Multicenter assessment of a hemoglobin A1c point-of-care device for diagnosis of diabetes mellitus

Abstract

Objective: A multisite investigation compared the analytical performance of a point-of-care (POC) HbA1c device with multiple commonly used HbA1c laboratory methods and an NGSP (National Glycohemoglobin Standardization Program) reference method.

Research Design and Methods: The Afinion AS100 POC device analyzed HbA1c using 618 EDTA whole blood excess patient specimens with clinically indicated HbA1c testing. Results were compared to measurements across five clinical laboratories and the NGSP reference method. Precision was evaluated over 8–10 consecutive days for low-, mid-, and high-range HbA1c specimens at all five sites.

Results: Over a wide range of HbA1c values (4.0%–15% HbA1c), 97.1% of the POC results and 94.5% of routine laboratory results fell within the target value of ±6% of the NGSP reference method results. The POC HbA1c results at 6.5% exhibited a total relative bias of −0.6% (−0.04% HbA1c) compared to the reference method while the aggregate of laboratory methods displayed a relative bias of −0.9% (−0.06% HbA1c). The total imprecision of the POC results ranged from 0.74–2.13% CV across the analytic measurement range compared to 0.81–3.23% CV for the routine laboratory methods.

Conclusions: The accuracy and precision of the Afinion POC HbA1c method was comparable to the laboratory HbA1c methods supporting the FDA's recent approval of the Afinion HbA1c Dx device for use in the diagnosis of diabetes.

Introduction

Diabetes is a significant global public health concern, with an estimated mortality rate of over 1.5 million lives per year [1]. Diabetes is a chronic condition that results from autoimmune related insulin deficiency (type 1) or insulin resistance/β-cell dysfunction (type 2), with type 2 diabetes comprising a majority of diabetes cases and new diagnoses. Type 2 diabetes results from chronic hyperglycemia that leads to insulin insensitivity at the cellular level and ultimately the inability to adequately metabolize dietary glucose [1,2].

Hemoglobin A1c (HbA1c) is formed via non-enzymatic glycation on the terminal valine of the β-globin chain. The concentration of HbA1c is highly dependent upon the average lifespan of the red blood cell and blood glucose concentrations, but is representative of an individual's average blood glucose concentration over the last 2–3 months [3,4]. Therefore, monitoring HbA1c concentrations are beneficial for assessing long-term glycemic control. Clinical guidelines from the American Diabetes Association, World Health Organization, and the International Diabetes Federation recommend that a HbA1c cutoff ≥6.5% (48 mmol/mol) can be utilized for the diagnosis of diabetes, if testing is conducted using an assay which is standardized and certified by the National Glycohemoglobin Standardization Program (NGSP) and traceable to the Diabetes Control and Complications Trial (DCCT) reference method [1,2,5]. Recently, the FDA has cleared the Abbott (formerly Alere) Afinion AS100 HbA1c Dx device as a moderately complex test for use in the diagnosis of diabetes, which is a first for a point-of-care (POC) HbA1c method.

Historically HbA1c point-of-care (POC) devices demonstrated significant bias and variability when compared to non-POC assays, which led to clinical guideline recommendations against utilization for diagnostic purposes [[6], [7], [8], [9]]. However, there have been improvements in HbA1c assays and technologies over time and further investigation into the accuracy and precision of these devices is required. POC HbA1c measurements could expedite diagnostic decisions and medical interventions provided they meet performance standards [6]. The purpose of this multicenter study was to evaluate the analytical performance of HbA1c using the Afinion AS100 POC analyzer between multiple sites, and compare the performance characteristics to other frequently used automated HbA1c assays and an NGSP reference method.