Role of PoCT in diabetes

management: Analytical &

Clinical Perspectives
Daniel maina
 Outline

1. Performance characteristic of PoCT platforms

2. Quality requirements for PoCT assays

3. Considerations for introducing PoC tests

4. Role of PoCT in Diabetes monitoring

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 HbA1c Assays- Proficiency testing USA 2016

 Ion Exchange HPLC (31% of USA laboratories)

 Capillary Electrophoresis (1%)
 Boronate Affinity Chromatography (2%)
 Immunoaasays (26%)
 Point of care (PoCT) (40%)

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 Performance of PoCT devices
 Analytical performance of IVD key in determining clinical
application/suitability
- screening, follow-up or diagnosis

 Two analytical concepts to consider

- Imprecision (reproducibility)
- Accuracy (bias)

 Limits of imprecision and bias for a method to be clinically useful

HbA1c- CV <2% (reported in % units), Total error allowable 0.5% units 4
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 Performance of PoCT devices

 A systematic review and meta-analysis by Hirst et al evaluated 63 studies with

13 different POC devices (Comparator- laboratory method)

 Nine devices had a negative mean bias which was significant for three devices

 There was substantial variability in bias within devices

 There was no difference in bias between clinical or laboratory operators in two

devices
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Forest plot showing mean bias (in % HbA1c) and 95% CI and prediction intervals, by POC device, ordered by mean bias

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Manufacturer/instrument means in CAP 2014 GH2-A survey

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 PoCT HbA1c

 Mostly immunoassays
- One Boronate method seeking FDA approval

Current guidelines
- Diagnosis cannot be made using PoCT device
 Good quality assurance programs (QAP) are needed
- Capable of meeting quality goals when QC is used
 Cannot detect Hb variants

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 Interference
 Hb variants
- HbC, HbS, HbE, HbD, ↑HbF

 Any condition that results in shortened RBC lifespan (hemolysis)

 Iron deficiency anemia is associated with higher HbA1c

 HbA1c underestimates glycemic control in diabetic patients on dialysis

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Interference

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PoCT HbA1c Bias Comparison AKUHN Lab

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POCT Glucose Bias comparison to ISO 15197- AKUHN

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 Why the concerns with PoCT?

 PoCT ran by non- laboratory staff

 may not have the same checks and attention to details practised in the lab

 Mostly unregulated (in the region)

 Errors can go undetected- especially biases and shifts with lot changes

The WHO guidance states that HbA1c may be used for diagnosis of type 2 DM provided “stringent
quality assurance tests are in place and assays are standardized to criteria aligned to the
international reference values” 14
 Ensuring quality
 Careful selection of the meter, which meets set standards
-reviews, proficiency schemes performance, FDA approval

 Analytical and clinical validation of the device

 Quality control runs (IQC)

 Proficiency testing- external quality assurance

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 Why PoCT? - Unmet needs

 In a study conducted in a tertiary hospital within Nairobi out of the198 diabetic

patients 67% had heard of HbA1c and only 20.2% had done at least one test

 PoCT may have a role in bridging the gap

Matheka DM, et al. Globalization and health. 2013;9(1):55.

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 Before implementing PoCT
Carefully consider the following:
1. Cost, benefits and disadvantages
2. Literature search for evaluations of suitable instruments
3. Is appropriate quality testing material available (QC, EQA)
4. What support is available for training and on-going technical support
5. Life of consumables – will expiry date allow usage before expiring?
6. Do consumables require refrigeration and is there capacity to
accommodate this?
7. Do I have staff that can undertake tasks involved with implementing
intended PoCT technology 17
 Criteria to select PoCT devices
i. Robustness and suitability of use
ii. Ease of Use
iii. Education and Training
iv. Accuracy
v. Cost
vi. Connectivity
vii. Are appropriate quality control (QC) and external quality assurance (EQA)
materials available?

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 Standardization
 The purpose of the NGSP is to standardize HbA1c test results to those of the
Diabetes Control and Complications Trial (DCCT) and United Kingdom
Prospective Diabetes Study (UKPDS) which established the direct relationships
between HbA1c levels and outcome risks in patients with diabetes.

 NGSP works closely with IFCC

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 How does HbA1c relate to average glucose (AG)?

 Average Plasma Blood Glucose (mmol/L) = (HbA1c * 1.98) - 4.29

HbA1c (%) eAG (mmol/l)

5 5.4

6 7

7 8.6

8 10.2

9 11.8

10 13.4

11 14.9

12 16.5

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 PoCT & Clinical outcomes

New Zealand (remote rural areas)

 POCT was found to significantly increase diagnostic certainty^

 Alter outcomes for 43% patients (p<0.001) by reducing transfers to the base
hospital by 62% (52 pretest and 20 post-test)

 Increased discharges by 480% (7 pretest and 34 post-test)

 Overall financial benefits were estimated to be $452,360 (NZD) annually 21

 PoCT & Clinical outcomes
 A study by Tanya et al comparing the clinical effectiveness of PoCT and that of
pathology laboratory testing, as measured by therapeutic control in chronic
conditions concluded for HbA1c, ACR, total cholesterol and triglyceride but
not INR and HDL cholesterol, the PoCT approach demonstrated the same or
better clinical effectiveness than pathology laboratory testing.

CoaguChek S analyser- INR; DCA 2000 analyser- HbA1c, urine albumin level and ACR;
Cholestech LDX analyser- total cholesterol, triglyceride and HDL cholesterol).

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 PoCT & Clinical outcomes
 POCT for glucose is the most common point-of-care test performed with glucose
testing strips, making up 53.7% of the total POCT market.
 Self-monitoring blood glucose measurement (SMBG)
- A Cochrane review of 12 RCTs (3259 patients) of SMBG in subjects with type 2
diabetes not using insulin, showed a decrease in HbA1C of 0.3% at six months and
0.1% at 12 months
 Critical care monitoring –
- Berghe et al. followed up 1548 patients and described that intensive blood glucose
control to levels of 4.4–6.1 mmol/L using insulin decreased mortality from 8% to 4.6%

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 PoCT & Clinical outcomes

Continuous glucose monitoring (CGM)

 In a RCT by Beck et al among adults with type 1 diabetes who used multiple
daily insulin injections, the use of CGM compared with usual care resulted in a
greater decrease in HbA1c level during 24 weeks

 Currently, there are four FDA-approved CGM systems on the market

Beck et al; Jama 317.4 (2017): 371-378.

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 Conclusion
 PoCT can mitigate the unmet testing needs in diabetes management in under-resourced and
unreached areas

 PoCT is most impactful when performed in a regulated environment with quality assurance
processes in place

 Not all PoCT assays are the same; careful consideration of performance characteristics important
when selecting PoCT device

 Connectivity of PoCT devices in hospital setting improves quality, patient safety and minimises
revenue leakage.
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 References
 Hirst, Jennifer A., et al. "Performance of point-of-care HbA1c test devices: implications for use in clinical
practice–a systematic review and meta-analysis." Clinical Chemistry and Laboratory Medicine (CCLM) 55.2
(2017): 167-180
 Weykamp, Cas, et al. "Investigation of 2 models to set and evaluate quality targets for hb a1c: biological
variation and sigma-metrics." Clinical chemistry 61.5 (2015): 752-759.
 Bubner, T. K., Laurence, et al (2009). Effectiveness of point‐of‐care testing for therapeutic control of chronic
conditions: results from the PoCT in General Practice Trial. Medical Journal of Australia, 190(11), 624-626.
 Matheka, Duncan Mwangangi, et al. "Pattern, knowledge and practices of HbA 1C testing among diabetic
patients in a Kenyan tertiary referral hospital." Globalization and health 9.1 (2013): 1-4.
 Beck, Roy W., et al. "Effect of continuous glucose monitoring on glycemic control in adults with type 1
diabetes using insulin injections: the DIAMOND randomized clinical trial." Jama 317.4 (2017): 371-378.
 Florkowski, Christopher, et al. "Point-of-care testing (POCT) and evidence-based laboratory medicine
(EBLM)–does it leverage any advantage in clinical decision making?." Critical reviews in clinical laboratory
sciences 54.7-8 (2017): 471-494. 26
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