Scott Martin Vouri1,2, Xinyi Jiang1, Earl J Morris1, Babette A Brumback2,3, Almut G Winterstein1,2. 1. Department of Pharmaceutical Outcomes & Policy, University of Florida-College of Pharmacy, Gainesville, Florida, USA. 2. University of Florida-Center for Drug Evaluation and Safety (CoDES), Gainesville, Florida, USA. 3. Department of Biostatistics, University of Florida-College of Public Health & Health Professions College of Medicine, Gainesville, Florida, USA.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Scott M Vouri; Earl J Morris; Silken A Usmani; Rachel Reise; Xinyi Jiang; Carl J Pepine; Todd M Manini; Daniel C Malone; Almut G Winterstein Journal: Pharmacoepidemiol Drug Saf Date: 2021-10-06 Impact factor: 2.890
Authors: Ann S Doherty; Faiza Shahid; Frank Moriarty; Fiona Boland; Barbara Clyne; Tobias Dreischulte; Tom Fahey; Seán P Kennelly; Emma Wallace Journal: Pharmacol Res Perspect Date: 2022-10