Understanding the Analysis of Method Comparison Studies with Repeated Measurements of Clinical Data

Abstract

Method comparison studies consist of a unique study design aiming to examine agreement between two methods to measure a physiological or clinical parameter evaluated using continuous variables. Such physiological parameters are used by healthcare providers along with other clinical data to inform diagnoses and treatment decisions. When novel methods are proposed to measure a continuous physiological parameter, method comparison studies are needed to examine the agreement between this new method and an existing method that is used in standard clinical care. This standard method is generally considered as the gold standard measurement for a given physiological parameter. The issue of repeated measurements poses special challenges when conducting method comparison studies. Repeated measurements occur when a given individual included in a method comparison study has multiple measurements, which are inherently correlated with one another and are not independent (e.g., multiple glucose measurements carried out for the same patient throughout the day using a blood test, compared to a portable point-of-care device). The limits of agreement (LOA) method proposed by Bland & Altman has been adapted to adjust for the correlation between repeated measurements and is widely used for the analysis of method comparison studies that include repeated measurements. However, other statistical methods have been proposed as alternatives to LOA analysis to inform the analysis of method comparison studies with repeated measurements. There is a gap in the literature to inform this type of analysis, whereby no guidelines or synthesis of statistical methods that can be used as alternatives to the LOA method with repeated measurements have been published. Therefore, this thesis aimed to systematically review the existing literature to identify existing alternate statistical methods for the analysis of method comparison studies that include repeated measurements, using a scoping review framework. The findings of this scoping review were used to inform the analysis of the PREMISE (Point-of-care hemoglobin accuracy and transfusion outcomes in non-cardiac surgery) study, a large prospective observational method comparison study that included repeated measurements. The aim of the PREMISE study was to examine the agreement between frequently used point-of-care devices to measure hemoglobin (POCT-Hgb) and laboratory-measured hemoglobin (lab-Hgb) in the operative setting. To further increase the understanding of the challenges associated with the analysis of method comparison studies that include repeated measurements, the analyses pertaining to agreement were performed in the context of this thesis. The findings of the PREMISE study fill an important gap in the literature pertaining to transfusion decision-making in the operative setting, where there is a paucity of evidence on the accuracy of POCT-Hgb devices, as well as from trials and transfusion guideline.