How valid are claims for synergy in published clinical studies?
How valid are claims for synergy in published clinical studies?
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DOI：
10.1093/annonc/mdr608
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发表时间：
2012-08-01
影响因子：
50.5
通讯作者：
Tannock, I. F.
中科院分区：
文献类型：
--
作者：
Ocana, A.;Amir, E.;Tannock, I. F.
评价药物组合的临床试验经常受到临床前模型中协同相互作用的要求的刺激。过度使用或误用术语协同作用可能导致设计不良的临床研究。我们使用术语"协同作用"或"协同作用"和"癌症"检索PubMed，以选择2006年至2010年期间发表的文章。符合条件的研究是指那些在临床前研究中提到协同作用，以证明在临床试验中评价的药物组合的合理性。86篇临床文章符合资格标准，其中引用了132篇临床前文章。大多数临床研究是I期（43%）或II期试验（56%）。在临床前研究中评价协同作用的适当方法包括18项研究（13.6%）中的等效线图分析和10项研究（7.6%）中的中位效应。只有26项使用动物模型的研究（39%）试图评估治疗指数。临床试验结果与使用适当方法评价协同作用之间无关联（P = 0.25，卡方检验）。协同作用在I期和II期研究中经常被引用，以证明对特定药物组合的评价是合理的。在大多数临床前文章中，使用了不适当的协同作用评价方法和治疗指数评估不佳。
Clinical trials evaluating drug combinations are often stimulated by claims of synergistic interactions in preclinical models. Overuse or misuse of the term synergy could lead to poorly designed clinical studies.We searched PubMed using the terms 'synergy' or 'synergistic' and 'cancer' to select articles published between 2006 and 2010. Eligible studies were those that referred to synergy in preclinical studies to justify a drug combination evaluated in a clinical trial.Eighty-six clinical articles met eligibility criteria and 132 preclinical articles were cited in them. Most of the clinical studies were phase I (43%) or phase II trials (56%). Appropriate methods to evaluate synergy in preclinical studies included isobologram analysis in 18 studies (13.6%) and median effect in 10 studies (7.6%). Only 26 studies using animal models (39%) attempted to evaluate therapeutic index. There was no association between the result of the clinical trial and the use of an appropriate method to evaluate synergy (P = 0.25, chi-squared test).Synergy is cited frequently in phase I and phase II studies to justify the evaluation of a specific drug combination. Inappropriate methods for evaluation of synergy and poor assessment of therapeutic index have been used in most preclinical articles.