| アブストラクト | BACKGROUND: Change-point analysis (CPA) is a powerful method to analyse pharmacovigilance data but it has never been used on the disproportionality metric. OBJECTIVES: To optimize signal detection investigating the interest of time-series analysis in pharmacovigilance and the benefits of combining CPA with the proportional reporting ratio (PRR). METHODS: We investigated the couple benfluorex and aortic valve incompetence (AVI) using the French National Pharmacovigilance and EudraVigilance databases: CPA was applied on monthly counts of reports and the lower bound of monthly computed PRR (PRR-). We stated a CPA hypothesis that the substance-event combination is more likely to be a signal when the 2 following criteria are fulfilled: PRR- is greater than 1 with at least 5 cases, and CPA method detects at least 2 successive change points of PRR- which made consecutively increasing segments. We tested this hypothesis by 95 test cases identified from a drug safety reference set and 2 validated signals from EudraVigilance database: CPA was applied on PRR-. RESULTS: For benfluorex and AVI, change points detected by CPA on PRR- were more meaningful compared with monthly counts of reports: More change points detected and detected earlier. In the reference set, 14 positive controls satisfied CPA hypothesis, 6 positive controls only met first requirements, 3 negative controls only met first requirement, and 2 validated signals satisfied CPA hypothesis. CONCLUSIONS: The combination of CPA and PRR represents a significant advantage in detecting earlier signals and reducing false-positive signals. This approach should be confirmed in further studies. |
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| ジャーナル名 | Pharmacoepidemiology and drug safety |
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| Pubmed追加日 | 2018/7/12 |
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| 投稿者 | Trinh, Nhung T H; Sole, Elodie; Benkebil, Mehdi |
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| 組織名 | Inserm UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team,;Research Center for Epidemiology and Biostatistics Sorbonne Paris Cite (CRESS),;Paris Descartes University, Paris, France.;Adverse Events and incidents Department-Surveillance Division, Agence nationale;de securite du medicament et des produits de sante (ANSM), Saint Denis, France. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/29992679/ |
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