Optimisation of Approaches to Adverse Event Analysis in Bioequivalence Clinical Trials

Abstract

SCIENTIFIC RELEVANCE. The safety assessment of investigational medicinal products is a mandatory step in clinical trials of all phases, including bioequivalence studies. However, there are no approaches providing for the individualised assessment of adverse drug reactions (ADRs), which contributes to the quality of decisions on the safety of pharmacotherapy.AIM. The study aimed to develop and justify approaches to the individualised assessment of the safety of pharmacotherapy based on quantitative integrative analysis of adverse events (AEs).MATERIALS AND METHODS. The authors carried out a systematic review of open-access publications and adapted quantitative integrative analysis methods for assessing the safety of pharmacotherapy in clinical trials involving healthy volunteers. The developed methodology is a step-by-step individualised assessment of ADRs, where each case is assigned a certain score and a weight, with subsequent data aggregation to obtain an integrated indicator at the system/organ and organism levels.RESULTS. The authors developed a five-step procedure for assessing the safety of pharmacotherapy based on quantitative integrative ADR analysis. This procedure involves scoring an AE, converting the score using membership functions, assigning weights, aggregating data to obtain an integrated indicator, and interpreting individual and group indicators. The sequential implementation of the analysis steps in accordance with the proposed procedure makes it possible to assign each volunteer (study subject) to a specific group in accordance with the likelihood of developing AEs. In addition to individual assessment, the article presents an algorithm for interpreting indicators for groups of study subjects, depending on the treatment group (study or comparator medicinal product).CONCLUSIONS. The described algorithm for converting and presenting integrative AE assessments will improve the reliability and validity of conclusions on the safety of medicinal products, which is important for planning and implementing further clinical development programmes.

Keywords

• adverse event
• adverse drug reaction
• pharmacovigilance
• clinical trial
• bioequivalence
• statistical analysis
• drug safety
• integrative estimates
• individualisation