Strengthening the Quality of Clinical Pharmacokinetic Studies: Development and Validation of a Critical Appraisal Tool For Clinical Pharmacokinetic Research

Abstract

Background: Critical appraisal process is central to the practice of evidence-based medicine that aids in assessing the quality of the published scientific knowledge. To our knowledge, there is no critical appraisal tool for clinical pharmacokinetics studies. Therefore, this study aimed to develop the first valid and reliable clinical pharmacokinetics critical appraisal tool. Methodology: A systematic review was conducted through Embase and Pubmed to identify quality markers related to clinical pharmacokinetic studies. Questions that helped in appraising pharmacokinetic studies were formulated from these quality markers. Twenty-five clinical pharmacokinetics experts were involved in a modified Delphi process to achieve their consensus regarding the formulated questions. Percentage of agreement between panelists, median and interquartile range were calculated for each question to determine whether they achieved expert’s consensus. Content and face validity of the developed critical appraisal tool were assessed twice through modified Delphi process and by a psychometric expert. Four raters were selected to apply the developed tool on 30 clinical pharmacokinetic articles to evaluate the inter-rater and intra-rater reliability by calculating Kappa values for each of them. Results: Quality markers of clinical pharmacokinetic studies were identified out of fifteen articles included in the systematic review which encompassed 19 subcategories, most of them were related to the methods and results subcategories. The modified Delphi process consisted of 3 rounds. Sixty-four quality-related questions were formulated out of these quality markers to appraise clinical pharmacokinetics studies but 42 were sent to round 1. Of 42 items,12 items reached ≥80 % of agreement, median ≥ 4, and interquartile range ≤ 1 consensus from experts. In round 2, of 25 questions, 6 items met ≥80% of agreement, a median ≥ 4, and interquartile range < 1 from experts. In round 3, of 3 questions, 3 items achieved ≥80% of agreement, a median ≥ 4, and interquartile range < 1 from experts. Twenty-one questions achieved expert consensus to be included in the final critical appraisal tool. This tool proved to be valid and reliable to help end-users in appraising retrospective and prospective clinical pharmacokinetics, bioequivalence, and population pharmacokinetics studies. Conclusion: A clinical pharmacokinetics critical appraisal tool consisting of twenty one questions was developed.