HF pressure measurement system receives split vote from FDA panel

The FDA’s Circulatory System Devices Advisory Panel today voted that the CardioMEMS Champion HF Monitoring System is safe and its benefits outweigh its risks, but the panel also decided the device is not effective.

The panel voted 11-0 that the device is safe, 7-4 that it is not effective and 6-4-1 that its benefits outweigh its risks.

The system is designed to wirelessly measure and monitor pulmonary artery pressure and heart rate in patients with NYHA class III HF who have been hospitalized for HF in the previous year. The patient can send measurements to a secure database for review and evaluation by his or her physician, who can use the data for HF management and to help reduce HF hospitalizations.

This marked the second time the panel has considered the monitoring system. The panel voted against approval in December 2011, voting 9-1 that the system was safe, but 7-3 that it was not effective and 6-4 that the risks outweighed the benefits.

Considering CHAMPION

Much of the apprehension about the device stems from controversy over the conduct of the CHAMPION trial, a single blind study of 550 patients. This study served as the crux of CardioMEMS’ case for approval in 2011. The FDA discovered that nurses employed by CardioMEMS were contacting physicians to make medical therapy recommendations regarding some patients in the treatment group. Some advisory panel members said this created doubt as to whether the positive results in the treatment group should be attributed to the monitoring system or to the support system.

The FDA sent the firm a Not Approvable letter in January 2012, asking that it conduct a new trial that minimized or eliminated treatment advice from company employees and hire an auditor to monitor nurse communications between the company and the investigator sites as well as provide additional data addressing differences in treatment effect due to sex.

CardioMEMS asked to do a statistical analysis of follow-up data excluding nurse communications instead of starting a new trial, and the agency agreed.

The CHAMPION trial and its follow-up analyses indicated that the system may reduce HF-related hospitalizations.

However, some panel members were not convinced by the longitudinal, propensity score, clinical and gender analyses performed by the company since the 2011 hearing.

“I believe the analysis and the data are not valid or convincing,” panel member David Milan, MD, who voted no on effectiveness and risk/benefit, said. “The appropriate approach to take was following the FDA’s original recommendation of a properly performed randomized clinical trial.”

A major problem, panel member Joaquin E. Cigarroa, MD, said, is that the a large number of patients from the CHAMPION trial were not included in the follow-up analyses, and that many of those in the treatment arm of the CHAMPION trial had very different clinical profiles by the time they were analyzed in the post-2011 studies. “I am unable to resolve the substantial problem of the difference in patients at the outset of part two of the study,” Cigarroa, who voted no on effectiveness and risk/benefit, said.

Risk vs. benefit

Kristen K. Patton, MD, one of two panel members who voted that the device is not effective but that its benefits outweigh its risks, said she did so because “I’m not completely convinced by the data on efficacy … but the risk potential is so low that I felt it could be clinically useful.”

Valluvan Jeevanandam, MD, who voted yes to all three questions, said that despite the flaws in the data, the device is “an excellent diagnostic tool, and there is an innumerable number of HF patients that I’d love to put it in.”

Panelist Jeffrey S. Boyer, MD, who also voted yes to all three questions, said that despite the issues with methodology, the data were consistently favorable. “Everything I’ve seen is consistent with pulmonary pressure coming down and patients having fewer events,” he said.

There was consensus from the panel that if the device is approved, there should be a post-approval study that addresses a number of concerns, most notably evidence that there may be little to no treatment effect in women. Panel members said the CHAMPION trial and its follow-up analyses did not contain nearly enough women, and Boyer said he would have voted to contraindicate the device for women pending post-approval study results had that been an option.

The FDA is not required to follow panel recommendations, but it usually does.

For more information:

Circulatory System Devices Advisory Panel Briefing Document. PMA P100045/A004.