What Is Off-Label Use of Pharmaceutical Drugs and Medical Devices?

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 pediatric devices make off-label use a necessary and appropriate part of care.^{3, 4} Areas of unmet demand in pediatrics 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 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

Is Off-Label Use Legal and Safe for Patients?

In general, off-label use is legal unless it violates ethical guidelines or safety regulations. It nevertheless carries risks for young patients and legal liabilities may vary for prescribers.⁷

When it comes to patient and drug safety, pediatrics is no different from adult healthcare. When your patients are children, however, the issue of safety is even more important because they cannot fully assess potential risks and consequences and make decisions on their own. The decisions are made by the patient's parents or relatives. The aforementioned consequences can be enormous when weighing dosing limits for young patients.

A small drop in an adult is an ocean in a child or baby.

The off-label use of medical or surgical devices corresponds to off-label medications use in children.

Routine studies of medical devices in children are not required in the U.S. during product development. This differs from requirements for drug studies in children. Off-label pediatric device use is common due to the lack of products approved or cleared under regulatory mechanisms for specific pediatric indications. It is considered appropriate practice in pediatrics because there are no therapeutic options for many children.³

The problem of clinical trials in pediatric patients

A lack of pediatric-specific data regarding dosing, efficacy, and safety leads to off-label prescription in pediatrics.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 but are nevertheless used in them.

Drug studies are challenging in pediatrics and neonatology. Knowledge about appropriate dosing and efficacy of drugs is low.  Pediatric 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 meagerdue 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.^{9, 7} In addition, predicting the long-term effects of medical treatment is also difficult because children are in the maturation process.⁷

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 pediatric 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, Pediatric Medical Device Safety and Improvement Act) to advance medical device development and protect the pediatric population during clinical trials, needs in all pediatric subgroups remain unmet and thus off-label use remains high.²

Off-label use in pediatric 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 pediatric intensive care unit (PICU) and hospital stays^{10
  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 pediatric 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 pediatric population.^{6, 9, 7, 3} 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 Pediatrics (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 pediatric treatment. With our steadily growing pediatric product portfolio, you and your young patients are on the safe side.