PharmaTherapeutics Clinical Research, Clinical Pharmacology, Pfizer Inc., Groton, CT, USA.
J Pharmacokinet Pharmacodyn. 2012 Jun;39(3):283-94. doi: 10.1007/s10928-012-9250-8. Epub 2012 May 9.
Treatment decisions for hypertension using sphygmomanometer based measurements and the current clinical practice paradigm do not account for the timing of blood pressure (BP) measurement. This study aimed to evaluate the clinical implications of discordance between measured and true BP, to quantify BP misclassification rate at a typical clinical visit in current clinical practice, and to propose a BP calibration system to decrease the impact of timing of BP measurement. A clinical trial simulation case study was performed using an in silico Monte Carlo Simulation approach. The time-courses of BPs with and without an antihypertensive treatment effect were simulated from a baseline BP model combined with an antihypertensive PK/PD model. Virtual subject characteristics were sampled from the FDA internal database. The baseline BP model was qualified using observed 24 h ambulatory BP monitoring (ABPM) data from 225 subjects by a visual predictive check as well as a global sensitivity analysis. First of all, our results showed that the measured cuff BP in current typical clinical practice deviated from the true values. (1) Cuff BP deviated from the true values by more than 5 mmHg in 57 % (95 % CI: 54-61 %) of patients and more than 10 mmHg in 26 % (95 % CI: 22-32 %) of patients respectively. (2) These discordances were reduced to 28 % (deviation ≥ 5 mmHg, 95 % CI: 18-40 %) and 9 % (deviation ≥ 10 mmHg, 95 % CI: 4-18%) of patients assuming perfect sphygmomanometer measurement and thus represent the contribution of ignoring the daily circadian rhythm of BP. Secondly, our results showed 23-32 % of patients were misclassified to an incorrect BP category for a casual clinical visit based on JNC 7 guideline. In addition, the accuracy of the measured cuff BP varied by time of clinic visit. Specifically, 11:00 AM to 3:00 PM was identified to be the better time frame, while times before 9:00 AM were the worst time frame. Therefore, clinic visit time may need to be adjusted accordingly. Finally, we proposed an easy BP calibration method for clinic use to adjust for time of day differences due to circadian variability in case that the desirable clinic visit time cannot be tailored for practical reasons.
使用基于血压计的测量值和当前临床实践模式来做出高血压治疗决策并未考虑血压测量的时间。本研究旨在评估测量血压与真实血压之间的差异所带来的临床意义，量化当前临床实践中典型就诊时血压分类错误的发生率，并提出血压校准系统以降低血压测量时间的影响。通过基于计算机的蒙特卡罗模拟方法进行临床试验模拟研究。从与降压药 PK/PD 模型相结合的基础血压模型中模拟具有和不具有降压治疗效果的血压时程。虚拟受试者特征从 FDA 内部数据库中抽样。使用 225 名受试者的 24 小时动态血压监测（ABPM）数据通过可视化预测检查和全局敏感性分析对基础血压模型进行了验证。首先，我们的结果表明，当前典型临床实践中的血压计测量值与真实值存在偏差。（1）分别有 57%（95%CI：54-61%）和 26%（95%CI：22-32%）的患者的血压计测量值与真实值偏差超过 5mmHg 和 10mmHg。（2）这些偏差分别降低到 28%（偏差≥5mmHg，95%CI：18-40%）和 9%（偏差≥10mmHg，95%CI：4-18%），这归因于忽略了血压的日常昼夜节律。其次，我们的结果表明，根据 JNC 7 指南，在进行常规临床就诊时，有 23-32%的患者被错误分类到不正确的血压类别。此外，血压计测量值的准确性随就诊时间而变化。具体来说，上午 11 点至下午 3 点被确定为更好的时间段，而上午 9 点之前的时间段则是最差的时间段。因此，就诊时间可能需要相应调整。最后，我们提出了一种简单的血压校准方法，用于在因昼夜节律变化导致的日间差异情况下进行临床使用调整，以便在实际情况下无法定制理想的就诊时间时进行调整。
