What do the designations
“sensitive,” “intermediate,” “resistant,” and
“EDR” (extreme drug resistance) signify?
These
are determined
by the degree of tumor cell death, relative to an appropriate (“apples
to
apples,” not “apples to oranges”) subset of comparison, database assays.
The way this works
is as follows: For each specimen, we
determine relevant parameters (tumor histology, specimen transit time
before
testing, degree of spontaneous tumor cell loss (or gain) in control
cultures,
degree of tumor cell three dimensionality, strength of metabolic
signal, etc.).
Our computer then searches through our database of more than 500,000
assay
results and retrieves the most closely-matched dataset of assays. Then
for each
drug tested, at each concentration, and with each assay endpoint, we
determine
the mean and standard deviation for degree of cell death. Plus or minus
0.5
standard deviations from the mean denotes an “intermediate” assay
result.
Greater than 0.5 standard deviations denotes a “sensitive” result (i.e.
a clearly greater than average degree of
cell death). Less than 0.5 standard
deviations denotes a “resistant” result (i.e. a clearly
below average degree of cell death.
Less than a full standard deviation denotes "EDR" (extreme
drug resistance). Applying Bayesian statistics to the
“S,I,R,E” results (lower right figure) allows us to
estimate the assay predicted probability of response
for each drug. This (lower right) graph shows the
relationship between expected, pre-test probability
of response (i.e. the chance of the drugs working
before we did the assays) versus the new, revised
chances of the drug working, given the reality of a
“sensitive,” “intermediate,” “resistant,” or “extreme-
ly resistant” assay result. The lower right graph was
generated by applying Bayes’ theorem to the published
clinical correlation data shown in the lower left graph.
References
at: http://weisenthal.org/oncol_t.htm