ABCDXXX: The obscenity of postmarketing surveillance for teratogenic effects.
Our current system of postmarketing surveillance, which is based on voluntary reporting of suspected teratogenic effects, is a failure. Postmarketing surveillance should, at a minimum, provide reassurance that every approved drug treatment does not produce a teratogenic effect as great as thalidomide embryopathy or fetal alcohol syndrome. This means that postmarketing surveillance should be able to detect a twofold or greater increase in the frequency of major congenital anomalies, a fivefold or greater increase in the frequency of intellectual disability, or a characteristic pattern of minor anomalies and functional abnormalities that occurs with a frequency of at least 10% among the children of women who were treated with the drug during pregnancy. Effective surveillance for teratogenic effects could be accomplished through a complementary set of mechanisms that includes pregnancy exposure registries or cohorts as well as direct examination of a small subset of infants whose mothers received the treatment during various periods of pregnancy. If this routine surveillance reveals a "signal" (i.e., an indication suggesting a possible teratogenic effect), further study would be needed to establish whether the observed effect is real and causal. Once a signal of possible teratogenicity in humans has been recognized, validating or refuting it would become an urgent matter.
Department of Medical Genetics, University of British Columbia, Child and Family Research Institute, Vancouver, British Columbia, Canada. frid@interchange.ubc.ca
Jan M
JM
Friedman
D000014:Abnormalities, Drug-Induced / Q000517:prevention & control*; D002648:Child; D002658:Developmental Disabilities / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000139:chemically induced / Q000517:prevention & control; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D055553:Prescription Drugs / Q000009:adverse effects*; D011358:Product Surveillance, Postmarketing / Q000592:standards*; D012042:Registries; D013723:Teratogens / Q000633:toxicity*; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence
D055553:Prescription Drugs; D013723:Teratogens