title: Preanalytical investigations of phlebotomy: methodological aspects, pitfalls and recommendations.
abstract: Phlebotomy is often addressed as a crucial process in the pre-analytical phase, in which a large part of laboratory errors take place, but to date there is not yet a consolidated methodological paradigm. Seeking literature, we found 36 suitable investigations issued between 1996 and 2016 (April) dealing with the investigation of pre-analytical factors related to phlebotomy. We found that the largest part of studies had a cohort of healthy volunteers (22/36) or outpatients (11/36), with the former group showing a significantly smaller median sample size (N = 20, IQR: 17.5-30 and N = 88, IQR: 54.5-220.5 respectively, P < 0.001). Moreover, the largest part investigated one pre-analytical factor (26/36) and regarded more than one laboratory test (29/36), and authors preferably used paired Student's t-test (17/36) or Wilcoxon's test (11/36), but calibration (i.e. sample size calculation for a detectable effect) was addressed only in one manuscript. The Bland-Altman plot was often the preferred method used to estimate bias (12/36), as well as the Passing-Bablok regression for agreement (8/36). However, often papers did assess neither bias (12/36) nor agreement (24/36). Clinical significance of bias was preferably assessed comparing to a database value (16/36), and it resulted uncorrelated with the size of the effect produced by the factor (P = 0.142). However, the median effect size (ES) resulted significantly larger if the associated factor was clinically significant instead of non-significant (ES = 1.140, IQR: 0.815-1.700 and ES = 0.349, IQR: 0.228-0.531 respectively, P < 0.001). On these evidences, we discussed some recommendations for improving methodological consistency, delivering reliable results, as well as ensuring accessibility to practical evidences.
authors.affiliation: Department of Human Physiology and Pharmacology, University of Rome Sapienza, Rome, Italy; Laboratory Medicine Department, "Tor Vergata" University Hospital, Rome, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Ialongo
authors.affiliation: Laboratory Medicine Department, "Tor Vergata" University Hospital, Rome, Italy; Experimental Medicine and Surgery Department, "Tor Vergata" University, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
mesh_terms: D019411:Clinical Laboratory Techniques / Q000592:standards*; D003951:Diagnostic Errors / Q000517:prevention & control*; D006801:Humans; D010338:Pathology, Clinical / Q000592:standards*; D018962:Phlebotomy / Q000379:methods* / Q000592:standards*; D017410:Practice Guidelines as Topic / Q000592:standards*; D011785:Quality Assurance, Health Care; D011786:Quality Control
keywords: methods; phlebotomy; preanalytical phase; statistical data analysis