Criteria for the use of omics-based predictors in clinical trials: Explanation and elaboration

High-throughput 'omics' technologies that generate molecular profiles for biospecimens have been extensively used in preclinical studies to reveal molecular subtypes and elucidate the biological mechanisms of disease, and in retrospective studies on clinical specimens to develop mathematical models to predict clinical endpoints. Nevertheless, the translation of these technologies into clinical tests that are useful for guiding management decisions for patients has been relatively slow. It can be difficult to determine when the body of evidence for an omics-based test is sufficiently comprehensive and reliable to support claims that it is ready for clinical use, or even that it is ready for definitive evaluation in a clinical trial in which it may be used to direct patient therapy. Reasons for this difficulty include the exploratory and retrospective nature of many of these studies, the complexity of these assays and their application to clinical specimens, and the many potential pitfalls inherent in the development of mathematical predictor models from the very high-dimensional data generated by these omics technologies. Here we present a checklist of criteria to consider when evaluating the body of evidence supporting the clinical use of a predictor to guide patient therapy. Included are issues pertaining to specimen and assay requirements, the soundness of the process for developing predictor models, expectations regarding clinical study design and conduct, and attention to regulatory, ethical, and legal issues. The proposed checklist should serve as a useful guide to investigators preparing proposals for studies involving the use of omics-based tests. The US National Cancer Institute plans to refer to these guidelines for review of proposals for studies involving omics tests, and it is hoped that other sponsors will adopt the checklist as well. © 2013 McShane et al.; licensee BioMed Central Ltd

Plant community dynamics of lomas fog oasis of Central Peru after the extreme precipitation caused by the 1997-98 El Niño event

Despite El Niño events being one of the main forces shaping the coastal desert vegetation in South America, the impacts of the high precipitation typical of this rare but recurrent climatic event remain understudied. Here we monitored the plant community of a coastal lomas, a seasonal desert ecosystem, during 1998 and 2001 to analyse its changes during the 1997-98 El Niño and the following La Niña events. We measured species abundance and vegetation cover in 31 plots, and recorded climate variables in Lomas de Lachay, Peru. We found a significant positive correlation between precipitation and vegetation cover, density, alpha diversity (species diversity at the plot level), total richness and abundance of several key species but no correlation with gamma diversity (species diversity at the whole loma level). During the El Niño event, the seasonality, typical of the lomas ecosystem, disappeared, as evidenced by both the similarity of species composition and mean vegetation cover values between most sampling campaigns of 1998 and 1999. Moreover, total richness was lower during the El Niño event than during the humid season of 2000 and 2001 resulting from the dominance of only a few species, such as Nicotiana paniculata and Loasa urens. Temporal-spatial changes in the abundance of the dominant species caused the differences between alpha and gamma diversity, especially during 1999. Within that year, mean alpha diversity showed similar values whilst gamma diversity values were different. The reestablishment of the seasonality of most plant community characteristics and a clear difference between species composition of the humid and the dry season occurred two years after the El Niño event, suggesting a resilient community. This study provides one of the few quantifications of the Peruvian lomas' response to the 1997-98 El Niño event and the following La Niña, one of the most extreme climatic events in the last century