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May 28th, 2024

What a Medical Device Company Learned from Discontinuing a Clinical Trial

An Interview with Cook chief medical officer Dr. John Kaufman

About 20 years ago, Cook started working on a venous valve. Our goal was to create a long-term solution for patients suffering from chronic venous insufficiency (CVI) due to reflux by creating a synthetic valve to replace the body’s natural ones. For two decades, we tested different models and gathered data, including a trial in the early 2000s.  

Dr. John Kaufman, Cook’s chief medical officer

However, in December 2023, we decided to discontinue the trial. It was a tough decision. However, we feel it was the right choice, both for patients and for our company. Here’s what we learned from the experience—and here’s what we hope other life sciences companies can learn from it, too.  

Can you give us some background on the goal of this trial?  

Cook had been researching CVI and making solutions for it for decades. CVI affects roughly 40% of the US population, making it a huge patient population that currently doesn’t have any one-and-done cures. 

Several other Cook products address some of the complications of CVI, and the valve would have fit perfectly into our portfolio of vascular venous products, such as our Zilver Vena stent, Serenity balloon, TriForce® Peripheral Crossing Set and CXI crossing catheter. However, none of those products solved the root problem. We thought a functioning valve would be the most important part of caring for these patients, so our goal was to find a percutaneous valve replacement. Cook Medical developed a valve that functions similar to the way valves the veins naturally work. The artificial valve we made was a novel proprietary design that mimicked native venous valves. To test it, we began a global, multi-site trial.  

The first patient in the trial was treated in April 2023. The patient was treated by Dr. Mauricio Alviar in Barranquilla, Colombia, and the global principal investigator of the study was Dr. Paul Gagne. Our vision for the rest of the trial was that we would continue to evaluate safety, efficacy, wound healing, leg pain, and disability levels in patients over the next five years. 

What outcomes did you see from the data? 

As we collected data on the trial, we noticed a strange phenomenon in the clinical outcomes. Patients were reporting that they were feeling better. That’s a good thing—the only problem was that the duration of their improvement significantly outlasted the functioning of the valves. Patients were feeling better even in the absence of functioning valves. Traditional clinical outcome measures were not directly correlating to replacement valve function, raising concerns of demonstrating safety and effectiveness. Patients felt better, but the valve wasn’t functioning better.  

Ultimately, we didn’t cancel this trial due to adverse events—we only canceled the trial because patients were getting better irrespective of valve function. After 20 years in this space, we firmly believe that a replacement venous valve is not a complete solution to CVI. There may be room for it to be part of a larger set of solutions for this intricate disease state. CVI is more complex than we thought, and the condition will take more than a valve to completely solve.  

How did you decide to cancel the trial? 

We decided to cancel the trial because the data clearly showed that the valve was not feasible and was not benefiting patients the way we had hoped it would. Without data that connects valve performance to clinical benefit, there was no way we could definitively prove the valve’s effectiveness. There was no pathway forward for approval with regulatory bodies, which pushed us to cancel the trial.  

One of our Cook values is Continuous Improvement. We can’t continuously improve if we aren’t willing to change course when necessary. Twenty years of investment is a lot and it’s hard to leave. However, we prioritize patients, and if it’s not benefiting patients in a measurable way, we need to pivot.  

For context, how often are clinical trials canceled?  

Clinical trials are canceled more often than most people realize. In fact, only one in five clinical trials end up being completed within their original timeframe.1 About 90% of clinical drug development fails, too.2 It’s part of the innovation process.  

The significant change is that the life sciences industry is starting to be more transparent about clinical trials and more willing to share knowledge. The percentage of trials with no disclosed or available information as to why the study was terminated has been decreasing steadily over the past several years, dropping from 24.1% in 2010 to 8.7% in 2021.3 In a spirit of collaboration and transparency, we are also sharing the lessons we’ve learned from canceling our venous valve clinical trial.  

What did Cook learn from the clinical trial, and why are you sharing this publicly?  

One of the biggest lessons we learned was that traditional outcome measures were not capturing the outcomes patients were experiencing. Traditional measures were global and encompassed the whole leg. However, these measures weren’t specific enough to capture what this one small valve was accomplishing.  

We also learned that there are a lot of complexities in the venous system. Part of the struggle with this trial was that it was hard to find patients with singular pathologies with venous valve malfunction. Identifying the target population was much more difficult than expected. Most patients with venous disease have multiple comorbidities confounding the clinical benefit of an implantable venous valve, thereby limiting the target patient population. We realized that venous disease was far more complex than what a valve alone can fix, and we couldn’t enlarge the scope of the trial to cover it all. 

Over the last twenty years, we’ve also learned a lot about material science. Biodesigning a valve from porcine tissue took a lot of research that will benefit us in other areas. We’ve learned about material properties that supported the valve in both animals and humans, and we can share that information. 

We are sharing these learnings because research and knowledge are always valuable. Even though we discontinued the trial, the data is still valuable and can help us make better solutions in the future. We hope it will also benefit other companies that are striving to treat patients with venous conditions.  

What can physicians take away from this?  

If a physician is looking forward to a product in a clinical trial and then the trial is canceled, what should the physician think and feel? We understand if you’re a bit disappointed, but here are some takeaways we hope you gain.  

We must challenge our own assumptions. We had made assumptions about CVI and what would cure it. Physicians also frequently need to realize the assumptions they make about disease states and treatments and be open to failure and learning from new data. Disease states can be more complicated and have more factors than previously thought; keep that in mind when treating patients. Diseases that we thought we were familiar with and thought we understood may be more complicated than we realized. 

Even failures help advance knowledge. Any canceled trial can still provide more direction for future research. If you’re disappointed (as we are) about canceling a trial, there’s a silver lining that points us in the right direction for upcoming treatments.  

What’s next for Cook? 

Our next step is to continue to follow the patients who were treated. Although enrollment in the trial was terminated and will not be reopened, we’ll still follow patients for the planned duration of the study.  

In following the industry transparency trend and in our own commitment to data transparency, we plan to publish our findings externally. Companies tend to only want to publish their positive results, but publishing negative results is important too. Cook’s unique structure as a privately owned company gives us the freedom to be open—even about the less glamorous parts of innovation. 

We hope that what we have learned can benefit future efforts to help patients dealing with CVI. As we share this data, perhaps other companies will be inspired to be transparent with their data. If you are a physician, please share your personal experience treating patients with CVI. We can all learn from each other and build off publicly available data and make progress together.