ACTTION Consensus Provides Best Practices for the Design of Pediatric Clinical Trials Focused on Acute Pain
It is recommended that placebo groups be eliminated from trials in neonates and infants in order to maintain ethical standards.
In a meeting held by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) Pediatric Pain Research Consortium (PPRC), the key factors for improving the design of clinical trials on analgesics for acute pain in pediatric populations were reviewed and recommendations were recently published in Pain.
Prior to designing pediatric trials that assess analgesic strategies for acute pain, the consensus statement suggests researchers should take into account the level of renal clearance and drug metabolizing enzymes present in this population. It is also recommended that trial outcome measures be based on assessment tools that take into account levels of cognitive maturation and behavior.
In toddlers between the age of 6 and 24 months, clinical trials can be effective for the study of procedural and needle pain associated with immunization. In addition, the researchers suggest that this patient population should be homogenous, with the goal of using healthy cohorts devoid of any significant comorbidities.
It is also recommended that placebo groups be eliminated from trials in neonates and infants in order to maintain ethical standards, that safety monitoring be introduced during the trial, and that total blood sampling volume be restricted. The inclusion of a crossover design is not recommended as such studies have a lengthier timeline than studies with no crossover component.
According to the investigators, the conduct of pediatric clinical trials is often limited by aggressive timelines for trial performance and inadequate scientific review. For pediatric clinical trial success, the researchers suggest improving communication between research teams and implementing education initiatives on the clinical trial process for patients' parents.
The investigators note that even subtle age changes can affect the design of pediatric clinical trials as many of the challenges associated with interventions in young children “are overcome due to maturation of many of the physiologic systems by about 6 months of age.”
Walco GA, Kopecky EA, Weisman SJ, et al. Clinical trial designs and models for analgesic medications for acute pain in neonates, infants, toddlers, children, and adolescents: ACTTION recommendations [published online November 13, 2017]. Pain doi:10.1097/j.pain.0000000000001104