BETHESDA, Md--The increasing commercial interest in developing
tests for genetic disorders makes it imperative to come up with
guidelines for use of such tests as quickly as possible, Neil
Holtzman, MD, MPH, head of the genetic task force assembled by
the NIH and DOE, told the National Cancer Advisory Board (NCAB).
Dr. Holtzman, director of Genetics and Public Policies Studies,
Johns Hopkins Medical Institutions, said that the goals of the
task force are to review genetic testing in the United States
and make recommendations to ensure the development of safe and
effective genetic tests, their delivery in laboratories of assured
quality, and their appropriate use by health care providers and
Dr. Holtzman stressed that the genotypes to be detected by a genetic
test must be shown by scientifically valid methods to be associated
with the occurrence of a disease. Then data must be collected
to establish the clinical validity of the test.
Clinical validity can be shown in three ways, he said--sensitivity
(the probability that a person with a disease, or who will develop
a disease, will have a positive test result); specificity (the
probability that a test will be negative in a person free of a
disease and who will not develop the disease); and positive predictive
value (the probability that a person with a positive test result
has, or will develop, a disease).
Must Show Risks and Benefits
Before a test can be used in clinical practice, he said, data
also have to be collected to show the risks and benefits from
both positive and negative results. This can be done through randomized
clinical trials, through nonrandomized trials that allow patients
to choose their own interventions, or by enrolling tested patients
in registries and giving researchers access to that data.
Women who get positive test results for BRCA1, the so-called breast
cancer gene, for example, need to be followed up to see what types
of treatment they choose and how well the treatments work.