NCAB Hears Report From Genetic Testing Task Force

BETHESDA, Md--The increasing commercial interest in developingtests for genetic disorders makes it imperative to come up withguidelines for use of such tests as quickly as possible, NeilHoltzman, MD, MPH, head of the genetic task force assembled bythe 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 thetask force are to review genetic testing in the United Statesand make recommendations to ensure the development of safe andeffective genetic tests, their delivery in laboratories of assuredquality, and their appropriate use by health care providers andconsumers.

Dr. Holtzman stressed that the genotypes to be detected by a genetictest must be shown by scientifically valid methods to be associatedwith the occurrence of a disease. Then data must be collectedto 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 developa disease, will have a positive test result); specificity (theprobability that a test will be negative in a person free of adisease and who will not develop the disease); and positive predictivevalue (the probability that a person with a positive test resulthas, or will develop, a disease).

Must Show Risks and Benefits

Before a test can be used in clinical practice, he said, dataalso have to be collected to show the risks and benefits fromboth positive and negative results. This can be done through randomizedclinical trials, through nonrandomized trials that allow patientsto choose their own interventions, or by enrolling tested patientsin registries and giving researchers access to that data.

Women who get positive test results for BRCA1, the so-called breastcancer gene, for example, need to be followed up to see what typesof treatment they choose and how well the treatments work.

For instance, Dr. Holtzman said, such women may choose prophylacticmas-tectomies, especially if they have already lost several familymembers to breast cancer. Yet there are no data to show that sucha choice will guarantee removal of all potentially cancerous tissue.