Developmental pharmacology and toxicology: principles of study design and problems of methodology

Pharmacologic investigations in the fetus, neonate and child are difficult for the various reasons outlined above, ranging from ethical constraints to difficulties with microanalytic techniques. Attempts to circumvent these difficulties through animal studies, retrospective analyses, and prospective surveys have provided only partial answers. These studies have often helped to guide subsequent similar studies in humans. Results of developmental pharmacologic studies applied to the human must be conducted in humans. The alternatives to randomized, controlled trials presented above may help with these studies, but these innovative study designs must be applied carefully to avoid biasing the results. Although difficult, definitive studies in developmental pharmacology are possible with investigators willing to work within the ethical constraints outlined above, to sensitively consider the needs of perinatal and pediatric patients, and to adhere to the strictest standards of study design.