Surge in Pediatric Testing Creates New Ethical Concerns

The recent rise in pediatric testing of pharmaceutical drugs has lead to "improved treatments" but also has created a host of ethical dilemmas for physicians, researchers and parents, the New York Times reports. In the past, drug companies "routinely" excluded children from clinical trials, but new federal actions have created incentives for drug makers to pursue pediatric testing. For example, a 1997 law allows a drug's patent to be extended for six months if its producer conducts additional research to see how children respond to the drug, and the FDA in December promulgated a new rule that "make[s] pediatric drug testing mandatory for nearly all new medicines and biotechnology products." The results have been tangible: the FDA estimates that 58 postmarketing studies involving children have been conducted since 1997, compared to 11 between 1991 and 1996. In addition, according to the Pharmaceutical Research and Manufacturers of America, 217 new vaccines and medicines have been found by drug companies through pediatric testing. But this surge in children's trials has raised several concerns, including:

• Risk: The Times reports that some pediatric drug trials use healthy children, "raising questions about whether they are being exposed to risks without possible benefit." It is also more difficult to find sick children than sick adults, and children "metabolize medicine differently from adults."
  
• Reward: Many studies offer children a payment to enroll, while participating physicians can receive up to $2,000 for every patient recruited. Dr. Norman Fost, a professor of pediatrics and medical ethics at the University of Wisconsin, said, "There's something worrisome about parents getting money to enroll their kids in a study that has, at the least, discomfort, and, at the worst, risk. The same applies to physicians. There is enormous opportunity for profit now because of the explosion of drug testing in children."
  
• Placebos: Whereas adult clinical trials employ placebo control to study the effects of a drug, this practice is "thought to be unethical" in pediatric testing, according to Dr. Barbara Finck, medical director for Immunex. The Times discusses the drug trial of Enbrel, a drug designed by Immunex for the treatment of juvenile rheumatoid arthritis -- and eventually approved for use in children by the FDA in 1999 -- to illustrate the potential pitfalls of using placebos in pediatric trials. Under the study design, all 69 children in the study received Enbrel injections for three months; then those who "responded well" were split into two groups, one of which continued treatment while the other received a placebo. Those in the latter category who relapsed were placed back on the drug, but the Times reports that one child went through "agonizing pain" in the interim, while two others "who were doing extremely well on the drug ... never completely recovered."

In a New York Post column today, Douglas Montero criticizes a nationwide study designed to test the effects of the attention deficit hyperactivity disorder drug Ritalin on young children. Using a $6 million grant from the National Institute of Mental Health, researchers at six institutions are looking for children who have symptoms of ADHD but "have never been medicated." Montero cites concerns that "researchers are playing fast and loose with the brains of children." Dr. Laurence Greenhill of Columbia University, who will lead the study, said that the research has been approved by five ethics panels, but others are worried that "the unknown, long-term side effects of [Ritalin] might harm kids," Montero writes. The NIMH grant followed a report published in the Journal of the American Medical Association last year that found that roughly 250,000 children ages two to four take Ritalin or other psychiatric drugs. The report "inspired" Sen. Hillary Rodham Clinton (D-N.Y.), then first lady, to "prod" the government to examine ways to halt the trend, which "translates into experiments" such as the new study, Montero writes. Discussing the new study, Clinton spokesperson Karen Dunn said that the senator "has strongly supported efforts to determine whether [Ritalin] is being used appropriately and effectively" in children. But Montero concludes: "That sounds politically and morally correct, but the folks in Washington, D.C., aren't going to be around to see what becomes of these kids who donate their brains to science" (Montero, New York Post, 2/12).