R igorous scientific investigation is the foundation for many of the remarkable advances in medical care that have occurred over the course of the last century. Patients with cardiovascular diseases, in particular, have received considerable benefit from such research, especially that which pertains to drugs and medical devices. Infants and children, however, have not benefited proportionately from this great increase in knowledge, due to several factors: the economic return on investment is often insufficient for industry to justify the commitment of substantial resources to meet the opportunity cost of a relatively small patient population; the research capacity for pediatrics has been limited; and child patients have been considered ethically unsuitable subjects for study. As a result, drug therapy of many sorts in pediatric patients has been guided too often by theory or extrapolation from practice with adults and by expert experience and good intentions rather than by evidence obtained through clinical trials. To this day, most pediatric pharmacotherapy is based on the off-label use of drugs. 1 This must change.
Article see p 74Pasquali et al, 2 writing in this issue of Circulation: Cardiovascular Quality and Outcomes, report the experience of off-label drug use in patients 18 years old and younger who have congenital and acquired heart disease severe enough to require hospitalization. Using the Pediatric Health Information System database, they identified potential study subjects through International Classification of Diseases, Ninth Revision codes pertinent for congenital and acquired cardiovascular diseases; both diagnostic and procedural codes were screened, and only infants with an isolated patent ductus arteriosus were excluded. Qualified patients were then assessed for use of a wide variety of cardiovascular medications: antiarrhythmic drugs; adrenergic agents; -and ␣-adrenergic blocking agents; vasodilators; calcium channel blockers; antihypertensive agents; angiotensin-converting enzyme inhibitors and receptor blockers; diuretics; and additional agents, eg, prostaglandin, sildenafil, and milrinone.Off-label drug use was defined as prescribing a drug for a patient who was younger than the age specified on the drug label approved by the US Food and Drug Administration. Where weight-based drug ranges were specified, the 75th percentile for age was used in calculations. Data regarding patient demographics, drug charges, payer status, and limited outcome variables were also collected. A value of PϽ0.05 was considered to be statistically significant.The authors' results underscore the concern. A total of 31 432 patients were studied, with a median age of 10.4 months. Those with congenital heart disease constituted 67% of the study population; within this group, approximately half were managed medically alone, whereas the remainder required a surgical or catheter-based intervention. Sixty-five different cardiovascular medications were prescribed. For this group of drugs, 60% were used off-label 100% of ...