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      A comparison of methods for estimating the temporal change in a continuous variable: Example of HbA1c in patients with diabetes

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          Abstract

          Purpose

          To compare the more complex technique, functional principal component analysis (FPCA), to simpler methods of estimating values of sparse and irregularly spaced continuous variables at given time points in longitudinal data using a diabetic patient cohort from UK primary care.

          Methods

          The setting for this study is the Clinical Practice Research Datalink (CPRD), a UK general practice research database. For 16,034 diabetic patients identified in CPRD, with at least 2 measures in a 30‐month period, HbA1c was estimated after temporarily omitting (i) the final and (ii) middle known values using linear interpolation, simple linear regression, arithmetic mean, random effects, and FPCA. Performance of each method was assessed using mean prediction error. The influence on predictive accuracy of (1) more homogeneous populations and (2) number and range of known HbA1c values was explored.

          Results

          When estimating the last observation, the predictive accuracy of FPCA was highest with over half of predicted values within 0.4 units, equivalent to laboratory measurement error. Predictive accuracy improved when estimating the middle observation with almost 60% predicted values within 0.4 units for FPCA. These results were marginally better than that achieved by simpler approaches, such as last‐occurrence‐carried‐forward linear interpolation. This pattern persisted with more homogeneous populations as well as when variability in HbA1c measures coupled with frequency of data points were considered.

          Conclusions

          When estimating change from baseline to prespecified time points in electronic medical records data, a marginal benefit to using the more complex modelling approach of FPCA exists over more traditional methods.

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          Most cited references12

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          A Geometric Approach to Maximum Likelihood Estimation of the Functional Principal Components From Sparse Longitudinal Data

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            The general practice research database: role in pharmacovigilance.

            The General Practice Research Database (GPRD) is the world's largest computerised database of anonymised longitudinal clinical records from primary care. The database already has an international reputation in the field of drug safety signal evaluation where the results of GPRD-based pharmacoepidemiological studies have been used to inform regulatory pharmacovigilance decision making. The characteristics and richness of the data are such that the GPRD is likely to prove a key data resource for the proactive pharmacovigilance anticipated in risk management and pharmacovigilance plans. An update of recent developments to the database and new data available from it -- including spontaneously recorded suspected adverse drug reactions -- is presented in the article, with a description of how the data can be used to support a variety of pharmacovigilance applications. The possibility of using the GPRD in signal detection and assessment of the impact of pharmacovigilance activities in the future is also discussed.
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              Evaluation of two-fold fully conditional specification multiple imputation for longitudinal electronic health record data

              Most implementations of multiple imputation (MI) of missing data are designed for simple rectangular data structures ignoring temporal ordering of data. Therefore, when applying MI to longitudinal data with intermittent patterns of missing data, some alternative strategies must be considered. One approach is to divide data into time blocks and implement MI independently at each block. An alternative approach is to include all time blocks in the same MI model. With increasing numbers of time blocks, this approach is likely to break down because of co-linearity and over-fitting. The new two-fold fully conditional specification (FCS) MI algorithm addresses these issues, by only conditioning on measurements, which are local in time. We describe and report the results of a novel simulation study to critically evaluate the two-fold FCS algorithm and its suitability for imputation of longitudinal electronic health records. After generating a full data set, approximately 70% of selected continuous and categorical variables were made missing completely at random in each of ten time blocks. Subsequently, we applied a simple time-to-event model. We compared efficiency of estimated coefficients from a complete records analysis, MI of data in the baseline time block and the two-fold FCS algorithm. The results show that the two-fold FCS algorithm maximises the use of data available, with the gain relative to baseline MI depending on the strength of correlations within and between variables. Using this approach also increases plausibility of the missing at random assumption by using repeated measures over time of variables whose baseline values may be missing.
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                Author and article information

                Contributors
                will.dixon@manchester.ac.uk
                Journal
                Pharmacoepidemiol Drug Saf
                Pharmacoepidemiol Drug Saf
                10.1002/(ISSN)1099-1557
                PDS
                Pharmacoepidemiology and Drug Safety
                John Wiley and Sons Inc. (Hoboken )
                1053-8569
                1099-1557
                15 August 2017
                December 2017
                : 26
                : 12 ( doiID: 10.1002/pds.v26.12 )
                : 1474-1482
                Affiliations
                [ 1 ] Division of Musculoskeletal and Dermatological Sciences, Arthritis Research UK Centre for Epidemiology, School of Biological Sciences, Faculty of Biology, Medicine and Health The University of Manchester, Manchester Academic Health Science Centre Manchester UK
                [ 2 ] Department of Epidemiology, Biostatistics and Occupational Health McGill University Quebec Canada
                [ 3 ] Department of Medicine McGill University Quebec Canada
                [ 4 ] Clinical and Health Informatics Research Group McGill University Quebec Canada
                [ 5 ] Centre for Health Informatics, Division of Informatics, Imaging and Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health The University of Manchester, Manchester Academic Health Science Centre Manchester UK
                [ 6 ] Health e‐Research Centre, Farr Institute The University of Manchester, Manchester Academic Health Science Centre Manchester UK
                Author notes
                [*] [* ] Correspondence

                W G Dixon, Division of Musculoskeletal and Dermatological Sciences, Arthritis Research UK Centre for Epidemiology, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Room 2.900, Stopford Building, Oxford Road, Manchester M13 9PT, UK.

                Email: will.dixon@ 123456manchester.ac.uk

                Author information
                http://orcid.org/0000-0002-1550-6528
                Article
                PDS4273 PDS-16-0505.R1
                10.1002/pds.4273
                5724699
                28812323
                7003c75b-1353-46a1-8e75-427265e5ce62
                © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 November 2016
                : 12 May 2017
                : 15 June 2017
                Page count
                Figures: 3, Tables: 3, Pages: 1, Words: 3488
                Funding
                Funded by: Canadian Institutes of Health Research (CIHR)
                Award ID: 201009MOP
                Funded by: Medical Research Council (MRC) Clinician Scientist Fellowship
                Award ID: G0902272
                Award ID: MR/K006665/1
                Categories
                Original Report
                Original Reports
                Custom metadata
                2.0
                pds4273
                December 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.8 mode:remove_FC converted:11.12.2017

                Pharmacology & Pharmaceutical medicine
                continuous variable,functional principal component analysis,linear interpolation,mean prediction error,pharmacoepidemiology,predictive accuracy,sparse longitudinal data

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