A Review of Methods for Monitoring Adverse Events in Pediatric Psychopharmacology Clinical Trials

Abstract

Pediatric psychotropic prescription rates are rising, emphasizing the need for careful monitoring of drug safety in this population. Currently, no standardized assessments are used in clinical trials for adverse event (AE) elicitation focused on long-term drug treatment in pediatric patients. Despite a lack of standardized AE elicitation methods in psychiatric clinical trials, it is clear that psychiatric medications have developmentally dependent AEs that differ from those observed in adults. In this review, we discuss the use of general inquiry elicitation, drug-specific checklists, and systematic elicitation scales for AE reporting in pediatric psychopharmacology trials. The checklists evaluated include the Barkley Side Effect Rating Scales (SERS), the Pittsburg side effect rating scale, and the Systematic Monitoring of Adverse events Related to TreatmentS (SMARTS) checklist. The systematic assessment scales discussed include the Systematic Assessment for Treatment of Emergent Events (SAFTEE) and the Safety Monitoring Uniform Report Form (SMURF). We review the advantages and disadvantages of each method and discuss the need for optimal assessment of AEs. AE instruments that are created and utilized for pediatric psychiatric trials must begin to incorporate symptoms that are relevant to this population and account for the nature of the disorders to better characterize treatment-emergent AEs and monitor long-term safety.

Serious Adverse Drug Reactions in Children and Adolescents Treated On- and Off-Label with Antidepressants and Antipsychotics in Clinical Practice

“…However, any comparison between the incidence and prevalence rates of ADRs reported in clinical trials is difficult to draw, as there are large differences in the classification systems, recorded periods, treatment settings, methods of data assessment, and patient and medication groups. Additionally, information about the severity of the ADRs is often missing 31 .…”

“…Given these critical safety issues with potentially high impact on the individual patient and the resulting burden on health care systems, the importance of short- and long-term drug safety monitoring as well as the introduction of efficient pharmacovigilance methods in pediatric trials and as part of routine clinical practice have been increasingly recognized 21 22 27 30 31 . However, surveillance on ADRs is far from optimal, as appropriate monitoring practices are not yet established or were found to be inconsistent, and underreporting is still an unsolved problem 32 33 .…”

Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review

“…Second, only few studies assessed AEs consistently or systematically. Unfortunately, this is a general problem in psychopharmacology ( Coates et al, 2018 ) and not unique for psychedelic drug studies. Instead, most studies relied on spontaneously reported and/or therapist-observed AEs.…”

Rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B)

“…As in any phase 2 study, priority was also given to identifying potential safety signals in this large population. To date, adverse event monitoring in pediatric trials of oxytocin have used a variety of methods, which is a prevalent issue across pediatric clinical trials in general [101]. The SOARS-B trial therefore moved to standardize AE monitoring by using a prospective systematic (body systems approach) elicitation of adverse events using the Systematic Longitudinal Adverse Events Scale (SLAES), complemented by both physical exam and monitoring of safety labs and ECG over the course of the trial.…”