Chen Yong, Cai Kangjun, Li Jinjian, Xu Mengdan
Objective To establish an active monitoring model for adverse reactions/events of sodium-glucose cotransporter 2 inhibitor (SGLT2i) for application and promotion in medical institutions. Methods The subjects were type 2 diabetes patients who were discharged from the First Affiliated Hospital of Guangdong Pharmaceutical University (our hospital) from March 1, 2021 to October 1, 2022 and treated with SGLT2i. The patients were divided into 2 parts and assigned to the pre-trial phase and clinical application validation phase, respectively. SGLT2i-related adverse reactions/events from domestic and foreign databases and drug labels were retrieved, and triggering items were developed preliminarily. After soliciting opinions from experts in our hospital, referring to relevant medical orders, disease course records, and laboratory indicator reference values, the triggering items were modified, and a questionnaire survey was conducted using the Delphi method. According to expert opinions, the items were sorted, analyzed, discussed, and modified to form preliminary triggering items. A monitoring model was established based on the Chinese hospital drug surveillance system, the triggering items were improved during the pre-trial phase, and validated during the clinical application phase. Results A total of 218 and 858 patients were obtained in the pre-trial phase and clinical application validation phase, respectively. Based on literature and drug labels, 44 triggering items were preliminarily formed. A total of 16-survey questionnaires from experts were collected. After being modified based on expert opinions, and further improved during the pre-trial phase, 24 triggering items were determined finally, including 8 laboratory indicators (A), 4 rescue agents (B), 11 clinical symptoms (C), and 1 intervention measure (D). The number of positive cases monitored by the model during the pre-trial phase and clinical application validation phase was 56 and 189, respectively. The actual number of positive cases under manual review was 12 and 57, respectively. The positive predictive value (PPV) of the triggering items in the pre-trial phase and clinical application phase were 25.0% (18/72) and 30.9% (77/249), respectively, with adverse reaction/event detection rates of 5.5% (12/218) and 6.6% (57/858), sensitivity of 92.3% (12/13) and 100% (57/57), and specificity of 78.5% (161/205) and 83.5% (669/801). Among the 12 positive cases in the pre-trial phase and 57 positive cases in the clinical application validation phase, the association evaluation was probable and possible (4, 8 cases and 16, 41 cases, respectively). The severity of adverse reactions/events was mainly grade 2 (11 cases and 55 cases, respectively). The main adverse reactions/events of SGLT2i were hypoglycemia, urinary tract infections, rashes, etc. Pancreatitis, weight loss, etc., which were not stated in the drug labels, were evaluated as probable. Conclusion Through pre-trial and internal clinical validation phase, the adverse reaction/event active monitoring model established for SGLT2i in this study has high sensitivity and specificity, and can be applied practically in medical institutions.
