I think we're getting hung up in semantics. Yes, to use Afrezza in the pediatric population is considered "off-label", but use of off-label drugs happens quite frequently as not many drugs are tested in the pediatric population. I don't think there will be a big hang up. Here is the current statement from the American Association of Pediatrics (AAP):
www.medscape.org/viewarticle/821424AAP Issues Policy Statement on Pediatric Off-Label Drug Use CME/CE
News Author: Diedtra Henderson
CME Author: Charles P. Vega, MD, FAAFP
Faculty and Disclosures
CME/CE Released: 03/18/2014 ; Valid for credit through 03/18/2015
CME/CE Information Earn CME/CE Credit »
Clinical Context
The off-label use of medications for indications not approved by the US Food and Drug Administration (FDA) is rampant among hospitalized children, according to a previous study by Shah and colleagues. This research, which was published in the March 2007 issue of the Archives of Pediatrics & Adolescent Medicine, demonstrated that 78.7% of children hospitalized in US tertiary children's hospitals received at least 1 off-label medication in 2004. Medications targeting the central nervous system and gastrointestinal tract system were most frequently prescribed off label. More severe illness, surgical procedures, and age older than 28 days were associated with higher rates of off-label drug use among children.
The current Policy Statement from the American Academy of Pediatrics (AAP) addresses the important issue of off-label drug use among children.
Study Synopsis and Perspective
Because more than half of the medications approved for marketing by the FDA lack evidence of safe and effective use in pediatric patients, the practice of medicine will "more than likely" require that practitioners prescribe medicines off label to appropriately treat pediatric patients, according to the AAP.
The group published an updated policy statement on the topic in the March 1 issue of Pediatrics.
The AAP last issued a statement on off-label use of prescription medicines in 2002 and reaffirmed it in 2005. Since then, more than 500 medicine label revisions have been made by the FDA to reflect information about use in pediatric patients, a trend accelerated by passage of the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA). Acting as complementary federal sticks and carrots, the PREA mandates that almost all new medicines be studied in children if pediatric use of the product is likely, whereas the BPCA opens the door for an additional 6 months of market exclusivity for sponsors that submit completed pediatric studies to the FDA.
Still, the number of pediatric-tested remedies is exceeded by the number of FDA-approved prescription medicines that have not specifically been tested for safe and efficacious use in pediatric patients.
The AAP statement indicates that clinicians' decision making in this instance "should always be guided by the best available evidence and the importance of the benefit for the individual patient. Practitioners are in agreement regarding the importance of practicing evidence-based medicine. However, for the pediatric population, gold standard clinical trials are often not available, so practitioners must rely on either less definitive information, such as expert opinion for the age group that they are treating, or use evidence from a different population to guide practice."
The FDA does not regulate the practice of medicine, according to the statement. "The administration of an approved drug for a use that is not approved by the FDA is not considered research and does not warrant special consent or review if it is deemed to be in the individual patient's best interest," the policy statement explains.
"To conform to accepted professional standards, the off-label use of a drug should be done in good faith, in the best interest of the patient, and without fraudulent intent," according to Kathleen A. Neville, MD, MS, from the AAP Committee on Drugs, and coauthors.
According to the statement,
clinicians are responsible for deciding which medicine at which dose the pediatric patient will receive for which purpose;
pediatricians should continue to advocate for incentives and requirements that promote the study of medicines in children;
physician researchers should conduct well-designed pediatric drug studies or collaborate in them;
journals should publish studies about well-designed trials, irrespective of the results; and
institutions and payers should not settle for labeling revisions as the sole determinant of which medicines to include in formularies.
The statement draws a distinction between individual clinician decision making on behalf of individual patients and the active promotion of off-label use that is prohibited, whether by the sponsor or by the clinician speaking on behalf of the sponsor.
Truly investigational off-label prescriptions should be done in the context of a well-designed clinical trial, the statement indicates. Patients and their legal guardians should be duly informed, and clinicians should document consent to proceed. In addition, because off-label prescriptions can heighten liability risks for practitioners, the statement counsels clinicians to document their decision-making process in the patient's record.
"Off-label drug use remains an important public health issue, especially for infants, young children, and children with rare diseases," Dr. Neville and the AAP committee coauthors conclude. "Evidence, not label indication, remains the gold standard from which practitioners should draw when making therapeutic decisions for their patients."
The study authors have disclosed no relevant financial relationships.
Pediatrics. 2014;133:563-567.
Policy Statement Highlights
The FDA usually requires at least 2 well-controlled trials before considering a medication for a particular indication.
Drug manufacturers or sponsors are disallowed from publicizing off-label uses of their products, but original research on off-label use is permitted.
Medications, vaccines, and biologic agents all have different algorithms to qualify for FDA approval. Therefore, many agents that may benefit children lack pediatric information and indications.
Off label does not imply that the use of a drug is improper or illegal. Gold standard clinical evaluations are frequently lacking for medication use among children. Therefore, clinicians may have to rely on data from peer-reviewed journal, practice guidelines, and policy statements.
Shared decision making is of paramount importance when off-label medications are used in children. In general, no special consent is necessary beyond what is expected from usual medical care, but patients should be informed if the off-label medication is experimental.
Higher degrees of potential risk associated with the use of off-label medications may require institutional review or written consent.
Off-label medication use may increase the risk for clinicians' liability in patient care, which again emphasizes the value of documentation of shared decision making.
The BPCA and the PREA mandate increased research into the pediatric application of new and some established treatments. These laws and other regulations have led to an expansion of pediatric labeling information.
Nonetheless, less than 50% of drugs include pediatric labeling information.
The FDA has a system for postmarketing drug surveillance of medication adverse events. Although this system is passive, and the number of pediatric cases is dwarfed by adult cases, it is particularly relevant to investigate potential complications of off-label use of drugs.
Clinical Implications
A previous study by Shah and colleagues of pediatric inpatients found that 78.7% of children hospitalized in US tertiary children's hospitals received at least 1 off-label medication in 2004. Medications targeting the central nervous system and gastrointestinal tract system were most frequently prescribed off label. More severe illness, surgical procedures, and age older than 28 days were associated with higher rates of off-label drug use among children.
The current AAP Policy Statement condones the use of off-label drugs when they are necessary in the treatment of children, providing that shared decision making is practiced. In general, no special consent is necessary beyond what is expected from usual medical care.
