Should Studies of Diabetes Treatment Stratification Correct for Baseline HbA1c?
Public Library of Science
Copyright: © 2016 Jones et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
AIMS: Baseline HbA1c is a major predictor of response to glucose lowering therapy and therefore a potential confounder in studies aiming to identify other predictors. However, baseline adjustment may introduce error if the association between baseline HbA1c and response is substantially due to measurement error and regression to the mean. We aimed to determine whether studies of predictors of response should adjust for baseline HbA1c. METHODS: We assessed the relationship between baseline HbA1c and glycaemic response in 257 participants treated with GLP-1R agonists and assessed whether it reflected measurement error and regression to the mean using duplicate 'pre-baseline' HbA1c measurements not included in the response variable. In this cohort and an additional 2659 participants treated with sulfonylureas we assessed the relationship between covariates associated with baseline HbA1c and treatment response with and without baseline adjustment, and with a bias correction using pre-baseline HbA1c to adjust for the effects of error in baseline HbA1c. RESULTS: Baseline HbA1c was a major predictor of response (R2 = 0.19,β = -0.44,p<0.001).The association between pre-baseline and response was similar suggesting the greater response at higher baseline HbA1cs is not mainly due to measurement error and subsequent regression to the mean. In unadjusted analysis in both cohorts, factors associated with baseline HbA1c were associated with response, however these associations were weak or absent after adjustment for baseline HbA1c. Bias correction did not substantially alter associations. CONCLUSIONS: Adjustment for the baseline HbA1c measurement is a simple and effective way to reduce bias in studies of predictors of response to glucose lowering therapy.
The Predicting Response to Incretin Based Agents (PRIBA) study was funded by the National Institute of Health Research (NIHR) (UK) and supported by the NIHR Clinical Research Network. The GoDARTS study was funded by the Wellcome trust and is supported by Diabetes UK. ATH, ERP, BMS, WEH and ML are funded for this analysis as part of the MRC/ABPI MASTERMIND project. AGJ is an NIHR Clinician Scientist. ATH is an NIHR Senior Investigator and a Wellcome Trust Senior Investigator. ERP is a Wellcome Trust New Investigator. ATH and BMS are core staff members of the NIHR Exeter Clinical Research Facility. WEH is partially supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula. The views given in this paper do not necessarily represent those of NIHR, the NHS or the Department of Health.
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Vol. 11, article e0152428
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