Recommendations on Off-Label Drug Use in Pediatric Guidelines

Abstract

Objective: To systematically analyze the supporting evidence, drug information, and the type of off-label drug use in recommendations on off-label drug use in pediatric guidelines.Methods: A cross-sectional study was performed by systematic search through MEDLINE (via PubMed) and Embase databases to identify literature published from 1 January 2018, to 31 December 2020. Only pediatric clinical practice guidelines that included recommendations on off-label use of drugs were included. We present descriptive information on the sources of the included guidelines, country, publication year, evidence grading system used, details on the types of off-label drug use, and the types of studies used as references to support the recommendations.Results: A total of 66 pediatric guidelines with 605 recommendations were included. Eighty-seven (14.4%) recommendations did not cite any references; and the remaining 518 recommendations were supported by 2,240 references (mean 4.3 references/recommendation). The most common types of studies cited were pediatric RCTs (n = 314, 14.0%), pediatric case series studies (n = 260, 11.6%), and reviews (n = 255, 11.4%). Twenty-one percent (n = 470) of the references were studies on adults. One hundred and forty (23.1%) recommendations were graded using the Grading of Recommendations, Assessments, Development, and Evaluations (GRADE) system, of which 37 (26.4%) were graded as strong but supported with only C or D level of evidence. The most commonly reported type of information in the recommendations was indication (n = 499, 82.5%). The most commonly addressed type of off-label drug use in the 523 positive recommendations was unapproved population (n = 255, 48.8%). Sixty-nine (11.4%) recommendations explicitly reported the drug use as off-label.Conclusion: Children may be exposed to medical risks due to gaps in reporting and evidence of off-label drug use recommendations in pediatric guidelines.

Pediatric Drug and Other Shortages in the Age of Supply Chain Disruption

“…Pediatric intensive care unit beds are less profitable than adult ones, leading many hospitals to close their pediatric units and thereby to struggle to find open beds during spikes of respiratory syncytial virus. Children often have more limited options for medications than adults, with off-label prescription a common practice due to limited manufacturer interest in pursuing pediatric clinical trials . Alarmingly, desperate parents may resort to harmful solutions when faced with shortages, such as trying to make their own formula or dose children with adult-strength analgesics.…”

“…Children often have more limited options for medications than adults, with off-label prescription a common practice due to limited manufacturer interest in pursuing pediatric clinical trials. 3 Alarmingly, desperate parents may resort to harmful solutions when faced with shortages, such as trying to make their own formula or dose children with adultstrength analgesics.…”

Pediatric Drug Development Process: A Review

“…Many pediatric guidelines suggest NSAIDs or paracetamol for pain, fever or inflammation in children they should be taken with caution due to the possibility of adverse reactions such as hypersensitivity reactions renal damage, and even kidney failure. However, the reporting of recommendations on NSAIDs in pediatric guidelines is inadequate, which is due to several reasons and may potentially lead to inappropriate drug use [31].…”

Against Authority: The Bioethics of Ivermectin Use for COVID-19 Infection

“…26 Paradoxically, some physicians do not even know that they have used off-label medications. Many medications are used more often off-label than for their original indications, approved especially in pediatrics, 27,28 oncology, 29 and psychiatry. 30,31 Avastin is a medication to treat cancer, but it is also used off-label -successfully-for macular degeneration.…”

“…It is accepted that: “This off-label prescribing is most commonly done with older generic medications that found new uses but lacked the formal (and often expensive) applications and studies required to officially approve the medication for these new indications.” 26 Paradoxically, some physicians do not even know that they have used off-label medications. Many medications are used more often off-label than for their original indications, approved especially in pediatrics, 27,28 oncology, 29 and psychiatry. 30,31 Avastin is a medication to treat cancer, but it is also used off-label—successfully—for macular degeneration.…”