Persistence, persistence, persistence: Lessons in device innovation from three prolific inventors

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Innovation from interventional inventors
Left to right: Lindsay Machan, Rodney Raabe, Aravind Arepally

Timothy Clark, director of Interventional Radiology at Penn Presbyterian Medical Center, Philadelphia, USA and co-founder and chief executive officer of Forge Medical, which has commercialised the Vasostat, radial artery haemostat device, interviews three interventional radiology “serial inventors”: Lindsay Machan (Vancouver, Canada), Rodney Raabe (Spokane, USA) and Aravind Arepally (Atlanta, USA) on their “Eureka!” moments, innovation, the rocky path to successful commercialisation, and current opportunities for inventors.

Biographies

Lindsay Machan is professor of Radiology at the University of British Columbia (UBC) and an unrelenting entrepreneur. He is the co-inventor of the first drug-eluting stent. He co-founded Angiotech (now Surgical Specialties), which developed paclitaxel coating and delivery technologies subsequently licensed to Boston Scientific and Cook Medical for their drug-eluting stent programmes.

Rodney Raabe recently retired from private practice. Throughout his prolific research and publishing career (he was the first to demonstrate a cognitive improvement after carotid artery stenting) he developed many new technologies and devices (eg. the Raabe sheath). He was the first to pioneer adhesive closure technology for treating saphenofemoral insufficiency for which he co-founded Sapheon (later acquired by Covidien/Medtronic).

Aravind Arepally is former associate professor of Radiology at Johns Hopkins University and currently serves as chair of Radiology at Piedmont Health System in Atlanta, USA. He is widely credited as the inventor of bariatric embolization as well as targeted transcaval portal vein delivery for islet cell transplantation. He is the co-inventor of the Surefire antireflux embolization catheter for which he co-founded Surefire Medical; the company’s device is sold and distributed throughout the world.

The treacherous journey from an idea to a product

Timothy Clark innovation and persistence
Timothy Clark, director of Interventional Radiology at Penn Presbyterian Medical Center, Philadelphia, USA and cofounder and CEO of Forge Medical

Interventional radiology colleagues and trainees often ask me about pathways for commercialising their ideas for improved devices, therapies and imaging technologies. It is a challenging process and one which is difficult to balance with the demands of a busy clinical practice or research programme.

My own background includes founding Forge Medical, a company which developed the VasoStat device used in the USA and Japan for radial artery and tibial artery haemostasis. I also spent years designing a high-performance dialysis catheter which reduces platelet activation and thrombosis risk (the Arrow-Clark VectorFlow), developing two push-button torque devices (the SeaDragon and SeaDragon2) and a suture locking device (the SlipNot).

However, the reality is that most of my inventions to date have not been commercialised. A partial list of those which have thus far failed to reach the market (despite exhaustive efforts including extensive prototyping and preclinical validation in animal models) include an inferior vena cava filter designed to prevent caval penetration and retrievable via either jugular or femoral veins, a pulmonary thrombectomy device, an adjustable-flow transjugular intrahepatic portosystemic shunt (TIPS) stent, a biliary benign stricture dilation device, a device for contralateral limb catheterisation during endovascular aneurysm repair (EVAR), and a semiautomated drainage catheter device.

I list these “failures” not to dissuade would-be interventional radiology inventors but only to illustrate that successful commercialisation of ideas is heavily dependent on persistence, timing, and fluctuating clinical needs and market demands. The cost and complexity of securing intellectual property can also be a barrier for many great ideas in interventional radiology.

Innovation is intrinsic to the DNA of interventional radiology. Every interventional radiology procedure that involves a particular challenge, hurdle, complication or failure can be seen as an opportunity to improve upon existing techniques and technologies to make them safer and more effective. I recently interviewed three luminaries who have successfully commercialised innovative ideas that emerged from realising unmet clinical needs in their everyday clinical practices. I asked each of them a series of questions revolving around the innovation process.

Finding three interventional radiologists who have succeeded in the invention process was not difficult as there are so many men and women in our field I know who have successfully done so. However, for this interview I selected three individuals whose contributions were for particularly unique and disruptive innovations.

Interview

Timothy Clark (TC): Was there a “Eureka!” moment for an idea which led to your product?

Lindsay Machan (LM): Actually, there was one. Back then, we were stenting the superficial femoral artery with early self-expanding stents and were seeing a huge problem with restenosis. One day our weekly vascular surgery conference was found to be short of a speaker. A medical student at UBC, William (Bill) Hunter, offered to present his summer research involving targeting inflammation in an animal model of rheumatoid arthritis. This involved the use of paclitaxel and similar agents to target the inflammatory component of joint destruction in what we now refer to as angiogenesis.

As Bill gave his presentation, my “Eureka” moment was the sudden realisation that if paclitaxel could inhibit angiogenesis, then it could potentially reduce restenosis if delivered locally using vascular stents. Bill and I soon teamed up and formed Angiotech. Early on, we saw potential for vascular devices including stents, embolic agents to release paclitaxel as well as a vascular wrap around surgical anastomoses. Obviously this was too broad at first, so we eventually narrowed our focus to developing just a drug-eluting stent.

Rodney Raabe (RR): I was doing a lot of neurointerventional cases at that time. After performing a complex paediatric central nervous system embolization case with another colleague, I got to thinking that glue remained a challenging embolization agent due to its low viscosity. It was a vascular “filler” but not something one could use to treat a very long vascular segment. I was also doing a lot of thermal ablation for greater saphenous vein (GSV) insufficiency. One day while performing a GSV ablation I thought “if glue (n-Butyl cyanoacrylate; NBCA) can be used for a wide range of vascular embolizations, why can’t we just glue the GSV shut? We just need to co-apt the vein walls and figure out the right glue viscosity.”

Aravind Arepally (AA): It was not really a single “Eureka!” moment; it was more of a step-wise process. Jim Chomas, my co-founder of Surefire, and I were contemplating a variety of device technologies around which to form a company. Jim was visiting a high-volume interventional radiology practice which did a lot of interventional oncology. He witnessed reflux resulting in non-target embolization during transarterial chemoembolization (TACE). We discussed this as to how much an issue this was in clinical practice. The more we looked, the more we saw. After I saw additional cases of pancreatitis and gastric ulceration among my colleagues, I knew we were onto something. Wanting to solve that clinical problem led to our antireflux embolization catheter.

TC: How long did you think it would take to commercialisation and how long did it actually take?

LM: We were pretty confident that we could do it in about nine months for less than US$100,000. In reality, it was closer to eight years and cost over US$20 million, including capital invested by industry. It probably would have taken even longer if not for serendipity and the amazing outcome of one particular patient.

He was a grandfather of several young grandchildren who developed dysphagia from advanced oesophageal cancer. He was constantly drooling which frightened his grandchildren. He told his physicians all he wanted was to be able to swallow so that he could play with his grandchildren and eat ice cream. He consented to enroll in a first-in-human trial of a paclitaxel-eluting oesophageal stent we had under investigation at that time. The stent insertion went very smoothly.

The morning after I inserted his stent, I went to his room and found his hospital tray table covered with empty ice cream cups and two of his grandchildren sitting beside him. I gave him a big hug and nearly burst into tears. It was a hugely emotional moment seeing him and his family so happy.

Nearly a year later, when he succumbed to his cancer, he had consented to an autopsy. The histologic findings of how paclitaxel had inhibited his tumour’s ingrowth was so compelling that the US Food and Drug Administration (FDA) allowed it to become part of our submission for eventual regulatory approval.

RR: We thought commercialisation and strategic exit would take a couple of years, and that the cost would be around US$500,000 (£378,000, €426,000). The actual time was closer to seven years and took multiple rounds of investment totaling over US$35 million, US$8 million of which we returned to our shareholders after the sale of the company. It turned out there was a lot of science and iteration needed to impart the right level of viscosity to NBCA and to developing a delivery system that made the embolization material visible with ultrasound. It became a huge undertaking and took us years. At one point we even had a full-time team of chemists.

What helped early on is that we partnered with a technology incubator affiliated with an academic medical centre. They were also able to assist with obtaining seed capital and really get the ball rolling. It turns out that they were independently working on a percutaneous venous ligation device, which really complemented our technology, so that they knew the space and the clinical need.

AA: We thought that we could approach this non-target embolization problem head-on and develop a device with US FDA clearance in one year, from concept to product.  In actuality it took about one and a half years, so we were not too far off.  Most people are surprised how quickly we did this. What really accelerated the process is that we partnered with a medical device engineering firm early on, and used dedicated engineering workspace within their facilities. As they were also a contract manufacturer of medical devices, they were able to help us navigate us through the design iterations to a commercially-viable design freeze.

TC: Do you think the opportunities for interventional radiologist inventors are better now in the era of consolidation within the medical device industry, or worse?

LM:  I think that the recent consolidation in the medical device industry is both an opportunity and a threat. Larger companies present increasing layers of bureaucracy which can make it difficult to navigate. This can be intimidating for a lot of physician inventors. On the other hand as companies merge, realign their business units and move forward, they can become hampered in innovation without ongoing physician input.

You cannot simply task a team of engineers and marketing people to come up with a new type of product line without knowing in depth what the clinical needs are. I also see this happening in academic medical centres who create centres for innovation, often with little to no physician input.

RR:  I would advise interventional radiology inventors to remember that we are a unique breed. Our culture of innovation is a big part of why we went into this specialty. Large companies need us, and there are too many people in their business and research and development ranks afraid of getting fired for taking on bold initiatives which do not pan out. This can lead to enormous inertia within their development programmes.

My advice to young inventors is to not give up, just keep on being creative. It also helps to do a small licensing deal or two early on in your career with existing companies. You will not make much money off the royalties but you will learn a lot from the device development process. You will also get a reputation within industry as an innovator.

AA: I think the challenges facing interventional radiology inventors are worse these days with the all of the consolidation going on within the medical device industry. There seems to be less innovation and less willingness to take risks compared to when there were more small and mid-sized companies. The regulatory pathways for US FDA clearance and European CE mark approval are also getting more complex and expensive. However, interventional radiology as a field is full of entrepreneurs, and entrepreneurs will always find a way.

TC: Thank you, gentlemen, for sharing your insight and perspectives. It seems the message to innovators is to accelerate the development of your idea through collaboration and using outside resources such as medtech engineering firms and incubators. If there was one word which summarises what is required to successfully commercialise an idea to a product, what would that be?

LM: Persistence.

RR: Persistence.

AA: Persistence.

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