability of those results was then examined using measures of heterogeneity and testing for selective reporting biases.ResultsThree hundred ninety-two studies were screened to eventually identify 111 eligible studies on 127 datasets. In total, these represented 16,754 independent participants pertaining to 53 individual and 6 grouped lncRNAs within a total of 19 cancer sites. Overall, 83 % of the studies we identified addressed overall survival and 32 % of the studies addressed recurrence-free survival. For overall survival, 96 % (88/92) of studies identified a statistically significant association of lncRNA expression to prognosis. Meta-analysis of 6 out of 7 lncRNAs for which three or more studies were available, identified statistically significant associations with overall survival. The lncRNA HOTAIR was by far the most broadly studied lncRNA (n = 29; of 111 studies) and featured a summary hazard ratio (HR) of 2.22 (95 % confidence interval (CI), 1.86–2.65) with modest heterogeneity (I2 = 49 %; 95 % CI, 14–79 %). Prominent excess significance was demonstrated across all meta-analyses (p-value = 0.0003), raising the possibility of substantial selective reporting biases.ConclusionsMultiple lncRNAs have been shown to be strongly associated with prognosis in diverse cancers, but substantial bias cannot be excluded in this field and larger studies are needed to understand whether these prognostic information may eventually be useful.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-016-0535-1) contains supplementary material, which is available to authorized users.

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Historical control data (HCD) are information about control animals of toxicity studies and clinically healthy animals that have not received any treatment. The term describes the spontaneous incidence of a finding or the background variation in continuous parameters, observed in the same species and the same type of toxicity study as the study under evaluation. Although the principles and general conditions for submission of HCD across different regulatory frameworks may sound very similar, understanding of the purpose and interpretation of these data is very heterogeneous, and can end up in differences in the interpretation of study results and final risk assessment for one and the same compound. EFSA has recognised the need for closer understanding on the criteria regarding the use, reporting and interpretation of historical control data in the evaluation of toxicity studies submitted under the substance classes primarily under the EFSA remit. Within the framework of this project and in order to better explore the community perception on HCD, three activities have been considered critical. Under the first activity, a literature search was conducted and retrieved relevant publications were summarised and allocated to thematic clusters. Most of the relevant papers were related to long‐term/carcinogenicity studies, developmental toxicity, and statistics. In addition, public databases containing HCD (Charles River, MARTA, NTP, RITA) and relevant OECD documents (Testing Guidelines, Guidance documents and Guidance Notes) were screened for further information concerning HCD. Topics identified from the literature have been used on the one hand to draft specific questions for a worldwide survey (second activity), in order to capture the experience of toxicologists and risk assessors on the use of HCD. On the other hand, the identified topics were aimed to explore the relevant points for discussion in the workshop organised with relevant stakeholders (third activity). The feedback captured by the survey showed that there is very high interest in the topic and strong need for more harmonisation on requirements for use of HCD has been expressed. This has been confirmed in the workshop, held as virtual event from May 3 to 5, 2022, where the main conclusions were that clear set of criteria need to be fulfilled before HCD are taken into account for interpretation of results, that high level of granularity in HCD is necessary when these are compiled and submitted and that close exchange between different domains (toxicology, statistics) is crucial when HCD are included in the interpretation of study results. Outcome of the project activities will be considered by EFSA PPR Panel in drafting a Scientific Opinion on use, reporting and interpretation of HCD.

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