Analgesic Drug Development for Children: A History of Shortcomings … Until Now

Abstract

1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA; 2Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA With hundreds of pharmaceutical companies internationally, each sharing a portion of a global, multi-trillion dollar business, and with international drug approval regulations varying widely in terms of restrictions, timing, and cost, each decision made by pharmaceutical companies in planning the development of a new drug has immense financial consequences. Grünenthal, a family-owned pharmaceutical company that now employs over 4500 individuals, has funded and executed multiple clinical drug trials of the analgesic tapentadol, a novel molecule with both muopioid and SNRI-like (serotonin and norepinephrine reuptake inhibitor) properties that have been shown to be effective in the treatment of acute and chronic pain in adults. In taking the necessary steps to demonstrate pharmacokinetics, efficacy and, safety in the pediatric population for their drug, Grünenthal has established a precedent and set the bar for other pharmaceutical companies – one that has remained largely absent from the most recent drug releases. Medical advances and new drug development have grown at a tremendous pace, and continue to reach new heights year after year. In 1996, the United States Food and Drug Administration (FDA) approved a record-breaking 50 new drug approvals. In the year 2018, another benchmark was set when the FDA issued approvals for 61 new drugs. While used as evidence of the progress of the economies of medically advanced countries, these numbers do not reflect the myopic perspective that predominates the world of pharmaceutical development in ignoring 25% of the population – children. Of the 61 new drug approvals in 2018, only 4 approvals were for the pediatric age group (ages 2–17) in spite of the fact that children and adolescents represent one-quarter of the population, suffer from many of the same ailments as do their elders, and from many more that are unique to their age group. Today, only about half of analgesic medications used in either inpatient or outpatient settings have been thoroughly evaluated for efficacy and safety, and have dosing guidelines approved by the international regulatory agencies for use in pediatrics. The number of analgesic medications approved in ages less than 2 years, including preterm infants, is even more humbling at only 35%. Yet in spite of the lack of clinical trials by industry and thorough evaluation by governmental bodies, analgesics are still widely prescribed in pediatrics and are used “off-label,” which increases the risk to the patient for both toxicity and lack of efficacy, as well as medicolegal exposure for the healthcare provider. Correspondence: Andrew Dinh Email [email protected]