Big Pharma Neglecting ‘Required’ Pediatric Studies

A recent retrospective study (TJ Hwang et al. JAMA Pediatr 2019; 173: 68-74) examined the completion rate of FDA-required pediatric studies. Thanks to Ben Gold for this reference.

Background: In 2003, the Pediatric Research Equity Act (PREA) was signed into law and authorized the FDA to require clinical stuides to assess the safety and efficacy of new drugs and drugs with new indications in pediatric subpopulations.  However, the FDA cannot withdraw approval for a drug if a manufacturer fails to comply with PREA.  In addition, the authors note that “to our knowledge, to date, no financial penalties or enforcement proceedings have been brought against manufacturers fo noncompliance…and only 31 noncompliance letters have been issued.”

Key findings:

  • Between 2007-2014, there were 438 new drugs and/or new indications.  114 were subject to PREA. 84 were new drugs and 30 were new indications.
  • 222 studies required pediatric postmarketing clinical studies (in these 114 drugs). Only 75 (33.8%) were completed; rates were lower for efficacy studies (38 of 132 –28.8%) compared to pharmacokinetic studies (19 of 34 –55.9%).
  • As a result of the PREA-mandated studies, there was an increase in some pediatric information of drug labels in 41.2% after a median follow-up of 6.8 years, compared with 15.8% at time of approval of these 114 drugs.

The authors note that PREA is responsible for “nearly 80% of pediatric drug studies completed for FDA.” Congress also passed the Best Pharmaceuticals for Children Act which provides a financial incentive to companies if they perform certain pediatric studies.

My take: Pharmaceutical companies, for a multitude of reasons, are not completing requied pediatric studies.

Cool Genetic Facial Dysmorphism App

I recently downloaded a free Genetics App called Face2Gene.  My colleague Jeffery Lewis told me about this app.  This App helps identify specific genetic syndromes based on facial appearance.  In the first few weeks, a few syndromes that were identified included the following & this was based on very limited usage:

  • Coffin-Lowry
  • Williams Syndrome

New Strategy to Overcome Severe Reactions to Peanuts

A recent study (N Engl J Med 2018; 379:1991-2001) showed that

Link to abstract: AR101 Oral Immunotherapy for Peanut Allergy

Methods: Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. 

Conclusions: In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo.

Related blog posts:

Are We Making Progress on Infant Sleep-Related Deaths? (Not anymore)

An interesting commentary (KP Quinlan. JAMA Pediatrics; 2018; 172: 714-6) points out the need for better surveillance and prevention efforts for sudden unexpected infant deaths (SUIDs).

Key points:

  • Since the late 1990s, there has NOT been significant improvement in SUID.  In 1999, there were 3716 SUIDs compared with 3684 in 2015.
  • This rate of SUID is 9 times the rate of deaths to motor vehicle crashes for an 18 year-old driver.  The author notes the driving-related fatalities have declined by ~50% for persons younger than 20 years since 2000.
  • Promotion of safer sleeping habits is important. Bed sharing raises the SUID risk but is commonly practiced by parents from all backgrounds.
  • There is very little publicity of this problem and there is not a systematic surveillance system.  . How often do we here about a teenager involved in a crash and how often do we here about an infant with SUID? If there was more awareness of this danger, it is likely that there would be more actions taken

Related posts:

Useful website: This website has a book called “Sleep Baby Safe and Snug” which incorporates updated recommendations on safe sleep practices.

Children should sleep in the same room but on a separate surface from their parents for at least the first six months of their lives, and ideally the first year. They say that this can halve the risk of SIDS…You can read the AAP’s full guidance here. These are a few more of the pediatricians’ recommendations:

  • Infants under a year old should always sleep lying on their backs. Side sleeping “is not safe and is not advised,” the AAP says.
  • Infants should always sleep on a firm surface covered by only a flat sheet. That’s because soft mattresses “could create a pocket … and increase the chance of rebreathing or suffocation if the infant is placed in or rolls over to the prone position.”
  • Any other bedding or soft objects, like pillows or stuffed animals, could obstruct a child’s airway and increase the risk of SIDS and suffocation, according to the AAP.
  • The pediatricians say breastfeeding reduces the risk of SIDS.
  • The same goes for pacifiers at nap time and bedtime, although the doctors say the “mechanism is yet unclear.” They add that “the protective effect is observed even if the pacifier falls out of the infant’s mouth.”
  • Smoking – both during pregnancy and around the infant after birth – can increase the risk of SIDS. Alcohol and illicit drugs during pregnancy can also contribute to SIDS, and “parental alcohol and/or illicit drug use in combination with bed-sharing places the infant at particularly high risk of SIDS,” the pediatricians say.

Is there a link between fitness and academic performance?

Briefly noted:  A Muntaner-Mas et al. J Pediatr 2018; 198: 90-7.  This cross-sectional study with 250 Spanish children  (10-12 year olds) examined obesity measures, physical fitness measures and academic performance.  Key finding: “Children considered fit had better academic performance than their unfit peers…the association between body mass index and GPA was mediated by cardiorespiratory fitness and speed-agility.”  The design of this study precludes establishing this association as a causal relationship.

Gibbs Gardens

Common Sense Media Web Site

“Common sense is not so common.” Voltaire,, Dictionnaire Philosophique 1764

A website that I learned about recently from the Journal of Pediatrics article, “The Elephant in the Examination Room: Addressing Parent and Child Mobile Device Use as a Teachable Moment:”

“Common Sense is the nation’s leading nonprofit organization dedicated to improving the lives of kids and families by providing the trustworthy information, education, and independent voice they need to thrive in the 21st century.”
This website has extensive resources for families regarding all forms of media.  This includes advice on apps, age for using smartphones, encouragement for device-free dinners, movie/TV reviews and more.
The AAP also has a media use plan tool: based on children’s ages.