Department of Pharmaceutical Outcomes & Policy, University of Florida-College of Pharmacy, Gainesville, Florida, USA.
University of Florida-Center for Drug Evaluation and Safety (CoDES), Gainesville, Florida, USA.
Pharmacoepidemiol Drug Saf. 2021 Sep;30(9):1192-1199. doi: 10.1002/pds.5293. Epub 2021 Jun 7.
There is an increased use in the (prescription) sequence symmetry analysis (PSSA); however, limited studies have incorporated a negative control, and no study has formally quantified and controlled for within-patient time-varying bias using a negative control. Our aim was to develop a process to incorporate the effect of negative controls into the main analysis of a PSSA.
Using a previously assessed dihydropyridine calcium channel blocker (DH-CCB) and loop diuretic PSSA, we directly compared the adjusted sequence ratios (aSRs) of DH-CCBs to each of the two negative control index drugs (levothyroxine and angiotensin converting enzyme [ACE] inhibitor/angiotensin-2 receptor blocker [ARB]) using the ratio of the aSRs to estimate a relative aSR with a Z test. Further, we utilized the relative aSR in stratum-specific analyses and varying exposure windows.
The relative aSR of DH-CCBs decreased from 1.87 to 1.72 (95% CI 1.66-1.78) using levothyroxine as a negative control index drug. ACE inhibitor/ARB negative control index drug resulted in an aSR of 1.27 thus reducing the relative aSR for DH-CBB from 1.84 to 1.45 (95% CI 1.41-1.49). When restricting the exposure window to 180 and 90 days, the relative aSR of DH-CCBs increased to 1.68 (95% CI 1.62-1.74) and 1.86 (95% CI 1.78-1.94), respectively, relative to the ACE inhibitor/ARB negative control index drug.
We illustrated how to incorporate negative control index drugs into a PSSA and generate relative aSRs. Stratum-specific assessments and varying the exposure windows while using negative control index drugs can yield more informative results.
处方序列对称性分析（PSSA）的应用日益增多；然而，有限的研究纳入了阴性对照，并且没有研究使用阴性对照正式量化和控制患者内时间变化的偏差。我们的目的是开发一种将阴性对照的影响纳入 PSSA 主要分析的过程。
使用先前评估的二氢吡啶钙通道阻滞剂（DH-CCB）和噻嗪类利尿剂 PSSA，我们直接比较了 DH-CCB 与两种阴性对照指数药物（左甲状腺素和血管紧张素转换酶[ACE]抑制剂/血管紧张素-2 受体阻滞剂[ARB]）的调整后序列比（aSR），使用 aSR 的比值估计相对 aSR，并进行 Z 检验。此外，我们在分层特异性分析和不同暴露窗口中利用相对 aSR。
使用左甲状腺素作为阴性对照指数药物时，DH-CCB 的相对 aSR 从 1.87 降至 1.72（95%CI 1.66-1.78）。ACE 抑制剂/ARB 阴性对照指数药物导致 aSR 为 1.27，从而将 DH-CBB 的相对 aSR 从 1.84 降至 1.45（95%CI 1.41-1.49）。当将暴露窗口限制为 180 和 90 天时，DH-CCB 的相对 aSR 分别增加到 1.68（95%CI 1.62-1.74）和 1.86（95%CI 1.78-1.94），与 ACE 抑制剂/ARB 阴性对照指数药物相比。
我们说明了如何将阴性对照指数药物纳入 PSSA 并生成相对 aSR。使用阴性对照指数药物进行分层评估和改变暴露窗口可以产生更具信息量的结果。
