Validation of the DBS sampling method of cyclosporin in TDM practice
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The CLSI EP09-A guideline is adapted.
EP9 assumes that the two methods being compared will yield essentially
identical results. The Medically Allowable Error is defined 15%. This Medical
Allowable Error will be used to determine:
1. the maximum allowable difference between specimens across methods,
2. the maximum allowable difference between duplicate specimens for the same
method,
3. the distance between the scatter plot bounds and the regression line.
Secondary outcome
Outlier determination. The outlier identification process is quite complex.
(See the EP9 document for details). In general, an outlier is detected either
when duplicate results for the same method are too different, or when a pair of
results across methods is too different. In either case, all results for both
specimens are declared to be outliers.
Test for adequate range of results.
Computation of key statistics: regression slope, intercept, and standard error
of estimate; 95% confidence interval for predicted Medical Decision Points.
Visual check for linearity.
Visual check for "uniform scatter". The purpose of this test is to decide how
to compute the medical decision points: by Partitioned Residuals or by Deming
regression.(13) Whereas the ordinary linear regression method assumes that only
the Y measurements are associated with random measurement errors, the Deming
method takes measurement errors for both methods into account.
Examination of the bias plot. The bias at the high end and the bias at the low
end will be compared.
Background summary
The immunosuppressive drug cyclosporin has a narrow therapeutic window and
large inter- and intraindividual variability of pharmacokinetics (1;2).
Therapeutic drug monitoring (TDM) of cyclosporin is usually performed in
ethylenediamine tetraacetic acid (EDTA) blood, obtained by venous sampling by
technicians. Dried blood spot sampling (DBS) could be a useful alternative
sampling method. With DBS, capillary blood is obtained from a fingerprick with
an automatic lancet by the patients themselves and the drop of blood is applied
to sampling paper. After drying, the paper with the blood spot sample is sent
by mail to the laboratory
Study objective
Validation of the DBS sampling method of cyclosporin in TDM practice
Study design
We will collect venous and fingerprick blood samples at the same time. Venous
sampling will be done by venapuncture and the EDTA blood samples are collected
and stored at 4°C until analysis. Fingerprick blood samples are collected using
Glucolet 2 Automatic Lancing Device (Bayer, Mishawaka). Samples are collected
from the fingertip. The first drop is discarded and the next 2 drops are
collected to fill 2 8-mm premarked circles on the sampling paper (no.
10,535,097, obtained from Whatman Schleicher & Schuell, Dassel, Germany).
Volume of the blood drops of patients will be approximately 30 µl and blood
spots of about 10-mm diameter are produced. The blood spots are allowed to dry
at room temperature and packed in sealable plastic minibags. On arrival in the
laboratory, the blood spots are visually inspected. Criteria are complete,
homogenous, and symmetric filling of the 8-mm circle and dark-red colour on
both sides of the paper. Paper disks with a diameter of 7.5mm are punched out
with an electromagnetic driven hole puncher. Dried blood spot sampling is
compared with our routine assays in venous blood.
Study burden and risks
The study bears minimal risk for the subjects.
de Boelelaan 1117
1081 HV Amsterdam
Nederland
de Boelelaan 1117
1081 HV Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
older than 18 years
Exclusion criteria
No informed consent
Design
Recruitment
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| CCMO | NL23749.029.08 |