PI Insights From A Heart Failure Trial: Part 1
By Dan Schell, Chief Editor, Clinical Leader
The good folks at Abbott are going to be disappointed with me. They pitched me a story about their “first-of-its-kind global clinical trial designed to improve outcomes in patients with worsening heart failure.” And I’ll admit, I was intrigued, so I took the bait and agreed to an interview with Jennifer Cowger, MD, the co-principal investigator of the TEAM-HF trial. But as we got into the interview, I became more fascinated with the information Cowger was telling me about what it’s like to be a PI on a study of this size (i.e., planned to enroll up to 850 patients at 75 sites worldwide) than the study itself.
Cowger is the medical director of mechanical circulatory support and section head of the advanced heart failure program at Henry Ford Health, which includes six hospitals serving southeastern Michigan, including the Detroit area. The health system is very involved in clinical research with trials of all types happening concurrently.
Abbott’s TEAM-HF trial is designed to measure pulmonary artery pressure data using Abbott’s CardioMEMS HF System to identify advanced heart failure patients at high risk of mortality who could benefit from a HeartMate 3 left ventricular assist device (LVAD, or heart pump) earlier in their disease progression. “Everything I’ve done in my career has been dedicated to LVAD research or temporary mechanical support research,” Cowger says. “So, I've been working very heavily in the LVAD space, and that is why I've engaged in the TEAM-HF trial.”
The Abbott study isn’t the only one in which she’s currently involved. She explained that sometimes her role is called a PI and other times it’s called being part of a “leadership committee.” She’s a national PI on another VAD leadership committee, and she’s on the steering committee of one temporary support device and about four other heart-failure-related devices. For two of the latter, she also serves on the DSMB (Data And Safety Monitoring Board). “I do a lot of research, and get really involved,” she says with a smile. “I’m kind of nerdy, and that's my happy place.” Shockingly, Cowger says with this TEAM-HF trial, she may be the first female in the U.S. to be named co-PI of this large of a trial.
“NERD HERDING” TOWARD TRIAL DESIGN
As you can imagine, any PI role is a huge obligation that includes an immense amount of scrutiny and oversight, as well as planning. Cowger says she devotes time every day to the two national trials she’s involved with, including helping CRCs identify patients who are a good fit for a trial. Then, in the evening after her kids go to bed, she grabs a cup of tea and heads to her home office where she catches up on the status of studies; making sure recruitment is on track and answering emails about the various questions that may come up.
I asked her to walk me through the process of being selected as a trial’s PI and the subsequent trial design process. Often, she says, what happens is a sponsor will ask a potential PI to consult or be on an advisory board for an upcoming trial. “[The sponsor] will ask us questions and we will go back and forth poking holes in the protocol until we finally can identify which patients will benefit the most and what the most important endpoints will be,” she explains. “We decide what we’re testing for and for how long. Then, we’ll identify the sites and the people who are going to lead the trial. This process usually takes well over a year, and then there’s likely another year of recruiting and enrolling until you start the trial. If it's a device that’s never been tested, this process may take even longer.”
When listing best practices of trial design, the obligatory statement, “develop a good working relationship with the FDA” is usually uttered. Of course, there are a lot of nuances to how you execute that goal, and some people can get frustrated or even nervous about this step, not seeing the value in the collaboration and only focusing on the possible delays. Cowger is not one of those people. Instead, she relishes the review and validation a regulatory agency can provide, sort of like a fresh set of eyes on a trial design. “The individuals at the FDA are usually experts who have been doing this for a long time,” she says. “Sometimes they can come up with things that maybe through all of our “nerd herding” — as I call it — we just kind of lost sight of. The way I look at the FDA in this step of the process is that they are there to try to help. Sure, they're there to protect the patient, but they're also there to help your trial and make sure you’ve considered everything.”
In part 2, Cowger talks about her involvement with patient education for a trial like TEAM-HF, and why that — and consent — are a little different from a traditional pharma trial.