Test-Retest Reliability and Consistency of HVPG and Impact on Trial Design: A Study in 289 Patients from 20 Randomized Controlled Trials
Test-Retest Reliability and Consistency of HVPG and Impact on Trial Design: A Study in 289 Patients from 20 Randomized Controlled Trials
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DOI：
10.1002/hep.32033
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发表时间：
2021-08-15
期刊：
影响因子：
13.5
通讯作者：
Abraldes, Juan G.
中科院分区：
文献类型：
--
作者：
Bai, Wayne;Al-Karaghouli, Mustafa;Abraldes, Juan G.
背景和目的门静脉高压症(PH)是导致肝硬变并发症的主要原因。在实际应用中，门脉压力是由HVPG估计的。HVPG变化的评估已被用于PH的药物开发。这项研究的目的是在随机对照试验(RCT)的特定背景下量化HVPG的测试-重测的可靠性和一致性，以及它对试验设计功率计算的影响。方法和结果我们对已发表的关于肝硬变患者的随机对照试验进行了检索，这些患者报告了基线和干预后的HVPG水平数据，其中包括安慰剂或未经治疗的对照组。将图像数字化后，提取对照组的基线和随访期的高频心电图。我们评估了研究特征的可靠性和一致性以及潜在的影响。在安慰剂/未治疗组中，我们从20个随机对照试验中检索了在HVPG测量前后总共289个样本。两次HVPG测量之间的时间跨度从20分钟到730天不等。在仅包括代偿患者的研究中，HVPG前后的变异性较低；因此，代偿性肝硬化组试验的模型化样本量计算低于失代偿期肝硬化组。酒精相关性肝硬变和单中心性试验的比例越高，基线和随访测量之间的差异越小。在代偿和失代偿患者中，个体可检测到的最小差异分别为26%和30%。结论HVPG的重测信度总体较好。在包括失代偿患者比例较高的研究中，个体内差异较大。在根据对HVPG的影响进行试验的功率分析时，或者在考虑将HVPG作为指导PH治疗的工具时，应考虑这些发现。
Background and Aims Portal hypertension (PH) is a major driver for cirrhosis complications. Portal pressure is estimated in practice by the HVPG. The assessment of HVPG changes has been used for drug development in PH. This study aimed at quantifying the test-retest reliability and consistency of HVPG in the specific context of randomized controlled trials (RCTs) for the treatment of PH in cirrhosis and its impact on power calculations for trial design. Approach and Results We conducted a search of published RCTs in patients with cirrhosis reporting individual patient-level data of HVPG at baseline and after an intervention, which included a placebo or an untreated control arm. Baseline and follow-up HVPGs in the control groups were extracted after digitizing the plots. We assessed reliability and consistency and the potential impact of study characteristics. We retrieved a total of 289 before and after HVPG measurements in the placebo/untreated groups from 20 RCTs. The time span between the two HVPG measurements ranged between 20 minutes and 730 days. Pre-/post-HVPG variability was lower in studies including only compensated patients; therefore, modeled sample size calculations for trials in compensated cirrhosis were lower than for decompensated cirrhosis. A higher proportion of alcohol-associated cirrhosis and unicentric trials was associated with lower differences between baseline and follow-up measurements. The smallest detectable difference in an individual was 26% and 30% in compensated and decompensated patients, respectively. Conclusions The test-retest reliability of HVPG is overall excellent. Within-individual variance was higher in studies including higher proportions of decompensated patients. These findings should be taken into account when performing power analysis for trials based on the effects on HVPG or when considering HVPG as a tool to guide therapy of PH.