We well recognize the need to prevent and treat pain in infants and children. Besides being the humane thing to do, there is mounting evidence to show that poorly treated pain in children has lasting negative effects, both physiological and psychological, that may follow children for many years. However, we also know that the majority of medications, approximately 80 percent, prescribed to infants, children, and adolescents have not been approved by the FDA for use in these age groups.

Conscientious providers for young children are faced with a real dilemma. Does one try to be humane and treat a child’s pain, but do so “off label” without the usual array of data on effectiveness and safety or does one respect the lack of evidence for the safe and efficacious use of a drug and not prescribe it? The obvious way to reduce this dilemma is to conduct the needed clinical studies to show the effects of these drugs on even the youngest patients.

How big is this gap? The number of medications approved to treat pain in children is shockingly small. For children under 6 months of age, there are no analgesic drugs with a pediatric label; for children 6 to 24 months, only one drug (ibuprofen); for children older than 24 months, only two additional drugs (acetaminophen and a fentanyl patch); and for older children and adolescents, only two additional drugs (naproxen sodium and OxyContin) have been approved and granted labeling.

But doing clinical research is far from simple. For a pain drug to be approved, a placebo-controlled trial is a virtual necessity. The usual research model is to ask adults to participate in a trial where they will be paid to either receive active drug or placebo to treat pain in the wake of a procedure, such as a tooth extraction or bunionectomy. The adult is considered to be capable of an informed cost-benefit analysis (possible pain versus cash) and make a decision to consent to participate or not. Because young minds are not capable of such a determination, the research community has agreed that it is unethical for a child to experience even an iota of discomfort as a function of participating in a research study. This is just one of many ethical and pragmatic challenges to doing research in the young.

So we have a conundrum. To treat children’s pain more responsibly, we need to have medications approved for use in that age group. For that approval to be forthcoming, placebo-controlled trials are essential. But a simple placebo-controlled trial is unethical to pursue in children. In 2011, the Pediatric Research Network for Pain (PRN-Pain) was established. It later morphed into a related organization, the Pediatric Pain Research Consortium of ACTTION, a public-private partnership with the Food and Drug Administration (FDA). A major focus of that network is to help design and implement clinical trials to demonstrate the safety and effectiveness of various drugs to treat pain in children. This requires thoughtful and creative methods that answer the scientific questions without relying on simple placebo-control designs.

The group now includes 35 pediatric hospitals in the US and Canada and to date we have generated a consensus paper on models and methodologies for acute pain trials in infants, toddlers, children, and adolescents, as well as an array of advocacy activities in service of improving clinical research on pain in children. Our goal is to continue to partner with academic researchers, pharmaceutical companies and the FDA in order to facilitate optimal research to help the most vulnerable members of our society.


Gary A. Walco, PhD, Pediatric Psychologist | 29 April 2016