Drug approval and testing on children.

Eliot Marshall's description of the Food and Drug Administration's (FDA's) vacillation about retaining the requirement for drugmakers to test drugs on children (“Challenge to FDA's authority may end up giving it more,” News of the Week, 3 May, p. 820) is unbalanced. He gives short shrift to the shortcomings of the policy, which makes drug development more costly, might actually be detrimental to children, and could delay the availability of new drugs, if the FDA were to withhold approval for adult uses while data from pediatric studies are being collected (as the agency has threatened to do). Moreover, the regulation is a rigid, governmental solution to a nonproblem, according to many pediatricians. Even the FDA concedes that physicians routinely and safely prescribe pain relievers, asthma drugs, antihistamines, antibiotics, and other therapeutics for children, despite the fact that clinical trials for those products have been performed only in adults. The requirement for pediatric testing ignores the nuances of drug development. Creating a dosage form appropriate for children is often especially challenging, for a number of reasons. Can the active ingredient be incorporated into a chewable or syrup form? Will it have special storage requirements and adequate shelf-life? Does it taste good enough so that kids will actually take it? A pediatric form of GlaxoSmithKline's antibiotic, Ceftin, required more than double the cost and man-hours to develop than did its adult formulation. The same company also experienced serious problems in finding effective preservatives for its pediatric syrup form of Epivir, an anti-HIV drug, even after the adult formulation had been fully developed. Clinical trials are difficult to perform with children. For ethical reasons, testing is done in subjects who are ill, not in healthy volunteers. Study participants may be scarce because a disease is rare in children, because the population is geographically diverse, or because parents are reluctant to enroll their sick children in an “experiment.” Finally, for the purposes of drug testing, the term “children” implies several groups that are physiologically and metabolically distinct: newborns, infants, preschoolers, primary-schoolers, and teens. Moreover, children may pass through two or more age groups during the course of a multiyear clinical study, complicating statistical analysis. Even if additional testing of drugs in children were needed, there are more imaginative and effective ways to accomplish it. For example, the FDA could simply require a prominent label or logo on drugs whose safety and efficacy have not yet been determined in children, or the agency could publish a list of such drugs annually. This would make parents and physicians aware that such information is not available, and they, in turn, could exert pressure on drug companies to obtain it. (Consider, too, that it is in drug companies' own interest to expand the population that will purchase and benefit from their products, and to avoid harming patients.) The pediatric rule further increases the already high costs of drugs to consumers and puts them at greater risk.