Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston MA; Department of Medicine, Cardiology Division, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA.
Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston MA.
Am Heart J. 2022 Jan;243:77-86. doi: 10.1016/j.ahj.2021.09.002. Epub 2021 Sep 14.
Regulatory agencies have endorsed more limited approaches to clinical trial site monitoring. However, the impact of different monitoring strategies on trial conduct and outcomes is unclear.
We conducted a patient-level block-randomized controlled trial evaluating the effect of intensive versus limited monitoring on cardiovascular clinical trial conduct and outcomes nested within the CoreValve Continued Access and Expanded Use Studies. Intensive monitoring included complete source data verification of all critical datapoints whereas limited monitoring included automated data checks only. This study's endpoints included clinical trial outcome ascertainment as well as monitoring action items, protocol deviations, and adverse event ascertainment.
A total of 2,708 patients underwent transcatheter aortic valve replacement (TAVR) and were randomized to either intensive monitoring (n = 1,354) or limited monitoring (n = 1,354). Monitoring action items were more common with intensive monitoring (52% vs 15%; P < .001), but there was no difference in the percentage of patients with any protocol deviation (91.6% vs 90.4%; P = .314). The reported incidence of trial outcomes between intensive and limited monitoring was similar for mortality (30 days: 4.8% vs 5.5%, P = .442; 1 year: 20.3% vs 21.3%, P = .473) and stroke (30 days: 2.8% vs 2.4%, P = .458), as well as most secondary trial outcomes with the exception of bleeding (intensive: 36.3% vs limited: 32.0% at 30 days, P = .019). There was a higher reported incidence of cardiac adverse events reported in the intensive monitoring group at 1 year (76.7% vs 72.4%; P = .019).
Tailored limited monitoring strategies can be implemented without influencing the integrity of TAVR trial outcomes.
监管机构已经认可了更为有限的临床试验现场监测方法。然而，不同监测策略对试验进行和结果的影响尚不清楚。
我们进行了一项以患者为基础的分块随机对照试验，评估了强化监测与有限监测对心血管临床试验进行和结果的影响，该试验嵌套在 CoreValve 持续准入和扩大使用研究中。强化监测包括对所有关键数据点的完整原始数据验证，而有限监测仅包括自动数据检查。本研究的终点包括临床试验结果确定以及监测行动项目、方案偏离和不良事件确定。
共有 2708 名接受经导管主动脉瓣置换术（TAVR）的患者被随机分配至强化监测组（n=1354）或有限监测组（n=1354）。强化监测时更常见监测行动项目（52%比 15%；P<0.001），但任何方案偏离的患者比例无差异（91.6%比 90.4%；P=0.314）。强化监测和有限监测的死亡率（30 天：4.8%比 5.5%，P=0.442；1 年：20.3%比 21.3%，P=0.473）和卒中（30 天：2.8%比 2.4%，P=0.458）的报告发生率相似，除出血（强化监测：30 天 36.3%比有限监测 32.0%，P=0.019）外，大多数次要试验结果也是如此。强化监测组在 1 年时报告的心脏不良事件发生率更高（76.7%比 72.4%；P=0.019）。
可以实施量身定制的有限监测策略，而不会影响 TAVR 试验结果的完整性。
