Methods for identifying long-term adverse effects of treatment in patients with eye diseases: The systemic immunosuppressive therapy for eye diseases (SITE) cohort study
Methods for identifying long-term adverse effects of treatment in patients with eye diseases: The systemic immunosuppressive therapy for eye diseases (SITE) cohort study
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DOI：
10.1080/09286580701585892
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发表时间：
2008-01-01
影响因子：
1.8
通讯作者：
Suhler, Eric B.
中科院分区：
文献类型：
--
作者：
Kempen, John H.;Daniel, Ebenezer;Suhler, Eric B.
目的：评价研究免疫抑制对死亡率和致命性恶性肿瘤风险的长期影响的潜在流行病学方法，并介绍眼部疾病全身免疫抑制治疗（SITE）队列研究的方法学细节。研究方法：潜在的研究设计，以评估罕见的，迟发性事件的优点和缺点进行了审查，并提出了网站队列研究的方法。结果如下：随机对照试验是评估治疗效果的最可靠方法，但研究时间长，成本高，以及研究毒性时的伦理问题限制了其在这种情况下的使用。回顾性队列研究可能更具成本效益和及时性，如果有记录提供所需的信息，在过去足够的随访时间。病例对照方法需要非常大的样本量来评估与罕见暴露相关的风险，并且在研究死亡率时存在回忆偏倚问题。SITE队列研究是一项回顾性队列研究。过去使用抗代谢药，T细胞抑制剂，烷化剂和其他免疫抑制剂是从五个三级中心的9，250名眼部炎症患者的医疗记录中确定的，长达30年。使用国家死亡指数确定了类似于10万人年的死亡率和死因特异性死亡率结果。免疫抑制和非免疫抑制组的患者进行了比较，并从美国人口统计的一般人群死亡率。计算得出的死亡率/致死性恶性肿瘤相对于一般人群的可检测差异为：抗代谢药为22%/49%，T细胞抑制剂为28%/62%，烷化剂为36%/81%。结论：来自SITE队列研究的信息应该澄清使用这些免疫抑制药物治疗眼部炎症是否会增加死亡率和致命性癌症的风险。这种流行病学方法可能有助于评估其他眼部疾病全身治疗的长期风险。
Purpose: To evaluate potential epidemiologic methods for studying long-term effects of immunosuppression on the risk of mortality and fatal malignancy, and present the methodological details of the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study. Methods: Advantages and disadvantages of potential study designs for evaluating rare, late-occurring events are reviewed, and the SITE Cohort Study approach is presented. Results: The randomized, controlled trial is the most robust method for evaluating treatment effects, but long study duration, high costs, and ethical concerns when studying toxicity limit its use in this setting. Retrospective cohort studies are potentially more cost-effective and timely, if records exist providing the desired information over sufficient follow-up time in the past. Case-control methods require extremely large sample sizes to evaluate risk associated with rare exposures, and recall bias is problematic when studying mortality. The SITE Cohort Study is a retrospective cohort study. Past use of antimetabolites, T-cell inhibitors, alkylating agents, and other immuno-suppressives is ascertained from medical records of 9,250 ocular inflammation patients at five tertiary centers over up to 30 years. Mortality and cause-specific mortality outcomes over similar to 100,000 person-years are ascertained using the National Death Index. Immunosuppressed and non-immunosuppressed groups of patients are compared with each other and general population mortality rates from US vital statistics. Calculated detectable differences for mortality/fatal malignancy with respect to the general population are 22%/49% for antimetabolites, 28%/62% for T-cell inhibitors, and 36%/81% for alkylating agents. Conclusions: Information from the SITE Cohort Study should clarify whether use of these immunosuppressive drugs for ocular inflammation increases the risk of mortality and fatal cancer. This epidemiologic approach may be useful for evaluating long-term risks of systemic therapies for other ocular diseases.