Off-label use occurs not only in drug prescriptions. It also occurs in the use of medical devices. The unmet need for products intended for children is due to many barriers to availability.²

Challenges in developing and designing paediatric devices make off-label use a necessary and appropriate part of care.^{3, 4} Areas of unmet demand in paediatrics range from catheters to intubation tubes, from cardiovascular devices to surgical instruments and more.² This is where healthcare providers come in.

Off-label use does not automatically mean the same as a contraindication. It means that there are a lack of studies and formal evidence to develop guidelines for drug safety and effectiveness in children and neonates⁵, or a lack of approval for a drug in this patient group on ethical or financial grounds, among other reasons. It does not mean “without evidence”, as there may be enough prior research on certain drugs to support their use.⁶

The problem of clinical trials in paediatric patients

A lack of pediatric-specific data regarding dosing, efficacy, and safety leads to off-label prescription in paediatrics.⁶

The proven efficacy of a drug in adults cannot simply be applied to children. There are also no safe rules for calculating a child's dosage based on an adult dosage.¹¹ Moreover, children in developing countries may have different comorbidities that lead to issues with proper medication decisions.¹² Thus, many drugs and medical devices are not approved for children. 

Drug studies are challenging in paediatrics and neonatology. Knowledge about appropriate dosing and efficacy of drugs is low.  Paediatric and neonatal patients can participate in drug trials only to a limited extent and with greater effort as part of the drug approval process.

Research in this sensitive patient population remains meager due to ethical reasons or unfamiliarity with age-related developmental pharmacology in pediatric patients, as well as a lack of financial incentives for the pharmaceutical industry.^7,9 In addition, predicting the long-term effects of medical treatment is also difficult because children are in the maturation process.⁷

These Off-label use results from limited clinical evidence.

The use of drugs for other purposes than those for which they are intended may lead to ineffective or even harmful treatment. The risk of potentially dangerous medication errors is three times higher in paediatric patients than in adult patients.¹²

Although the U.S. has already taken significant legislative measures (e.g., Medical Device User Fee and Modernization Act, Medical Devices Technical Corrections Act, Paediatric Medical Device Safety and Improvement Act) to advance medical device development and protect the paediatric population during clinical trials, needs in all paediatric subgroups remain unmet and thus off-label use remains high.²

Off-label use in paediatric patients can lead to:

• Adverse outcomes⁶ such as fever, diarrhea, and rash⁹
• Short-term toxicity or treatment failure resulting from incorrect dosage¹²
• Administration errors such as dosage errors in calculation and dilution, and intravenous infusions running too fast¹²
• Longer paediatric intensive care unit (PICU) and hospital stays¹⁰

Children with respiratory, cardiovascular, or renal failure are at an increased risk of receiving off-label medication.¹⁰ Further risk factors for more likely off-label prescription in the paediatric ICU are: a young age (≤ 5 years), existing chronic complex conditions (CCC), acute organ failure, and the need of critical care interventions.¹⁰

The need for more research and documentation

It is clear that there is still a lot of work to do to ensure safety and efficacy when prescribing medication to children.

Most of all, more and continued research is necessary in drug development to evaluate the safety, efficacy, pharmacokinetics, and optimal dosing in the paediatric population.^3,6,7,9 Thus, the Pediatric Research Equity Act (PREA) demands almost all new drugs with a potential to be used in children to be studied in this group⁷, and the American Academy of Paediatrics (AAP) recommends policy makers to “explore opportunities to facilitate and encourage the design and testing of medical and surgical devices specifically for children through scientific and regulatory innovation […]”.³

Development of drugs suitable for children with regard to strength, taste, and formulation, and continuous documentation of drug-related problems are also needed to reduce the risks associated with off-label use.⁷

Good medical practice in the best interest of patients and prescribing drugs to the best of the physician's knowledge is the preferred practice to keep risks of off-label use low until there is more research and, thus, evidence.⁷

Many products by B. Braun are already approved for paediatric treatment.