Updated October 10, 2013, at 5 p.m. with comments from the CDRH panel.
An FDA panel on Wednesday issued a mixed recommendation on CardioMEMS Champion permanently implantable pressure measurement system for daily pulmonary arterial pressure measurements, voting against its effectiveness due to confounding factors in the study backing the device’s pre-market approval application but saying it is safe and that its benefits outweigh its risks.
Champion, which wirelessly measures systolic, diastolic, and mean pulmonary arterial pressure, is indicated for measuring pulmonary artery pressures in subjects with New York Heart Assn. Class III heart failure who have been hospitalized for heart failure in the previous year.
The FDA’s Circulatory Systems Devices panel voted 11-0 that Champion is safe and 6 to 4 with 1 abstention that its benefits outweigh its risks. But the committee voted 4-7 on Champion’s effectiveness, citing confounding factors in the study that make it hard to attribute positive study outcomes to the device itself.
Panelist Brent Blumenstein of Trial Architecture Consulting in Washington, D.C., explained why he voted "no" on effectiveness for Champion.
"I didn’t feel that the additional analyses clearly demonstrated that the device could be used without nurse assistance based on the fact that there is a lack of experimental structure in the data analog," he said.
Physicians use the hemodynamic data for heart failure management and to reduce heart failure hospitalizations, according to the FDA’s executive summary released ahead of the meeting. Doctors can use Champion in the office and hospital setting and the device was designed to also allow patients to use Champion to remotely send heart data to their doctors.
FDA in 2012 issued a Not Approvable letter for Champion after the panel voted in 2011 that the device had not proved effective for use in the subject population studied due to patient-specific management recommendations contained in nurse communications that confounded the study results. The panel also voted in 2011 that the benefits of Champion do not outweigh the risks. St. Jude Medical (NYSE:STJ) owns a 20% stake in CardioMEMS with an option to buy.
To address the deficiencies in FDA’s letter, CardioMEMS continued to follow subjects already enrolled in the pivotal study between August 12, 2010, and April 30, 2012 and conducted a number of statistical analyses on the additional follow-up data as well as the original data set discussed at the previous panel meeting.
CardioMEMS submitted an Amendment to the original PMA that includes the results of these analyses, which FDA reviewed and asked the panel to discuss and vote on.
Champion consists of an implantable sensor/monitor, transvenous catheter delivery system to deploy the sensor within the distal pulmonary artery (PA), and an electronics system and database which acquires and processes signals from the implanted sensor and transfers Implantable Sensor/Monitor and transfers PA pressure measurements to a secure database, which can be reviewed by medical professionals.
Input from the panel
The effectiveness analyses designed with the FDA’s input that CardioMEMS conducted after receiving a Not Approvable letter for Champion in 2012 seem to prove the device is effective in reducing HFR hospitalization rates, the agency said ahead of the meeting.
But, the FDA asked the panel to comment on the requirement for patient hospitalization for device implantation, and the absence of a sustained quality of life benefit at 12 months in the treatment group, or increased survival benefit in the presence of reduced hospitalizations.
Panelist Dr. Jeffrey Borer of Downstate Medical Center at State University of New York noted that patients significantly improved after 6 months using the device. The fact that no significant difference was observed after a year had more do with the study not being sufficiently powered to record a significant difference, he said.
"So that suggests if you act on the basis of what you saw with the device, people actually do feel better. It’s not just that they don’t go to the hospital as frequently, which is a big deal, but they actually feel better, too, I think," Borer said.
"The significance of the treatment effect is definitely impressive," Dr. David Yuh of Yale University School of Medicine agreed. "I think though, the device is exerting its effect in ways perhaps different than what the sponsor had intended. If you put the spotlight on the heart failure patient, I think truly the heart failure cardiologist may use it in a way as a crutch or assurance to treat outpatient heart failure more aggressively and it may actually give heart failure cardiologists the confidence not to admit a patient because they know what the PA pressures are."
Some of the unanswered questions from the pre-approval study for Champion could be addressed with a post-approval study, according to the panel. Panelists wanted more robust data showing the device is effective at one year. Champion also did not show the same benefit for women in the pre-approval study as it did for men, likely because not enough women were included.
"A historical control form doesn’t cut it," stressed Dr. Richard Lange of the University of Texas in San Antonio, TX. "You need to either do it with a run-in phase or a randomized control, there are ways to get it done, but what we’re telling you is we’re uncomfortable with that."
Dr. Lange further suggested evaluating post-market safety for 3-4 years instead of 2 years due to potential erosions that were observed with similar implants into the pulmonary artery.