Presented by Murray M. Lumpkin, M.D.
Deputy Center Director,
Center for Drug Evaluation and Research,
U.S. Food and Drug Administration
For too long, pediatricians have all too often been prescribing medications to their patients on the basis of insufficient clinical research data. In addition, there has been a lack of standardized pediatric formulations for many drugs; insufficient data to support dosing, efficacy, and precaution statements; and lingering and persistent concerns about the disclaimers put in labeling and promotion, despite the widespread use of these products for pediatric patients. When a child is given a prescription drug under these circumstances, he or she is essentially being used as a nonconsenting participant in an "N-of-one" trial.
This past record is shameful. However, the discussion at this workshop has demonstrated a sense that the government and the pharmaceutical industry have a shared interest and mutual desire to use newly acquired legislative and regulatory tools to improve this record.
Even with this shared interest, however, serious issues must be resolved if real progress is to be made. Legal and ethical concerns pertaining to institutional review board review and informed consent must be resolved. Careful attention must be paid to recruitment incentives, clinical trial designs, the use of placebos, and the sufficiency of the data required for use of a drug by adults before children are involved.
The workshop has raised concerns about whether sufficient numbers of pediatric patients and sufficient numbers of qualified clinical researchers can be recruited to carry out the ambitious studies that workshop participants agreed were desirable. Although participants expressed optimism that new laboratory methodologies have been developed to make drug testing more applicable to children, they also expressed concern about the lack of appropriate formulations and com-
mercial incentives for the development of some drugs that are of high import to the pediatric population but not covered by the new legislative incentives.
It is very important that the extension of marketing exclusivity granted under the Food and Drug Administration Modernization Act (FDAMA) to sponsors of certain pediatric drugs be carefully evaluated to make sure that it is being used appropriately for a societal good. It has been a tool used by the U.S. Congress in the past to promote the development of orphan and generic drugs. Now, for the third time, the Congress is using this tool to encourage the development of drugs for use in infants and children.
This financial incentive carries with it a serious scientific responsibility to implement it effectively in the public interest. It is likely to result in changes in attitudes about the feasibility of studies with children and, as a result, a larger infrastructure for studying the effects of drugs in children. Health care professionals should all be held accountable for how well this authority is used. It is hoped that this will result in better labeling of drugs for use by the pediatric population, more appropriate formulations, better dosing guidelines for more age ranges, and better information about efficacy and toxicity of drugs in children.
The U.S. Food and Drug Administration (FDA) is required to submit a report to the Congress by January 1, 2001, on how well this FDAMA provision has worked to improve information regarding pediatric uses of drugs. The Congress will want to know whether the exclusivity tool was used well and whether the children of the United States have benefited. If the result does not meet expectations, it could be said that children were exploited for the financial gain of a few corporations. However, failure is not expected or the many challenges that will need to be met. The following four challenges will be the most difficult to address:
Some good metrics must be developed to determine whether the goals of the new incentive programs have been met.
If heavy reliance on extrapolation of data from adult populations is used to establish efficacy in children, there must be a way of evaluating, over the long-term, whether this was a valid surrogate.
Longer-term follow-up studies must be developed, financed, and conducted to assess the effect of drugs on unique pediatric safety issues such as children's growth and their neuronal, psychosocial, and endocrinologic maturation.
If it is concluded that this incentive program is effective in spurring the development and appropriate use of drugs in the pediatric population and that it is worth the overall cost to society, the question of whether it should be applied to other populations (such as pregnant women, elderly people, or members of minority groups) and, if so, whether doing so will it be at the expense of maintaining the program for children, will need to be addressed.