Daniel Horton, MD, on Increased Off-Label Prescribing in Children

Research published in Pediatrics indicates that US-based office physicians have been increasingly prescribing systemic drugs off-label for pediatric patients, often for unapproved conditions.

In a new study, researchers analyzed data from 2006-2015 National Ambulatory Medical Care Surveys, which are national representative surveys of office-based physicians. Their findings showed that relative and absolute rates of off-label prescriptions had risen over time, with physicians prescribing at least 1 off-label systemic drug during 18.5% of visits, most often for unapproved conditions (74.6% of cases). Off-label prescribing was most common proportionally in neonates (83%) and in absolute terms among adolescents (322 orders per every 1000 visits), the authors of the study noted.

In addition to variations by age, off-label prescribing was also associated with female sex, subspecialists, polypharmacy, and chronic conditions. Off-label orders for antihistamines and several psychotropic drugs had increased over time, while off-label prescribing for several classes of antibiotics had either stabilized or declined.

Consultant360 discussed these findings and their clinical implications further with lead study author Daniel Horton, MD, MSCE, assistant professor of pediatrics and epidemiology at Rutgers University in New Brunswick, New Jersey.

Consultant360: Could you discuss your study and the significance of the findings?

Dr Horton: Prior literature has shown that off-label use of medicines is common in children. More recent studies on this topic have focused on hospitalized children and children in intensive care units, as well as individual drug classes and European populations. My colleagues and I were interested in studying drug use and prescribing in children receiving care in the outpatient setting in the United States, examining a broad range of medicines to help prioritize future research on off-label medicines. We found physicians have been prescribing medicines off-label for children at increasing rates, particularly for unapproved conditions.

Despite the success of laws and regulations that have attempted to improve evidence and expand labeling for medicines used in children, our study indicates that the use of medicines off-label is still increasing. I think this is a call for better evidence for medicines that children use, as well as more education and guidance for pediatricians who are prescribing medicines off-label and parents who request them.

C360: Were these findings anticipated, or did some of them come as a surprise?

Dr Horton: Based on prior studies, we anticipated high rates of off-label medication use, and we hypothesized that these rates had risen over time. As a result, the general findings of our study were not surprising to us. However, we were surprised to see which classes of medicines were increasingly being ordered off-label, particularly antihistamines, which seem to be used increasingly for the treatment of upper respiratory infections in lieu of traditional cough and cold medicines, the use of which has been declining. We were also surprised by the extent to which various psychotropic drugs had been increasingly prescribed off-label over time.

C360: What are the potential consequences of off-label prescribing of systemic drugs in children, both positive and negative?

Dr Horton: It is important to note that some off-label use of medications is supported by good published evidence that these drugs work well and are safe, and other off-label medicines are supported by extensive clinical experience in children. A very positive aspect to off-label prescribing is that children can access drugs that may be needed for the treatment of their condition, despite the lack of FDA approval either for children or for their condition.

The drawback, though, is when we lack evidence to support the use of medicine off-label in children or for certain conditions. This begs the question of whether the uncertainty of benefit outweighs the risks of those medicines in children. Other questions that this study raises for me are, are we as physicians helping families make informed decisions about medicines that lack enough evidence, and are we communicating this uncertainty about evidence sufficiently? Also, do physicians’ schedules allow for the shared decision-making that we strive for when the risks or benefits of off-label medicines in children are unclear?

C360: What key takeaways about your study would you like to leave with clinicians?

Dr Horton: Some off-label use of medicines in children is clinically appropriate and well-supported by evidence or clinical experience, but this is not necessarily the case for all off-label use. When considering an off-label, off-evidence treatment for a child, clinicians should engage the family in shared decision-making. This process should include discussing what is and is not known about a medicine's effects, understanding the family's values and priorities, and determining whether the potential benefits of the medicine outweigh the potential risks for that child. Generally, we need more research and better evidence about medicines that are off-label in children, as well as improved education and more guidance to help physicians prescribe off-label, off-evidence medicines properly and safely.

—Christina Vogt

Reference:
Hoon D, Taylor MT, Kapadia P, Gerhard T, Strom BL, Horton DB. Trends in off-label drug use in ambulatory settings: 2006 to 2015 [Published online September 16, 2019]. Pediatrics. doi:10.1542/peds.2019-0896.