FDA Panel Comments Adele Schneider, MD, FACMG Victor Center for the Prevention of Jewish Genetic Diseases, Director, Clinical Genetics Albert Einstein Medical Center, Philadelphia

Victor Center for the Prevention of Jewish Genetic Diseases Education, counseling and carrier screening for 18 diseases more common in the Ashkenazi Jewish population Community and college screenings Medical model Informed consent Results with genetic counseling

Victor Center major concerns with DTC testing Accuracy/detection rates of genetic testing, primarily carrier screening (Tay-Sachs disease) Lack of informed consent Absence of genetic counseling (to help interpret results) No medical professional in the process Information may not reach all family members if no counseling for carriers

Tay-Sachs Disease (TSD) testing Hexosaminidase A enzyme is deficient in TSD 1970s -- measure serum Hex A easily and economically, population screening became available Today DNA testing with variable number of mutations in each lab Best sensitivity for TSD testing is Hex A enzyme and DNA together (98%)

Tay-Sachs Disease (TSD) testing Several methods of measuring Hex A levels: –Serum is standard in most labs High inconclusive rate (20%) Affected by birth control pills, pregnancy and diabetes –Leukocyte (WBC) Hex A levels used as confirmation if serum is inconclusive, more reliable (inconclusive ~4%) –Platelet Hex A has very low inconclusive rate (0.4% in recent study)*--most reliable, least available (*Schneider et al, AJMG 11-09)

Tay-Sachs Disease (TSD) testing Study of 1036 randomly screened individuals* Of TSD carriers, 11.4% were carriers on platelet Hex A measurement, negative on DNA using the AJ mutation panel One was sequenced and identified a novel mutation All had at least one parent not born Jewish (*Schneider et al, AJMG 11-09)

Tay-Sachs Disease (TSD) testing Conclusion: –AJ population demographics changing –Gene pool being modified by intermarriage and adoption –Cannot rely on DNA only –If do DNA only, will miss 11.4% of carriers based on this recent study –Sensitivity of 88.6% does not meet ACMG standards of reliable test

Tay-Sachs Disease (TSD) testing –Must do enzyme for a highest sensitivity TSD test (on blood) –In non-Jewish person enzyme is the first line of testing, AJ mutations not useful –Buccal and spit tests do not work for TSD (DTC) The problem if do buccal or spit test: –People think they have been screened for TSD –Tay-Sachs is a severe, preventable disease …………if testing done incorrectly (no enzyme) the number of babies born with this devastating disease will increase

History of genetic testing Traditionally ordered by geneticist or other health professional with genetics background Genetic counseling an integral part of process Genetic counseling part of result disclosure

Components of good carrier screening for Jewish Genetic Diseases Informed consent with genetic counseling Accurate Tay-Sachs testing (blood for enzyme) Full panel of tests and mutations that have a higher carrier rate in the AJ population, sensitivity >90% Result with genetic counseling

American College of Medical Genetics Statement on Direct-to-Consumer Genetic Testing (2004) …“ Due to the complexities of genetic testing and counseling, the self-ordering of genetic tests by patients over the telephone or the Internet, and their use of genetic “home testing” kits, is potentially harmful. Potential harms include inappropriate test utilization, misinterpretation of test results, lack of necessary follow-up, and other adverse consequences.”

ACOG Committee Opinions 2008: Direct to consumer marketing of genetic testing Should be discouraged –Difficulty in interpretation of genetic test results –Lack of federal oversight of lab, validity and accuracy of tests unknown –Privacy and confidentiality –No counseling, no MD involved –DNA samples after testing??? And are you sure your own sample was used?? –Questionable value of tests to patient

Other concerns related to DTC Testing a minor possible Privacy issues Missed opportunity for preventive care without physician involved Genetic counseling General physicians may be unfamiliar with the correct follow-up for a specific genetic test At home genetic tests do not address the totality of medical care for an individual, impact of other factors on health

Concerns related to DTC Quality of tests/labs, some outside USA, not CLIA certified Genetic horoscopes with potential for harm (medical care based on “do no harm”) Consumers are vulnerable to being misled by the results of unproven or invalid test Even clinically available genetic tests, which may provide legitimate test results, can be difficult to interpret without genetic counseling ( cancer susceptibility testing)

Labs must be CLIA certified at minimum Carrier test sensitivity >90%, residual risk explained in report Informed consent Pre- and post test counseling must be available from appropriately qualified genetics professionals Tests reported back to healthcare professionals Testing of minors should not be done without a physician order, good reason Recommendations for DTC monitoring ( for medical tests)