| Autor: |
Takeuchi, Yoshinori, Shinozaki, Tomohiro, Kumamaru, Hiraku, Hiramatsu, Tatsuo, Matsuyama, Yutaka |
| Zdroj: |
Expert Opinion on Drug Safety; November 2018, Vol. 17 Issue: 11 p1071-1079, 9p |
| Abstrakt: |
ABSTRACTObjective: To apply a causal analysis approach to estimate the intent-to-treat and per-protocol effects in a safety outcome study of the 30-day risk of liver injury associated with antibiotic use (macrolides, penicillin-based antibiotics, and fluoroquinolones).Research design and methods: For each antibiotic class, we constructed a pooled cohort of treated episodes matched with untreated episodes using an electronic medical record database from a university hospital. High-dimensional propensity scores were calculated using baseline patient characteristics, concomitant medications and medical history as surrogate confounders. Intent-to-treat hazard ratios (HRs) were estimated using inverse probability of treatment weighted discrete hazard models that ignored subsequent treatment changes. Per-protocol HRs were calculated using inverse probability of treatment and censoring weighted models after terminating each episode’s observation at the first treatment change.Results: For macrolides, the intent-to-treat HR (95% confidence interval) was 1.22 (0.75–1.98) and the per-protocol HR was 1.22 (0.67–2.22). For penicillin-based antibiotics, the intent-to-treat HR was 4.01 (3.16–5.08) and the per-protocol HR was 7.25 (5.58–9.41). For fluoroquinolones, the intent-to-treat HR was 1.60 (1.27–2.03) and the per-protocol HR was 1.69 (1.23–2.30).Conclusion: Researchers should clearly define the target estimands, and carefully estimate and interpret both effects. |
| Databáze: |
Supplemental Index |
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