JAMA: Automated monitoring of PCI registry IDs device safety risks
Implementation of a computer-automated safety surveillance system of a clinical outcomes registry for cardiovascular devices in Massachusetts resulted in the identification of a drug-eluting stent (DES) that had significantly higher rates of major adverse cardiac events than similar stents, according to a study in the Nov. 10 issue of the Journal of the American Medical Association.
The findings indicate that this type of system appears feasible and useful in identifying new cardiovascular devices with early low-frequency potential safety issues that are not observed in premarket approval studies, according to the study.
"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," the authors wrote.
Frederic S. Resnic, MD, of Brigham and Women's Hospital and Harvard Medical School in Boston, and colleagues examined in-hospital safety signals for recently introduced cardiovascular devices using an automated safety surveillance system.
The study included an analysis of seven 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 PCI from April 2003 through September 2007. Patient, physician and hospital data for 74,427 coronary interventional procedures performed during the study period were evaluated.
The seven devices were the Taxus Express2 (Boston Scientific) and Cypher (Cordis) DES, the Mini-vision (Abbott Vascular) bare-metal stent, the FilterWire (Boston Scientific) embolic protection device and three vascular closure devices: Angio-Seal STS (St. Jude Medical), Perclose ProGlide and StarClose (both from Abbott).
Of the 21 safety analyses performed, three generated a repeated or sustained safety signal involving implanted devices, prompting detailed sensitivity analysis per study protocol.
The safety alerts included an increased risk of post-procedural MI, as well as an increased risk of major adverse cardiac events (MACE) following implantation of Taxus Express2 DES. By the end of the study period, the rate of post-procedure MI was 27.6 percent higher for the Taxus DES compared with the alternative DES (2.87 vs. 2.25 percent; absolute risk increase, 0.62 percent).
The rates of MACE were increased by 21.1 percent, driven by the increased post-procedural MI difference for the Taxus DES relative to the MACE rate for the control population (4.24 vs. 3.5 percent; absolute increase, 0.74 percent); and a sustained safety alert for MACE was triggered beginning in July 2007. The researchers observed no increased risk of death among the exposure groups.
"Our findings regarding the increased risk of periprocedural MI with the Taxus Express 2 stent are supported by trends reported in prospective randomized clinical trials, including the Taxus V trial, in which patients receiving multiple Taxus Express2 stents experienced significantly increased risk of MI within 30 days of the procedure compared with patients randomly assigned to receive bare-metal stents," the authors wrote.
Investigators also found an increased rate of major vascular complications following implantation of the Angio-Seal STS vascular closure device. By the end of the observation period, the matched subset of Angio-Seal STS case patients experienced a 51.3 percent increased risk of major vascular complications compared with the control population (1.09 percent vs. 0.72 percent; absolute increased risk, 0.37 percent).
Sensitivity analyses confirmed increased risk following use of the Taxus Express2 stent but not the Angio-Seal STS device.
The risk associated with the Angio-Seal STS reversed over time. The authors concluded, "[C]ase patient selection, changes in medical therapy and potential learning curve effects likely explain a significant proportion of the increased risk observed in the early period of use."
Overall, Resnic and colleagues found that "automated safety surveillance of medical devices is feasible using automated monitoring tools applied to detailed clinical registries and can efficiently help identify emerging potential postmarket safety risks."
In an accompanying JAMA editorial, John S. Rumsfeld, MD, PhD, from the University of Colorado in Denver, and Eric D. Peterson, MD, from the Duke Clinical Research Institute in Durham, N.C., commented: "[T]his investigation demonstrates the value of robust statistical methods in comparative safety evaluations using observational data, such as propensity matching and sensitivity analyses, supporting responsible interpretation of potential safety signals."
Still, Rumsfeld and Peterson said the study also shows how far the U.S. is from achieving proactive device surveillance. Among their concerns were that the data had limited power to compare outcomes of many devices and noise in the system and confounding factors need better scrutiny.
The editorialists mentioned several similar proactive device surveillance systems, including one from the Institute of Medicine and another from the FDA. "However, these are works in progress, and effective, coordinated national device surveillance still hangs in the balance."
The many national registries already in place support the "strong need to expand the work of Resnic et al to a national level," they said.
Rumsfeld and Peterson concluded that the movement to achieve meaningful use with EMRs should also include achieving meaningful device surveillance.
"This includes deploying automated surveillance tools, using national data, coupling point-of-care device surveillance with comparative outcomes studies and leveraging national data platforms to facilitate efficient follow-up studies when a potential safety signal is identified," they said.
The findings indicate that this type of system appears feasible and useful in identifying new cardiovascular devices with early low-frequency potential safety issues that are not observed in premarket approval studies, according to the study.
"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," the authors wrote.
Frederic S. Resnic, MD, of Brigham and Women's Hospital and Harvard Medical School in Boston, and colleagues examined in-hospital safety signals for recently introduced cardiovascular devices using an automated safety surveillance system.
The study included an analysis of seven 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 PCI from April 2003 through September 2007. Patient, physician and hospital data for 74,427 coronary interventional procedures performed during the study period were evaluated.
The seven devices were the Taxus Express2 (Boston Scientific) and Cypher (Cordis) DES, the Mini-vision (Abbott Vascular) bare-metal stent, the FilterWire (Boston Scientific) embolic protection device and three vascular closure devices: Angio-Seal STS (St. Jude Medical), Perclose ProGlide and StarClose (both from Abbott).
Of the 21 safety analyses performed, three generated a repeated or sustained safety signal involving implanted devices, prompting detailed sensitivity analysis per study protocol.
The safety alerts included an increased risk of post-procedural MI, as well as an increased risk of major adverse cardiac events (MACE) following implantation of Taxus Express2 DES. By the end of the study period, the rate of post-procedure MI was 27.6 percent higher for the Taxus DES compared with the alternative DES (2.87 vs. 2.25 percent; absolute risk increase, 0.62 percent).
The rates of MACE were increased by 21.1 percent, driven by the increased post-procedural MI difference for the Taxus DES relative to the MACE rate for the control population (4.24 vs. 3.5 percent; absolute increase, 0.74 percent); and a sustained safety alert for MACE was triggered beginning in July 2007. The researchers observed no increased risk of death among the exposure groups.
"Our findings regarding the increased risk of periprocedural MI with the Taxus Express 2 stent are supported by trends reported in prospective randomized clinical trials, including the Taxus V trial, in which patients receiving multiple Taxus Express2 stents experienced significantly increased risk of MI within 30 days of the procedure compared with patients randomly assigned to receive bare-metal stents," the authors wrote.
Investigators also found an increased rate of major vascular complications following implantation of the Angio-Seal STS vascular closure device. By the end of the observation period, the matched subset of Angio-Seal STS case patients experienced a 51.3 percent increased risk of major vascular complications compared with the control population (1.09 percent vs. 0.72 percent; absolute increased risk, 0.37 percent).
Sensitivity analyses confirmed increased risk following use of the Taxus Express2 stent but not the Angio-Seal STS device.
The risk associated with the Angio-Seal STS reversed over time. The authors concluded, "[C]ase patient selection, changes in medical therapy and potential learning curve effects likely explain a significant proportion of the increased risk observed in the early period of use."
Overall, Resnic and colleagues found that "automated safety surveillance of medical devices is feasible using automated monitoring tools applied to detailed clinical registries and can efficiently help identify emerging potential postmarket safety risks."
In an accompanying JAMA editorial, John S. Rumsfeld, MD, PhD, from the University of Colorado in Denver, and Eric D. Peterson, MD, from the Duke Clinical Research Institute in Durham, N.C., commented: "[T]his investigation demonstrates the value of robust statistical methods in comparative safety evaluations using observational data, such as propensity matching and sensitivity analyses, supporting responsible interpretation of potential safety signals."
Still, Rumsfeld and Peterson said the study also shows how far the U.S. is from achieving proactive device surveillance. Among their concerns were that the data had limited power to compare outcomes of many devices and noise in the system and confounding factors need better scrutiny.
The editorialists mentioned several similar proactive device surveillance systems, including one from the Institute of Medicine and another from the FDA. "However, these are works in progress, and effective, coordinated national device surveillance still hangs in the balance."
The many national registries already in place support the "strong need to expand the work of Resnic et al to a national level," they said.
Rumsfeld and Peterson concluded that the movement to achieve meaningful use with EMRs should also include achieving meaningful device surveillance.
"This includes deploying automated surveillance tools, using national data, coupling point-of-care device surveillance with comparative outcomes studies and leveraging national data platforms to facilitate efficient follow-up studies when a potential safety signal is identified," they said.