Phases of Biomarker Development for Early Detection of Cancer
Margaret S. Pepe,Ruth Etzioni,Ziding Feng,John D. Potter,Mary Lou Thompson,Mark D. Thornquist,Marcy Winget,Yutaka Yasui +7 more
TLDR
The purpose of this commentary is to define a formal structure to guide the process of biomarker development and to provide a checklist of issues that should be addressed at each phase of development before proceeding to the next.Abstract:
Recent developments in such areas of research as geneexpression microarrays, proteomics, and immunology offer new approaches to cancer screening (1). The surge in research to develop cancer-screening biomarkers prompted the establishment of the Early Detection Research Network (EDRN) by the National Cancer Institute (2). The purpose of the EDRN is to coordinate research among biomarker-development laboratories, biomarker-validation laboratories, clinical repositories, and population-screening programs. By coordination of research efforts, the hope is to facilitate collaboration and to promote efficiency and rigor in research. With the goals of the EDRN in mind, the purpose of this commentary is to define a formal structure to guide the process of biomarker development. We categorize the development into five phases that a biomarker needs to pass through to produce a useful population-screening tool. The phases of research are generally ordered according to the strength of evidence that each provides in favor of the biomarker, from weakest to strongest. In addition, the results of earlier phases are generally necessary to design later phases. Therapeutic drug development has had such a structure in place for some time (3). The clinical phases of testing a new cancer drug are as follows: phase 1, determinations of toxicity, pharmacokinetics, and optimal dose levels; phase 2, determinations of biologic efficacy; and phase 3, definitive controlled trials of effects on clinical endpoints. For each phase, guidelines exist for subject selection, outcome measures, relevant comparisons for evaluating study results, and so forth. Although deviations are common, the basic structure facilitates coherent, thorough, and efficient development of new therapies. A phased approach has also been proposed for prevention trials (4,5). In a similar vein, we hope that our proposed guidelines or some related construct will facilitate the development of biomarker-based screening tools for early detection of cancer. Although deviations from these guidelines may be necessary in specific applications, our proposal will, at the minimum, provide a checklist of issues that should be addressed at each phase of development before proceeding to the next.read more
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References
More filters
Journal ArticleDOI
Comparison of discrimination methods for the classification of tumors using gene expression data
TL;DR: Different discrimination methods for the classification of tumors based on gene expression data include nearest-neighbor classifiers, linear discriminant analysis, and classification trees, which are applied to datasets from three recently published cancer gene expression studies.
Book
Evaluation of diagnostic systems : methods from signal detection theory
John A. Swets,Ronald M. Pickett +1 more
Journal ArticleDOI
Human neoplasms elicit multiple specific immune responses in the autologous host.
Ugur Sahin,Özlem Türeci,Holger Schmitt,Bjorn Cochlovius,Thomas Johannes,Rudolf Schmits,Frank Stenner,Guorong Luo,Ingrid Schobert,Michael Pfreundschuh +9 more
TL;DR: The unexpected frequency of human tumor antigens indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.
Journal ArticleDOI
Recent advancements in surface-enhanced laser desorption/ionization-time of flight-mass spectrometry.
TL;DR: The overall history and recent advances in surface enhanced laser desorption/ionization‐time of flight‐mass spectrometry (SELDI‐TOF‐MS) technology is reviewed and its application to functional genomics and biomarker discovery is discussed and exemplified by elucidating a biomarker candidate for prostatic carcinoma.
Journal ArticleDOI
Analyzing a portion of the ROC curve.
TL;DR: The area under the ROC curve is a common index summarizing the information contained in the curve when comparing two ROC curves, though, problems arise when interest does not lie in the entire range of false-positive rates.