Evidence Based Health Care Program, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
BMC Cancer. 2013 Feb 14;13:76. doi: 10.1186/1471-2407-13-76.
Randomized controlled trials (RCTs) that are inappropriately designed or executed may provide biased findings and mislead clinical practice. In view of recent interest in the treatment and prevention of thrombotic complications in cancer patients we evaluated the characteristics, risk of bias and their time trends in RCTs of anticoagulation in patients with cancer.
We conducted a comprehensive search, including a search of four electronic databases (MEDLINE, EMBASE, ISI the Web of Science, and CENTRAL) up to February 2010. We included RCTs in which the intervention and/or comparison consisted of: vitamin K antagonists, unfractionated heparin (UFH), low molecular weight heparin (LMWH), direct thrombin inhibitors or fondaparinux. We performed descriptive analyses and assessed the association between the variables of interest and the year of publication.
We included 67 RCTs with 24,071 participants. In twenty one trials (31%) DVT diagnosis was triggered by clinical suspicion; the remaining trials either screened for DVT or were unclear about their approach. 41 (61%), 22 (33%), and 11 (16%) trials respectively reported on major bleeding, minor bleeding, and thrombocytopenia. The percentages of trials satisfying risk of bias criteria were: adequate sequence generation (85%), adequate allocation concealment (61%), participants' blinding (39%), data collectors' blinding (44%), providers' blinding (41%), outcome assessors' blinding (75%), data analysts' blinding (15%), intention to treat analysis (57%), no selective outcome reporting (12%), no stopping early for benefit (97%). The mean follow-up rate was 96%. Adequate allocation concealment and the reporting of intention to treat analysis were the only two quality criteria that improved over time.
Many RCTs of anticoagulation in patients with cancer appear to use insufficiently rigorous outcome assessment methods and to have deficiencies in key methodological features. It is not clear whether this reflects a problem in the design, conduct or the reporting of these trials, or both. Future trials should avoid the shortcomings described in this article.
设计或执行不当的随机对照试验（RCT）可能会提供有偏差的结果并误导临床实践。鉴于最近对癌症患者血栓并发症的治疗和预防的关注，我们评估了癌症患者抗凝治疗 RCT 的特征、偏倚风险及其时间趋势。
我们进行了全面的搜索，包括对四个电子数据库（MEDLINE、EMBASE、ISI Web of Science 和 CENTRAL）进行的搜索，截至 2010 年 2 月。我们纳入了干预和/或比较包括维生素 K 拮抗剂、未分级肝素（UFH）、低分子肝素（LMWH）、直接凝血酶抑制剂或磺达肝素的 RCT。我们进行了描述性分析，并评估了感兴趣的变量与出版年份之间的关系。
我们纳入了 67 项 RCT，共 24071 名参与者。在 21 项试验（31%）中，DVT 诊断是通过临床怀疑触发的；其余试验要么对 DVT 进行筛查，要么对其方法不清楚。分别有 41（61%）、22（33%）和 11（16%）项试验报告了主要出血、轻微出血和血小板减少症。符合偏倚风险标准的试验百分比为：充分的序列生成（85%）、充分的分配隐匿（61%）、参与者的盲法（39%）、数据收集者的盲法（44%）、提供者的盲法（41%）、结局评估者的盲法（75%）、数据分析者的盲法（15%）、意向治疗分析（57%）、无选择性结局报告（12%）、无提前因获益而停止（97%）。平均随访率为 96%。充分的分配隐匿和意向治疗分析的报告是唯一两项随时间改善的质量标准。
许多癌症患者抗凝治疗的 RCT 似乎使用了不够严格的结局评估方法，并在关键的方法学特征上存在缺陷。目前尚不清楚这是反映了这些试验的设计、实施还是报告中的问题，或者兼而有之。未来的试验应避免本文所述的缺点。
