Selecting a Hemoglobin A1C Point of Care Instrument. Objectives. Disclosure / Conflict of Interest 3/11/2015

Transcription

1 Selecting a Hemoglobin A1C Point of Care Instrument Heather P. Whitley, PharmD, BCPS, CDE Associate Clinical Professor of Pharmacy Practice Auburn University Harrison School of Pharmacy Objectives Compare certification requirements by the National Glycohemoglobin Standardization Program (NGSP) to that of the College of American Pathologists (CAP) for hemoglobin A1C instruments Objectively compare and contrast the three NGSPcertified A1C POC devices approved in the USA in terms of accuracy and precision, ease of use, and additional features. Disclosure / Conflict of Interest I, Heather Whitley, have no actual or potential conflict of interest in relation to this program. 1

2 Epidemiology of Diabetes National Statistics (2014) Alabama Statistics (2013) Diabetes Diabetes Prevalence: 9.3% (29.1 million) Prevalence: 13.8% (448,912) 72% (21 million) aware/diagnosed 27.8% (8.1 million) unaware/undiagnosed Incidence: 1.7 million/yr Prediabetes Prevalence: 27.5% (86 million) 11% aware; 89% unaware basics/statistics Prediabetes Prevalence: 37% (1,203,605) 7% aware; 93% unaware Diagnosed Prevalence (2011) Green 18.8% Hale 14.9% Montgomery 14% Madison 11% Tuscaloosa 10.7% Lee 9.7% Shelby 8.5% Basic Pathophysiology Hyperglycemia Impaired insulin secretion Insulin resistance (type 2) 2

3 Consequences Permanent organ damage Macrovascular risks Heart attack, strokes Microvascular risks Blindness Kidney failure Amputation Glycemic Goals of Therapy Test Diabetes Fasting BG (FBG) mg/dl 2 hr PPBG < 180 mg/dl A1C < 7% A1c to Average Glucose Assessment of the past 2 3 months 3

4 A1C Testing Options Conventional measurements Venipuncture blood sample Skilled personnel required to extract sample Results available next day Point of Care (POC) Finger prick blood sample Results available in 3 6 minutes POC A1C Benefits POC Outcomes 52% intervention rate 1 A1C reduction: 1.03 ± 0.33% 1 to 0.4 ±1.65% 2 Cost savings via glycemic control: Q1% A1C increase above 6% $33,958 for long term complications of hyperglycemia 3 A1C <8% vs >10% lower hospital admission rates: p< Conventional Outcomes 27% intervention rate 1 A1C reduction: 0.33% 1 1 Ferenczi, et al. Endocr Pract. 2001;7(2): Cagliero, et al. Diabetes Care. 1999;22(11): Gilmer, et al. Diabetes Care. 1997;20(12): Menzin, et al. Diabetes Care. 2001;24(1):51 5. NGSP Certified A1C POC Instruments Hand Held A1C Now Bench Top Models Afinion DCA Vantage Chek Diagnostics Axis Shield shield.com Siemens 4

5 A1C POC Dimensions Hand Held A1C Now 2.5 in Bench Top Models Afinion DCA Vantage 7.4 in 9in 2 in 6.7 in 13.4 in 10.5 in 11.5 in Device weight: 0.4 lbs Device weight: 11 lbs Device weight: 9lbs Performance: Accuracy and Precision Label the Target Low accuracy Low precision High accuracy High precision High accuracy Low precision Low accuracy High precision Verifying Accuracy and Precision American Association for Clinical Chemistry (AACC) National Glycohemoglobin Standardization Program (NGSP) Endorsed by American Diabetes Associate (ADA) Since 1996 authority in standardizing A1C testing to DCCT equivalent values Diabetes Control and Complications Trial (DCCT) 5

6 DCCT Results A1C and microvascular complications NEJM. 1993;329(14): NGSP Annual Certification Controlled environment Performance under optimal conditions By the manufacturer 40 sample comparison A1C range 4% 10% A1C = 7 ±6% = ±0.42% = A1C = 10 ±6% = ±0.6% = Certification = 37/40 samples fall ±6% Of the NGSP secondary reference laboratory (SRL) NGSP List of Certified Methods Listed methods document NGSP certification No additional detail is provided 6

7 College of American Pathologist (CAP) Biannual proficiency testing (GH2) Performance in clinical and realistic environments Includes end user influences N=2000 individual clinical laboratories 3 pooled whole blood samples: Low: % Medium: % High: % Pass = 2/3 samples with accuracy ±6% of the target value Performance: CAP Survey Average Accuracy Imprecision Recommended goals: Mean: 37/40 samples ±6% = Certification Mean bias: < 0.2; > 0.3 not acceptable Confidence of variance (CV): < 3; > 5% not acceptable Performance: CAP Survey Data 2013 GH2 B Therefore, predominately impacts mean bias 7

8 Performance: CAP Survey Data 2014 GH2 B Overall Variability (B 2014) NGSP Low Target Bias and Variability NGSP Mid Target Bias and Variability 8

9 NGSP High Target Bias and Variability Assay Methodology Structural differences Boronate affinity chromatography A1CNow Immunoassays DCA Vantage Afinion Charge differences Cation exchange chromatography Agar gel electrophoresis No difference clinically Affinity Chromatography Separates biochemical mixtures Based on highly specific interaction Antigen and antibody Enzyme and substrate Receptor and ligand 9

10 Immunoassay Methodology Use antibodies or immunoglobulins to separate differences of compounds based on structure Measures concentration of antibodies bound to a macromolecule Label Glycated hemoglobin Antibody Sources of Interference Hemoglobin variants interfere >50% of the time with A1C assay instruments Method HbC HbS HbE HbD HbF Bayer A1CNow Yes Yes No No assumed * Axis Shield Afinion No No No No assumed * Siemens DCA Vantage No No No No Yes > 10% * In the absence of specific method data, it can generally be assumed that both immunoassay and boronate affinity methods show interference from HbF levels above ~10 15% J Diabetes Sci Technol. 2009;3(3): Hemoglobin C (HbC) & S (HbS) > 300,000 American with diabetes carry the trait Commonly asymptomatic Many unaware of carrier status A1CNow produces a clinically and significantly positive bias when present Potentially results in unnecessary increased pharmacotherapy and hypoglycemic rates J Diabetes Sci Technol. 2010;4(6): J Diabetes Sci Technol. 2010;4(6):

11 Hemoglobin F (HbF) Normally < 1% Abnormal levels > 10% Hinder recognition of antigenic sites on immunoassays to glycated hemoglobin Non glycated HbF contribute to the total hemoglobin assay estimate Producing falsely low A1C results May result in unintended clinical inertia Clin Chem Lab Med. 2007;45(8): Clin Chem. 2000;46: Amer J Clin Path. 2008;129: A1C POC Logistics Hand Held A1C Now Bench Top Models Afinion DCA Vantage Cartridge stability: Air stability: Blood sample size: In cartridge stability: Analysis time: A1C reporting range: Memory capacity: 4 months 2 min 5 µl 5 min 4 13% None; 60 min 3 months 10 min 1.5 µl 5 min 3 min 4 15% results 3 months 5 min 1µL 5 min 6 min % 4000 results A1C POC Features Hand Held A1C Now Bench Top Models Afinion DCA Vantage Display: Calibration: Data export: Accessories: Black and white None; 20 test each None None Color touch None USB, Ethernet, RS232 Barcode scanner (purchased separately) Color touch Lot specific USB; Ethernet Barcode scanner Onboard printer 11

12 Ease of Use PTS Diagnostics A1CNow (4 minutes) Axis Shield Afinion 6Rf_H142l4 (2 minutes) Siemens DCA Vantage (40 seconds) (2 minutes) Summary Comparison Summary Comparison Cont. 12