The Case For Research-Naive PIs

By Dan Schell, Chief Editor, Clinical Leader

I’ve lost count of how many times I’ve heard the same refrain at conferences: We’re running out of experienced PIs. The pipeline is drying up. Veterans are retiring. Younger physicians aren’t interested. Everyone nods. Everyone agrees it’s a problem. But, rarely does everyone agree on responsibility.

That tension sits at the center of my recent conversation with Carrie Lewis, executive director, clinical program optimization, at Keenova (formerly Endo), and a longtime Clinical Leader editorial board member. For years, Lewis has pushed sponsors to rethink their aversion to research-naive principal investigators. Not as a theoretical exercise, but as something she has personally championed, resourced, defended internally, and then taken on the road — often to rooms full of, what I’m guessing were, skeptical sponsors (I attended some of those conference sessions).

“Over the course of my career, I kept hearing people says that PIs are going to retire, PIs don’t want to do this [clinical research], and we’re going to run out of them,” Lewis said. “But everywhere I worked, no one would let you bring in fresh PIs or sub-Is, and no one was really doing anything about it.” Her argument is simple and uncomfortable: The industry complains constantly about the PI shortage, but very few sponsors are willing to invest in fixing it.

How One Naive PI Got In The Door

The example Lewis is best known for didn’t start with a strategy deck or an executive mandate. It started at breakfast.

While attending a podiatry conference alongside colleagues from clinical development and medical affairs, Lewis met a physician who had never run a clinical trial but was deeply engaged with the science. research andew the approved drug well, had ideas about future research and had actively reached out to multiple companies looking for opportunities to get involved.

Most of them never called him back.

When that fact came up in conversation, the assumption was predictable. He’s naive. You wouldn’t want anything to do with him. Lewis’ response went the other direction.

“You could see the passion right away,” she said. “He brought his notes. He was talking about our product. That resonates with me.”

What followed wasn’t blind optimism. A dedicated site relationship manager visited the practice, spoke with the PI and his staff, and laid out exactly what participation would require — equipment purchases, calibration, staffing realities, and the financial risk involved. Nothing was hidden. Nothing was subsidized. The site still had to qualify like any other.

Lewis is quick to emphasize that this wasn’t about lowering standards. “We’re not promoting just taking anyone who wants to do research,” she said. “You have to give people a chance, but you also have to talk to the staff. If they don’t have the time or interest, it’s not going to work.”

Why Support Matters More Than Experience

If there’s a recurring theme in Lewis’ experience, it’s that experience alone does not guarantee quality. To me, the quiet hero in this story was the site relationship manager — a position Lewis says far fewer sponsors have than many people assume. This wasn’t a CRA or CTM calling because something was late. It was someone whose job was explicitly to ask, “What can I do for you?” — and mean it.

For a research-naive PI, having that kind of person on staff is super valuable. Early on, the physician called frequently. He asked questions. He double-checked decisions. From a traditional efficiency mindset, that behavior can look like a liability. From a quality standpoint, Lewis saw the opposite. “He’s the one who’s going to call and ask questions. He’s the one who’s going to double-check,” she said. “There are PIs you work with for years who don’t call you at all. They just assume they’re doing it right.”

Over time, as confidence grew, the calls tapered. The attentiveness didn’t. The site’s deviation profile wasn’t abnormal — and certainly wasn’t worse than veteran sites that had been running trials for decades.

ROI Anxiety, CRO Concerns, And The Myth Of “One-And-Done”

Every time Lewis presents this story publicly, the same objections surface:

• Isn’t it expensive?
• Doesn’t it slow timelines?
• What does your CRO think?
• How do you know you’ll get ROI?

Her answer to the ROI question is refreshingly direct. “You don’t know that with KOLs all the time either,” she said. “I’ve had great success with some, and some don’t recruit at all. There’s no site you bring on that you’re 100% confident in.”

In this case, the CRO wasn’t resistant. They were involved early, budgeted for enhanced training where appropriate, and treated the site like any other during qualification. The only real friction came later, when the PI leaned heavily on the sponsor-side relationship manager instead of the CRO team — a boundary that had to be clarified, not eliminated.

Lewis also sees this work as directly connected to the industry’s fixation on the so-called “one-and-done PI.” Clinical Leader has explored that dynamic before, including in “The One-And-Done Investigator: A Clinical Trial Story” and “The One-And-Done PI: Measuring The Current Site Landscape.” Her experience reinforces a key takeaway from both: Many physicians don’t leave research because they failed — they leave because momentum disappears between studies.

“He is having trouble getting his next study,” Lewis said of the research-naive PI she worked with. “This is a common problem. That’s why we focus on helping our sites build connections. We believe collaboration is essential, not just for individual success but for advancing clinical investigation as a whole. Supporting these efforts may go beyond our formal role, but it reflects our commitment to strengthening the field.”

The Uncomfortable Truth Sponsors Keep Avoiding

Here’s the part of the conversation sponsors tend to resist: Most of what makes research-naive PIs successful has nothing to do with AI, new platforms, or radical operational redesign. It comes down to communication, expectation-setting, and giving someone permission to ask questions without being labeled “high maintenance.”

Lewis doesn’t pretend this approach scales endlessly. Even she says that if every sponsor brought on just one truly naive PI, it would meaningfully help the industry. “I really don’t think it’s that much extra work. But when you have a passion for something, it doesn’t feel like extra work.”

The real barrier isn’t operational; it’s cultural. Bringing in a research-naive PI forces sponsors to confront how much of their comfort comes from habit rather than evidence. And once you do it successfully, it becomes much harder to keep saying, “That’s not our job.”