Designing Medtech Clinical Trials For Approval & Beyond
A solid clinical study does more than get you regulatory approval — it sets your device up for market adoption. Explore insights from medtech leaders who’ve designed trials with payers, acquirers, and real-world success in mind.
Your endpoints define your success: Once you get an approval, you can’t go back. When picking your primary endpoint, focus on the claims you’ll make, the patients you’ll serve, and how your device will stand out in the market.
Prove for the real world: Clinical trials take place in controlled environments, but payers and providers need to know your therapy works in everyday practice. Avoid being biased when picking your patient population in order to show your treatment can deliver reliable results in the real world, too.
Be open and transparent: Honesty and clarity will get you much further than trying to outsmart the regulatory system. Regulators can spot shortcuts and sidesteps a mile away. Address challenges head-on to build trust and maintain your momentum.
Cascade secondary endpoints strategically: Start with the most direct measure of success—what your device is designed to do—but don’t put all your weight on a single endpoint. Build a sequence of secondary endpoints that progressively strengthen your hand.
If you’re not the pioneer, be a game-changer: Learn from those who came before you to avoid mistakes and reduce risk, but don’t settle for small improvements. Being late to the game isn’t a problem if you bring something that’s truly transformational.
Think Beyond the Approval
Dr. Eric Fain began his career with startups developing implantable defibrillators at Ventritex. He held key leadership roles as the company grew, through its acquisition by St. Jude Medical, and later Abbott, where he served as Group President. He’s now the President and CEO of Procyrion, where the team is developing a percutaneous mechanical circulatory support (pMCS) device. It’s a novel, minimally invasive heart failure treatment for patients who don’t respond to traditional therapies.
Eric likes to think like an acquirer, even in the clinical phase. “It always starts with the study design—thinking about the clinical evidence you're going to have at the end,” he shares.
“Think about the claims that you're going to want to make about your device, when it's approved,” Eric notes. After FDA approval, you have to stay within the guardrails of the data you have to support your claims. Take the definition of the target patient population, for example. Your device should clearly outperform standard care on your defined subgroups. This is one way you lay the groundwork for future opportunities from the very beginning.
Acquirers need to see that they can pick up and gather even more evidence with your device. That’s why you need to signal what’s next—to demonstrate scalability and vision. For example, beyond primary effectiveness endpoints, consider secondary claims that may resonate with physicians, hospitals, or payers.
Thinking like an acquirer from the start means aligning with FDA, considering the end claims you want to make, and designing studies that give you the best possible chance to hit your goals. This will better position your startup for not only regulatory approval, but also for market success and a greater possibility for an eventual acquisition.
Insurers are Your Customers
Jason Hannon, a Stanford-educated attorney turned medtech executive, has built a reputation for driving innovation and growth in the medical device industry. Over 12 years at NuVasive, he rose to Chief Operating Officer, helping the company achieve groundbreaking revenue milestones and solidify its position as a frontrunner in the space. In 2017, Jason took the helm as President and CEO of Mainstay Medical, where he is leading the commercialization of ReActiv8, a first-of-its-kind neurostimulation device targeting chronic mechanical lower back pain.
Jason underlines that reimbursement is the ultimate gatekeeper in healthcare. He explains: “You have to anticipate what payers will need because you can’t go back and rerun the study.” Start by consulting medical directors from multiple payers to understand their priorities. While no one will give you a binding commitment, broad feedback helps you understand their goalposts and what data points matter most. “Think of insurers as customers—figure out what they want so you can deliver it,” Jason shares. “Our first senior hire was a head of reimbursement,” Jason adds—it’s not something you leave for later.
One thing he learned through his interactions with such consultants is not to pick your control groups in a biased fashion. “Patient selection shouldn't just be written to optimize the study,” he explains, “It's to be written so that in the real world, you can actually pick these patients.” That’s why his team designed a study largely based on the input from medical directors at various payers. “We have real-world data showing that when you turn this therapy loose, physicians will be able to get the same results,” he shares. One of the best ways to prove this out is to turn the economic analysis over to an independent party. Third-party validation addresses skepticism about perceived bias while building trust and credibility.
Transparency Beats Cleverness
Timothy Boire and Geoffrey Lucks co-founded VenoStent to improve dialysis access. Timothy’s background includes a PhD in Biomedical Engineering and research experience in biomaterials, while Geoffrey combines expertise in bioethics, finance, and venture capital. Their flagship device, SelfWrap, is a bioabsorbable vascular wrap to reduce complications and improve the success rates of arteriovenous fistulas (AVFs) for chronic kidney disease patients. They’ve already completed chronic large animal studies, a 20-patient trial overseas, and are now running a 200-patient randomized controlled trial to bring SelfWrap to market.
The duo’s first advice, before diving into trial design, is to invest the time to understand the landscape. “Look at all the other trials in the space, what worked, what didn’t, and why,” says Tim. “Our superpower is learning from others’ failures,” Geoffrey adds. For that, studying existing research, clinical endpoints, and various technologies is paramount.
Building confidence in your solution starts long before clinical trials. For VenoStent, this meant chronic large animal studies, computational modeling, and biocompatibility testing before initiating their first 20-patient clinical trial. Moving step by step and demonstrating success at each stage, you can build a strong foundation of evidence and pave the way for larger trials.
Getting FDA feedback can be a humbling process, as Tim and Geoffrey learned during a grueling pre-submission meeting. “It was absolutely humiliating but incredibly valuable,” Tim recalls. But no matter what, transparency is a cornerstone of clinical development. “It’s easy to get frustrated with their feedback, but you really need to take the time to understand where they’re coming from and address it point by point,” Tim advises. In VenoStent’s case, their team was able to gain a Breakthrough Designation after demonstrating promising six-month data, following FDA’s specific recommendations.
Focus on What You Can Control
Amar Sawhney is a serial entrepreneur and inventor whose innovations have impacted over 8 million patients worldwide. He has over 120 patents in absorbable and biocompatible materials across surgical applications. His previous ventures have brought game-changing products like SpaceOAR, DuraSeal, and Dextenza to market.
Today, Amar is the driving force behind several life sciences companies, including Instylla, Rejoni, Sealonix, and Pramand. At Instylla, Amar and his team are taking on embolization with Embrace, an aqueous, absorbable liquid embolic designed to shut down blood flow without leaving permanent materials behind. With a pivotal clinical trial underway, Instylla is close to delivering a solution that could transform how hypervascular tumors are treated—and redefine what’s possible in embolization therapy.
Traditional trials often involve a separate pilot study, followed by a pivotal study, adding significant delays. Amar recommends building adaptive studies with a pilot phase included. “We do 10-15 patients, report back to the FDA, and then progress to the full protocol,” he explains.
The closer your primary endpoint reflects your device’s core function, the greater your chance of success. Amar offers a clear example: “For an embolic, the endpoint is the cessation of blood flow—it’s simple and direct.” Moving too far from your device’s purpose, like focusing on tumor regression or survival rates, introduces external variables and noise, increasing the risk of failure.
Avoid committing to endpoints that hinge on factors outside your control, especially pre-market. Amar recalls a women’s health trial where preventing uterine adhesions was the primary goal, but FDA pushed for fertility outcomes. Instead of combining them, Amar split fertility into a separate, consented study. “If you sign up for endpoints like that pre-market, you’re dead,” he warns. Stay focused on what you can measure and influence directly.
When setting up secondary endpoints, start with the most achievable and progress to the more complex. “If you naively start with the hardest metric, you’ll fail,” Amar cautions. For example, in a lung sealant trial, they began with treating individual lesions, then expanded to more challenging measures like chest tube removal. A well-designed cascade ensures you build credibility step by step. By layering these endpoints in order of difficulty, you create a structure that increases your chances of meeting at least some of your objectives.
Balance Technical and Regulatory Risk
Brian Fahey, co-founder and CEO of Adona Medical, has a PhD from Duke University and experience as a Stanford Biodesign alumnus. He has led ventures spanning critical care, oncology, and neuromodulation. He also founded Niveus Medical, later acquired by Stryker, where they improved recovery outcomes for ICU patients, and held leadership roles at J&J Innovation and Arrinex.
Adona Medical is a Shifamed portfolio company. Their interatrial shunt combines therapeutic and diagnostic capabilities for heart failure, like adjustable flow control and integrated sensors for real-time, remote pressure monitoring. With a $33.5 million Series C funding round secured, Adona recently completed its first-in-human study.
Instead of being a first mover in an unknown therapy class, Brian prefers learning from others who have already paved the way. “We’re not the first company in heart failure to run pivotal trials—we’re learning what works and what doesn’t,” he says. This helps him identify the crucial metrics such as the right patient population, endpoints, dosing, and timing.
While learning from others minimizes clinical or regulatory risks, it increases the pressure on technical execution. If the clinical path is clearer, the product itself has to stand out. “If you’re only 30% better and you’re five years late, that’s not enough to disrupt the ingrained momentum of the pioneers. If you're going to be late, you have to be transformational,” Brian notes. If you’re entering an established market, your product must offer undeniable value to overcome existing momentum and set a new standard of care.
Brian’s ultimate lesson is about ambition: a clear clinical path isn’t enough if the product doesn’t deliver exceptional results. “If you’re going to be late, you have to obsolete everything else. You have to be a next-generation version of therapy,” he says.
Final Thoughts: Strategic Clinical Design Can Set the Stage For Growth
A solid clinical study does more than get you regulatory approval — it lays the foundation for market adoption.
Success starts with setting the right endpoints, proving your device works beyond controlled trials, and maintaining transparency with regulators. A thoughtful approach to study design — one that balances strategic endpoint selection with real-world applicability — can build credibility and maximize your chances of market impact.
Whether pioneering a new space or improving on existing solutions, the goal is the same: bring something truly valuable to patients and providers.