Determination of biological variation of several special clinical chemical tests

The result of a laboratory measurement is influenced by analytical variation,
biological variation and pathophysiological circumstances. The differences
between 2 consecutive measurements (eg by follow up of patients) is determined
by many factors, including treatment, and at least analytical and biological
variation (within subject). It is important to determine the biological
variation to be able to determine the reference change value. In addition,
biological variation determines the desired analytical variation. The reference
change value is important in establishing whether two results differ
significantly. In addition, biological variation is important to estimate the
variation around the homeostatic setpoint of an individual. In case of large
variation, a single measurement does not provide information regarding the
homeostatic setpoint of an individual subject. Together, the analytical and
biological variation determine the number of samples that is necessary to
estimate the homeostatic setpoint of an individual. In addition, biological
variation can be used to establish the *index of individuality* , that
indicates the usefulness of reference values of laboratory tests.
Biological variation can be devided in intra individual (within subject) and
interindividual (between subjects). The first is important in follow-up of
patients.
Many data on biological variation of routine clinical chemical measurements can
be found in the Westgard database, (www.westgard.com/biodatabase1.htm).
However, this database is not complete and does not include data that will be
investigated in this project.
Guidelines are presenty for the establishment of biological variation (1). It
is important that the subjects are healthy, to minimalize the influence of
pathophysiology. Subjects are not to change their diet, and other lifestyle
factors during the study, and medication, except pain killers, should be
avoided.
Samples should be collected under comparable conditions and stored
appropriately and immediately. To minimalize the contribution of analytical
variation, the samples should be analyzed in duplo within 1 series and with a
tracable method, if possible. The determination in duplo is neccessary to
establish analytical variation and accordingly the biological variation
Some of the laboratory parameters have cut-off values, eg RBC-DHA+EPA >8 g; (2)
and vitamin D. Some of the included parameters need the establishment of
reference values. Thus, the samples are also used for the determination of
reference values.It should be noted that some of the parameters are tumor
markers (PSA, free PSA, S100).

1; determination of biological variation of special clinical chemical
measurements
2: determination of reference values of a.o. Factor VIII, XI, XII and future
measurements

Blood of 30 healthy subjects will be collected using venapuncture during 5
occasions, separated by 4 weeks and during 4 months

Burden: filling out questionnaires, venapuncture with included risk (hematome),
loss of 3 times 28 ml and
2 times 48 ml of blood. blood pressure measurement
Risk: discomfort resulting from hematoma.