Automated surveillance to detect postprocedure safety signals of approved cardiovascular devices

Abstract

Context: Ensuring the safety of medical devices challenges current surveillance approaches, which rely heavily on voluntary reporting of adverse events. Automated surveillance of clinical registries may provide early warnings in the postmarket evaluation of medical device safety.

Objective: To determine whether automated safety surveillance of clinical registries using a computerized tool can provide early warnings regarding the safety of new cardiovascular devices.

Design, setting, and patients: Prospective propensity-matched cohort analysis of 7 newly introduced cardiovascular devices, using clinical data captured in the Massachusetts implementation of the National Cardiovascular Data Repository CathPCI Registry for all adult patients undergoing percutaneous coronary intervention from April 2003 through September 2007 in Massachusetts.

Main outcome measure: Presence of any safety alert, triggered if the cumulative observed risk for a given device exceeded the upper 95% confidence interval (CI) of comparator control device. Predefined sensitivity analyses assessed robustness of alerts when triggered.

Results: We evaluated 74,427 consecutive interventional coronary procedures. Three of 21 safety analyses triggered sustained alerts in 2 implantable devices. Patients receiving Taxus Express2 drug-eluting stents experienced a 1.28-fold increased risk of postprocedural myocardial infarction (2.87% vs 2.25%; absolute risk increase, 0.62% [95% CI, 0.25%-0.99%]) and a 1.21-fold increased risk of major adverse cardiac events (4.24% vs 3.50%; absolute increase, 0.74% [95% CI, 0.29%-1.19%]) compared with those receiving alternative drug-eluting stents. Patients receiving Angio-Seal STS vascular closure devices experienced a 1.51-fold increased risk of major vascular complications (1.09% vs 0.72%; absolute increased risk, 0.37% [95% CI, 0.03%-0.71%]) compared with those receiving alternative vascular closure devices. Sensitivity analyses confirmed increased risk following use of the Taxus Express2 stent but not the Angio-Seal STS device.

Conclusion: Automated prospective surveillance of clinical registries is feasible and can identify low-frequency safety signals for new cardiovascular devices.

Figures

Figure 1. Summary safety analysis of the Taxus Express2® Drug Eluting Stent

Each panel represents the longitudinal propensity matched analysis of the cumulative incidence of peri-procedural myocardial infarction (panel A), in-hospital death (panel B) and major adverse cardiac event (a combination of death, myocardial infarction or urgent revascularization – panel C) following implantation of at least one Taxus Express2® drug eluting stent. Circles indicate the cumulative observed event rates for patients receiving Taxus Express2® DES with circle size proportional to number of Taxus Express2® stents used in the State during the calendar quarter. The light blue area represents the 95% confidence interval for the propensity matched control population (receiving alternative DES) after correction using the O'Brien-Fleming method for multiple comparisons. The solid blue line within the confidence interval represents the mean event rate of the comparator group. The original uncorrected an upper and lower 95% confidence interval is represented by the dashed black line. The left vertical axis indicates the cumulative adverse event rate. Green circles indicate cumulative event rates within propensity matched expectations, while red circles indicate higher than expected event rate (safety alerts) indicating that the observed event rate exceeded the upper 95% confidence interval boundary for the propensity matched control group. The purple line indicates the cumulative sample size.

Figure 2. Summary safety analysis of the Angio-Seal® STS vascular closure device

Each panel represents the longitudinal propensity matched analysis of the cumulative incidence of in-hospital major vascular complication (panel A), minor vascular complication (panel B) and any vascular complication (panel C) following implantation of at least one Angio-Seal® STS vascular closure device (VCD). Circles indicate the cumulative observed event rates for patients receiving the Angio-Seal STS VCD with circle size proportional to number of Angio-Seal® STS VCD used in the State during the calendar quarter. The light blue area represents the 95% confidence interval for the propensity matched control population (receiving alternative closure methods), after correction using the O'Brien-Fleming method for multiple comparisons. The solid blue line within the confidence interval represents the mean event rate of the comparator group. The original uncorrected an upper and lower 95% confidence interval is represented by the dashed black line. The left vertical axis indicates the cumulative adverse event rate. Green circles indicate cumulative event rates within propensity matched expectations, while red circles indicate higher than expected event rate (safety alerts) indicating that the observed event rate exceeded the upper 95% confidence interval boundary for the propensity matched control group. The purple line indicates the cumulative sample size.