Use of biological assignment in hematopoietic stem cell transplantation clinical trials
Use of biological assignment in hematopoietic stem cell transplantation clinical trials
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DOI：
10.1177/1740774508098326
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发表时间：
2008-01-01
期刊：
影响因子：
2.7
通讯作者：
Geller, Nancy
中科院分区：
文献类型：
--
作者：
Logan, Brent;Leifer, Eric;Geller, Nancy
背景：当比较特定疾病的治疗方法时，进行随机临床试验（RCT）有时是不切实际或不可能的。生物分配试验是另一种设计。在造血干细胞移植（HCT）试验中，人类白细胞抗原（HLA）匹配的兄弟姐妹供体被认为是最佳的，但只有20-30%的其他符合条件的患者可以获得这样的供体。在最近的一项多发性骨髓瘤试验中，每位患者接受的HCT类型是基于生物学的，即根据患者是否有匹配的兄弟姐妹供体来选择，而不是只随机选择那些有匹配的兄弟姐妹供体的患者。目的：本文介绍了生物指派试验的设计和实施，以及它们的优缺点。方法：我们关注这类试验的几个方面，包括试验持续时间的效率、伦理问题和潜在的偏倚来源。统计问题包括样本量计算，监测有偏入组，以及调整患者特征的不平衡。以多发性骨髓瘤试验为例。结果：虽然它们通常需要更大的样本量，但当随机试验的累积速度较慢时，生物分配试验在研究持续时间方面可以提供实质性的效率。样本量的确定需要考虑具有生物学优势（hla匹配的兄弟姐妹）供体的患者的预期比例。没有匹配的兄弟姐妹供体的患者的附加随机化可能减轻对研究结果适用于所有患者的伦理担忧，而不管生物学分配组在结果方面是否不同。局限性：预后因素不平衡和入组偏倚可能发生在生物学分配试验中。对预后因素的潜在不平衡进行统计调整是很重要的，就像监测中心累积入组偏倚和进行适当的意向治疗分析一样。结论：当金标准随机试验设计不切实际或不可能时，生物学分配试验可以是比较基于生物学的治疗方法的合理方法，例如hla匹配的兄弟姐妹移植。实施这样的试验需要仔细考虑伦理问题和潜在的偏见。临床试验2008；5: 607 - 616。http://ctj.sagepub.com
Background: When comparing treatments for a specific illness, it is sometimes impractical or impossible to conduct a randomized clinical trial (RCT). Biological assignment trials are one alternative design. In hematopoietic stem cell transplantation (HCT) trials, a human leukocyte antigen (HLA)-matched sibling donor is considered optimal, but such donors are available for only 20-30% of otherwise eligible patients. Rather than randomizing only those with a matched sibling donor, in a recent multiple myeloma trial, the type of HCT each patient received was biologically based, i.e., chosen according to whether or not the patient had a matched sibling donor.Purpose: This article describes the design and implementation of biological assignment trials as well as their advantages and disadvantages.Methods: We focus on several aspects of such trials, including efficiency of trial duration, ethical issues, and potential sources of bias. Statistical issues are considered including sample size calculations, monitoring for biased enrollment, and adjustments for imbalances in patient characteristics. A multiple myeloma trial is used as an illustration.Results: Although they often require a larger sample size, biological assignment trials can provide substantial efficiency in terms of study duration over randomized trials when accrual to a randomized trial would be slow. Determination of sample size requires consideration of the anticipated proportion of patients with a biologically favored (HLA-matched sibling) donor. An add-on randomization of patients without a matched sibling donor may alleviate ethical concerns about applicability of study results to all patients regardless of whether the biological assignment groups differ with respect to outcome.Limitations: Prognostic factor imbalance and enrollment bias can occur in a biological assignment trial. Statistical adjustment for potential imbalance in prognostic factors is important, as is monitoring center accrual for enrollment bias and performing an appropriate intention-to-treat analysis,Conclusions: A biological assignment trial can be a reasonable way to compare treatments which are biologically based, such as HLA-matched sibling transplants, when the gold-standard randomized trial design is impractical or impossible. Implementing such a trial requires careful consideration of the ethical issues and potential biases. Clinical Trials 2008; 5: 607-616. http://ctj.sagepub.com