Patents in the United States expire after 20 years; however, on approval of a new drug application (NDA) the holder is eligible for exclusivity ranging from 3 years to 7 years. In 1997, the US FDA Modernization Act incentivized drug developers to perform studies in children by extending the term of this exclusivity another 6 months. Additional legislation both in the United States and Europe has continued these incentives and added requirements for manufacturers to study their drugs in children.

So, why are there so few trials in pediatric retina, given these laws? The most obvious is the smaller market for pharmaceutical companies. Another is the ethical concerns of legal consent. Unlike in adult studies, in pediatric trials patients do not of their own free will join the clinical study; the guardians or parents give consent. Moreover, there are many additional rules in studies involving children, including balancing risk exposure and numerous safeguards to protect research trial participants.

A drug’s pharmacokinetics and pharmacodynamics are fundamentally different in children, making dosing difficult. Often, the delivery method may even need to be changed in children. For example, intravitreal injections in young patients may require a trip to the operating room. But making a pill or drop is not possible. Finally, manufacturers are often worried about long-term effects on development of their drugs (ie, tetracycline and teeth or steroids and growth).

These factors lead to a high level of off-label drug use in children without guidance as to dosage adjustment. Very few of our adult retinal therapies are approved in children. The best example of this is how much bevacizumab is used in ROP babies, which you would have had to call off-off-label before the results of the BEAT-ROP study reported excellent efficacy. Ranibiuzmab and aflibercept have also been tested in ROP.

But what about diseases unique to pediatrics or that begin in childhood? The best current example is the explosion of gene therapy studies in inherited retinal degenerations (IRDs). Although many of these therapies should probably be administered in children, the risks dictate that most studies be in adults with the IRD. This largely stems from lesson learned in 1999, when 18-year-old Jesse Geisinger was the first person identified as having died in a gene-therapy clinical trial from a massive immune response to the adenoviral vector, leading to multiorgan failure. His death led to a halt in all gene-therapy studies and serves as a stark reminder of the risks to children in these studies.

We are excited to bring you our pediatric retina issue, looking at many of these issues. There are actually many clinical studies in pediatric retina patients, which are highlighted in this issue. Ethical concerns in treating pediatric patients are also explored. Hopefully, more clinical studies in IRD will enroll pediatric patients in the future, once safety and efficacy in adults is established. RP