Biology Reference
In-Depth Information
disease and to de
ne criteria for a positive
screening test in preparation for the next phase.
2
de
nition of validation that applies to cancer
and other diseases:
“
Markers for urothelial cancer must be
expressed exclusively as a consequence of the
presence of cancer cells. The test must be sensitive
in detecting disease and must be validated in
non-selected populations. It must be sensitive in
excluding non-disease, and non-cancer condi-
tions must have little in
Phase 4: Prospective screening studies
This phase, unlike the previous three phases, is
applied to samples taken from individuals and
not on stored specimens. The primary aim is to
determine the operating characteristics of the
biomarker-based screening test in a relevant pop-
ulation by determining the detection rate and
false referral rate.
2
The sensitivity and speci
uence on its accuracy.
There must be little or no inter-assay or intra-
assay variability. Interpretation of an assay for
a tumor marker should be all or none, or based
on a threshold level. The assays must have suffi-
city
of the biomarker is determined at this phase.
-
cient sensitivity and speci
city in populations
and in the individual to have practical clinical
applicability.
Phase 5: Cancer control studies
The aim of this phase is to determine the value
and effectiveness of the biomarker as a screening
clinical test on the number of cancer cases in
a population. Does screening help reduce the
number of cancer cases? The most effective and
useful biomarker is one that can detect the disease
at an early stage, prior to clinical symptoms.
2
a biomarker is considered
validatedwhen the factors identi
”
Finally,
“
ed in a training
set of patients give a statistically signi
cant asso-
ciation in an independent validation cohort con-
ducted in an independent laboratory.
7
”
References
1. Clanciulli C, Watzig H. Analytical instrument quali
ca-
CONCLUSIONS
:1499
e
508.
2. Pepe MS, Etzioni R, Feng Z, et al. Phases of biomarker
development for early detection of cancer.
J Nat Cancer
Inst
2001;
tion in capillary.
Electrophoresis
2012;
33
The search for a protein or metabolite
biomarker in biological
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e
61.
3. Khleif SN, Doroshow JH, Hait WN. AACR-FDA cancer
biomarkers collaborative consensus report: advancing
the use of biomarkers in cancer drug development.
Clin
Cancer Res
2010;
93
fluids and tissues is chal-
lenging and involves people with different types
of expertise and analytical techniques. The results
must be con
rmed and validated and should be
free from over
:3299
e
318.
4. Chau CH, Rixe O, Mcleod H, et al. Validation of analytic
methods for biomarkers used in drug development.
Clin
Cancer Res
2008;
16
tting of the data (which can
happen when a large number of variables are
measured on a small number of samples) and
should be free of bias. The method used to vali-
date a biomarker must also be accurate, sensitive,
and reproducible.
5
The instrumentation needs to
meet speci
:5967
e
76.
5. Brenner DE, Normolle DP. Biomarkers for cancer risk,
early detection, and prognosis: the validation conun-
drum.
Cancer Epidemiol Biomarkers Prev
2007;
14
:1918
e
20.
6. Droller MJ. Current concepts of tumor markers in
bladder cancer.
Urol Clin North Am
2002;
16
:229
e
34.
7. Roos PH, Golka K, Hengstler JG. Predictive biomarkers
and signatures in urinary bladder cancer.
Cur Opn Mol
Therapeutics
2008;
29
ed for its
intended purpose. Using urothelial cancer as an
example, Droller
6
ed criteria and be quali
exquisitely summarizes the
10
:243
e
50.
