Turn-of-the-century ethical issues in child psychiatric research.

National concern in 2000 about increased psychoactive drug prescription for preschoolers accentuated the 1990s thrust for more pharmacologic research in children. Preschoolers are prescribed potent drugs without adequate evidence for efficacy or safety at this plastic age of the rapidly developing brain. Implementation of needed preschool research poses special ethical complications. Children with mental disorder qualify for special protection under both rubrics. Parental informed consent is crucial for preschoolers, who appear incapable of assent because of their preoperational, magical, animistic, egocentric thinking, with inability to comprehend relative risks and benefits. Whether they can dissent is an open question. Possibly for research with direct benefit outweighing the risk, parental permission/consent could override attempted preschooler dissent. Subject recompense should be adjusted for age differences in perception of amount, although parent reimbursement needs to be realistic. Insurance for research risk is desirable. Placebo controls appear justified for preschoolers because there is little evidence base to say that a proven effective treatment already exists. Disruptive behavior disorders, including attention-deficit/hyperactivity, have enough evidence of preschool diagnostic validity to justify therapeutic trials. In preschool pharmacologic research, a brief trial of a nonpharmacologic treatment should precede the drug trial to ensure that placebo responders and responders to the alternative treatment are not exposed to drug risk.