Anne Skrobala

Developing Methodologies for Monitoring Long-Term Safety of Psychotropic Medications in Children: Report on the NIMH Conference, September 25, 2000

OBJECTIVE To improve the methods for long-term assessment of drug-associated side effects and advance knowledge of the safety profile of psychotropic medications in children and adolescents. METHOD A multidisciplinary, interactive workshop was hosted by the National Institute of Mental Health (NIMH) and the Research Units on Pediatric Psychopharmacology network. Participants were experts in child and adolescent psychiatry, psychopharmacology, pharmacoepidemiology, and statistics from academia, the pharmaceutical industry, the Food and Drug Administration (FDA), and the NIMH. Evaluation of drug safety was examined from five perspectives: research design and methods, industry, regulatory requirements, bioethics, and practice settings. For each of these areas, special emphasis was placed on identifying barriers and generating solutions. RESULTS A major obstacle is the lack of standardization of the methods used for collecting safety data. The limitations of both randomized clinical trials and passive postmarketing surveillance in assessing long-term safety were recognized. The need to consider alternative approaches, such as registries and trend analysis of population-based databases, was highlighted. Recommendations were proposed together with possible approaches to implementation. CONCLUSIONS A concerted effort by academic researchers, industry, FDA, practitioners, and NIMH is needed to standardize methods and lay the foundations for systematic research on the long-term safety of psychotropic medications in children.

Improving the methods for evaluating the safety of psychotropic medications in children and adolescents

Abstract Background: Given the considerable importance of drug safety in children and adolescents and the potential effects of psychotropic medications on growth rates and developing central neurotransmitter systems, there is a need for valid methods for detecting possible drug-induced adverse events during prolonged exposure. Objectives: The aims of this study were to discuss challenges involved in the collection of safety information on psychotropic medications when administered to children and adolescents and suggest methods for improving existing approaches. Methods: Current methods for collecting and assessing safety data during pediatric psychopharmacological trials are critiqued and possible alternatives reviewed. Results: Methods used for collecting and assessing drug safety data remain less sophisticated than efficacy evaluations. Multisite trials, although demonstrating statistical power to detect placebo/active drug differences, remain too small to detect infrequent but serious drug-related adverse events. Other active surveillance approaches, such as long-duration follow-up studies and clinical epidemiological studies, using case-control, cohort designs, or trend analysis of population-based treatment data must be used. Conclusions: Research is needed to standardize the basic ascertainment approaches, definitions of adverse events, lists of preferred terms, and recording procedures to a common core battery. A possible approach to developing and testing these procedures is proposed. Then more detailed lists of drug-related adverse events can be added, which can be study specific. The increasing use of psychotropic medications in youths should be accompanied by increased efforts to standardize the ascertainment of drug-related adverse events.