title: Application of Mixed Effects Limits of Agreement in the Presence of Multiple Sources of Variability: Exemplar from the Comparison of Several Devices to Measure Respiratory Rate in COPD Patients.
abstract: BACKGROUND
  The Bland-Altman limits of agreement method is widely used to assess how well the measurements produced by two raters, devices or systems agree with each other. However, mixed effects versions of the method which take into account multiple sources of variability are less well described in the literature. We address the practical challenges of applying mixed effects limits of agreement to the comparison of several devices to measure respiratory rate in patients with chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  Respiratory rate was measured in 21 people with a range of severity of COPD. Participants were asked to perform eleven different activities representative of daily life during a laboratory-based standardised protocol of 57 minutes. A mixed effects limits of agreement method was used to assess the agreement of five commercially available monitors (Camera, Photoplethysmography (PPG), Impedance, Accelerometer, and Chest-band) with the current gold standard device for measuring respiratory rate.
  
  
  RESULTS
  Results produced using mixed effects limits of agreement were compared to results from a fixed effects method based on analysis of variance (ANOVA) and were found to be similar. The Accelerometer and Chest-band devices produced the narrowest limits of agreement (-8.63 to 4.27 and -9.99 to 6.80 respectively) with mean bias -2.18 and -1.60 breaths per minute. These devices also had the lowest within-participant and overall standard deviations (3.23 and 3.29 for Accelerometer and 4.17 and 4.28 for Chest-band respectively).
  
  
  CONCLUSIONS
  The mixed effects limits of agreement analysis enabled us to answer the question of which devices showed the strongest agreement with the gold standard device with respect to measuring respiratory rates. In particular, the estimated within-participant and overall standard deviations of the differences, which are easily obtainable from the mixed effects model results, gave a clear indication that the Accelerometer and Chest-band devices performed best.
authors.affiliation: Edinburgh Clinical Trials Unit, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Richard A
authors.identifier: http://orcid.org/0000-0002-2658-5022
authors.initials: RA
authors.lastname: Parker
authors.affiliation: Edinburgh Clinical Trials Unit, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Weir
authors.affiliation: Edinburgh Lung and the Environment Group Initiative (ELEGI), Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Noah
authors.initials: N
authors.lastname: Rubio
authors.affiliation: Edinburgh Lung and the Environment Group Initiative (ELEGI), Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rabinovich
authors.affiliation: Allergy and Respiratory Research Group, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Hilary
authors.initials: H
authors.lastname: Pinnock
authors.affiliation: Edinburgh Clinical Trials Unit, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom.|Edinburgh Napier University School of Nursing, Midwifery and Social Care, Edinburgh, United Kingdom.
authors.forename: Janet
authors.initials: J
authors.lastname: Hanley
authors.affiliation: e-Health Research Group, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Lucy
authors.initials: L
authors.lastname: McCloughan
authors.affiliation: Edinburgh Lung and the Environment Group Initiative (ELEGI), Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Drost
authors.affiliation: Edinburgh Lung and the Environment Group Initiative (ELEGI), Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Leandro C
authors.initials: LC
authors.lastname: Mantoani
authors.affiliation: Edinburgh Lung and the Environment Group Initiative (ELEGI), Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: William
authors.initials: W
authors.lastname: MacNee
authors.affiliation: Edinburgh Clinical Trials Unit, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom.|e-Health Research Group, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Brian
authors.initials: B
authors.lastname: McKinstry
mesh_terms: D061725:Accelerometry; D000704:Analysis of Variance; D006801:Humans; D017156:Photoplethysmography / Q000379:methods; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology* / Q000628:therapy*; D015272:Pulmonary Medicine / Q000295:instrumentation*; D015203:Reproducibility of Results; D012119:Respiration; D056152:Respiratory Rate; D012720:Severity of Illness Index