Biology Reference
In-Depth Information
ses before, during, and for two weeks after administration was discontinued,
and measure a variety of potential markers in serum and blood. The data were
analyzed by various statistical models that provided the optimum combination
of variables and the weight to attach to each. The main study compared place-
bo-treated with rHuEPO-treated subjects who received 50 U/kg three times per
week for 25 days [58]. The treatment group comprised 49 Australian subjects
and 24 Chinese subjects.
The study found that five markers provided the most discrimination
between the placebo-treated and rHuEPO-treated groups. These were hemat-
ocrit, reticulocyte hematocrit (MCV of reticulocytes multiplied by the number
of reticulocytes), percent macrocytes, serum concentration of EPO, and serum
concentration of serum TfR. The total score was referred to as the “on-score”
[58]. By the end of the 3-week rHuEPO administration period, the “on-scores”
of the placebo-treated and rHuEPO-treated groups differed significantly.
Serum EPO and sTfR were particularly increased in the rHuEPO-treated group
compared with the placebo group. No differences were noted between the
Australian and the Chinese subjects or between men and women.
The Australian investigators also calculated the “on-score” on approximate-
ly 1,200 elite athletes from 12 countries [58]. Based on these data, they calcu-
lated cut-offs for the “on-score” values beyond which the risk of a false-posi-
tive was very low. At a meeting of experts three months before the Sydney
Games [59], the “on-score” was not approved as a standalone index of use of
erythropoietic proteins largely due to legal and medical concerns. It was
approved, however, as a technique to indicate which urine samples should be
tested by the recently developed, definitive urine test (discussed later). The
rules stated that an athlete could not be declared “positive” for rHuEPO unless
the “on-score” was greater than the cut-off score and the urine test showed
rHuEPO. Samples could be declared “suspicious” if the “off-score” was
increased or if only one of the blood or urine tests was positive. No athletes
were declared positive during the Games of Sydney, but seven were reported
as “suspicious” [60].
Index of recent use of erythropoietic proteins
The Australian researchers found that after rHuEPO was discontinued, the
reticulocyte count and serum EPO concentrations were depressed while the
hematocrit remained increased [58]. From these three parameters they calcu-
lated an “off-score” and proposed that an increased “off-score” be used to
identify athletes who had recently discontinued rHuEPO. The “off-score” was
increased from day three to day 13 post-administration of rHuEPO. Although
the statistical certainty that the “off-score” indicated recent use was quite high,
the IOC expert committee did not accept the test largely because of the legal
difficulty of proving that an athlete used rHuEPO on the basis of an indirect
test. The “off-score” is used today to indicate which athletes should be fol-
lowed closely with other testing.
