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Pediatric pharmacology, part 2
In my last column (“Moonshot for pediatric pharmacology,” DDNews August 2016 issue), I focused on the rationale for a moonshot on pediatric pharmacology research to optimize drug therapy for children. This topic has been long neglected for good reasons, but today we have the tools to do much better.
The limitations of research and the reporting of research on this topic have recently been studied by a team at Boston Children’s Hospital (N. Pica and F. Bourgeois, Pediatrics, August 2016). They retrospectively examined randomized controlled trials registered with www.clinicaltrials.gov over a two-year period. The good news is there were 559 such trials. The bad news is that 19 percent were discontinued early, with 37 percent of those having difficulty with patient recruiting. For the 455 trials actually completed, 30 percent resulted in peer-reviewed publications.
Not surprisingly, industry-sponsored trials were more likely to be completed and less likely to be published than academically sponsored trials. Professors, of course, count publications as a primary product. Similar conclusions have been noted for clinical trials more generally, leaving future researchers and patients without the benefit of data collected in earlier studies. Those who sign informed consent to help advance medicine deserve better than to not have the data they contributed shared.
At times, without appropriate trials, there is evidence that pharma, the healthcare bureaucracy, K-12 educators and caring/hopeful parents have been winging it with drugs not fully vetted in the pediatric population. Perhaps the best example of this is with real or perceived psychiatric illnesses in young people. Three excellent books cover the topic from different perspectives. First, we have a distinguished professor of psychiatry and a former editor of the famous Diagnostic and Statistical Manual of Mental Disorders (now DSM-5) decrying the expanding definition of such disorders to the extent that we all are a little off our rockers, especially we males. Dr. Allen Frances published Saving Normal (2013). I recommend the book to colleagues wishing a broad view of how mental disorders have been considered over millennia and how the DSM series has been assembled and coupled with direct-to-consumer marketing. This suggests a catalytic combination that has changed the view of what our species considers normal. In only a few decades we have narrowed the normal curve of error (pun intended). Our once quirky friends have been conveniently medicalized when perhaps they might have been tolerated.
As a further result, in recent decades we’ve had school teachers and general practitioners without formal training in psychiatry or psychology issuing prescriptions rather casually. Since there are no biomarkers to aid diagnosis, it takes considerable time to get it right, time that today is not invested or even available. Just this year, the topic has been reviewed by Alan Schwarz in ADHD Nation: Children, Doctors, Big Pharma, and the Making of an American Epidemic (2016). ADHD is a serious disease with an incidence of perhaps 3 percent, yet in some locales 10 times that are diagnosed and put at considerable risk. There have been two decades of concern, with still little action. In my college days, amphetamines were drugs of abuse, but only after they evolved from wide usage by the military and long-distances truckers in the ‘40s and ‘50s. They clearly help the seriously ill, but continue to be abused with help from new brand names, marketing and too-casual diagnostics.
Finally, let me suggest the courageous and moving narrative by pharmaceutical executive Steven Francesco, Overmedicated and Undertreated (2015), a story of one family’s tragedy with an adverse event in a troubled teenage son. Steve is dedicated to bringing attention to the very problem Allen Frances has been warning about.
The three volumes mentioned here give support to a substantial pediatric pharmacology problem that needs some serious work and has been slowly getting more play since the Best Pharmaceuticals for Children Act in 2002. These books also support the notion that direct-to-consumer advertising was a good idea that went bad, letting hype trump science.
The country is currently in a bad mood and the pharma news in resonance has been exceptionally negative, in part because “pricing” is much easier to grasp than biology. The good news is also crowded out by the recent heroin/fentanyl epidemic linked to abuse of pain medications, the ongoing noise about ADHD and wild inflation for Epi-pens. These things will pass, albeit slowly.
There is also good news for kids. For example, in the case of acute lymphoblastic leukemia, the five-year survival rate is today over 90 percent from being less than 10 percent in my teenage years in the 1960s. That’s science at work. In September, the American Academy of Pediatrics added more reservations regarding the use of codeine for children, a common remedy in my youth. With better measurements we can now make better decisions, but the lag time can still be decades. Never have we had a better measurement toolbox than today to combat the tyranny of averages from randomized controlled trials. For example, the FDA recently approved several longer-term in-vivo glucose sensors linked to insulin infusion pumps, opening a better quality of life for individual teenagers with type 1 diabetes. And finally, the FDA reacted positively with an accelerated approval process for a unique drug to treat a subpopulation of kids with Duchenne muscular dystrophy—a first. May Sarepta’s Exondys 51 continue to show positive results for this fatal pediatric disease. Give the good news a chance.