64% of New Drug Indications Lacked Pediatric Prescribing Info

A recent Health Affairs study found that 64 percent of new biologic and drug indications deemed relevant to pediatric patients lacked pediatric prescribing information five years after FDA approval. 

Over the years, concerns have been raised that delays with study requests contribute to high rates of off-label and potentially unsafe or ineffective medication use in children. 

Researchers used publicly available FDA documents to analyze all indications for new drugs and biologics approved by FDA from 2002 through 2018. 

They uncovered that just 16 percent of indications included pediatric prescribing information under the Best Pharmaceuticals for Children Act (BPCA) and 22.6 percent under the Pediatric Research Equity Act (PREA).

Additionally, as of December 2018, only about 35 percent of BPCA requests and 29 percent of PREA requests had been fulfilled. 

The median time to fulfillment of pediatric study requests under BPCA was 6.7 years. Under PREA, median time to fulfillment was 4.1 years. 

Researchers highlighted that at the time of approval, 21.6 percent of indications for new drugs and biologics included any pediatric safety or efficacy information in the FDA label. This then increased to 46.6 percent over the study period. 

Additionally, for indications that received pediatric data after approval, the median time between approval and addition of any pediatric prescribing information was 5.9 years for BPCA study requests and 4.6 years for PREA study requests.. 

In addition, there was no difference in the time to addition of pediatric information based on year of approval. 

After analyzing the data, researchers concluded that enforcement of pediatric drug study policies should be strengthened to reduce non-evidence-based medication use in pediatric patients. 

“Our study provides a comprehensive assessment of the primary US pediatric drug policies implemented to promote drug research and labeling for children,” researchers said.

“The results indicate that completion of requested pediatric studies is often slow, resulting in prolonged periods of potential off label use for a large proportion of drugs and biologics deemed relevant to pediatric patients.”

The most notable difference between BPCA and PREA is that BPCA provides mechanisms to facilitate a pediatric study of drugs that are already marketed, while PREA requirements are applied to products in development and under FDA review. 

But because the majority of pediatric study requests are issued under PREA, measures providing FDA with additional tools to ensure timely completion of PREA studies may have the most impact on pediatric drug development, researchers explained. 

Notably, the availability of pediatric prescribing information varied widely for indications across therapeutic classes. 

The therapeutic classes with the highest number of indications associated with pediatric study requests were antineoplastic and immunomodulating agents, which had 65 indications total.

Anti-infectives for systemic use had 59 indications and nervous system agents had 56 indications. 

The rates of pediatric labeling for these therapeutic classes were 38.5 percent, 47.5 percent, and 51.8 percent, respectively, researchers noted. 

Currently, BPCA contributes a small proportion of pediatric labeling changes, with a previous analysis reporting that just 9.5 percent of pediatric labeling additions were attributed strictly to BPCA during the period between 2014 and 2018.

But researchers highlighted that also under BPCA, there is a process to support the study of off-patent medications to which the six-month exclusivity incentive would not apply.

They determined that their findings conclude that the “majority of requests issued under BPCA remain unfulfilled.” 

“To better monitor progress under the pediatric programs, the FDA should consider alternative reporting approaches that enable the efficient assessment of the availability of pediatric prescribing information for drugs and biologics, including for specific age groups.”