Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Centre for Human Drug Research, Leiden, The Netherlands.
Pituitary. 2018 Jun;21(3):310-322. doi: 10.1007/s11102-018-0884-4.
In rare disease research, most randomized prospective clinical trials can only use limited number of patients and are comprised of highly heterogeneous populations. Therefore, it is crucial to report the results in such a manner that it allows for comparison of treatment effectiveness and biochemical control between studies. The aim of this review was to investigate the current methods that are being applied to measure and report growth hormone (GH) and insulin-like growth factor-1 (IGF-1) as markers for drug effectiveness in clinical acromegaly research.
A systematic search of recent prospective and retrospective studies, published between 2012 and 2017, that studied the effects of somatostatin analogues or dopamine agonists in acromegaly patients was performed. The markers of interest were GH, IGF-1, and the suppression of GH after an oral glucose tolerance test (OGTT). Additionally, the use of pharmacokinetic (PK) measurements in these studies was analyzed. The sampling design, cut-off for biochemical control, reported units, and used summary statistics were summarized.
A total of 49 articles were selected out of the 263 screened abstracts. IGF-1 concentrations were measured in all 49 studies, GH in 45 studies, and an OGTT was performed in 11 studies. A wide range of different cut-off values and sampling designs were used to determine biochemical control in acromegaly patients. The summary statistics were reported in various ways, with the percentage of biochemical control most frequently used. Nine studies sampled the PK at one or more time points. Non-compartmental analyses were commonly performed on the available PK data.
The way GH and IGF-1 are measured and reported in acromegaly research varies considerably. A consensus on how to report study results would enable better comparisons between studies, thereby improving evidence based decision making to optimize treatment in acromegaly.
在罕见病研究中，大多数随机前瞻性临床试验只能使用有限数量的患者，且患者人群高度异质。因此，以允许比较研究之间的治疗效果和生化控制的方式报告结果至关重要。本综述的目的是调查目前用于测量和报告生长激素（GH）和胰岛素样生长因子-1（IGF-1）作为药物在临床肢端肥大症研究中有效性的标志物的方法。
系统检索了 2012 年至 2017 年期间发表的最近的前瞻性和回顾性研究，这些研究研究了生长抑素类似物或多巴胺激动剂对肢端肥大症患者的影响。感兴趣的标志物是 GH、IGF-1 和口服葡萄糖耐量试验（OGTT）后 GH 的抑制。此外，还分析了这些研究中使用的药代动力学（PK）测量。总结了采样设计、生化控制的临界值、报告单位和使用的汇总统计量。
从 263 篇筛选的摘要中，共选择了 49 篇文章。49 项研究均测量了 IGF-1 浓度，45 项研究测量了 GH，11 项研究进行了 OGTT。用于确定肢端肥大症患者生化控制的不同临界值和采样设计范围广泛。汇总统计量以各种方式报告，最常使用的是生化控制的百分比。9 项研究在一个或多个时间点采样 PK。非房室分析通常用于可用的 PK 数据。
肢端肥大症研究中 GH 和 IGF-1 的测量和报告方式差异很大。就如何报告研究结果达成共识将能够更好地比较研究，从而改善基于证据的决策，以优化肢端肥大症的治疗。
