Limited Generalizability of Registration Trials in Hepatitis C: A Nationwide Cohort Study
Limited Generalizability of Registration Trials in Hepatitis C: A Nationwide Cohort Study
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DOI：
10.1371/journal.pone.0161821
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发表时间：
2016-09-06
期刊：
影响因子：
3.7
通讯作者：
Kievit, Wietske
中科院分区：
文献类型：
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作者：
Berden, Floor A. C.;de Knegt, Robert J.;Kievit, Wietske
慢性丙型肝炎药物的批准得到注册试验的支持。这些试验由于使用严格的合格标准，可能具有有限的普遍性。我们比较了有效性和安全性的真实的世界丙型肝炎患者合格和不合格的registration trials.MethodsWe进行了一项全国性的，多中心的，回顾性队列研究慢性丙型肝炎患者治疗的真实的世界。我们将一组注册试验的入选和排除标准应用于我们的队列，以确定合格性。我们比较了合格与不合格患者的有效性和安全性，并采用严格的标准进行了敏感性分析。此外，我们使用对数二项回归，以评估相对风险的标准outcomes.ResultsIn这个队列（n = 467）47%的患者将不符合注册试验。主要排除标准与肝功能失代偿和合并症（心脏病、贫血、恶性肿瘤和中性粒细胞减少症）相关，并与严重不良事件风险增加相关（RR 1.45-2.31）。不合格患者发生的严重不良事件明显多于合格患者（27% vs. 11%，p
BackgroundApproval of drugs in chronic hepatitis C is supported by registration trials. These trials might have limited generalizability through use of strict eligibility criteria. We compared effectiveness and safety of real world hepatitis C patients eligible and ineligible for registration trials.MethodsWe performed a nationwide, multicenter, retrospective cohort study of chronic hepatitis C patients treated in the real world. We applied a combined set of inclusion and exclusion criteria of registration trials to our cohort to determine eligibility. We compared effectiveness and safety in eligible vs. ineligible patients, and performed sensitivity analyses with strict criteria. Further, we used log binomial regression to assess relative risks of criteria on outcomes.ResultsIn this cohort (n = 467) 47% of patients would have been ineligible for registration trials. Main exclusion criteria were related to hepatic decompensation and co-morbidity (cardiac disease, anemia, malignancy and neutropenia), and were associated with an increased risk for serious adverse events (RR 1.45-2.31). Ineligible patients developed significantly more serious adverse events than eligible patients (27% vs. 11%, p