title: Charting a roadmap for heart failure biomarker studies.
abstract: Heart failure is a syndrome with a pathophysiological basis that can be traced to dysfunction in several interconnected molecular pathways. Identification of biomarkers of heart failure that allow measurement of the disease on a molecular level has resulted in enthusiasm for their use in prognostication and selection of appropriate therapies. However, despite considerable amounts of information available on numerous biomarkers, inconsistent research methodologies and lack of clinical correlations have made bench-to-bedside translations rare and left the literature with countless publications of varied quality. There is a need for a systematic and collaborative approach aimed at definitively studying the clinical benefits of novel biomarkers. In this review, on the basis of input from academia, industry, and governmental agencies, we propose a systematized approach based on adherence to specific quality measures for studies looking to augment current prediction model or use biomarkers to tailor therapeutics. We suggest that study quality, rather than results, should determine publication and propose a system for grading biomarker studies. We outline the need for collaboration between clinical investigators and statisticians to introduce more advanced statistical methodologies into the field of biomarkers that would allow for data from a large number of variables to be distilled into clinically actionable information. Lastly, we propose the creation of a heart failure biomarker consortium that would allow for a comprehensive list of biomarkers to be concomitantly analyzed in a pooled sample of randomized clinical trials and hypotheses to be generated for testing in biomarker-guided trials. Such a consortium could collaborate in sharing samples to identify biomarkers, undertake meta-analyses on completed trials, and spearhead clinical trials to test the clinical utility of new biomarkers.
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmad
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Mona
authors.initials: M
authors.lastname: Fiuzat
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pencina
authors.affiliation: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Geller
authors.affiliation: Nancy University, Nancy, France.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: University of Hull, Yorkshire, United Kingdom.
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.affiliation: Critical Diagnostics, San Diego, California.
authors.forename: James V
authors.initials: JV
authors.lastname: Snider
authors.affiliation: Johannes Gutenberg University, Mainz, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Blankenberg
authors.affiliation: Division of Cardiology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Kirkwood F
authors.initials: KF
authors.lastname: Adams
authors.affiliation: Division of Cardiology, UCSF, San Francisco, California.
authors.forename: Rita F
authors.initials: RF
authors.lastname: Redberg
authors.affiliation: Amgen, Thousand Oaks, California.
authors.forename: Jae B
authors.initials: JB
authors.lastname: Kim
authors.affiliation: Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
authors.forename: Alice
authors.initials: A
authors.lastname: Mascette
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mentz
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: jjanuzzi@partners.org.
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
mesh_terms: D015415:Biomarkers / Q000097:blood*; D003299:Cooperative Behavior; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D006801:Humans; D011379:Prognosis; D012107:Research Design
chemical_list: D015415:Biomarkers
keywords: biomarkers; heart failure; studies