Technical Study: ACCU-CHEK Inform 3 (ACI 3) Pilot Study CIM RD003651

The ACI3 is a new meter/ test strip system for use in POCT settings (Point of
Care Testing). The ACI 3 can measure the blood glucose concentration, manage
data and transmit data wirelessly to a facility*s internal Data Management
System (e.g hospital or laboratory information system). Diabetic, non-diabetic
patients and a number of critically ill patients (IC patients) will be
approached to participate in this study in order to be able to examine the
accuracy of measurements of the ACI 3 on patient samples.
After informed consent, clinical data is recorded using Medrio and an
Electronic Data Capture (EDC) tool. Technical data is recorded using WinCAEv
(EDC).

The primary objective of this pilot study is to determine the accuracy of
measurement of the new Point of Care Test (POCT) glucose meter ACI3 from Roche
Diagnostics on venous, arterial and capillary whole blood samples from adult
hospital patients.
The ACI3 has been improved compared to its predecessor in both ease of use
(smaller and therefore more manageable) and measuring comfort (blood is more
easily transfered into the meter than before). In addition, the expectation is
that by using two electrodes on the glucose measuring strip instead of one can
be directly corrected for interfering substances, as a result of which the
measuring accuracy increases.
The measurement accuracy is determined by comparing the results of the ACI3
meter with those of reference methods, analyzed on a Roche Cobas c501 system.
The collected reference samples are coded before they are transferred to Roche
Mannheim for measurement.

In order to be able to determine the measurement accuracy of the ACI 3 over the
largest possible glucose concentration range more than one type of patients
need to be included. Therefore, diabetic patients (usually increased glucose
concentration, sometimes reduced glucose concentration) and healthy test
subjects (usually glucose concentration between the reference values) are
needed in this study. Also, Roche Diagnostics intends to launch the ACI 3 for
use in the IC. For this purpose, it is necessary to demonstrate that the ACI 3
can also accurately measure the glucose concentration within this specific
patient group.

The study is designed in three phases:
a. Familiarization phase: In this part of the study protocol, the staff is
introduced to the instrument and trained on how to use the glucose test strips.
The correct functions of the instrument and the operation of the test strips
are verified by performing a precision experiment using quality controls. The
measurement data obtained from this phase are not used for the evaluation of
the ACI 3 performance.
During the familiarization phase no patient samples will be measured.

b. Initial phase: In this part, a one-day repeatability experiment will be
carried out using one ACI3 instrument and the corresponding glucose test
strips. For both capillary and venous whole blood three different glucose
concentration ranges are tested (2.2 to 4.1 mmol / L (low), 4.2 to 11.1 mmol /
L (middle), > 11.1 mmol / L (high). For each glucose concentration range, blood
samples from 3 adult subjects are measured in triplicate, for which only one
blood sample (venous) / finger prick (capillary) is required.
During the initial phase samples are needed from 9 aldult patients. For this
part patients that come for their policlinic glucose meter checked will be
asked for informed consent. The needed samples will be collected as part of
their regular patient care. There will be no collection of additional
materials.
If the ACI 3 meets the proposed criteria, the study can enter the main phase:
- Glucose concentration < 4,2 mmol/L (75 mg/dL): SD < 0,33 mmol/L (6 mg/dL).
- Glucose concentration * 4,2 mmol/L (75 mg/dL): CV * 6%.

c. Main phase: A comparison between the measurement results of the ACI3 with
the reference method will be performed on different cohorts:
- about 60 arterial samples from adult diabetic or non-diabetic patients, of
which at least 10 intensive care (IC) patients.
For these patients the study consists of a comparison between a measurement on
the ACI 3 and the reference method. They will not have an additional finger
puncture.

- about 60 venous of adult diabetic or non-diabetic patients, of which at
least 10 intensive care (IC) patients.
For these patients the study consists of a comparison between a measurement on
the ACI 3 and the reference method. They will not have an additional finger
puncture.

- about 80 capillary samples from adult diabetic or non-diabetic patients, NO
IC patients needed.
The capillary samples are requested by their physician for a glucose POCT
measurement. Simultaneously, the glucose is also measured on the ACI 3 glucose
meter. There willnever be an additional finger puncture.

The measurements on the ACI3 are performed on location (Catharina Hospital
Eindhoven). The samples for the reference method are coded and sent to
Mannheim, where they will be measured.
In addition to the glucose measurement, the percentage of hematocrit is
determined per patient (from material of the same decrease). As additional
information, the medication use and, if determined, the diagnosis 'diabetes' is
included.
The sodium concentration and measured partial oxygen pressure (pO2) are only
provided if a blood gas is routinely performed.
NB. The added study protocol is an official, but general version applicable to
all hospitals involved. For the Catharina Hospital it has been decided not to
include the pediatric and neonatal patients in this technical validation. This
has been confirmed in the site-specific protocol (K6 - version 2) that is also
included.

There is noadditional risk for the patient. The burden only consists of reading
and possibly signing the information letter and the associated informed consent
form:
A quality analysis will be carried out between a new glucose POCT meter (ACI 3)
and a reference method. Almost the entire validation can be performed on
residual material from patient samples that are routinely drawn (all venous and
arterial samples).
Patients are already regularly checked for their glucose concentration by means
of a currently in use POCT device at Catharina Hospital. A good example of this
is the patients with diabetes, who come to check their glucose home meter. In
addition, the glucose concentration gets checked about 100,000 times per year
in clinical patients by means of a POCT measurement. For both patient groups, a
finger prick provides sufficient material to also measure the glucose on the
ACI 3.
Only the capillary samples used in the main phase of this validation, require
additional material for the comparison with the reference method, in addition
to the required whole blood for the glucose measurement (routine collection).
This is, strictly speaking, not residual material, but can be obtained from the
same finger prick because of the small volume (maximum 160 uL) and therefore
does not provide an extra treatment for the patient. This method of blood
collection is also routinely used in patient groups where a venous blooddraw is
not possible. For the use of the residual material, the retrieval of the
medication data and the diagnosis of diabetes and / or the additional removal
of a maximum of 160uL of capillary blood during a routine finger prick informed
consent will be requested from the patient.