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Abstract
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The aim of this study was to assess the accuracy of blood glucose monitors (BGMs) from studies reported in the
medical literature. A literature review was performed of publications between 2010 and 2017 that presented data
about the accuracy of BGMs using ISO 15197 2003 and/or ISO 15197 2013 as target standards. We found 58
publications describing the performance of 143 unique BGM systems, 59 of which were Food and Drug Admin-
istration (FDA) cleared. When compared with non-FDA-cleared BGMs, FDA-cleared BGMs were significantly
more likely to pass both ISO 15197 2003 (OR = 2.39, CI 1.45–3.92, P < 0.01) and ISO 15197 2013 standards
(OR = 2.20, CI 1.51–3.27, P < 0.01). Newer meters were more likely to pass both ISO 15197 2003 and ISO 15197
2013 standards. Many of the studies were supported by BGM manufacturers, and when compared with independent
studies, an FDA-cleared BGM was significantly more likely to pass in a manufacturer-supported study for both ISO
15197 2003 (OR = 22.4, CI 8.73–21.57, P < 0.001) and ISO 15197 2013 (OR = 23.08, CI 10.16–60.03, P < 0.001).
BGM accuracy should be assessed independently following regulatory clearance to ensure accurate performance.
Failure to meet performance levels mandated by standards can result in deleterious clinical and economic effects.
Introduction Some BGMs that have previously been cleared by the FDA
have been tested by independent investigators with protocols
843
844 KING ET AL.
Table 1. International and Food and Drug (personal use) portion. Articles were also excluded if they
Administration Analytical Accuracy Requirements only used venous blood as the substrate to test BGM systems,
for Blood Glucose Monitors for Self-Monitoring although articles using venous blood for the comparator
method were included. In studies where data from laboratory
Accuracy standard Minimum accuracy requirements
accuracy studies (healthcare professionals assessed BGMs)
ISO 15197 2003 95% of glucose values must be and user performance accuracy studies (lay users and health-
within –15 mg/dL of reference care professionals assessed BGMs) was reported, they were
for values <75 mg/dL or treated as separate studies. For the user performance accuracy
within 20% of reference for studies, data from lay users and healthcare professionals were
values ‡75 mg/dL combined. A BGM needed to pass ISO requirements in both
ISO 15197 2013 95% of glucose values must be studies to receive a ‘‘pass’’ for that article. It should also be
within –15 mg/dL of reference noted that we did not exclude articles in which the total number
for values <100 mg/dL or
of data points and/or the distribution of data points did not
within 15% of reference for
values ‡100 mg/dL conform to ISO recommendations.2,3 In some articles the
FDA 2016 for 95% of glucose values must be reference method used differs from the one recommended by
over-the-counter within 15% of reference, and the manufacturer.10–24 If a BGM was compared against two
BGMs (FDA 2016) 99% of glucose values must be different reference methods, then the BGM was assessed with
within 20% of reference respect to the reference method specified by the manufacturer.
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(N compliant/N tested). Finally, we determined whether each significantly better for both ISO 15197 2003 (OR 1.06, CI
study was manufacturer supported, and if so, whether the 1.06–1.07, P < 0.001, odds ratio reported for a 1-year period)
product was tested by its own manufacturer. and ISO 15197 2013 standards (OR = 1.06, CI 1.03–1.06,
BGMs passing ISO 15197 2013 are assumed to pass ISO P < 0.01, odds ratio reported for a 1-year period).
15197 2003 because ISO 15197 2013 is stricter than ISO In addition, FDA-cleared meters and the total sample were
15197 2003; however, those that fail ISO 15197 2013 are not analyzed and sorted by their test strip enzyme: either glucose
assumed to pass or fail ISO 15197 2003. Similarly, in studies dehydrogenase (GDH) or glucose oxidase (GOX). We found
that only address ISO 15197 2003, BGMs that fail are as- that among our entire cohort of tested BGMs, those that used
sumed to also fail ISO 15197 2013; however, for BGMs that a GDH test strip chemistry outperformed those that used
passed ISO 15197 2003, no assumption is made about ISO GOX test strip chemistry for both ISO 15197 2003 and ISO
15197 2013. Similarly, a product failing to meet ISO 15197 15197 2013. Around 46/57 (80.7%) and 32/55 (58.2%) of
2013 would fail the FDA 2016 guidance; however, a product GDH systems passed ISO 15197 2003 and ISO 15197 2013,
passing ISO 15197 2013 will not necessarily pass the FDA respectively (Table 3), whereas only 47/80 (58.8%) and 23/
2016 guidance. Of note, we only found a single study in the 81 (28.4%) of GOX systems passed ISO 15197 2003 and
current literature that addressed the analytical accuracy of 2013, respectively (Table 4). GDH’s improved performance
BGM systems with respect to the recently published FDA over GOX was statistically significant for both the ISO 15197
2016 guidance, and this study showed identical results when 2003 (OR = 0.23, CI 0.13–0.38, P < 0.001) as well as the ISO
using the ISO 15197 2013 and FDA 2016 standards.10 Eva- 15197 2013 standard (OR = 0.24, CI 0.15–0.35, P < 0.001).
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luation against the two ISO standards remains most practical This same statistically significant trend occurred when only
at this current point in time for assessing compliance with considering FDA-cleared meters, with 25/28 (89.3%) of
current and past BGM analytical accuracy levels. FDA-cleared BGMs using any type of GDH chemistry
We conducted bias-reduced logistic regression (Firth27) to passing ISO 15197 2003, and 16/25 (64%) passing ISO
analyze the relationships between predictors of passing each 15197 2013. For BGMs using GOX chemistry, 18/29
standard, using pigeonhole bootstrap (Owen28) to adjust for (62.1%) passed ISO 15197 2003, whereas 10/31 (32.3%)
clustering of meters and studies. Statistical significance is passed ISO 15197 2013. FDA-cleared BGMs using GDH
defined as a P-value of 0.05 or less. We used a Spearman significantly outperformed FDA-cleared BGMs using GOX
correlation to measure monotone relationships with respect to in both ISO 15197 2003 (OR = 0.17, CI 0.06–0.38, P < 0.001)
manufacturer bias. and ISO 15197 2013 (OR = 0.24, CI 0.13–0.45, P < 0.001).
The effect of test strip enzyme on accuracy as it relates to
clearance year is presented in Figure 2.
Results
We also looked at the association of the recently popular
One hundred forty-three different BGMs were reviewed in GDH enzymatic cofactors flavin adenine dinucleotide (FAD)
a total of 58 studies.10–24,29–71 The minimum number of and nicotinamide adenine dinucleotide (NAD) compared
BGMs analyzed per study was 1, and the maximum was 43. with GDH without these new cofactors and containing the
The mean was 4.86 BGMs per study. earlier used cofactor, pyrroloquinoline quinone (PQQ), on
Around 93/137 (67.9%) of evaluated BGMs passed ISO performance (Tables 5 and 6). With respect to all analyzed
15197 2003, and 55/136 (40.4%) evaluated BGMs passed BGMs using GDH-FAD or GDH-NAD chemistry irrespec-
ISO 15197 2013. Out of the 143 total BGMs that we re- tive of FDA clearance status, 25/31 (80.6%) passed ISO
viewed, 59 BGMs had received FDA clearance. Around 43/ 15197 2003, and 18/28 (64.3%) passed ISO 15197 2013.
57 (75.4%) of FDA-cleared BGMs passed ISO 15197 2003, Among all analyzed BGMs using GDH but not specifying
whereas only 26/56 (46.4%) of FDA-cleared BGMs passed FAD or NAD as the enzymatic cofactor irrespective of FDA
the stricter ISO 15197 2013 standard. Among non-FDA- status, 21/26 (80.8%) passed ISO 15197 2003 and 13/27
cleared BGMs, 50/80 (62.5%) passed ISO 15197 2003 and (48.1%) passed ISO 15197 2013. We do not find evidence
29/80 (36.3%) passed ISO 15197 2013. FDA-cleared BGMs that FAD/NAD is more likely to be associated with passing
were found to be significantly more likely to meet both the the ISO 2003 standard (OR = 0.66, CI 0.24–1.50, P = 0.29) or
ISO 15197 2003 (OR = 2.39, CI 1.45–3.92, P < 0.01) and ISO ISO 2013 standard (OR = 0.91, CI 0.50–1.65, P = 0.76).
15197 2013 standards (OR = 2.20, CI 1.51–3.27, P < 0.01). Among FDA-cleared BGMs using GDH-FAD or GDH-
We also analyzed the 59 FDA-cleared BGMs with respect NAD, 15/17 (88.2%) passed ISO 15197 2003, and 9/14
to their year of clearance. The range of clearance years (64.3%) passed ISO 15197 2013. Among FDA-cleared
spanned from 2001 to 2017. We divided these BGMs into BGMs using GDH but not specifying FAD or NAD as the
four groupings of 4-year increments, with the exception of cofactor, 10/11 (90.1%) passed ISO 15197 2003 and 7/11
the oldest category, which was a 5-year increment. The re- (63.6%) passed ISO 15197 2013. These differences between
sults are presented in Table 2 and Figure 1. For BGMs cleared BGMs with GDH enzymes containing FAD or NAD com-
from 2001 to 2005, 4/7 (57.1%) passed ISO 15197 2003, pared with those containing PQQ for noncleared BGMs were
whereas 3/8 (37.5%) passed ISO 15197 2013. For BGMs also not statistically significant for the ISO 2003 standard
cleared between 2006 and 2009, 13/23 (56.5%) passed ISO (OR = 0.51, CI 0.15–3.24, P = 0.38) or the ISO 2013 standard
15197 2003, whereas 7/23 (30.4%) passed ISO 15197 2013. (OR = 0.62, CI 0.23–1.48, P = 0.29).
For BGMs cleared between 2010 and 2013, 11/12 (91.7%) Among FDA-cleared products tested in manufacturer-
passed ISO 15197 2003, and 6/12 (50%) passed ISO 15197 supported studies,11,14–21,23,29–65,67–71 95/107 (88.8%) passed
2013. For BGMs cleared between 2014 and 2017, 15/15 in tests as per ISO 15197 2003 and in 59/88 (67%) passed in
(100%) passed ISO 15197 2003, and 10/13 (76.9%) passed tests as per ISO 15197 2013. FDA-cleared products tested in
ISO 15197 2013. BGMs approved more recently performed independent studies10,12,13,21,24,66 passed in 19/23 (82.6%) of
846 KING ET AL.
tests as per ISO 15197 2003 and in 16/27 (59.3%) of tests For non-FDA-cleared products tested in manufacturer-
as per ISO 15197 2013. The likelihood of an FDA-cleared supported studies, 78/106 (73.6%) passed in tests as per ISO
product passing in a manufacturer-supported test compared 15197 2003, and 48/95 (50.5%) passed in tests as per ISO
with an independent test was significantly greater according 15197 2013. The likelihood of a noncleared product passing
to both ISO 15197 2003 (OR = 22.4, CI 8.73–21.6, P < 0.001) in a manufacturer-supported test compared with an inde-
and ISO 15197 2013 (OR = 23.08, CI 10.2–60.0, P < 0.001). pendent test was significantly greater according to both ISO
Table 2. Performance of Blood Glucose Monitor Systems Stratified by Clearance Year Intervals
Approval Clearance
year range BGM Manufacturer year ISO 2003 ISO 2013
2001–2005 Accu-Chek Active Roche Diagnostics 2001 Pass Pass
Accu-Chek Compact Roche Diagnostics 2002 Pass Pass
Ascensia BREEZE Bayer Healthcare LLC 2003 n/a Fail
Accu-Chek Go Roche Diagnostics 2004 Faila Faila
EZ Smart Tyson Bioresearch, Inc. 2004 Fail Fail
Accu-Chek Aviva Roche Diagnostics 2005 Pass Faila
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(continued)
A REVIEW OF BLOOD GLUCOSE MONITOR ACCURACY 847
Table 2. (Continued)
Approval Clearance
year range BGM Manufacturer year ISO 2003 ISO 2013
2014–2017 Element Infopia Co. 2014 Pass Faila
EGV1 EPS Biotechnology Corp. 2014 Pass n/a
Accu-Chek Aviva Plus Roche Diagnostics 2014 Pass Pass
Accu-Chek Performa Roche Diagnostics 2014 Pass Faila
(dependence unspecified)
In Touch Livongo Health 2014 Pass Pass
FreeStyle Freedom Lite Abbott Diabetes Care 2015 Pass Pass
FreeStyle Lite Abbott Diabetes Care 2015 Pass Fail a
GE 200 Bionime Corp 2015 Pass Pass
Rightest GM700 Bionime Corporation 2015 Pass Pass
FreeStyle InsuLinx Abbott Diabetes Care 2015 Pass Pass
Contour Next USB Bayer Healthcare LLC 2015 Pass Pass
FreeStyle Freedom Abbott Diabetes Care 2015 Pass n/a
Accu-Chek Guide Roche Diagnostics 2016 Pass Pass
Contour Next ONE Ascensia Diabetes Care 2016 Pass Pass
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15197 2003 (OR = 37.8, CI 15.7–35.8, P < 0.001) and ISO and 40/115 (34.8%) for alternative manufacturers. We con-
15197 2013 (OR = 163, CI 68.4–158, P < 0.001). cluded that the difference between independent tests and tests
To assess whether other products tested in a manufacturer- by alternative manufacturers was statistically significant as
supported study besides the manufacturer’s own products per ISO 15197 2003 (OR = 1.88, CI 1.02–4.08, P = 0.04), but
were more or less likely to receive a passing score than was not statistically significant as per ISO 15197 2013
products tested by their own manufacturer, and we deter- (OR = 1.50, CI 0.93–2.41, P = 0.08). We also concluded that
mined the passing percentage for products made by com- there was a statistically significant difference between man-
peting manufacturers compared with products tested by their ufacturers testing their own products versus a competitor’s
own manufacturer. Seventeen manufacturer-supported stud- product according to both ISO 15197 2003 (OR = 37.2,
ies also tested one or more products from other manufac- CI 4.62–299, P < 0.01) and ISO 15197 2013 (OR = 56.1,
turers.14,17,18,20,23,33,36,38,46–50,59,63,70,71 We also compared CI 11.9–263, P < 0.01).
this with independent tests to investigate the possibility of a
monotonic relationship between manufacturers testing their Discussion
own products, independent tests, and manufacturers testing
other products. We would expect there to be a relationship in The purpose of this review was to analyze factors con-
that order from most passing to least passing. The passing tributing to BGM compliance with ISO and FDA 2016
percentages for these three classes of products (against ISO guidelines for analytical accuracy in hopes of promoting
15197 2003 and ISO 15197 2013 were 80/80 (100%) and 67/ development and use of BGMs with greater accuracy. The
68 (98.5%) for products’ own manufacturer, 32/39 (82.1%) factors analyzed were FDA clearance (yes or no), time period
and 28/63 (44.4%) for independent tests, and 93/133 (69.9%) of clearance (2001–2005, 2006–2009, 2010–2013, or 2014–
2017), the type of chemistry used by the BGM (GOX vs.
GDH and GDH-FAD and GDH-NAD vs. GDH not using
FAD or NAD), and manufacturer support of the study (which
could potentially introduce bias).
We would expect FDA-cleared BGMs to perform better than
non-FDA-cleared BGM’s in the medical literature, and FDA-
cleared BGMs did in fact perform significantly better than
noncleared BGMs. Even so, only 75.4% of FDA-cleared BGMs
managed to pass the older ISO 15197 2003 standard by which
they had initially been cleared. When evaluated according to
the newer ISO 15197 2013 standard, only 46.4% of FDA-
cleared BGMs passed the test. Furthermore, we can deduce that
even fewer would pass the more rigorous 2016 FDA Guidance.
One possible limitation to our approach is a slight bias
toward the fail mark. BGMs that are close to meeting the ISO
FIG. 1. Percentage of BGMs passing ISO 2003 and ISO 2013 accuracy standards, and may be on average meeting them,
over four intervals of time. BGMs, blood glucose monitors. will be marked as ‘‘fail’’ in our review if one lot falls below
(Color graphics available at www.liebertonline.com/dia) the requirement. Our review was designed as such because
Table 3. Performance of Blood Glucose Monitor Systems Using Glucose Dehydrogenase
Test Strip Chemistry (With and Without Cofactors)
Test strip ISO FDA
BGM Manufacturer enzyme 2003 ISO 2013 cleared
Accu-Chek Mobile (dependence unspecified) Roche Diagnostics GDH Fail a Faila No
Accu-Chek Mobile (maltose dependent) Roche Diagnostics GDH Pass Pass No
Accu-Chek Mobile (maltose independent) Roche Diagnostics GDH Pass Pass No
Accu-Chek Performa Nano Roche Diagnostics GDH Pass Pass No
Contour Plasma Bayer Healthcare LLC GDH n/ a Fail No
Glucocard G+ Menarini Diagnostics GDH Pass Fail No
Glucocard G+Meter GT-1820 Arkray, Inc. GDH Pass Fail No
GlucoCheck XL (TD-4277) aktivmed GmbH GDH Faila Faila No
GlucoHexal II Med-WatchDoc GmbH GDH Fail Fail No
GlucoSmart Swing MSP Bodmann GmbH GDH Pass Fail No
GlucoSure ADVANCE Apex Biotechnology GDH Fail Fail No
GlucoTel BodyTel Europe GmbH GDH Pass Fail No
mylife Unio Bionime Corp GDH Pass Pass No
On Call Advanced ACON Biotech GDH Pass Fail No
Contour Next Link 2.4 Bayer Healthcare LLC GDH-FAD Pass Pass No
Contour Plus Bayer Healthcare LLC GDH-FAD Pass Pass No
Contour Plus ONE Ascencia Diabetes Care GDH-FAD Pass Pass No
Contour TS Bayer Healthcare LLC GDH-FAD Faila Faila No
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848
A REVIEW OF BLOOD GLUCOSE MONITOR ACCURACY 849
Table 4. Performance of Blood Glucose Monitor Systems Using Glucose Oxidase Test Strip Chemistry
FDA
BGM name Manufacturer Enzyme ISO 2003 ISO 2013 cleared
alphacheck professional i-SENS, Inc. GOX Pass Pass No
BeneCheck PLUS JET General Life Biotechnology GOX Fail Fail No
Beurer GL 30 Beurer GmbH GOX Fail Fail No
Beurer GL 32 Beurer GmbH GOX Pass Fail No
Beurer GL 40 Beurer GmbH GOX Pass Faila No
Beurer GL 50 Beurer GmbH GOX n/ a Fail No
Finetest Infopia Co. GOX Pass n/a No
Finetest Auto-coding Infopia Co. GOX Fail Fail No
FineTouch Terumo Corp GOX Fail Fail No
Futura Monometer TaiDoc Technology GOX Fail Fail No
Gluco-Test TD-4209 TaiDoc Technology Corp GOX Fail Fail No
Gluco-Test Plus+ TD-4230 TaiDoc Technology Corp GOX Pass Pass No
GlucoCheck Classic TaiDoc Technology Corp GOX Pass Fail No
GlucoCheck Comfort aktivmed GmbH GOX Pass Pass No
Glucofix Mio Menarini Diagnostics GOX Fail Fail No
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(continued)
850 KING ET AL.
Table 4. (Continued)
FDA
BGM name Manufacturer Enzyme ISO 2003 ISO 2013 cleared
CareSens II i-SENS, Inc. GOX Pass Fail Yes
CareSens N i-SENS, Inc. GOX Pass Pass Yes
CareSens N POP i-SENS, Inc. GOX Pass Pass Yes
Clever Check TD-4222 TaiDoc Technology Corp GOX Fail Fail Yes
Element Infopia Co. GOX Pass Faila Yes
Embrace Apex Biotechnology Corp GOX Fail Fail Yes
EZ Smart Tyson Bioresearch, Inc. GOX Fail Fail Yes
Fora G31 TaiDoc Technology GOX Pass Fail Yes
Fora TD-4227 TaiDoc Technology GOX Fail Fail Yes
GE 100 Bionime Corp GOX Pass Pass Yes
iBGStar AgaMatrix, Inc. GOX Pass Faila Yes
In Touch Livongo Health GOX Pass Pass Yes
my glucohealth Mendor Oy/Entra Health Systems LCC GOX n/a Fail Yes
Nova Max Nova Diabetes Care GOX Fail Fail Yes
OKmeter Match Ok Biotech GOX Pass Fail Yes
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patients depend on every lot fulfilling minimum accuracy 1.06, CI 1.06–1.07, P < 0.001, odds ratio reported for a 1-year
standards. period) and ISO 15197 2013 standards (OR = 1.06, CI 1.03–
Some studies adhered strictly to ISO recommendations for 1.06, P < 0.01, odds ratio reported for a 1-year period). A
the distribution of data points, and BGMs in these studies point of caution, however, is that while newer BGMs cer-
may also be at a disadvantage when compared with those who tainly outperformed older BGMs, 23.1% of BGMs cleared by
used tighter distributions with fewer extreme blood glucose the FDA in the most recent 4 years still did not meet the ISO
(BG) values at which some BGMs may be less accurate. 15197 2013 standard, and even fewer would likely pass the
More studies are needed to determine the accuracy of BGMs more rigorous 2016 FDA guidance.
at extreme hyperglycemic and hypoglycemic ranges. Which technological advances are contributing most to the
Many stakeholders in the diabetes community expect or as- improved performance of newer SMBGs? Pfützner73 identified
sume that all cleared meters will perform to the standards under the following four factors: (1) changes in test strip chemistry;
which they were approved, as well as to current standards. (2) the elimination of hematocrit interference; (3) improved
Parkin72 speculates that many FDA-cleared BGMs are failing to electrode design; and (4) improved mathematical algorithms.
meet the current standard because: (1) perhaps in some cases Our review demonstrated that approved BGMs utilizing GDH
quality standards in the manufacturing process have declined or as their test strip enzyme significantly outperformed those us-
(2) perhaps in some cases companies are falsifying data to ing GOX for ISO 15197 2003 (OR = 0.23, CI 0.13–0.38,
present to the FDA (who might lack the resources to investigate, P < 0.001) and ISO 15197 2013 (OR = 0.24, CI 0.15–0.35,
especially when the companies are overseas). We recommend P < 0.001), which could be why GDH is increasingly replacing
that additional surveillance studies be conducted on BGMs that GOX over time as the test strip enzyme of choice. Unlike GOX
have already been cleared by the FDA to ensure that BGMs meters, BGMs utilizing GDH are not dependent on the partial
continue to adhere to accuracy standards following the initial pressure of oxygen in the blood.74 Looking deeper, our analysis
clearance. Failure to remain accurate over time can put some of FAD/NAD as an enzymatic cofactor for GDH (as opposed to
patients who depend on this technology at risk of harm. the older PQQ cofactor) did not find a significant correlation
With respect to how long an existing blood glucose mon- with compliance to either ISO standards (ISO 15197 2003
itoring system (BGMS) has been on the market and cleared OR = 0.66, CI 0.24–1.50, P = 0.29; ISO 15197 2013 OR = 0.91,
by the FDA, our analysis showed that newer BGMs per- CI 0.50–1.65, P = 0.76). It is also possible that BGMs using
formed significantly better for both ISO 15197 2003 (OR GDH are on average newer than those using GOX and the
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FIG. 2. Percentage of BGMs passing ISO 2003 and ISO 2013 based on clearance year and test strip enzyme. (Color
graphics available at www.liebertonline.com/dia)
851
852 KING ET AL.
Table 6. Performance of Blood Glucose Monitor Systems Using Glucose Dehydrogenase Test Strip
Chemistry with Flavin Adenine Dinucleotide or Nicotinamide Adenine Dinucleotide Cofactor
BGM Manufacturer Test strip enzyme ISO 2003 ISO 2013 FDA cleared
Contour Next Link 2.4 Bayer Healthcare LLC GDH-FAD Pass Pass No
Contour Plus Bayer Healthcare LLC GDH-FAD Pass Pass No
Contour Plus ONE Ascencia Diabetes Care GDH-FAD Pass Pass No
Contour TS Bayer Healthcare LLC GDH-FAD Faila Faila No
Contour XT Bayer Healthcare LLC GDH-FAD Pass Pass No
EXIMO Meril Diagnostics GDH-FAD Pass Pass No
GlucoHexal Allmedicus Co. GDH-FAD Fail Fail No
iDia IME-DC GDH-FAD Pass Fail No
Omni Pod LifeScan, Inc. GDH-FAD Pass Pass No
OneTouch Verio Pro LifeScan, Inc. GDH-FAD Faila Faila No
OneTouch Verio Vue LifeScan, Inc. GDH-FAD Pass Pass No
TRUEyou Nipro Diagnostics GDH-FAD Pass Pass No
TRUEyou mini Nipro Diagnostics GDH-FAD Pass Pass No
Optium Xceed Abbott Diabetes Care GDH-NAD Faila Faila No
Total fraction passing 10/14 9/14
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perceived improved accuracy of BGMs using GDH cannot be the manufacturer. We believe that BGM supplies for accu-
entirely attributed to the enzyme itself. racy studies should ideally be obtained through the same
Lastly, our analysis of manufacturer-supported studies avenues that are used by patients, such as retail or mail-order
revealed that BGMs supported by the manufacturer signifi- pharmacies. Doing so would best recreate a patient’s ‘‘real-
cantly outperformed BGMs from other manufacturers, both world’’ experience and prevent the possibility of nonrandom
according to ISO 15197 2003 (OR = 37.2, CI 4.62–299, selection of products.
P < 0.01) and ISO 15197 2013 (OR = 56.1, CI 11.9–263, The most accurate assessment of a blood glucose monitor-
P < 0.01). While some studies we reviewed were performed ing system (BGMS)-measuring capillary blood is obtained by
by independent investigators, many were carried out or fun- also measuring capillary blood on a comparator method. In
ded by a manufacturer with protocol input (to the extent that some cases, comparison between capillary blood tested on a
the manufacturer was not declared to have been excluded BGM and venous blood tested on a comparator method could
from significant participation in the design of the study have a negative impact on the perceived accuracy of a BGMS.
protocol for an independent investigator). We think it is pos- In other instances, the difference between the two matrices
sible that a manufacturer might be more likely to publish a could cause a BGM to appear to be more accurate than it
study with favorable results and less likely to publish such a actually is. Whether the impact would be negative or positive
study with unfavorable results regarding the accuracy of their would depend on whether the BGM-measuring capillary blood
BGM. Therefore, it is possible that even fewer BGMs would is biased away from or toward the direction where the refer-
pass ISO or FDA guidance if all studies were completed by ence method measuring venous blood is biased.75
independent investigators and not subject to being selectively BGM accuracy is of the utmost importance because patients
reported by a manufacturer. rely on the information obtained from their BGMs to make
Additionally, even in independent studies, supplies (such treatment decisions. When results obtained are inaccurate,
as the BGM system and test strips) are frequently supplied by clinical consequences can be potentially life threatening and
Table 7. Studies Included with N Blood Glucose Monitors and N Lots Tested
Study name Publication year PubMed ID Manufacturer supported? N BGMs assessed LotN2003 LotN2013
Angelides et al. 2015 26002836 Yes 1 3505 3505
Bailey et al.a 2012 22853721 Yes 1 1152
Bailey et al.a 2015 26070512 Yes 1 1036
Bailey et al.a 2017 28617617 Yes 1 868
Baumstark et al. 2012 23063033 Yes 5 800 800
Baumstark et al. 2014 25107707 Yes 1 600
Baumstark et al. 2016 26428935 Yes 1 600
Baumstark et al.b 2017 28704063 Yes 6
Berti et al. 2015 26224761 Yes 6 200
Brazg et al. 2013 23439170 Yes 7 600b 600b
Brazg et al. 2016 27271844 Yes 1 600
Caswell et al.a 2015 25494048 Yes 1 1033 1033
Chandnani et al. 2017 28658800 Yes 1 1005
Charoensri et al. 2015 26591392 Yes 1 153 153
Chen et al. 2012 22266375 Yes 1
Christiansen et al.a 2017 28745099 Yes 1 1261
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853
854 KING ET AL.
the economic repercussions can be costly. Modeling studies 5. US Food and Drug Administration. Self-monitoring of blood
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test system against ISO 15197: 2013. Expert Rev Med Address correspondence to:
Devices 2015;12:771–781. David C. Klonoff, MD, FACP, FRCPE, Fellow AIMBE
69. Yon Hin B, Bueno I, Lowe CR, et al. Clinical accuracy Medical Director, Diabetes Research Institute,
study of an GDH-NAD blood glucose monitoring system Mills-Peninsula Medical Center
using the performance criteria of ISO 15197: 2013. J Dia- 100 South San Mateo Drive, Room 5147
betes Sci Technol 2016;11:444–445. San Mateo, CA 94401
70. Yu-Fei W, Wei-Ping J, Ming-Hsun W, et al. Accuracy
evaluation of 19 blood glucose monitoring systems man- E-mail: dklonoff@diabetestechnology.org