Complexities of Off-label Prescribing in CV Pediatrics

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Off-label usage in cardiovascular (CV) pediatric patients is prevalent, but the lack of data makes it difficult to determine if this practice is harmful, requiring rectification. While not illegal, off-label prescribing has the potential to lead to wasteful or even injurious care in some instances, yet it can be advantageous in others. Most experts agree about the value of tracking these practices. Health IT solutions and larger studies may provide some answers.

Off-label prescribing, the use of drugs for indications that have not received regulatory approval, occurs with up to 21 percent of prescribed drugs among U.S. office-based physicians (Arch Intern Med 2006;166[9]:1021-1026). Yet, the problem isn’t unique to the ambulatory setting, and it seems to be particularly prevalent in the pediatric population.

One study found that 78.7 percent of 355,409 children discharged from 31 tertiary care pediatric hospitals were taking at least one off-label medication (Arch Pediatr Adolesc Med 2007;161[3]:282-290). Moreover, off-label use accounted for approximately $270.28 million of the total dollars spent on these medications. The study used an administrative database, which the authors acknowledged “cannot determine which of these treatments are unsafe or ineffective and which treatments result in substantial benefit to the patient.”

Specific to pediatric cardiology, one study that examined 31,432 patients in the Pediatric Health Information System database found that 78 percent received at least one cardiovascular (CV) medication off-label, and 31 percent received at least three CV medications off-label (Circ Cardiovasc Quality and Outcomes 2008;1:74-83). Paquali et al found that the most commonly used CV medications were furosemide, epinephrine, dopamine, lidocaine and milrinone. The latter three (prescribed in 69 percent of patients) were used off-label in all cases. Also, an analysis revealed that heart transplant recipients were most likely to receive a greater number of off-label CV medications.

The study’s senior author, Samir S. Shah, MD, of Cincinnati Children’s Hospital Medical Center, speaks to why off-label prescribing practices are common in the pediatric population. “Children have always been considered a vulnerable population, causing researchers to be hesitant to study the side effects of certain medications with them.” However, he points out that without definitive proof and a lack of alternate therapies, physicians still may be using these drugs in children—either appropriately or not.  

The bigger question may lie in understanding why and how that physician makes a clinical decision. “Traditionally, when physicians have written prescriptions, they do not have to write down an indication,” explains Surrey Walton, PhD, of the University of Illinois at Chicago. “Indications are typically coded for billing purposes with ICD-9 codes tending to be broad, and therefore, they aren’t very helpful for assessing clinical diagnostics or when trying to ascertain why a physician used one drug over another.”

For improved prescribing, Tewodros Eguale, MD, MSc, of McGill University in Montreal, says that physicians need to be made aware of three things at the time of decision-making: whether the drug is approved; whether there is strong evidence to use a particular drug for a particular indication; and whether there is any report of adverse drug reactions and the severity of that reaction.

Frequency Distribution of Patients Receiving Cardiovascular (CV) Medications Off-label

Frequency Distribution of Patients Receiving Cardiovascular (CV) Medications Off-label - 26.78 Kb
Source: Pasquali S K et al. Circ Cardiovasc Qual Outcomes 2008;1:74-83

Data collection is critical

“Off-label prescribing is not bad in and of itself, because there are many situations where a mountain of evidence supports the use of a particular drug for a particular condition or population, even when the FDA has not granted approval for that particular indication,” explains Shah, who adds that this is why continual data collection, especially in the pediatric population, is necessary.

The consensus on the need for improved data in this area might be best summarized by a recent editorial by Randall S. Stafford, MD, PhD, of the Stanford University School of Medicine in Stanford, Calif. “Objective, comprehensive and comparative syntheses of data relating to off-label use of drugs would be valuable to prescribers, patients and healthcare payers,” he wrote (Nature 2012;91[5]920-925). “Data from EHRs relating to drug prescriptions could