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caused by FIAU, an investigational drug for chronic hepatitis B. In 1994, a number of deaths were attributed to unknown side effects from newly approved drugs for epilepsy, migraine, and asthma. In response, the FDA recently revised regulations for AE reporting for investigational drugs and biologics [18]. The FDA has also amended the IND regulations to require a description of any adverse clinical or laboratory outcomes that investigators must immediately report to the sponsor [19]. Companies are required to estimate the expected incidence of deaths and serious AEs. Once the estimate is exceeded, the sponsor would have to notify all investigators and FDA within 15 days [20]. These regulations may increase the potential liability of manufacturers by establishing a presumption that the investigational drug was associated with the AE and injuries. These reports would be discoverable in any legal action and therefore would assist plaintiffs to prove causation [20]. |
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2. New Demographic Requirements for Clinical Trials |
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Testing of investigational drugs in special patient populations (i.e., pregnant females, severe renal or hepatic impairment, pediatric, or geriatric) for which little safety data exists may increase industry liability. Only after a significant period of human exposure can there be firm data on which to base a conclusion that a drug poses an appreciable risk of harm to the human fetus or special patient populations. |
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In 1990, under National Institutes of Health (NIH) sponsorship, Abbott Laboratories, Inc. developed hyperimmune globulin for prevention of maternal AIDS transmission. Two years later, when the clinical trials were scheduled to begin, Abbott sought NIH indemnification for potential future liabilities. The NIH refused and Abbott decided not to release the drug for clinical trials using women of childbearing age [21]. In July 1993, the FDA issued the Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs [22]. This guideline allows for the participation of women of childbearing potential in early clinical trials and defines means of determining sufficient female inclusion. While only a guideline, the FDA has indicated in its refusal to file policy that it will refuse to accept NDAs for review without adequate demographic analysis by gender, age, or racial group [23]. |
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The FDA also recently proposed an amendment to a 1979 regulation that required full clinical trials in the pediatric population as a basis for labeling for use in children. The rule would allow some pediatric labeling to be based on adult data when the disease treated is likely to be similar in adults and children [24]. However, the new rule requires manufacturers to examine existing information and submit an application for supplemental labeling by the end of 1996. Finally, it gives the FDA authority to request specific pediatric |
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