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N-terminal pro-B-type Natriuretic Peptides Prognostic Utility Is Overestimated in Meta-analyses Using Study-specific Optimal Diagnostic Thresholds
University of KwaZulu Natal, South Africa.
University of KwaZulu Natal, South Africa.
Greys Hospital, South Africa.
University of KwaZulu Natal, South Africa.
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2015 (English)In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 123, no 2, 264-271 p.Article in journal (Refereed) Published
Abstract [en]

Background:N-terminal fragment B-type natriuretic peptide (NT-proBNP) prognostic utility is commonly determined post hoc by identifying a single optimal discrimination threshold tailored to the individual study population. The authors aimed to determine how using these study-specific post hoc thresholds impacts meta-analysis results. Methods: The authors conducted a systematic review of studies reporting the ability of preoperative NT-proBNP measurements to predict the composite outcome of all-cause mortality and nonfatal myocardial infarction at 30 days after noncardiac surgery. Individual patient-level data NT-proBNP thresholds were determined using two different methodologies. First, a single combined NT-proBNP threshold was determined for the entire cohort of patients, and a meta-analysis conducted using this single threshold. Second, study-specific thresholds were determined for each individual study, with meta-analysis being conducted using these study-specific thresholds. Results: The authors obtained individual patient data from 14 studies (n = 2,196). Using a single NT-proBNP cohort threshold, the odds ratio (OR) associated with an increased NT-proBNP measurement was 3.43 (95% CI, 2.08 to 5.64). Using individual study-specific thresholds, the OR associated with an increased NT-proBNP measurement was 6.45 (95% CI, 3.98 to 10.46). In smaller studies (less than100 patients) a single cohort threshold was associated with an OR of 5.4 (95% CI, 2.27 to 12.84) as compared with an OR of 14.38 (95% CI, 6.08 to 34.01) for study-specific thresholds. Conclusions:Post hoc identification of study-specific prognostic biomarker thresholds artificially maximizes biomarker predictive power, resulting in an amplification or overestimation during meta-analysis of these results. This effect is accentuated in small studies.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS and WILKINS , 2015. Vol. 123, no 2, 264-271 p.
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-122778DOI: 10.1097/ALN.0000000000000728ISI: 000363537300006PubMedID: 26200179OAI: diva2:873336

Funding Agencies|CLS Behring Biotherapies for Life (Vienna, Austria); Astra Zeneca (Vienna, Austria); Boehringer Ingelheim (Ingelheim, Germany); CLS Behring Biotherapies for Life; Novo Nordisk Pharma GmbH (Vienna, Austria)

Available from: 2015-11-23 Created: 2015-11-23 Last updated: 2016-04-25

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Oscarsson, Anna
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Division of Drug ResearchFaculty of Medicine and Health SciencesDepartment of Anaesthesiology and Intensive Care in Linköping
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