Strengthening the Quality of Clinical Pharmacokinetic studies: Development and Validation of a Critical Appraisal Tool for Clinical Pharmacokinetic Research

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Background: Robust critical appraisal tools for pharmacokinetic studies are lacking. The aim of this study is to develop a valid and reliable critical appraisal tool for clinical pharmacokinetic studies. Methodology: A systematic review was conducted through Embase and Pubmed to identify quality markers of clinical pharmacokinetic studies. Quality-related questions were formulated to help in appraising pharmacokinetic studies. Experts were approached to participate in a modified Delphi process to achieve their consensus regarding the formulated questions based on percentage of agreement between panelists, median and interquartile range. Content and face validity of the tool were assessed twice and by a psychometric expert. Four raters were selected to apply the tool on 30 clinical pharmacokinetic articles to calculate Kappa values to determine interrater and intra-rater reliability. Results: Quality markers of clinical pharmacokinetic studies were identified from fifteen articles. Sixty-four quality-related questions were formulated, but 42 were assessed by twenty-five panelists, who consented to participate in the modified Delphi process rounds. In round 1, 12 out of 42 items reached ≥80 % of agreement, median ≥ 4, and interquartile range ≤ 1. In round 2, 6 out of 28 items met ≥80% of agreement, a median ≥ 4, and interquartile range < 1. In round 3, 3 out of 3 items achieved ≥80% of agreement, a median ≥ 4, and interquartile range < 1. This tool proved to be valid and reliable in appraising retrospective and prospective clinical pharmacokinetic, bioequivalence, and population pharmacokinetic studies. Conclusion: A valid and reliable clinical pharmacokinetic critical appraisal tool containing twenty-one questions was developed