Statistical assessment of the prognostic and the predictive value of biomarkers-A biomarker assessment framework with applications to traumatic brain injury biomarker studies
Year: 2022
Type: article
Abstract: Studies that investigate the performance of prognostic and predictive biomarkers are commonplace in medicine. Evaluating the performance of biomarkers is challenging in traumatic brain injury (TBI) and other conditions when both the time factor (i.e. time from injury to biomarker measurement) and different levels or doses of treatments are in play. Such factors need to be accounted for when assessing the biomarker's performance in relation to a clinical outcome. The Hyperbaric Oxygen in Brain Injury Treatment (HOBIT) trial, a phase II randomized control clinical trial seeks to determine the dose of hyperbaric oxygen therapy (HBOT) for treating severe TBI that has the highest likelihood of demonstrating efficacy in a phase III trial. Hyperbaric Oxygen in Brain Injury Treatment will study up to 200 participants with severe TBI. This paper discusses the statistical approaches to assess the prognostic and predictive performance of the biomarkers studied in this trial, where prognosis refers to the association between a biomarker and the clinical outcome while the predictiveness refers to the ability of the biomarker to identify patient subgroups that benefit from therapy. Analyses based on initial biomarker levels accounting for different levels of HBOT and other baseline clinical characteristics, and analyses of longitudinal changes in biomarker levels are discussed from a statistical point of view. Methods for combining biomarkers that are of complementary nature are also considered and the relevant algorithms are illustrated in detail along with an extensive simulation study that assesses the performance of the statistical methods. Even though the discussed approaches are motivated by the HOBIT trial, their applications are broader. They can be applied in studies assessing the predictiveness and prognostic ability of biomarkers in relation to a well-defined therapeutic intervention and clinical outcome.
Language: English
Subfield: Statistics and Probability
Field: Mathematics
Domain: Physical Sciences
Open Access status: green
Funders: U.S. Department of Defense, Honorable Tina Brozman Foundation, Ovarian Cancer Research Alliance, National Institutes of Health, Cancer Center, University of Kansas, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, Center for Scientific Review, National Center for Advancing Translational Sciences
Awards: G3969584785, Hyperbaric Oxygen BrainInjury Treatment (HOBIT) Trial-SDMC, G4425758525, G6778488390, G8120922673, Frontiers Clinical and Translational Science Institute at the University of Kansas, Extracellular Vesicle Proteomic Fingerprinting of Ovarian Cancer for Early Detection with a Nanoengineered Microsystem, Biomarkers in the Hyperbaric Oxygen in Brain Injury Treatment Trial, Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) - Data Coordinating Center, The Kansas Institute for Precision Medicine, Hyperbaric Oxygen Brain Injury Treatment (HOBIT) Trial
OpenAlex ID: W4311312919