Children represent about 40% of the world's population (with 4 kids they make up 66.7% of the population in my household), unfortunately, not long ago less than 10% of drugs on the market had been approved for the pediatric population. Great progress has been made in recent years with the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA). In fact 149 products have received pediatric labeling since 2012, when the FDASIA was enacted. Before BPCA and PREA became law, more than 80% of the drugs approved for adult use were being used in children, even though the safety and effectiveness had not been established in children. Today that number has been reduced to about 50%. Pediatric trials are still viewed as a niche component of the clinical research / drug development industry.
Best Pharmaceutical for Children Act (BPCA) - provides an incentive for drug companies to conduct FDA-requested pediatric studies by granting an additional six months of marketing exclusivity.
The Pediatric Research Equity Act (PREA) requires drug companies to study their products in children under certain circumstances. When pediatric studies are required, they must be conducted with the same drug and for the same use for which they were approved in adults.
The FDA realized that the pediatric population was underrepresented by the industry so they passed the aforementioned Acts to incentivize the pharmaceutical industry to provide additional focus on the pediatric population.
Why Were Incentives Needed?
Intuitively, you would think that since 40% of the overall population is made up of kids, that pharmaceutical companies would allocate at least 40% of their drug development budgets to service the pediatric segment of the population. The reality is that executing pediatric clinical trials is extremely difficult and expensive. In fact, in a report published in September 2015, 42% of recently completed pediatric trials have failed to establish either safety or efficacy, leading to an inability to label the product for use in children. The key challenges commonly cited with pediatric trials are:
Expertise - Clinical Research Organizations are attempting to build out additional expertise, but that doesn't come quickly or become part of your DNA overnight. I Googled Pediatric CROs and outside of a few of the large CROs (INC Research, Medpace & Quintiles), I came across Paidion, KinderPharm and Orphan Reach. Google another niche like Medical Device and a lot more hits come up.
Patient Recruitment - If you read my blog on Patient Recruitment, it doesn't get any easier with pediatric trials. I'll go into more detail in a bit.
Increased Study Complexity - Per Drug Dev, disease pathology, pharmacokinetics, and response to treatment often differ with age, patient size and/or maturation, meaning that multiple age groups must be studied, which leads to more complex, and expensive, clinical trials.
Challenges faced when recruiting for a pediatric trial are numerous:
Trial Awareness - A majority of parents will not be aware of the possibility of a clinical trial unless their physician communicates the opportunity to them. In reality, unless their physician is involved and educated on clinical research, there is a good chance a parent wouldn't be aware that a clinical trial was an option.
Parental Approval - Enrolling your son or daughter in a clinical trial is a major parental decision. A majority of drugs in pediatric trials are being tested for safety and efficacy. A good deal of parents don't want to view their child as a "guinea pig" for science so unless the situation is dire, they will oppose to enrolling their child in a clinical trial. That line of thinking may be unfair, but as a parent I know it exists.
Cost / Logistics - Finding the time and money to commit to a clinical trial is a real hurdle. There are a good deal of two and one parent households where all parents work. Time off from work, transportation and even child care for other siblings can be formidable challenges that can't be overcome.
While researching for this blog, I downloaded a good deal of pediatric trial data from clinicaltrials.gov. I have a few caveats on the data I want to communicate. Trials are not always reported on a timely basis. For example, I searched based on studies that were reported between the dates of 1/1/16 and 12/31/16 - that doesn't mean all the trials commenced in that time frame, they were just reported to clinical trials.gov during that period (there isn't an option to search based upon trial start date). Since this issue occurs every year, the data isn't conclusive, but I would say should be used directionally. Since all my blogs needs some numbers and charts, here goes:
Pediatric Trial Growth
As you can see the number of pediatric trials reported within each of the yearly time frames are increased greatly over the past several years. While that doesn't necessarily mean that all these trials have been or will be successful, it does show a greater interest in the pediatric segment.
On the chart below, I manually carved out the start dates for all pediatric clinical trials, you can still see some pretty good growth from 3,494 trials in 2012 up to 3,899 trials started in 2016. Keep in mind that the later years are likely to be understated as more trials will likely be reported in 2017 and 2018.
Below is a map displaying where most pediatric trials occur geographically. I think as you would expect a majority of pediatric trials are conducted in the US and Europe. However, I would have expected the gap between the US and Europe to be a little greater.
Not much of a surprise when it comes to pediatric studies by sponsor, really a who's who of the top pahrmaceutical and medical device companies in the world.
Rare Disease Indications
We've talked about the challenges with executing pediatric trials, government initiatives to incentivize additional research funding into the space and surveyed some of the macro level data. Where do we go from here to improve the process? Well the process has already started with the advent of Pediatric Clinical Trials Networks (PCTN). PCTNs are an alliance of clinical research sites cooperating in the design and conduct of pediatric clinical trials. More and more of these specialized pediatric networks have been established over the last several years. Here are a few:
Pediatric Trials Network - Sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The Global Pediatric Trials Network - Sponsored by the Critical Path Institute
IDeA States Pediatric Clinical Trials Network - Established by the National Institutes of Health
PPD Pediatric Investigator Network - Established by PPD
Site Networks have become very valuable influential forces within the clinical research industry in recent years. When you think about it, the sites have access to both patients and investigators and without those two, you can't run a clinical trial. Having strong pediatric networks with the expertise to run pediatric trials, recruit pediatric patients and effectively communicate to the parents of pediatric patients will go a long way towards advancing clinical research within the pediatric population. Important in my household as I will have a member of the pediatric population in my household for another 13 years and 56 days (but who's counting).
Jason Monteleone is President at Pivotal Financial Consulting, LLC. A Strategic Financial Consulting Firm serving the Clinical Research Industry. Jason can be reached at firstname.lastname@example.org. Follow me on Twitter @JMPivotal.