Public Health Sciences and Medical Statistics, School of Medicine, University of Southampton, Southampton, UK.
J Eval Clin Pract. 2012 Apr;18(2):209-15. doi: 10.1111/j.1365-2753.2010.01553.x. Epub 2010 Oct 10.
RATIONALE, AIMS AND OBJECTIVES: Open-label extension (OLE) studies following blinded randomized controlled trials (RCTs) of pharmaceuticals are increasingly being carried out but do not conform to regulatory standards and questions surround the validity of their evidence. OLE studies are usually discussed as a homogenous group, yet substantial differences in study design still meet the definition of an OLE. We describe published papers reporting OLE studies focussing on stated objectives, design, conduct and reporting.
A search of Embase and Medline databases for 1996 to July 2008 revealed 268 papers reporting OLE studies that met our eligibility criteria. A random sample of 50 was selected for detailed review.
Over 80% of the studies had efficacy stated as an objective. The most common methods of allocation at the start of the OLE were for all RCT participants to switch to one active treatment or for only participants on the new drug to continue, but in three studies all participants were re-randomized at the start of the OLE. Eligibility criteria and other selection factors resulted in on average of 74% of participants in the preceding RCT(s) enrolling in the OLE and only 57% completed it.
Published OLE studies do not form a homogenous group with respect to design or retention of participants, and thus the validity of evidence from an OLE should be judged on an individual basis. The term 'open label' suggests bias through lack of blinding, but slippage in relation to the sample randomized in the preceding RCT may be the more important threat to validity.
背景、目的和目标：越来越多的药品盲法随机对照试验（RCT）后进行开放性标签扩展（OLE）研究，但这些研究不符合监管标准，其证据的有效性也存在疑问。OLE 研究通常被视为一个同质群体，但研究设计的实质性差异仍然符合 OLE 的定义。我们描述了报告 OLE 研究的已发表论文，重点是既定目标、设计、实施和报告。
对 Embase 和 Medline 数据库进行了 1996 年至 2008 年 7 月的检索，共发现 268 篇符合入选标准的报告 OLE 研究的论文。随机抽取 50 篇进行详细审查。
超过 80%的研究将疗效作为目标。OLE 开始时最常见的分配方法是所有 RCT 参与者都转换为一种活性治疗或仅新药物的参与者继续，但在三项研究中，所有参与者在 OLE 开始时重新随机分组。入选标准和其他选择因素导致在前瞻性 RCT 中平均有 74%的参与者参加 OLE，只有 57%的参与者完成了 OLE。
已发表的 OLE 研究在设计或保留参与者方面并非同质群体，因此，应根据个体情况判断 OLE 证据的有效性。“开放性标签”一词暗示了缺乏盲法的偏见，但与在前瞻性 RCT 中随机分组的样本相比，脱落可能是对有效性的更重要威胁。
