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

Abstract

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.

Selecting a Single Embryo for Transfer after In-vitro Fertilization: A Translational Medicine Perspective

“…This makes validation important to support claims that biomarker discovered through this approach is reliable enough for clinical use in embryo selection. McShane et al [92] recommends that the predictability of an omics biomarker should be confirmed using completely independent training data sets and the training data sets should be made to fulfill the following criteria:…”

“…Assays for the validation specimen set should be run at a different time or in a different laboratory but according to the identical assay protocol as was used for the training set [92].…”

“…The candidate omics -based test should be defined precisely, including the molecular measurements, the computer code, the computational procedures, and the intended clinical use of the test, in anticipation of the test validation phase [92].…”

“…Table 7 Criteria for the use of omics-based predictors in National Cancer Institute-supported clinical trials. (Adapted from [92]). …”

In Pursuit of Greater Reproducibility and Credibility of Early Clinical Biomarker Research

“…This commentary focuses on overarching principles to consider in early clinical biomarker research to enhance reproducibility and provide a solid foundation for later stages of development. For more extensive discussion of best practices to be applied throughout the clinical biomarker development process, readers are referred elsewhere 2, 3, 4…”