Innovations In Ostomy: Measuring Sh** For A Living

14 min reading time

Innovations In Ostomy: Measuring Sh** For A Living

Presented by Michael Seres, Founder & CEO, 11 Health at the 10x Medical Device Conference – San Diego 2019

Reading Time: 14 minutes


The video and transcript follow.

Michael Seres: As you’re probably all aware, about 133 million people in the U.S. live with long term, complex chronic conditions. So it’s a huge burden of cost to the healthcare system that continues to spiral out of control.

And really, we have to think about a healthcare system that moves from reacting to problems to one that prevents problems. And my company, 11Health, which I get the privilege to talk to you a little bit about today, focuses on those people connected to medical bags, and specifically as Joe said, ostomy bags.

In case you don’t know, and hopefully you’ve digested the beautiful lunch, an ostomy is basically where part of your intestine, part of your bowel is brought to the outside of your body and you literally go to the toilet in a bag.

My son, sitting at the back with the mobile phone, takes great pride in telling his friends that his dad measures shit for a living. I might have put it a little bit more eloquently, but then he’s 21. Actually, 11Health now is the only company that analyzes what comes out the body, to determine how we think about what we put back in the body. Let me explain to you a little bit why.

About Me

I was diagnosed with the incurable bowel condition, Crohn’s disease, age 12. I had my first surgery at 14, and 25 further surgeries later, an intestine – most of you might know starts at around six foot in length – ended up at 40 centimeters and stuck to my pelvis. I was in what’s called intestinal failure; kept alive through intravenous feeding for 22 hours a day.

Then, on October the 8th, 2011, at exactly 6:01, I kissed goodbye to my wife and didn’t know if I’d see my kids again. And I became the 11th intestinal transplant patient in the UK at a hospital in Oxford. Since that moment, I’m a two-time cancer patient and currently waiting on a stem cell transplant.

So, now you know my background and you know more about my insides than most people know about my outside, you’ll understand why 11Health is not simply about making money. It’s about the ability to make a difference to someone else’s life. I’ve been connected to medical bags of a different variety for about 35 years, and so I’m also a customer of 11Health, so to speak.

As Joe very eloquently put, you go home after ostomy surgery not just with sheets, but a plastic jug, and with a request from your doctors: “please measure your shit in this jug and tell us how much is coming out your body.” Because unless we know how much is coming out, we don’t know what to put in and you’re going to be readmitted on a regular basis.

The reason I put this slide up is actually the icons you can see to the right, because the icons to the right, as we talk about medical devices and we talk about solutions in healthcare, are really how I live my life today as a 21st century patient and about how we all are going to start to live our lives in the future.

How we interact with patients is very different today to, perhaps, how it has been in the last few decades. The National Health Service, NHS, is the UK National Health Service that saved my life. The doctors you see up there. But there’s also a lot of social media icons. That’s where I met Joe, obviously online, not Tinder, or Grindr, but, I swiped left. Didn’t work. But no, Twitter, YouTube, Google, Skype are really all how I consume my life today; and it’s really about building a toolbox, a kit for patients and how we interact.

And now as I’m a patient in the U.S. health system, I get to see the difference between healthcare that’s a right and healthcare that’s a privilege. But we won’t go into the politics of that. But fundamentally, healthcare, for me, is just a series of relationships. It’s not actually about the device or the technology or the compliance. It’s about a series of relationships. And the closer you get to those relationships the closer your outcome will be. Because as a patient, from my perspective, I don’t actually want to consume health. I want to consume my life, and I want to live my life. And I want to have the tools and the equipment and the technologies and the devices around me to allow me to engage in life, not have to think about health the whole time.

The Market Problem

So, why medical bags? A few facts for you that might actually be quite interesting.

The ostomy market itself is a $14 billion market. That’s a lot of shit. And it’s part of a wider medical bag market. There are about five million patients around the world, one and half million patients in the U.S., and 130,000 people will have a bag attached to their body every year in the U.S.

For those of you who may have experienced it in your lives or know families or friends that do so, the challenge with managing a bag is they do burst. And they do leak, and they do spill. And, as Joe mentioned, your nerve endings are cut, so you don’t actually know when it’s going to happen. So, quality of life for patients in that situation is quite a challenge.

Just to give you a few facts and figures, because we’re in that industry. An ostomy, of which there are three types, but the two biggest, colostomy (closest to the colon) and ileostomy (further up the body) are the number one and number three most readmitted surgeries in the United States. So, huge problems.

84% of patients have skin, wound issues, lots of complications. And there’s no standard of care, sadly, for patients living with bags. It’s quite an antiquated sector, generally coming out of people that have bowel cancer or inflammatory bowel disease. So, quite well-known, quite established conditions.

And actually, it dawned on me, lying in bed in Oxford as these bags were leaking, that healthcare companies in this sector have actually had long enough to try and fix the problem. But what we see quite often is, we build further products to patch a problem the previous technology or the previous thing has created. And, actually, why are we doing that?

There are 2.1 billion dumb bags produced a year. That’s 2.1 billion bags that are causing other things to happen that we can then layer it on with other products and sell more things. And we can just spiral and spiral. So, you have to be a little bit crazy to think you can fix it.

11Health’s Solution

So, what we did was, at 11Health, we built a smart bag. We dissected an ostomy bag; we put sensors and technology in the bags to actually try and measure what’s coming out in real time. And see how we can get from there, we can start to pick up early warnings of the leaks and spills and infection markers, et cetera.

The big challenge everybody is talking about in healthcare is data. What about all that data? What about all that technology that’s coming out? What about that information we all know everybody’s thinking about, data? How do we manage it? How do we deal with it? And, oh my goodness, what about HIPAA and compliance around data?

There’s an interesting fact out there that the majority of patients share more of their healthcare data on social media than they do anywhere else. So, as a long term patient, there is nothing I wouldn’t share of my data to give me an opportunity to live a longer life. Or be at a school concert with my daughter or be at my kid’s events. Because actually, what happens when around data is, we get caught up with a vocal minority who say we can’t share this and we can’t share that. And you’re absolutely right. There has to be standards and there has to be opportunities.

But, actually, sharing the data gives us an opportunity to find solutions. What we happen to do in ostomy is create the largest data set of information so that we can actually try and deliver a solution. And what that allows us to do is work out in real time not only what’s happening from the bag but what’s happening around contextual data. Because just as important to people on devices and people on equipment is, what’s happening in your everyday life? When are you consuming your food? Are you sleeping, are you eating, are you walking, are you talking? All the information we can pick up from Fitbits and Apple watches and this and that.

But how do you bring it together to look at a patient’s life in the whole? How do you think about putting that together? And then what is the difference between clinical data, clinical evidence, and real world data? And how does the industry and how do clinicians and how does the FDA and how do other bodies look at the difference between clinical data and real world data?

For me, it’s the combination of two that actually allows us to deliver some personalization around healthcare. Because as we move to a healthcare industry that’s going to be about outcomes, about value-based care, moving away from fee-for-service to bundle payment models to outcomes, we have to understand what’s important to an individual in order to deliver those outcomes. And you can’t do that without talking to the individual.

Sources of Your Data

I mentioned to you that we share more of our data on social media. In fact, only 16% of our data comes from a health environment. The rest of it comes from outside, our real world. And as you can see on the top right there, it’s Google and Facebook. And the others are starting to try and predict trends.

So how do we use that data to deliver better outcomes? Facebook and Mark Zuckerberg conducted an organ donation campaign on Facebook. It got more people registered for organ donation than any other healthcare campaign in the history had ever done. So, we have to think about where all this data is coming from.

11Health – Combining Technology and Human Interventions

At 11Health, I think what I’m particularly proud about is how we then interact and what we do. And this is the combination where you see technology and human interventions. What we have the privilege to do is buddy up a brand new patient with an osto-mate.
From pre-op to the continuum of care, they get a buddy; they get a support network. They get someone who lived that experience, who’s not only using the technology but has walked in their shoes. Part of pre-op set up, and we now have 40 patients that have gone through our health coaching program.

As you’re starting to see with Medicare and other commercial pairs, you can start to bill and get reimbursed for patient coaching. And we can start to see how that changes outcomes. As an example, with our coaches, we’ve been able to reduce the clinical interaction by 40%. We’ve been able to take a readmission rate of about 30% of patients in the first 90 days down to zero, through a combination of technology and human intervention.

It’s not rocket science. Because the single biggest reason patients like me get readmitted is dehydration. Can’t stay on top of fluid balance. Too much output, not enough input. Logic to most people. Most of you will go, “I feel a little bit thirsty. Maybe my lips are dry or maybe I’m feeling a little bit tired. I’ll take onboard some more water.” Patients like myself can’t absorb that. We can’t regulate our fluid balance in time. So constantly you’re dehydrated, you go back. IV hydration, $16,000 of costs. How do we prevent it?

The New Gold Standard in Patient Care

Well, we can actually prevent it with a combination of human interventions. And what we’re trying to do is deliver a new gold standard. Because what also strikes me as you start to build solutions and we start to all think about how we build new technologies and the impactive devices – how many different standards are out there?

Just by way of a little anecdote. We were working at Cleveland Clinic. Cleveland Clinic have 18,000 ostomy patients and 21 colorectal surgeons and no standard of care. Every single person from every single different surgeon will be discharged with a different protocol. And a different way of doing it.

So how do you cope in that environment as a patient? And also, how do you build a solution, that doesn’t have a standard of care? Well, that’s where it goes back to, hopefully, the data and the ability to do things.

Patient Innovation

And as I come to the end of my talk, because Joe told me to be brief-ish, I wanted to raise a couple of challenges with you guys today as you think about it.

In healthcare, we have amazing people that deliver amazing solutions. You know, healthcare is predominantly paternalistic. The very best go to med school, trained unbelievably well, and we have to deliver a solution. But, as an end user, that solution is always given to us. It’s not often co-created with us.

So as we start to think about designing and developing solutions of the future, why wouldn’t we ever start with the end user? Why wouldn’t we ever build a solution from all those end users? Because in my case, the end user is me, the patient. But it’s the surgeon who’s operating. It’s the nurse who’s got to deal with it. It’s often the CIO, because I’ve got to integrate the data. It’s regulatory and compliance. Why wouldn’t we sit around the room together at the beginning and build a solution from the ground up?

In almost any other sector outside of healthcare, we start with the end user. Tesla wouldn’t make an update if it wasn’t what the customers wanted, et cetera. So my challenge back is, as you build CEOs, CIOs, chief nursing officers, chief this, chief that, why wouldn’t you have a chief patient officer on board?

There’s a movement in the U.S – #WeAreNotWaiting. It was created by a great friend of mine, Dana Lewis, who’s a diabetes patient, and she built an artificial pancreas and is now partnering with Medtronic in building that. There’s Sara Riggare, a Parkinson’s patient in Scandinavia, who effectively built the quantified self-movement. She sees her doctor once a year. Everything else is monitored through her Apple watch and other gadgets.

So there’s this movement of patients. Patients like me going, “We can’t wait for all you guys and all the companies to build solutions. We have to do it ourselves.” I live with a 50/50 survival rate. That’s the odds I live with every day. I can’t wait for years for a sector to come up with a solution.

So this is my last slide. My final request, other than putting chief patient officers, on all of your companies and boards, et cetera – Why are we not obsessed? Why do we not start with an obsession with the end user? We have to think a bit differently to change healthcare. Thank you very much.

[Applause]

Q&A

Joe Hage: As a performer in a chorus, when we sing a ballad, the audience is just like, and there’s this pause before they applaud. And that’s how I felt about your presentation. Because it was so personal and so relevant. And my first question is not for you.

Michael Seres: Good.

Joe Hage: It’s for your son. So you’re going to have to put down your phone. 21 year olds, I mean, am I right?

Michael Seres: Please embarrass him.

Joe Hage: First, I’ll ask a question, to which I know the answer. Are you proud of your dad? But then, a quick follow up, I understand you’re 21. Dad’s been having surgery as long as you’ve been alive. What’s it been like for you and the family? Please stand, introduce yourself and tell us what it’s like to be the child of patient like that.

Nathan Seres: So I’m Nathan, and I’m his son. And, I would say it’s been tough, but I have an extremely strong dad. I want to say just dad, but my mom as well. They’re both incredible. And I work for him now as well. I’m the digital content producer for his company. So, good things come from bad things basically.

And he hasn’t made it hard for me, you know, there would be Sunday visits. Every weekend after my Bar Mitzvah, we’d go up to the hospital and see him in bed, every Sunday. And my mom would stay up, stayed up there for, I think, about 8 weeks. But, we were around a community of people that helped us and people that loved us and, you know, supported us. And it wasn’t hard because they made it easy for us. Yeah.

[Applause]

Joe Hage: So, I’m sure there are other questions. But I do want to ask you, I recognize this has been basically a life-long journey for you. And you mentioned, you were diagnosed with Crohn’s at age 12.

So, even at that stage, it’s been part of your entire adult life. You have the skills needed to become an entrepreneur for a business that’s so meaningful for you. I think it’s a rare situation, certainly as a teen, that someone would be diagnosed with such a situation and, then, make it his life’s work to do something about it. Can you talk to us, just briefly, about, did you then go to school and say, “I’m going to be an engineer,” or “I’m going to enter medicine”?

Michael Seres: Ah, no, I really didn’t. All I wanted to be was a soccer player. And, then, realized I was pretty shit at that, so that was never going to happen. Excuse my language.

Joe Hage: We’ve been talking about shit the whole time, so you’re fine.

Michael Seres: I think the truth is there were two defining moments. One, I was 14 at the time, I went to see a gastroenterologist who ended up becoming the Queen’s physician. So, I guess if he could stick a tube up the Queen’s backside, he could do it to me, it was fine.

Joe Hage: Classy.

Michael Seres: Classy. But he said to me as a 14-year-old, “I won’t take you on as a patient unless we’re a team. You’re going to teach me as much about what it’s like to be you, and I’m going to teach you what it’s like to be me, and we do it as a team.”

And, then, when I went through transplant, my surgeon said the same thing, “This doesn’t work. You won’t survive unless we do this together.” And after transplant, I was given the greatest gift, another life. Out of some family’s worst possible moment, they gave me the chance of another life. So the opportunity to give back is huge. That’s the mission. It’s just to give back to something.

Joe Hage: What became of the 10 before you?

Michael Seres: Three are still alive. And, I was actually the first of a re-started program at Oxford because survival rates hadn’t been good. But I had an amazing surgeon, a guy that came from Miami. Came from Miami Jackson Hospital and re-started the program at Oxford, a genius. And, yeah, my best friend, we speak every week.

Joe Hage: Just the idea of it, I mean I’m sure everyone has someone in their life. I’m thinking if I were to kiss Beth goodbye and say, “I don’t know if I’ll ever see you again.” I mean, you must have just been terrified.

Michael Seres: Yes, of course, but I had absolute trust in my medical team. And I think, there isn’t a person in this room who hasn’t faced challenges or their family faced challenges of different degrees. Everybody will have had something. And so, you choose which way, you either go left and you give up or you go right and you get on. And you know, I’m lucky like that.

Manish Sharma: Manny Sharma. It’s very interesting about you, which I find fascinating, is you had a near-death experience literally, right? That’s why you had such clear perspective on what it makes work. And that’s what I find when we look at medical device industry. Patient centricity that we all talk about it, but not most of us are able to do it. We always think physician is our customer. But really, patient is our customer.

But only folks who have that near-death experience does it truly understand where the value really lies. Whose life really matters. Can you talk a little bit about, as you’ve taken this journey, like what is your advice to device companies and others? Once you have all of these, and you’re talking to them about creating a chief patient officer. But they can’t get out of their own way, because they’re still doing the things the way they are doing. And only the folks like you who have that type of experience have the clarity of thought, what really matters.

Michael Seres: I think, it’s also very hard because, if you’re building a med device company from a company perspective, you have to follow the money. And, ultimately, you get focused on – how am I going to get paid and how am I going to get reimbursed?

But I think you’ve got to have clarity of, why am I doing this and who am I doing this for? And quite often, the patient isn’t the only end customer. The physician is a customer. The payers are customers in their own way, and patients or others.

And I think what’s happened over time is, that’s got skewed so heavily towards physician and payers that the patient has, in a sense, been an afterthought, or just re-delivering a solution.

I think the advantage people like me have got today is, the healthcare trend is moving towards the consumer. It’s moving towards the patient. We are making more decisions. We are much more informed than we ever were in the past. And love it or hate it, Google and other things, we all come to the table now with a different mindset.

The challenge for medical device and for anybody in the medical sector is, in a sense, are you brave enough to engage with patients? It’s really hard for them to move, effectively, 180 degrees now. But I think, those that don’t will be the ones that won’t survive. Because the power now is going into the consumer’s hands. It’s coming away from physicians, fee for service is changing. Value-based care, outcomes-based care, how do you know how to deliver a solution for an outcome unless you ask the end user what outcome’s important to them? So I think the timing is also important.

Joe Hage: I’m so glad you joined us today, Michael. Let’s hear it for him.

[Applause]

Will hospitals break a contract to adopt your technology?

9 min reading time

What You Need to Understand Before You Sell That Device to My Cardiologists

A discussion between Joe Hage and Mahesh Mulumudi, MD. at the 10x Medical Device Conference – San Diego 2019

Reading Time: 9 minutes


Mahesh Mulumudi, MD was cath lab director before he became the Chief of Cardiology. Now he’s Division Chief of Medicine for Providence Regional Medical Center.

So if he likes your medical device, you’re in, right?

Not so fast. 😟

Mahesh Mulumudi, MD: The question that Joe asked is a pretty broad one: “How do you sell a device to a cardiologist?”

I’m old, but not that old yet. And even when I started practicing cardiology 2005, the dynamics of how sales forces interacted with a provider, with the cardiologist or any any surgical specialist, for example, was very different.

The olden days

They would approach us with a product, be it a new stent, or a new catheter, or new needle, or any simple things. They would approach us and they would kind of grab us between cases. We’d be in scrubs and say you want to grab a cup of coffee, and – sure – and buy me a cup of coffee, sit down, talk about the product. They will say how this is so different from the one next to you.

And then they would ask me. Your influence is basically your volume.

If you’re a high-volume operator, you got a bunch of influence in the lab. It’s ‘volume speaks.’

So I used to be a high-volume operator from the very beginning. So they would come to me even though I’m very junior member in on the team, they would ask me, How can I get the product into the lab? This is the classic thing.

Then I would approach the cath lab manager and the cath lab directors, medical director. And it used to be okay, well, let me leave you a few devices with you and wanting to give them a try. And if you like it, we’ll talk about a contract.

This was the process. This was this was true for a few years, and at the time was very, very true. And it was easy, in a way, because I felt good because I’m having some influence on what comes into the lab or doesn’t come into the lab. The sales force for the device company was feeling good, because they could approach me and get something in front of me directly, the operator.

The shift came in 2010

The shift for me, at least for my institution, started happening around 2010. There was a big shift.

And by the time I became the cath lab director, I became the chief of cardiology, I became the chief of medicine, of the entire division of medicine. So I had a little bit of a contractual influence. I started sitting at the contracting table. And the situation changed very differently.

The system started consolidating hospitals into larger entities. And these larger entities want to control the price of the product coming to them.

So they decided that reps cannot contact the providers directly.

Although people ping us and meet us and all this stuff. But most of the cardiologists today – it’s true with every specialty, by the way, this is at least I can speak for the system that I work for and work with.

I work with the Providence St. Joseph’s system, which is a pretty big system now. And Swedish is part of it so it’s a big system.

So now the concept is not one individual cardiologist trying to decide what to do with it. And all the hospitals in the system, close to 50 in my system, they come under one contract, they’re sitting at the table for one device and one product. And if it is a unique product, and nothing else in the market, kind of muscle the industry down saying that give me this price, otherwise, I wouldn’t use it concept.

And if it is multiple products and put it through a bunch of champions from different hospitals come and pitch to us as a group and pick a product and put it on the shelf.

Two major changes

This concept changed in two ways.

One is it’s good. It’s good that there’s not much noise for the cardiologists.

We could standardize the work, we could standardize what gets on the shelves in the cath lab or the or suites. And it allowed us to control the cost.

But on the downside, we started missing out on many important innovations.

And we started missing out on modifications to the competing product that is much better in many ways. Even though there are times that we kind of know that that’s a better product, since it’s coming with a large suite of other products coming in, and it made it very difficult for us to pick one out separately.

That is the biggest change that I’ve seen how the device is being bought and used by the surgical specialties, at least.

Does Mahesh still influence the decision?

Joe Hage: Let me ask. When you say it makes it difficult to pull out one because that one product replaced that one product, but that’s part of a bundle. Explain what that difficulty looks like?

Can you, as a key influencer, or perhaps even when you were younger in your career, go to the value analysis committee and say, “Hey, I found this thing I’d like you to consider. I know we buy it with this other bundle.”

Is that a thing anymore? Or is it’s just so unlikely to succeed that folks are even discouraged to independently say I read this thing, or I know this thing, or I saw this at a conference, I’d like you to consider it.

Mahesh: We can bring it up for discussion. But these are big dollars, that’s where the problem comes.

The best way to describe is with an example.

Say a manufacturer has stents they sell. They also have pacemakers and defibrillators. And say we pick one stent contract and say this is it, this is what we’re going to go with, this is the price. This is the workhorse for us. This is the volumes will promise you. And if you cross this volume, this is where the sliding scale for the price. And we can talk about all these fancy methodologies.

But in the background, there’s always this, if you do this for us, we’ll do the pacemaker at this price. If a competing product has a stent, but no pacemaker, that is a disadvantage.

Because it’s never written anywhere that this is all connected together. But that’s how it works because they go, all right, fine. So we give you a nice stent price, and we’ll give you a better price on the pacemaker also, if you do that.

That the other product, even though it can be superior, and if the superiority is not glaring, it’s very difficult for the second one to get into the lab.

Very difficult. And like I said, these we are talking big dollars, we’re talking a few million a year difference. So it makes it extremely difficult.

Joe: Does glaring mean twice as good?

Mahesh: It’s not that. What’s happening is many other products are sort of commodities now. Their performance is comparable. And again giving the example of a stent, the drug-coated stents that we have today, they have the risk of thrombosis, the clotting of the stent, and balanced against the risk of re-narrowing restenosis down the road. That’s the balance we play with all the time, if you put too much drug or kind of a drug that reduces restenosis, you increase the acute occlusion of the stent. So this is the balance that they play. And the difference, the numerical difference in these stent thrombosis rates are 0.34 versus 0.28 percent.

That’s what we’re talking about, this on a 15,000-patient trial.

These are very, very minute differences. How can you split hairs?

And of course, when sales folks come, they will show my stent is better by x percentage; that x percentage that you are talking in decimals.

And when that is there, it’s kind of a difficult sell to say that you know why, if I’m getting a better price on this, we’re getting better price on associated products with their company, we’ll go with that.

Are they commodities?

And the other thing that happens is the products have gone to a point where their physical performance characteristics a delivery of a product or the usability or any of those, they became comparable in matching. So when it is matching like that, that also makes it difficult.

The one thing I found out that is very – when I when I sit at the contracting and discussions and all that – there is one winning formula that I seem to see it’s a common trend.

I see it more now than ever before, is the product coming with not a sort of a guarantee or something but it’s more to do with associated services with it.

We’ll give you this, we’ll give you a patient monitoring system to go with it, or will give you a market outreach system that we have that we can help you with. These are the two things that I’ve seen consistently, especially a patient monitoring service.

Where’s the service?

Suppose you put the thing in and we have this extra service that we provide. The concept of SaaS, Software as a Service kind of a thing, and this SaaS thing is just is hitting everybody. It’s hitting the medical industry now. It’s coming to a point where it’s not just a device and if there is any service to go with it.

I think we need to move in that direction. That’s one thing that I realized is as, again, like I said, one of my things that I do is the medical device making. Device as a Service. I would, I call it DaaS. And this Device as a Services is going to be the next wave. I think we need to figure out how do you provide service along with the device.

I was discouraged and told Mahesh so. This was our exchange.

Joe Hage: What I’m hearing though, as a marketer, and sales strategy person is discouragement. I know that’s not your intended message.

But if I were sitting out there with my great innovation, and I’m a one product company, and I’m hearing you say, paraphrasing, it’s bundling, its pricing. And unless you are exponentially better, I don’t even know what to tell you.

Mahesh: I wouldn’t call it death of startup because – Joe knows me really well – I hustle quite a bit to keep startups alive. And I think there is value in what we do as startups and smaller device companies.

We need to find the uniqueness of the technology, at least the projection of the uniqueness of the technology. That’s where we need to struggle and try to find it.

I was pitching for my company in New York two weeks ago. We were invited to pitch at Medtech Innovators in the City. So I went up there and pitched.

And there were folks from big companies and they’re all listening to the pitch. And I came away with one, one lesson that I learned, at least for myself, and I’ll express it here.

When we create a product, when we try to create technologies, we tend to think of it as an innovative tool that we created, and we think it will solve a problem.

And we are hoping that somebody will take this precious plant and put it in their garden to grow. And what I’m figuring out is these bigger companies, and one of the exits that we look for is some big company buying this small company out, right? That’s what we all dream about.

But what it is, is they don’t see the value of this plant in their garden.

Sometimes we have to create the atmosphere our own with around our products, to let them flourish. So we have to create the ecosystem, sometimes we not only invent the device, we need to invent the business model around it.

Joe: That sounds like it requires a lot of resources. It basically sounds like you’re you’re creating a category, that’s no small feat!

Mahesh: I don’t know if I want to call it a category, it requires a little bit of a thought process to see where does the… it’s like finding the market fit. That’s one way of looking at it, just the market fit.

I believe there will be something else like the concept of Device as Service.

The DAAS kind of thing is, we need to think hard about how we can create a sort of a business model around this particular technology, how it can grow. We need to think hard about it.

And don’t take it lightly because this all looks like, you know, well, it’s a fancy talk – we all know that – but ‘how can you do it’ kind of a thing. But think hard about this and there will be gates out there.

Joe: It can make sense for anything that generates data, but I can’t sell an extra scalpel as a service, can I? (asked rhetorically)

Jon Speer felt the same.

Jon Speer: Jon Speer, Greenlight Guru. What you just shared is a little discouraging to me as a potential patient or as [someone] with loved ones that might be receiving procedures.

It doesn’t sound like the system is set up to make sure that patients are getting the best care possible. Can you comment on that?

Mahesh: I don’t, I don’t agree with that.

The reasoning is, as jaded as it sounds, there’s still some conscience left in these doctors, I can tell you that much. In almost all of them.

There’ll be some occasional outlier, but almost all of them are pretty good.

The concept of how do you directly deliver quality of care?

Sometimes simplicity is genius. Using these multiple tools during a surgery doesn’t always ensure quality; it actually induces complications. And that is where the trick comes from.

If a particular technology during a procedure or a surgery does help a lot, like really help a lot, a few degrees of standard deviation away from the norm, nobody will stop them from using it.

There’s no hospital system that will say don’t use it. No, that’s not what I’m talking about.

If it is incremental benefit, you see the benefit, but there is a complication associated with using the device, and if the balance is tight, that is where the entire trouble comes from.

So they claim anecdotally, “I can do better.” But if you look at the data, it’s not that clear.

There are enough complications going with it, then you go, why are you having complications with it?

Yes, you had good outcomes on this set. On this set, patients died.

So what you’re going to do with it? That is where the trouble comes from.

I don’t want to leave the audience here thinking that this is all a jaded system that we’re all getting, you know, screwed up in the hospitals. And it’s not.

No, that’s not my intention at all.

I’m just saying that the competing forces are such a way that it is our responsibility as as device makers and entrepreneurs to show that value, demonstrate the value properly, and that’s it.

If there’s no value, then we have to think about what we need to do next.


Editor’s Note: Mahesh seems to say if you attempt to disrupt an established market with one concept, it better be revolutionary, not incremental. Otherwise, without the help of an established partner (buying you out?), you have a tough road ahead. Let’s be careful out there.

What on Earth Happened to Proove Biosciences?

32 min reading time

What on Earth Happened to Proove Biosciences?

Presented by Brian Meshkin, Former CEO, Proove Biosciences at the 10x Medical Device Conference – San Diego 2019

Reading Time: 32 minutes


Former CEO of Proove Biosciences Brian Meshkin shares valuable lessons from the crushing downfall of his medical device company – so you don’t make the same mistakes he did. 🙁

Brian Meshkin: They said, “Well, can we collect the documents today?” We said

“Sure, come on in.” They said, “Can we call in a few other FBI agents to help us make all these photocopies?” We said, “Sure.”

About 25 FBI agents show up in our office in about an hour. And then, television cameras come. The local CBS, NBC, and ABC affiliates from Los Angeles show up reporting that our office was being raided by the FBI.

Good evening, everybody. And I can tell you yes, I have lost a lot of money and my wife was really upset. After many years of sacrifice.

So I appreciate Joe’s invitation to come and speak. Let’s give Joe and the team that organized this a big round of applause.

[applause]

It’s a great event, and I look forward to meeting many of you and, hopefully, following up even after this event because I think it will be great opportunities to collaborate.

So the title of my remarks tonight is “What on Earth Happened to Proove Biosciences?” But let me tell you a little bit about what we’ll be discussing tonight.

I’ll tell you a little bit about me, so I’ll introduce myself. A little about Profound Ventures, which is the early stage venture group that I currently lead. A little bit about Proove Biosciences, which is the tragic story after my seven years of success that I’ll be giving you some details and some insights on tonight.

And then, a little bit about what we achieved, where we were in December 2016, what happened next and, then, where do you go from there?

About Me

I’ve been married – still married after this experience, which is a remarkable achievement – for over 19 years to my best friend Catherine. We just celebrated our 19th anniversary. She’s a lawyer and a law professor at Chapman. We have three great kids. They’re the ones that sacrificed a lot of time away from dad as we were building the company.

We are very religiously devout. I’m an idealist, even after going through the crap that I went through.

I’m an activist in the community. I volunteer with a lot of things, do a lot of youth coaching, been a PTA president. I’ve even been a former publicly elected official, and I can tell you what I went through is far worse than anything I ever saw in politics.

And my background professionally, I have been an executive and a social entrepreneur in healthcare for about 20 years. I’ve been Emerging company CEO of the Year up in Orange County, won lots of different awards for things.

I spent my career either in pharmaceuticals or diagnostics at Eli Lily, Johnson & Johnson; engaged in digital health before it was called digital health, 20 years ago; and, then, was at Prometheus Laboratories which is where I cut my teeth on diagnostics here in San Diego. And then founded Proove Biosciences.

What I’m Doing Now – Profound Ventures

So with that introduction, let me just tell you a little bit about what I’m doing now. We have an early-stage seed fund called Profound Ventures.

We are minor league investors in the sense of we invest small amounts of money. We look for opportunities where we can act as operating partners to really help grow ventures.

Who We Are - Profound Ventures

My partners in this include:

  • My former chief legal officer at Proove, Laura Hunter, who was the head of Brobecks, co-chair of their life science practice internationally, has done over 75 IPOs, raised over two billion dollars.
  • Dr. Felix Frueh, who was the head of genomics at FDA, was Craig Venter’s founding CSO here at Human Longevity and was the president of the R&D division for MedCo before Express Groups bought them. He’s a scientist on our team.
  • And Khanh Nguyen who was my chief technology officer at Proove. He’s the technologist on our team.

Our Current Portfolio - Profound Ventures

A little bit about our portfolio. We have several different ventures:

  • We have a network of hospital partner laboratories in Revnostics Group;
  • IMCS group, which is the nation’s largest network of behavioral healthcare therapists in all 50 states, over 1,000 therapists providing support in the workers’ comp business;
  • Flint Rehab, which is up in Irvine, which is an at-home FDA cleared platform of medical devices for stroke recovery;
  • Ceraltum is a new one that we just started. It’s a spin-out of the DARPA subnets initiative, with a brain computer interface, both external device and internal device. It has a 510k pathway as well as an IDE pathway;
  • We acquired National Toxicology, which is the oldest toxicology laboratory in the United States. Two gentlemen in their eighties who are pioneers in the toxicology business built the U.S. Army’s toxicology network of laboratories;
  • an associated company, Bennufit Health;
  • The Brain Park, which is an initiative of the Society for Brain Mapping and Therapeutics; and,
  • we have two plays in the aging space (BlueStar and Eltere Life).

We look at technologies or business models that help solve profound societal problems. That’s something core to the mission that we are trying to do. We’re currently fairly overwhelmed with what we have, but we’re always open to new opportunities for collaboration.

What on Earth Happened to Proove Biosciences?

So, what on Earth happened to Proove Biosciences? Many rockets will blow up on the launch pad. Very few blow up far up into the sky like the Challenger Space Shuttle image that I have here.

Proove Biosciences was not like a start-up that dies in its first year or two or three, but died eight years after its founding.

And so, a little bit about Proove Biosciences. I started the company in December 2009.

Its mission basically was to deliver on the promise of precision medicine in the world’s largest and most expensive health condition, which is chronic pain. Bigger than cancer, diabetes and heart disease combined.

We did a lot of great things and were able to achieve a lot. And everyone that was involved with our organization understood our mission.

And so, speed up now, seven years to December 2016, let me tell you where we were. Right before the destruction happened, we were 278 full-time employees. We occupied those two buildings right there in Irvine Spectrum. We had a 60,00 square foot campus. We operated a CLIA- and CAP-accredited laboratory.

We, in 2016 alone, delivered physician orders of over 354,000 different genetic panels. We had 28 million in cash collective revenue. A little over a million in cash eDub.

We had made the Inc. 500 list a couple years in a row. We were number 16 on the Deloitte Technology Fast 500 as one of the fastest growing technology companies in all of North America.

We had built the world’s largest and highest-quality DNA biobank and big data clinical genetic database in chronic pain, with 153,000 patients, where we had characterized their DNA and had prospective data we collected under IRB, out six to 12 months on all of those patients.

The next closest was Sean Mackey’s database up at Stanford called the CHOIR that your tax-payer dollars spent $10 million to build and which had about 15,000 patients and no genetic information.

We had 15 different panels on the market, and we had lots of great research collaborations, won tons of awards from various different medical societies, had presented a lot of posters, had many peer-reviewed publications, had great relationships with the top brass at CMS including the Chief Medical Officer, Kate Goodrich, and her deputy, Chris Cox, the Chief Data Officer and her deputy, and others at NIH. A really strong Board of Directors, externally audited financials, and we were preparing to file our S-1.

We’re in the midst of raising a mezzanine crossover round and getting ready for an IPO. So things sound pretty good for where we were sitting.

And after seven and a half, eight years of sacrificing time away from my kids, pretty stoked with where we were at the time.

Then, we were victimized by something that I didn’t really understand at the time.

So Oxford-English Dictionary is, if you will, an authoritative source on the English language. And language, oftentimes, reflects culture.

Well, three years ago, the dictionary chose as its word of the year, post-truth, meaning as a society speaking English, we don’t value truth as much as we used to.

Then two years ago, it chose fake news as the word of the year. And last year the word was misinformation.

When you put those three words together, there’s a trend happening in this society around lies and their pervasiveness.

Well, we were victimized by fake news and some corporate espionage. Warren Buffet once said it takes twenty years to build a reputation and five minutes to ruin it.

And it was quite a fall from grace, to go from being listed in the newspapers as one of five earthly angels to then being the CEO of a company that was considered corrupt based on some of the media coverage.

We basically had three disgruntled former employees, actually two employees and one consultant, who were trying to compete with us.

We had all of their emails because they stupidly accessed it while they were employed, their personal emails in our Centrix environment. But we knew what their intentions were.

We terminated them. And trying to be nice guys and not sue them and make their lives miserable because they didn’t have any money, we just let them go.

But they ended up filing a whistleblower lawsuit against us about six months after their termination.

Well, they didn’t have any evidence to back it up, so the government didn’t take it. It took them about a year to make that determination.

So they, then, went to a website called Muckrat.com, which you can go to and you can see a listing of all these would-be journalist bloggers that dig into the mud on things. And they shopped it around.

They were able to find a gentleman by the name of Charles Piller, who at the time was writing for Stat News – he had been fired from the Los Angeles Times – and sold him on their story.

And so this reporter, Charles Piller, reached out to me on the Friday before Thanksgiving that year with a bunch of ridiculous questions.

We gave him all the primary sources, and he chose to ignore them. And this was his first article which was published at the end of December.

And then. he published a second article, which was over the top, in February 2017. To give you a sense, he completely ignored primary sources he was given, took quotes completely out of context, and even invented documents.

So if you were to pull up on your phone right now, pull up your Safari browser or your Google Chrome browser and you type in any company’s name, and then you click on the little images hyperlink, what will likely happen is you’ll see a bunch of logos for a particular company.

Anybody can pull down the logo of a company and put it on a Word document. And that’s exactly what this reporter did to create sources for what he was alleging.

The Dangers of a One-Sided Story

So this image right here, if you were someone like the individual who wrote this article, you may say “Prince William gives onlookers a rude gesture” by looking at that image. A one-sided story.

The Dangers of a One-Sided Story

Now, if you look at the exact same picture from a different angle, it’s a very different view. A professional journalist, a real investigative reporter, would maybe look at different sides of an issue to try and understand, maybe substantiate some of the allegations that were stated.

And so a professional journalist would write, “Prince William holds up the number three,” which being very different than the previous image. So whether you like Prince William or the royal family or not would likely define how you interpret that photo. Which is something called confirmation bias.

Oftentimes, people will interpret and understand things based upon their preconceived notions.

How One Discredited Reporter Fired from the Los Angeles Times Created His Lies

So, what happened with us? Well, the first thing this reporter did after he heard Bruce Gardner and John Hubbard’s accusations was, he then went to some third-party sources, credible folks, and gave them the accusations and said, “What do you think of this?”

How One Discredited Reporter from the Los Angeles Times Created Lies

So for example, one of those accusations was we had a pure genetic test to predict addiction, which is not true. But he took it to someone and said, “Do you think there could be a pure genetic test for addiction?” And the person said, “No, I think that’s hogwash.” Which ended up being his first title on his first article.

And so, then, he was able to take that quote and said this particular expert thinks Proove’s Technology is hogwash. It’s not what was said but that’s what was used.

He then took a quote from a key opinion leader who was on a medical advisory board and also misplaced that. He grabs some former employee opinions who had been fired. He took some things from billing practices completely out of context, research practices.

And the fact that one of our ordering clinicians over the previous seven years had been investigated by the DEA for some opioid prescribing behaviors and one of our employees was interviewed as part of the government investigation of that doctor, then became that our employees were now investigated by or interviewed by the FBI.

So he would share this misinformation with experts to get their reaction for the falsehood. He would then quote their reaction to the false information as an opinion of the company and then, voila, he had a credible quote, allegedly about the company, to provide him plausible deniability about fake news, which then protects his freedom of speech to lie.

And that’s a tactic oftentimes used in the media. So what were some of those lies? Well the bias was laboratory-developed tests are not credible because they are not approved by the FDA.

For those that don’t know, there’s a whole cadre of laboratory tests. In fact, most genetic tests on the market today are not approved by the FDA. They fall under laboratory-developed tests, including Genomic Health’s tests, a lot of Myriad’s tests et cetera.

So with that bias, his lie was there was no scientific evidence supporting our testing and that we were using a loophole in Federal law to exploit the system because our tests were laboratory-developed tests. Where the truth was we had extensive published scientific evidence. We had clinical validity papers, clinical utility papers.

In fact, when we met with the folks at CMS, they said they’d never seen an LDT have that type of data because we could sit down with CMS with 54,326 patients and we could show them we had saved them billions of dollars by pulling the data from the University of Minnesota.

So the truth was very different than the bias or the lies. He suggested laboratories were involved in paying an addiction, usually involved in some type of scheme like kickbacks and those types of things. And so the allegation was we paid docs to order tests.

Well that wasn’t true at all either. He used a fraudulent source document where basically someone had pulled down our logo from the internet and created a completely false document.

The reality was our research were all involved with IRB-approved studies, listed on clinicaltrials.gov, approved by many leading institutions like MD Anderson, USC and others. And no doctor was ever paid or financially induced to order testing.

But you could say that if you have a research contract with USC, maybe the reason you’re doing that is to hope that, at some point in the future, they’re going to order testing. I think that’s a little bit of a stretch but that was his approach.

Another bias was that laboratories were corrupt. And any successful lab must be like Theranos. He was big on this Theranos kick. And so he suggested our research was a sham when obviously the truth was very different than that.

And then, he suggests our billing practices were corrupt. Somehow we were engaged in a Medicare fraud when the reality was the coding we had approved by CMS in writing on four different occasions directly with the folks in Woodlawn, we actually under-billed CMS because I’m very conservative about things. And our technology was supported by the top brass at CMS.

What Did We Do About It?

So, then, what did we do about this?

We had these attacks coming in. They started coming in right before Christmas in December with the first article. Then, it was right after Valentine’s Day in February 2017.

And so, we consulted legal counsel. Legal counsel’s recommendation was, “Ugh. Don’t respond. It makes you look defensive.”

Our legal counsel reached out to the US Attorney’s Office down here in the Southern District in San Diego and the Central District up in Los Angeles. Reached out to the people in Northern District of Kentucky, which is where that doctor had been investigated. Reached out to the people in D.C. et cetera.

They said, “No, there’s no investigation approved.” And they shared with me something I came to learn – if you are an entrepreneur, a college professor, a CEO of a company, whatever it is, if you are mentioned in the newspaper or any form of media online, social media, as an expert in your field — because I’ve been on the cover of newspapers, and CNBC, and all this type of stuff — you were, then, considered something called a limited-purpose public figure. Which under a Supreme Court case, New York Times v Sullivan, means slander and libel laws or defamation laws do not protect you.

It’s one of the reasons why in politics they can say whatever they want to about you and destroy you and you can’t sue them for it. Those are public figures.

Limited-purpose public figures would be like the NCAA coaches that were allegedly investigated by the FBI but they had nothing on them and some of them lost their jobs. It’s because of that law that allows that to happen. Which is a huge, huge risk.

Our Board of Directors recommendation was, the quote that kept getting thrown out to me was, “Never pick a fight with people who buy ink by the barrel.” Which was a Mark Twain quote.

And they said, “We’ve been around for a long time.” We have the former Secretary of Health and Human Services on our Board, the former Head of EY’s Life Science Practice, the former President of Advance PCS, who was an executive with Lilly, the Head of Compliance at Cancer Treatment Centers of America; and they were like, “We’ve been around this for a long time. You’re doing all the right things. Take the high road.”

Mistake. Huge, huge, huge mistake in a world where negative information spreads much faster than positive information; where people can overreact. Where in the legal system it’s innocent till proven guilty, in the court of public opinion it’s guilty till proven innocent. So it’s the inverse.

I was scared and inexperienced. Didn’t know. Honestly, you hear that phrase — too big to fail? I really thought we were too big to fail and that there’s no way people will believe this garbage.

And so I listened to the advice of legal counsel and what I thought was an all-star Board of Directors, and we didn’t sue Stat News; we didn’t sue Charles Piller. We just said, “No, we’re just going to keep going the high road and everything is going to be fine.”

And, boy, was that a huge mistake. So the situation went from bad to worse. In May of 2017, I get a phone call from our HIPAA counsel at Sidley Austin in Washington D.C., and she goes, “Brian, do you know there’s been a whistleblower lawsuit filed against Proove?” I said, “No, but I’m not surprised after these Piller articles and that something’s been done.” I gave you obviously some insights before we knew it.

And so, the US Attorney’s Office in the Central District of California accidentally put sealed documents on a Federal database that I was unaware of — because I’d never been involved in lawsuits like this beforehand — called PACER which is a public database of court filings. And it accidentally leaked these documents. Hadn’t been unsealed but they did it.

And so we found out about it and our lawyers found out about it and so we said, “Okay. Well, let’s see if the government will fix it,” and to give them a couple of days.

They didn’t, so we went ahead and reached out to those US Attorney’s Offices down here and up in Los Angeles and just said, “Hey guys. We got this reporter who really hates our guts. You guys accidentally somehow must have leaked this. Could you please reseal it because everything’s marked sealed. There’s been no court order to unseal it. We really don’t want this guy to find out about it because there’s going to be another nasty article.” And they were like, “Oh my gosh. How did you guys find out about this? It’s not supposed to be unsealed.”

We’re like, “Yeah, we understand that. Can you please do it?” So the letters went back and forth over Memorial Day weekend. And we complied and did all that type of stuff.

And within a week, we came to learn that down here in San Diego at the US Attorney’s Office, they had convened a Grand Jury in the court down here to investigate all the big genetic testing companies.

Myriad Genetics up in Salt Lake had received a subpoena. Genoma Health, Natera up in Silicon Valley had received a subpoena. GenomeDx and Biotheranostics down here at San Diego had received subpoenas. And by virtue of the awful allegations that were made about Proove and the Charles Piller articles, June 7th 2017, an FBI agent shows up at our office at about 7:06 a.m. in the morning and hands us a subpoena for documents.

I was driving up with, at the time, my 10-year-old son to the office, and I turned around and went right back home because I wasn’t going to involve William in that.

We were obviously very cooperative. We said, “Sure, we’re happy to provide you whatever you’d like.” They said, “Well, can we collect the documents today?” We said, “Sure. Come on in.”

They said, “Could we call in a few other FBI agents to help us make all these photocopies?” We said, “Sure.” About 25 FBI agents showed up in our office in about an hour and, then, television cameras come. The local CBS, NBS and ABC affiliates from Los Angeles showed up, reporting that our office was being raided by the FBI.

A raid usually involves breaking the door down, an arrest, a charge of wrongdoing. These guys bought Papa John’s pizza for everybody. They were very, very nice; very professional. Went through the list of everything and we gave them boxes and boxes of photocopies of stuff.

But Charles Piller was very happy to publish that article that the FBI raids the offices of the lab that pays doctors to promote genetic tests. Which was his victory dance to suggest we had done something wrong. The media reports were awful.

Within 60 days of this happening, CMS notified us and shut us off. Said we have to put you on hold during the inquiry. United Healthcare shut us off. It was a disaster.

We went from the previous month 2.5 million in monthly revenue, by July 187,000. We had a 93% reduction in revenue within 60 days.

So where were we 90 days after the subpoena for documents, seven months after the second Piller hit piece? 90% reduction in revenue. Medicare, as I talked about, shut us off as well as United, which were our two largest payers. We had ordering clinicians that were spooked once the “FBI raid” happened.

On the same day they showed up with us, they showed up at nine of our doctors’ offices in the Midwest and the Pacific northwest, asking questions.

As senior management, we stopped taking pay at the VP and C-level. And, ultimately, within 60 days we had to fire almost all of our employees.

We were 278 beforehand, we were less than 5. We couldn’t cut costs fast enough. We built up an accounts payable about $3 million, and it was a disaster. An absolute disaster.

All the stuff we had talked about could never happen, happened. Ultimately in August, we put the company into something called a receivership. Which was a way to avoid bankruptcy. At least that’s what we were advised on – to restructure.

Ultimately, that ended up being another huge mistake. Don’t ever do it if anyone ever tells you to.

I had funded the company myself for the most part. I owned 96% of the outstanding shares, 73% fully deleted with the employee option pool. But once we appointed the receiver, the receiver was in complete control of everything. And after two weeks he decided, “Nah, I think we’re just going to liquidate the assets,” instead of the restructuring plan we initially agreed to when he was appointed.

And so, in a matter of a couple of months, September 30th, he shut down operations, turned over our buildings to the Irvine Company, told customers to stop ordering, and shut the business down completely.

So, by December 2017, eight years after founding the company, the company shuttered. Really crappy situation.

What Was the Result of the Inquiry?

A lot of other folks had to pay fines. Natera, big publicly traded company, had to pay 11.4 million; Myriad had to pay; GenomeDX down here had to pay almost two million.

A lot of different companies had to pay fines because they did something wrong. We had the autopsy without the benefit of death. We had whatever you want to call it – the rectal exam with steel wool. They went through everything they could think of.

We came down here in San Diego and sat down with this young AUSA who had no healthcare experience who was leading this. And he had all the different scary threats and all that type of stuff.

But I was confident. I was confident in what we did because I knew everything we did was above board.

And so the government inquiry resulted in no allegations of wrongdoing or charges, no fines, not even one single dollar of a call back to CMS, not even one. Because we actually were under-billing, they actually owed us money. And there were no indictments, no arrests.

So, unfortunately, the only technology that’s clinically proven in a peer-reviewed literature to help solve the opioid abuse crisis — I’ve been able to predict opioid addiction with 96.7% accuracy and help reduce pain — was pulled off the market. Stat News got tons of advertising revenue and Piller even got a new job.

Where Do You Go from Here?

All right, that was kind of a bummer story, wasn’t it? But well, you take the lessons you learn from the tragedy and you try to find meaning in it. You try to help others avoid the pain you went through.

You take the lessons learned from the tragedy and help others avoid the pain you went through.

So I threw up this orange over here for a second. Because as I’ve spoken to different groups beforehand, all of us at some point in time in our kitchens have had something like this emerge. Maybe we were traveling a bunch and there were some oranges we left that started to develop some fungus.

And when most of us see something like that, our reaction would be, “Ew.” It’s not particularly appealing. Pun not intended, but appealing in the sense of wanting to eat it.

However, back in 1928, Alexander Fleming looked at something that had been thrown away in the trash, something most people would consider a disappointment, and looked at it in a different way.

Instead of looking at it and saying, “Yuck,” he looked at it and said, “Mm hmm.” And by virtue of that was able to discover something that was able to save millions if not billions of lives because up until 1928 the greatest cause of death in the world was infection.

One in every three of us wouldn’t have survived to adulthood without antibiotics. And by virtue of that, he was able to discover penicillin. Again, a tragic image, that inspired something to do good. And I think that’s an important lesson to learn.

That very awkward picture of me there in the middle was when I was 13 years of age. This was a lesson I learned when I was young and having to deal with tragedy. It’s one of the reasons, I guess, why through my faith I’ve been able to deal with this particular situation.

When I was 13 years of age, a good friend of mine named Chris Kelly was killed when he was riding his bike in front of my house coming over to my home.

And I was one of the first people on the scene. It was one of those things that gets you over that superman complex you have — that invincibility idea you have as a teenager — pretty quickly.

And I wanted to do something to give something that was so incredibly unjust and unfair meaning. At the time, I thought I wanted to be a lawyer. Instead, I just married one.

But at the time I was interested in the law, and so I led an effort when I was 13 years of age to pass the very first bicycle helmet law for children in the United States back in Maryland where I grew up.

And during that time it was pre-internet, obviously. I got contacted by this gentleman who I’d only seen on TV, Dr C. Everett Koop, who was the former surgeon general of the United States, who was creating a non-profit organization called the National SAFE KIDS Campaign out of Children’s National Medical Center in Washington D.C.

They wanted me to volunteer and help build this nonprofit, which I did throughout my high school years. And we passed over 300 similar laws across the United States.

And I learned from that experience that you can take something that’s an awful situation, tragic, unjust and you can find meaning in it to be able to help others and to be able to make a difference in the world rather than just wallowing in the anger or the frustration because crap happens to everybody.

It’s kind of what we signed up for coming down here to earth. It’s an awful situation all of us have to go through, whether it’s health challenges, financial challenges, family issues, whatever it is.

We’re all going to have to deal with our crap. The question is, how do we handle it? And can we help others by virtue of what we go through?

And that’s a picture of me and my kids when they were young, with something we did with bicycle helmets to be able to help others.

Actually I think it was the 20th anniversary of the law. We had that picture taken back in Maryland.

You Finish the Mission You Started

The other aspect is, you finish the mission you started. You finish the mission you started That’s a picture of my wife and kids now, a lot older. A lot of their childhood was spent with dad working at Proove and building it up. But you finish the mission you started.

Proove did a lot of things, and I was a keynote speaker at the National Institute of Drug Abuse on Big Data and Personalized Medicine in Dealing with Addiction. Very good friends with a lot of the key opinion leaders in the field. And the mission got derailed by virtue of some people that lied, that made money on spreading the lie, good people in the government that overreacted, did their job but ended up destroying the company in the process.

And so you have to figure out a way to finish that mission.

And so obviously with the things we’re doing with Profound right now, we’re looking at ways to be able to pick up the pieces of the technology that was left, a lot of the data that’s published, a lot of things that can be done.

We’ve re-built the software, and we’ve got a new venture coming out to basically be able to address that because all of the key opinion leaders would want us to do so.

And so when you’re going through a difficult situation — and all of us will deal with it — hopefully you’ll never have to go through something like this, I pray you won’t.

I hope as you deal with the challenges, you’ll be able to find meaning and purpose in some of those difficult things — whether it’s an early stage company, whether it’s a professional challenge in your work, personal challenge, whatever it may be — and find a way to be able to help others, draw strength from that, gain empathy and compassion, and be able to help others that may be going through similar things, or prevent others from having to deal with the tragedy you dealt with.

I am writing a book on the Proove experience. There are a lot of things I learned about the nuances of having to deal with this and this new reputation threat that’s emerged in this post-truth, fake news and misinformation world we live in now.

And hopefully that’ll be able to help some executives and some entrepreneurs, coaches and athletes and others that are mentioned in the media, because their lives are at risk in light of the world we live in.

So I’ll be around there in the reception, looking forward to getting to know you guys better. Thank you so much for your attention. Hopefully, I didn’t bore you.

Thank you so much for the opportunity to present.

[audience clapping]

Q&A

Joe Hage: Well, don’t go anywhere. this is the question part. My first question now is, are you a hugger?

Brian Meshkin: Am I a hugger? Yes.

Joe Hage: I’m really moved by your faith and what you’ve done with– “Nah, keep the nice pictures up, Emma,” and making the best of a really crappy situation.

And I’m sure I’m not alone when you feel this indignation of “But that’s so unfair!”

Yes it is. And as I tell my Lucas, “Life’s not fair, son.” And it’s painful for a 15-year-old and it’s painful for, well, however old you are.

As a marketer, I can’t help but think to myself that you could have a rebirth, and try and prooves them wrong.

Brian Meshkin: The title of the book is going to be called Proove It. But yes.

Joe Hage: Unfortunately, my friend Laura Nobles is not here in the room tonight. You probably know her.

Brian Meshkin: I know Laura very well.

Joe Hage: Okay. I think it’s as even odds as anything to say, “Hey, everybody. Remember that guy? Well, he was found completely innocent.”

Personally, I was moved by your presentation tonight. I’m not going to ask for a show of hands. I’m willing to bet at least five others were.

And if we could tell that story through many different media now about why your product, which was the only one that did this thing, was derailed by misinformation and badness, there’s really, in my mind, no reason not to come back.

I’m sure this is not the first time you’ve thought of that.

Brian Meshkin: Absolutely, so one of the companies that we’ve funded with Profound is called Bennufit Health.

The bennu bird was the Egyptian firebird that preceded the great phoenix rising from the ashes. And so with Bennufit what we’ve basically done is we’ve rebuilt the technology as a software that we can then license to laboratories.

We bought National Tox so we can actually put it into a laboratory as well and, then, Felix because he’s so intimately familiar with genetic testing at the FDA. Since one of the challenges was, “Well, this is not FDA approved.”

And so we’ve already started talks with FDA and that type of thing, and say, “Okay. We’ll just 510(k) and then take it out that way.”

But without a doubt, we’re going to finish the mission. There’s a lot to be done in pain.

Unfortunately, with behavioral health in general, there is a stigma. And it’s not just in American society. It’s in most of Western Europe. It’s in Latin American cultures. It’s in Asian culture et cetera.

If someone has cancer, they’re a victim. But if someone has a behavioral health issue, whether it’s chronic pain, depression, anxiety, people think there’s something wrong with them.

There’s a measure of blame that’s apportioned to them, which is unfortunate because chronic pain is a neurological condition and, for those people that have it, it’s miserable, it’s ubiquitous.

In fact, the government’s overreaction to the opioid abuse epidemic, which has basically been to torture chronic pain patients by denying them the medications they need, has now resulted in the fact that 10% of all suicides in the United States are now due to chronic pain. People just kill themselves because it’s so bad.

And so there’s an absolute need to help these patients, to help these doctors, and that’s why I continue to work with the key opinion leaders in the field, the different Presidents of medical societies and those types of things, to give it a rebirth.

I just have to be careful because I know there’ll be people that’ll be gunning for me. Just by virtue there were some enemies that were made in the Proove process.

Joe Hage: That led to the misinformation.

Brian Meshkin: Yes, absolutely.

Joe Hage: So they’ll try again. They haven’t gone away. A bully is still a bully.

Brian Meshkin: That’s right.

Joe Hage: Now at least you’ll have a story that’s reinforced.

So I’m going ask you to raise your hand if you have a question.

My next question is when you put the company in receivership, do you have any ownership over the IP now?

Brian Meshkin: Great question. So it’s all locked in the receivership. So literally, the biobank for example that we have, the 153,000 DNA specimens and all of that data, the receiver didn’t think it was any value in it and just destroyed it.

Joe Hage: Smart.

Brian Meshkin: Didn’t even sell the CLIA license, just turned it back over. I was like, “What are you? An idiot?”

And so I got lawyers and filed things in court and all this type of stuff but receiverships are a bad idea. Don’t do them because they are like God and they can be a really dumb God and make some really, really, dumb, dumb decisions. Which is unfortunate because I look back on it and I’m like, “Gosh, we spent $20 million building that biobank and all of that data. I owned, at the time, 100% of the company.”

I could have put that in my pocket if I thought someone was going to trash it. But we were doing it for the common good because we wanted to share it with the researchers and do some crowd-sourcing innovation and that type of stuff, but that all got derailed. It is what it is.

Joe Hage: I could do this all day but there’s a question. Introduce yourself, stand up.

Ahmed Ramadan: Thank you. My name is Ahmed, I’m a medical engineer from New York.

So my question is basically, “So now you’re finally with a new company, it seems you did everything in the first time based on all the rules and everything. So do you now think every time you do something, “Oh, I’m not just going to do the minimum required. I’m going to go do beyond that just in case something else comes up in the future”?

Brian Meshkin: Yeah, great question.

So we actually did do way beyond the minimum required. When I [was growing] up — I’m sure your parents were the same way — my mom [would tell] me, “Everything you do and say and write, make sure it can be on the cover of the New York Times, and you’re fine.”

I’ve lived by that. I’m good with that. I mean, we’ve even sat down with the US Attorney. I said, “I hope you have wiretapped every single phone call I’ve had since the beginning of Proove. Go through every single email. You can come to my house if you want to. You’re not going to find anything.”

The challenge is, that’s not what you have to worry about. You don’t have to worry about whether you’re going to do the right thing or not. Hopefully, you’re the kind of person that wants to do the right thing.

What you have to prepare for is, what can they lie about? And a lie usually isn’t 100% a lie. There’s like 5% or 10% that’s true and then, they wrap a lie around it and they fall back to that one 5% or 10% to justify the rest.

So yes, there were things I would do differently. For example, we built, for all intents and purposes, a CRO in-house at Proove. We had a clinical operations team; we had a team of research assistants all across the United States. They were all credentialed and certified beyond what you would need to do as an NIH awardee and those types of things.

And so one of the questions we had to answer was, why were you guys investing so much in research? Why did you have this research operation? Was it designed in some way to be sales or that type of thing?

So I wouldn’t do something like that again. Our IT team, we did all our software development in-house as well. I didn’t know better. It wasn’t a regulatory issue or anything like that.

But again what happened with regard to the government investigation, if the IT was different than the lab, which was different than the research, which was different where the IP was held, and was broken up in multiple different companies, I could have just replaced the lab with another and been in business.

Another thing, as an entrepreneur you may think, “Oh gosh, I don’t want to raise a bunch of money because I don’t want to get deluded or that type of thing.”

Huge mistake. Pigs get fat, hogs get slaughtered. Been slaughtered. I didn’t want to get deluded. I wanted to try to hold on to as much of the company as I could and so I funded it all myself.

I’m a son of an immigrant. I’m kind of old fashion. You save up and you minimize your debt and all that kind of stuff.

And so we had people offering us money hand over fist. And I didn’t take it because I didn’t want to get deluded. Big mistake.

Should have had a big war chest nest egg because once you get to a point in time, people are going to come after you. And they’re going to come after you in very, very dishonest ways. And they have very powerful lobbyists in D.C., so they can use the levers of the government, which is unlimited resources, to hurt you.

So you’ve got to be prepared. If you’re going to play in the big leagues, you have to put your big boy pants on and do that type of thing. You have to raise that kind of capital to be able to do it.

So there are a lot of mistakes, I look back on all the should’ve, would‘ve, could’ve. And hopefully, we’ll do a better job moving forward.

Joe Hage: When’s the book coming out?

Brian Meshkin: I have my wife going through it right now because it’s something that exposes a lot of the family stuff. So once she’s comfortable with it, they’ll publish it soon.

Joe Hage: Just a quick aside. When I wrote my article, the original title was, “We just lost blank thousand dollars.” And, boy, was my wife pissed. She’s like, “Really, Joe, do you have to tell them how much you lost?” I was like, “Okay, I’ll put a lot of money.” So, that’s interesting.

If I’m not mistaken, you said that among your lessons learned were you would have outsourced more?

Brian Meshkin: Yes. So much of everything we were doing was in-house.

Fortunately, we had legal opinions out the wazoo. Even though we had an internal legal group, we had marquee legal opinions all over the place. Legal review of every single thing we did.

We had a lot of consultants review things and I would say — early stages of entrepreneur — honestly thought consultants were a waste of money. I was like, “Why am I going to pay somebody to tell me something I already know?”

If you ever have to be investigated, it is wonderful to have a third-party expert tell you something you already know. Because the government values that. They say, “Oh. You didn’t just make the decision on those billing codes. You had an expert tell you that’s what you should do. Fine.”

Because they’re looking for intent. They’re looking to say you’ve come up with something, that you have intention to do wrong. But if you rely upon a third party, even though you may say, “Oh gosh, it’s a waste of money, I already know this,” Really, really valuable.

Consultants and experts play a huge role in that, and I definitely would not have everything under one roof because when the legs got taken off, it all crumbled.

Joe Hage: Okay.

Gunjan Bagla: My name is Gunjan Bagla and I’m a consultant.

A really striking story. I have two questions for you. Number one, at any stage, did your Board or others advised you to hire a crisis PR firm? And number two, do you think things would have turned out differently if it weren’t for Theranos and Elizabeth Holmes?

Brian Meshkin: Answer to the second question, absolutely yes. Because that created confirmation bias.

Yes, that situation pissed me off so much. That lady raised so much money and never even had one frigging scientific poster to back up what she was doing.

And the nerve of this guy in his first article to suggest we were a Theranos, with all the awards we had won and all the key opinion leaders. How many posters do you want? I’ve got them coming out of my wazoo with all of the different studies we’ve done.

But yes, I definitely think that’s the case.

With regards to your first question around a crisis communications firm, by the time we actually retained a crisis communication firm, it was too late.

One of the lessons I mention in my book is around planning for the never happened. So when you’re going through scenario planning, there are certain situations you put off in a parking lot and say, “Those things will never happen.”

The Boy Scout motto of being prepared is really important. We live in a world where things do move much faster than they used to. And we absolutely thought about what would happen if a government investigation happened.

We brought in McDermott Will & Emery. We paid them $220,000, and we said, “If you spend the next two months and pretend you’re government investigators and go through everything just to make sure.”

Because when you’re 278 employees, you don’t really know everything everybody’s doing. So, let’s just pretend. Let’s go through this misery just to see what it was like. Which was a year before this happened because I just wanted to know.

I recommended it to our Board. I said, “I get paranoid about these things. Why don’t we pretend?” Which we did.

We didn’t prepare for lies. We just prepared that if the government was objective and came in and looked at things and went through all the evidence, would there be any evidence of wrongdoing?

And when there were little tweaks on things like, “Oh, that person said that over an email. That kinda sounds bad.” Or like, “Oh, if we can get Hopkins to do a study with us, then maybe they’ll use our technology in the future.” Oh, bad thing, don’t say that in an email.

Even though everyone in the industry thinks that way, you can’t say that because then it suggests, if we ever do research with Hopkins, there was intention for an inducement.

So you find these things when you do an investigation into forensics, and we paid McDermott Will & Emery to do that. We did this on a regular basis. But we didn’t plan for lies.

And so now, coming to your question, you don’t necessarily say, “We don’t want to get close to the line.” You don’t want to say, “We’re going to keep distance away from the line.”

You want to keep distance away from line, tell the world how far you are away from that line, and then say, “Gosh. What can people do to lie about us?” and, then, prepare for that so in the event something happens, you come back really, really hard.

I don’t know what your political persuasion is. I didn’t vote for him, but Donald Trump is actually very good at this.

He brings a machine gun to a knife fight every single time. Any time somebody talks crap about him, he is pummeling them publicly, legally, et cetera. Which is why [? 00:38:24] the accusations that are made around him.

That approach is, in the world of media we live in now, honestly the way you have to do it. You have to bring a machine gun to the knife fight, otherwise you’re going to get killed.

John Eckberg: In the interest of full disclosure, I was an investigative reporter. I was a former reporter of the newspaper and. man, I’m sorry about what happened to you. I’m John Eckberg.

You’ve heard the phrase “malice of forethought.” Not many people know about that little nuance, but it strikes me, one, you would have won hands down because he fabricated, and two, the deep pockets are the newspaper.

Brian Meshkin: Correct. He’s visibly the owner of the newspaper who owns the Boston Red Sox. I’d love to own Fenway Park.

John Eckberg: Big, deep pockets. But the three-headed question is this, would any of that matter?

Brian Meshkin: Yeah, it’s a great question.

So I have belabored this because the guy that owns Stat News — his name is John Dorsey — he owns the Boston Red Sox. Statute of Limitation in the state of Massachusetts is three years, so I technically can keep my powder dry for another few months.

And I thought about whether I go after him or not. But it’s going to open up a lot of wounds. It’s going to bring it all back into my life again. Might have to deal with that. And do I really want to deal with it or not? That’s been the question for me.

I should have done it right when it happened. Three years later, do I really want to go through that again? That’s the question mark – whether it’s worth it or not.

There is a tremendous amount of protection that’s given to the media from a slander standpoint. So when you read the articles, he does a nice job of saying, “Well, the company allegedly uses …” So he pulls himself out as the noun, uses the passive voice.

And then, I think the most disingenuous thing in the world is you give somebody misinformation and you ask them to respond to that and they say, “Oh yeah, if a company is paying doctors to order testing, that’s totally unethical.”

So this ethics expert at this university says this practice is unethical. Well, we’re not doing that practice.

And so, he was able to do enough that we may or may not win the lawsuit, to be honest. So the only reason I would do it is to trigger his liability insurance to see if his liability insurance would just settle.

But in all likelihood, he’s going to make me have to zip my mouth and not talk about it, so I’d rather just tell the truth and hold them accountable that way. Since I lost in the court of public opinion, I’m going to appeal in the court of public opinion.

Joe Hage: Are there any other questions?

Brian Meshkin: And I’m happy to talk with people outside, we don’t have to do with microphone.

Joe Hage: As I’m sure they will, I’m sure they will come out.

So you’ve certainly shared a lot of learning and you’re still as susceptible to me talking smack about you as soon as we leave this room.

Brian Meshkin: Yes.

Joe Hage: Is there a defense? Besides saying more bad stuff about me? “Yeah, well he’s not credible.”

Brian Meshkin: Right. There are steps you can take. I outlined it in the book.

I’ve put all those pieces into place now, for me, so that in the event something like that happens again, I respond much more effectively.

But at the end of the day, unfortunately, we do live in a world where people can do that. And so someone could take pictures of this event and go post it on social media afterwards, and say–

Joe Hage: With any caption they want.

Brian Meshkin: … “Meshkin admits to breaking the law.” Which I didn’t, but they can say it. And then it becomes he-said-she-said. And then, hopefully you guys video recorded, and I would very quickly put it all out there and respond to it rather than saying, “Oh, that’s such garbage. I’m not going to respond to it.”

Joe Hage: If that were to happen, I would prefer if they said, “Hage gets Meshkin.”

[laughter]

Ladies and gentlemen, Brian Meshkin.

Post-Market Data: What You Need to Know

14 min reading time

Post-Market Data: What You Need to Knows

Presented by Christine Zomorodian and Anne Leijsen at 10x for Design and Manufacturing – San Diego 2018

Reading Time: 14 minutes


Christine Zomorodian: We’re going to talk to you today about a vast global conspiracy. Something all of us should be interested in.

A lot of companies do risk management ONLY when making changes to a product. That’s going to change, says Principal Consultant at Gish Consulting, Christine Zomorodian. Regulators are looking at new requirements for risk-based clinical evidence of performance and safety for both new and existing products.

Anne Leijsen, Head of Medical Writing at Factory CRO, takes you through the new product development lifecycle — the interaction between risk management, clinical evaluation and post-market surveillance. She shows you how to collect post-market data and what to DO with it.

A Global Game of Connect the Dots

So how do product complaints, non-conformance, user experience, service events, supplier quality and reporting intersect?

What is the role of risk management in this intersection? And how does that affect clinical risk reporting and intended use?

More and more markets around the world are having an invigorated focus on post-market data. They want to know what your post-market data looks like.

It comes into many places in this world. They’ve been talking about it for a long time, and they’re finally doing things about it.

It’s incremental, but it’s happening. I think sometimes people get stuck in the incremental role out of this and thinking that’s where we’re at. And we want to open your eyes to what’s happening.

What Is Post-Market Surveillance?

The U.S. definition is, a process of “active systematic scientific validation, collected, analyzed, interpreted data and other information about a market and device,” versus what they’re saying in the EU, “a systematic procedure to proactively collect and review experience gained from devices placed on the market.”

  • US vs. EU Post-Market Surveillance Definitions – Post-Market Data

So there’s a little hint in that difference in definition of who’s where on this topic at the moment.

We like to think of post-market surveillance as the whole range of post-production product experience and what do you do with that data

PMS Data Management

It has to be monitored, collected, analyze, trended and reviewed and acted upon. For me, that phrase “acted upon” is really the key here. And I would venture the position most companies aren’t really quite there yet in how they act upon their data.

  • Managing PMS Data – Post-Market Data

So we have this growing obligation to:

  • have a systematic procedure to review the market experience of devices;
  • verify regularly the risk/benefit and implement corrective actions; and,
  • inform, obviously, your notified bodies and the regulators.

Reactive vs. Proactive PMS

So what is the difference between a reactive post-market surveillance program and a proactive?

Remember the definition – the US versus the European. Currently, maybe the Europeans are a little more ahead of us on that one.

So, what’s event driven? You have things happen; you analyze the risks that happened during events, and you report adverse events or not; then, you take a little further look at some trending and you say, “Oh, gosh. Do we have to have a recall?” – and that’s where a lot of companies stop – versus review driven which says, “You have a plan which is really a method and a procedure you’re going to develop for evaluating all your product experience information and bringing that back into the product development lifecycle.”

Risk Assessment

This ties back to the topic of risk assessment. And this is really not limited to product anymore.

We have 13485:2016 which says, “Guess what, it’s about your whole QMS.” So, for my money, pretty much everything regulatory in quality now has to be risk based.

It’s a big change in thinking. It has to do with not only how you’re approaching your whole quality management system; it has to do with what data you’re able to now pony up for the regulators because notified bodies, when they’re doing a 13485 audit, are supposed to be asking for it.

And within that context, what is the intersection of complaints and other PMS activities? And how do they impact product risk management?

So, a lot of companies, risk management is this exercise you undertake every time you make a change to the product. So if you have a product that’s not changing for five years, guess what, you don’t look at the risk assessment for five years. That’s going to not be able to be the case anymore.

There’s a recognition there are ongoing device issues. The regulators are all aware of this, and they really are fed up so they want to change things.

And what they’re looking at is new requirements for risk-based clinical evidence of performance and safety, both new and existing products.

I think the existing products is where a lot of people get caught because you think of it instantaneously with a new product you’re trying to get on the market and they’re reviewing your information very closely. What about your existing product suite? So, that’s what this is about.

I think that comes back to something MaryBeth talked about a little bit earlier – the focus on user and that being part of post-market surveillance.

Regulatory Focus on Use-Error Surveillance

So there are links between usability engineering process. I actually believe, in terms of a process, 62366 does a better job of laying out that process.

For my money, the guidance on human factors is the perfect one to follow for testing. But if you want to set up a system where you can continuously monitor and address your usability issues, you need to design a UEF (Usability Engineering File) – which is a subset of your DHF, so think of an extension of it that just deals with usability – and it needs to be just as dynamic as your DHF.

The 62366-2, which is the guidance that accompanies 62366-1, is a great roadmap for setting that up.

So, in terms of visibility, there’s this collaboration or accumulation, if you will, of all these different standards and, now, regulation that addresses these issues.

So, we get a 62366, of course, HE75, and risk management is now in the mix too much more than ever before.

Why am I making that case? Well, it’s because of ISO 13485:2016 which is, “Thou shalt have risk management in everything you do.” That means usability testing as well.

Anyway, there’s a new AAMI TIR I’ve started to fall in love with, and I’m going to be talking about it more and more because I want to promote it.

It’s this TIR50 which came out in 2014 and has gotten very little discussion and recognition. It talks about the post-market surveillance of use error management. And the premise is an exciting one.

Use Risk

We’re going to talk about use risk in a moment, but I’m going to jump down here.

  • What is Use Risk? – Post-Market Data

The FDA has estimated up to one third of device failures resulting in everything from sub-optimal treatment all the way to death are likely failures of device use rather than the actual device.

So what does this mean inside a manufacturer? So, they have a complaint that comes in. They do an assessment on it, and they determine if it’s reportable or not. They file the MDR if they need to.

What happens next? Well, they go through that little circus “Hey, do we need to do a recall? Is this trending?” And they take it to the engineering team and they say, “Is this a device failure?” And the team goes, “Nope, nope. Device works as intended.”

Well, guess what, it worked as intended for the engineer, it did not necessarily work as intended for the user – typically, that’s the clinician. Home use devices are a whole other can of worms. We’re just talking about clinical users here.

So compounding that issue is the clinical world, when they have a failure – and I just had a discussion yesterday with Nance about this – they think every failure that happens in a hospital is their fault. Something has to dramatically break in front of them or shut down or smoke before they think it’s the fault of the manufacturer.

So how do you get them to change their opinion on that? And how do you get them to start reporting more?

There’s another statistic I’ve seen – maximum of 20% of actual incidents that occur related to medical devices are actually reported.

Think about that – 20%. If we could get even doubling of that, what would that look like in everybody’s complaint roster and, then, the MDR reporting?

So back to use risk, it’s the act or omission of an act that has a different result to that intended by the manufacturer – here’s the best part of the phrase – or expected by the operator of the medical device.

I think that phrase is something a lot of people are struggling with taking in and understanding what that really means. You can also think of use risk as use-related hazards or the risk of use error.

So one way to start looking at this – uFMEAs. Usability FMEA. How are you incorporating that into your risk management?

User Requirements

This takes us back to user requirements. And the basic gist of this slide is it’s no longer remedial. You can’t think about usability like, “Oh, God. We got to go to validation. Gosh, where are our users? Do we have user requirements? Do we have use cases? Do we have anything to test?”

You have to think about it from the beginning. And a lot of us would say it really needs to happen during design planning all the way back in the beginning:

  • Those user requirements need to be risk-based;
  • They need to be rigorously studied;
  • You have to deal with residual risk. A lot of residual risk is really about the user. It’s really about usability. Are you incorporating those residual risks into your testing? And,
  • You have to revisit those user requirements. And your data is going to tell you that and if you have enough evidence, you will need to revisit your requirements. Sometimes you might even have to alter your intended use based on what you’re finding out from your data.

Product Development Lifecycle

Anne Leijsen: The European medical device regulation that went into force in 2017 and is being fully regulated in 2020 is allowing you to incorporate a new service because the focus was first in the pre-market phase and it’s now shifting to the post-market or lifecycle approach.

  • Product Development Lifecycle – Post-market data

So where you may often see user errors, not only after you’ve used it in the real world, it now asks you to go back to your risk management if you have post-market surveillance data.

And then, if you have some post-market surveillance data, you have to go back to your clinical information on your device – is there something I have to change? Is there something I didn’t see before?

And there is this interaction between those four different parts of the system – you have your risk management, but you have to get back to that based on your post-market data. And the other way around, how your post-market surveillance will look depends on the risk of your device.

So the EU medical device regulation does not outline “this is what you’re going to need to do for your device if it’s a class III or II.” It tells you, “If you have a high risk or certain risk on your device and you know about it, you have to evaluate it in a clinical evaluation. But you also have to make sure your post-market surveillance system or your post-market clinical follow-up system is based on that.

Passive vs. Active PMS

So there are several ways to collect a post-market surveillance data.

  • Passive vs Active PMS – Post-Market Data

Most of us are using the passive method already we see required in the U.S. by the FDA.

It is the method you can have fixed in your company. It’s the same for all the devices in your portfolio. You say, “Well, if there is a customer complaint, I will have a look at it. And if I have many of the same ones, I might want to update something in my approach.”

There is user feedback. You may go into social media to see whether there’s something wrong with your device.

But then, it’s for all devices you have this same approach independent of the risk related to the device.

Then, there is also that active part. And that’s what’s called the post-market clinical follow-up in the EU.

Depending on the risk of your device or what you’ve seen on your device before, you may want to have some focus group meetings with users. Especially for new products. You might learn a lot in a very short period of time. It’s low cost.

You may want to do some surveys. You may want to actively take products back, see what’s wrong with it, go from there.

But you may also want to do registry studies or full-blown clinical trials where you want to see – “Okay, I have this risk on my device. I do think it’s ready to be put on the market, but I think I need to follow it up actively for five years, for example, to see what it is doing in the body long term.”

Clinical Evaluation Requirements

And then, the next step is – What are you going to do it all that data?

Under the medical device regulation, they ask you to update your plans and write reports based on that date.

So one thing is your clinical evaluation plan you may have set up during the design phase of your product.

Based on the data that comes in and you write down in your clinical evaluation report, you may find out “Oh, there’s a very high risk of infection than I expected.” So, you go back to your risk management files. But you also may want to do an extra study searching for more information on this topic.

There are some other plans mentioned in a medical device circulation. It’s the post-market surveillance plan. So whatever’s outlined before – what type of studies or methods are you going to use to collect this data?

And new in the medical device regulation is also the summary of safety and clinical performance. So what they ask is, you have to write a summary on your device on what type of clinical evidence is available on your device and that’s going to be available to the end user.

So there will be a link or a QR code, for example, on your device label directly going back to the EUDAMED system, and the user can read what data is available. Something I think is missing now because, now, if you use a device, you have no idea unless you spoke to a notified body or to the manufacturer himself.

So if you put it in a graphic, it looks like this.

  • Clinical Evaluation Requirements – Post-Market Data

So you have all these plans, your risk management plan, and then your clinical evaluation plan.

And based on that, you may have decided to do some post-market surveillance or post-market clinical follow up. And for all of these, you write reports and they all contribute to each other.

So your post-market clinical follow up may give you news that feeds into your clinical evaluation and also in risk management.

Important to realize is, as soon as there is an emergency, you may want to feed back directly to your risk management plan. And you may have to change every approach you are planning to do on your device.

Reporting Requirements

Moving back, how does that compare, for example, to U.S.?

  • Reporting Requirements – Post-Market Data

I think we’re all familiar with the medical device reports we have in U.S. which has the same acronym as the Medical Device Regulation. And it’s similar to the medical device vigilance (MDV) we have in Europe right now.

The difference is we’re working on a new EUDAMED system that’s going to be active in 2020 –

which is a database where all of this information is collected and available to all notified bodies, all competent authorities, also to certain parties like the end user or the investigators and trials etc.

which is, in some part, similar to databases the FDA has as well – for example, the MedWatch is a system where you collect these type of data; the MedSun; all databases you might have heard.

Q&A

Joe Hage: Thank you. Do we have questions for the ladies?

I’ll start. I think post-market data is a scary concept for most medical device companies. Frankly, I’ve never been close enough to it on the marketing side to have a really good view of it.

Just as I asked MB about what percentage of medical device companies are doing human factors effectively, what percent of companies would you estimate are doing post-market data effectively?

Anne Leijsen: I think most manufacturers do have a system to do something with the complaints that come in.

So, for the passive methods, I think that’s settled in most device companies. Are there hands for who has a system for that?

[Hands raised]
Yes, perfect.

But then, the active part is something that might not always be asked for here in the US. And then in Europe, it’s fairly new as well.

So that’s where the real struggle is for many manufacturers at this moment – “We have to write this post-market clinical follow-up plan. I have no idea what it is, but my notified body is not accepting my technical file without this plan.” That’s what we heard from certain notified bodies.

So even if your plan is “I’m going to do nothing,” they want to have you write that down and give a justification. So that’s where I see a lot of struggle. And I haven’t seen many companies that actually have these post-market clinical follow-up plan ready to be submitted to the notified body.

Christine Zomorodian: I want to give a second part of that answer.

I think in terms of passive monitoring, for what’s required for reporting, most companies do a pretty good job.

In terms of really looking at what their post-market data is telling them, most companies are not there yet. And I think one of the reasons is the tools they’ve been using.

Most companies have a tool, it’s for collecting customer service information. They had people who were paid not a whole lot more than minimum wage sitting and answering the phones and putting the most important information they’re getting into a free text field.

So guess what happens? That gets dumped into a big file; and it gets sent over to complaints department; and they have to read through every single file; and they don’t have good buckets to put things into.

So what they’re pulling out is MDRs. What they’re pulling out is obvious device failures. Beyond that, I think most companies are not doing a very good job getting their arms around this data.

And it’s about the tools. It may be about intent as well and not having the intent yet to be active, but it’s about the tools.

Joe Hage: To me, this sounds like the other side of what we heard from Sarah [Wright] (ResMed: Leveraging Customer Support to Understand Customer Needs).

Christine Zomorodian: Yes.

Joe Hage: Is that effectively what they’re doing? They’re taking this data and they’re reincorporating it and getting engineers and the like involved in the product improvement?

Christine Zomorodian: Absolutely.

And when I was listening to her presentation, at first I thought, “Oh, yeah, this doesn’t have a lot to do with what I do.” And then, I thought, “Wait a second, it really does.”

Maren Nelson: I’m Maren Nelson, and I have a consulting company up in Seattle.

The active part of gathering this data seems like it could potentially have a very broad scope. Do you have any guidance or any thoughts about what is enough of the active post-market data?

Anne Leijsen: That’s something the notified bodies don’t know yet themselves.

It’s outlined in the medical device regulation. You need to have “sufficient clinical evidence” on your device in relation to the risks related to your device.

So if you ask notified body now, they’re like, “I have no idea. I don’t know what that’s going to mean.” So they’re working on a technical report now, outlining what sufficient clinical evidence is going to be.

But because the right range of medical devices is so broad, there is no good guideline.

And the notified bodies in Europe – I don’t know exactly how it is here in the U.S. – they ask you for justification. And they say, “You are the expert of your device. You know best what the risks are and what would be an appropriate way to collect active post-market data.”

Christine Zomorodian: So I think, in the long run, that’s also about risk. What is the risk of your device? How are you accounting for that? And how well can you justify your decisions on a risk-based model?

Scott Thielman: This is more of an observation. My name is Scott – we met – and I work at Product Creation Studio up in Seattle.

There’s a company I interviewed yesterday. They’re a local called Clarify Medical. They do a dermatology device.

Part of their solution is the digital health part in the mobile phone that monitors how the patient’s doing, sets up the parameters – that’s their hook because it makes this UV treatment a lot easier and more reliable.

And what really surprised me is they had a whole department called customer support and customer care plan. And he said, “In fact, we had it spread out all over the country. We brought it all back here because I want it right next door to me. I want to be able to get pulled in there and hear about actual customer– And some of that’s images.”

I’m just like, “Wow, that’s really unusual.”

Now I wish I could get him in the room with you guys to ask, “Was it part of a plan to meet some of the emerging requirements? Or was it just good business practice where they’re leveraging that?”

They know their customer now better than anybody else.

And so even though it’s a cost layered on top, they’re seeing real value crafting their product features and functions.

Anne Leijsen: It has always been the intention of the medical device directive, as we had already for a couple of years, to actively follow up your data. Don’t let it on the market and see what’s going to happen.

But because medical device companies, “If it’s not in a law, we won’t do it,” they wrote it out – No, you have to do something with it.

So I think it’s a good approach from them anyways even if the medical device regulation is not there. Even MDD, it’s required from you as well.

But it’s interesting to hear. It’s a good approach.

Scott Thielman: Yes, there’s more.

If you get a prescription for that device, you are going to get a call from a customer support and you’ll get trained and, then, they’ll follow up with you.

Anne Leijsen: Yes, so the active approach. Sounds good.

Christine Zomorodian: So, in terms of closing the loop between what’s happening in Europe versus the U.S. right now, FDA made a statement a couple of months ago they’re intending to begin to adopt and follow 13485:2016 to supersede the 820 regulations. So that’s coming.

They didn’t give any kind of a timeline. They didn’t put any teeth in that so far, but that’s a statement I’ve read from several new sources. And I think we should all just take that to heart and say, “Yes, it might be the Titanic, but the Titanic is moving along the sea.”

Joe Hage: Stellar job, ladies. Let’s hear it for Christine and Anne.

Leveraging Customer Support to Understand Customer Needs

10 min reading time

Leveraging Customer Support to Understand Customer Needs

Presented by Sarah Wright, Director, Global Customer Support, ResMed at 10x for Design and Manufacturing – San Diego 2018

Reading Time: 10 minutes


Sarah Wright: Good morning. Thanks for having me.

I’m Sarah Wright. I’m Director of Support Services at ResMed. I’m based in Halifax, Nova Scotia, Canada. And I’m really excited the conference is here in San Diego obviously because your weather is way better. Great location, Joe.

I’d gladly highlight Resmed as a medical device company that understands how to use their customer service data to continuously improve their products and services.

Sarah Wright, Resmed Director of Global Customer Support, is really, really good at her job – and as a presenter, which is why she’s returning as part of our faculty in May 2019.

I’ll let her tell the story, below (see video, slides and transcript), but the main point that so few medical device manufacturers fully leverage is this: “Data from support services, if stitched together, provides actionable business insight. It can inform how you market your products. It should inform how you prioritize feature enhancements. And it can reveal which customers you stand to lose.”

We Underutilize Customer Support

And I’m really excited to be here to talk to you about something that, throughout my 20 years in support operations, I’ve started to notice – we often underutilize or undervalue what people are saying when they’re calling into our companies. It could be patients, and it could also be different home medical equipment providers and clinicians who need our support.

When I came to ResMed I started to notice there were trends that were emerging after releases. In some cases, it would be as a result of a process change and who wanted to see this information. How can it be helpful? How can we learn from it? How do we aggregate it and, then, really start to turn this information into actionable insights for our customers and really build that trusted partnership?

What I’m talking about is customer support and how that data is collected, where it sent, and what we do with it.

Salesforce.com is our CRM, our ticketing platform, and it’s also our sales tool. So a ton of really great information stored there that, when you start to bring it all together, can tell quite the story.

We started to knock on product development and management teams and say, “Wait a second, everyone. This is not just a one and done. This is not just a siloed experience. This is something that, if we start to look at trends and patterns, is really telling us something important.”

How We Collect and Optimize Information

So, we’ve started to look at how we collect information, how we can optimize the collection of that information.

Probably, you’ve heard garbage in garbage out. If you’re not collecting the right information, and you’re not storing it in a way that makes it easy to pull, then why bother?

You don’t want to be looking for a needle in a haystack. You want these insights bubbling to the surface and telling you what you need to focus on.

Helping Customers Reach Their Desired Outcomes

I oversee support services – our contact centers, our solutions delivery, our customer success management team, and our education services team. I have a team of about 120 people at San Diego, Denver and Halifax.

  • Helping Customers Reach Their Desired Outcomes

This slide is the power of taking Salesforce data and plugging it into Gainsight, our success platform.

Customer Success typically have conversations about platform adoption, the health of utilization of the different software platforms that our customers are adopting, and really trying to drive more and more adoption.

That’s the conversation. It tends to be very proactive. In some cases, reactive.

But we started to notice that some of our top 10 customers either were very healthy in how they were utilizing our products and services and they believe they were running a great operation. However, their patients were telling us a different story.

My contact center is focused on medical resupply. That is for people on obstructive sleep apnea therapy. They require masks, tubing, and other equipment sent to them at a particular frequency as directed by the manufacturer of their device.

Insurance is complex and plays a role in that. So there are many rules that have to filter into how this platform works.

But we sell a platform to equipment providers to take away the pain of having to be at a storefront and sell masks when, really, you’d rather clinicians focused on sleep tests, on diagnosis, oxygen, ventilation, things that really drive that value add.

Having a clinician sell a mask is really underutilizing a costly resource.

In this case, one of our largest customers had a massive issue with order status checks. That means a patient has agreed to use our resupply service – our platform – and for some reason or another, the patient hangs up happy and, then, never gets their order.

So the idea is we don’t actually fulfill orders. That’s the functionality of our customer. We take the order; we create the platform by which you can capture that order, and we provide the contact center that offers that intervention should the patient need some help.

When we saw a massive number of calls and order status, it changed the conversation with success from “Hey, it looks like you’re using our platform” to “What can we do to help you with fulfillment?”

If you can’t fulfill orders, it’s a terrible patient experience. In many cases, it affects a patient being able to get their full insurance benefit because they may have now kicked into a new resupply cycle.

And what really matters to those customers is you’ve actually impacted your revenue in a negative way. You’ve likely lost the potential to collect revenue on a full resupply cycle if this is continuing month over month.

Then we had a captive audience when we started to show the bottom line revenue impact of not fulfilling orders. We became even further trusted partners by saying, “Can we help you with your workflows? Do you need help with fulfillment? Do you need some guidance on best practices we’ve seen from other customers?”

If your patients aren’t getting your orders, your patients are very dissatisfied. And why would they continue to resupply? And it can affect their interest in continuing with their therapy.

IVR Outreach VS. Service Level

Internally, as part of Integrated Voice Response (IVR) outreach, we have a platform that has a call out. Faith is her name. And she says, “Hello, it’s time to get your supplies.”

  • IVR Outreach VS. Service Level

It’s really important our customers set an expectation with their patients that this is not a hoax or any kind of a problem. People are very untrusting of phone calls these days. Lots of scams out there.

So we provide a voice sample to say, “This is what it’ll sound like. This is what you’re going to experience. You just need to validate a few detailed information such as date of birth, and your order will go out to you.

In this case, the trend line of service level has a really interesting impact from the number of IVR outreach attempts we make. So we had a massive disconnect between product development and the folks that own the IVF outreach platform and the contact center that takes the input of those calls.

Multiple attempts at outreach for these medical supplies, as they increased or we have an anomaly, it directly decreases service level delivered. What that means is, if a patient needs our help and they want to order and they come through to our contact centers and they can’t get through, they may abandon their desire to make that order.

And so what we started to do was meet with product development, meet with the people who are pushing these different protocols out and say, “How do we separate them?” because ultimately, by making sure we have the right capacity and staffing in place at the intervals you want to make this outreach happen, we can drive a far more positive customer experience by aligning the two.

We aim to deliver an 80% service level. That is, 80% of any interactions coming into the contact center out of the IVR in 90 seconds or less. And the only time in the past 12 months we did not deliver on that, it was around a 78% service level when we saw a massive IVF outreach increase. And it really triggered another one of those discussions.

So again, having multiple teams understanding how their work negatively impacts the customer experience can directly bring teams together but also drive the most positive customer experience.

I also have another line that can trend over this called abandon. And if you have people waiting too long, they just hang out. They don’t care. They don’t want to do this anymore.

So, as our service level decreases and rates go up, our abandoned rate goes up and directly impacts revenue from our customers.

Collect Customer Feedback – Even Negative Feedback Is Good Validation

I know some people believe very strongly in voice of customer and others don’t.

  • Collect Customer Feedback

Some people say, “Oh, I know we have room for improvement. I don’t really want to know what people think because what if it’s brutal.”

It’s great to know when it’s brutal. It’s good validation. The worst thing that happens is nobody responds. If nobody responds, you have a real problem because it may be there’s no engage. People may have just really abandoned and given up.

If people are really upset and they share that feedback, they’re still engaged. And if you take that feedback and you do something meaningful with it and you engage with the person who’s taking the time to share with you what they truly think about your products and services, they can turn around and they can be one of your most engaged and most satisfied customers.

They may even be willing to join panels to come and talk as trusted partners. They may be willing to tell their colleagues how they were really unsatisfied and now they’re extremely satisfied because you faced head on a challenge that they just thought wouldn’t be engaged with.

Survey Your Customers to Understand Where You Can Improve

So we dove into doing a Voice of Customer survey through a tool called Gainsight. Gainsight is a success platform. It plugs nicely into Salesforce.

We reached out to our home medical equipment providers to say, “How are we doing?” And we were doing okay.

In 2017, we had a net promoter score of 62 – other responders were willing to recommend our products or services to their friends or family. It’s very specific wording from a net promoter score.

Why Doesn’t Anyone Want to Fill Out Our Survey?

We fell below the benchmark of 10% response rate. And we thought, “What are we doing wrong? Why doesn’t anyone want to fill out our survey?”

I know people have more to do in life than fill out surveys. So we started to think, “What can we do to be creative? How do we take action on this? And how do we engage more customers?”

So we put in a few action plans.

  • Create an Action Plan from the Feedback Gathered
Action Plan #1 – Gainsight Adoption

We looked at how we drive Gainsight adoption across all of our teams that had that customer interface.

Action Plan #2 – Best Practices

We started to look at what is survey fatigue. We don’t want to put out too many surveys because customers stop responding.

There’s a lot of people talking about the fact that the right frequency is six months, maybe 12 months for a survey.

We engage with our customer insights team, our marketing team, to get some feedback on what really makes sense.

How do we ensure ResMed is not over-surveying customers? Do we cross-pollinate? Do we communicate? Do we let people know “we’ve just sent a survey, so please don’t send another survey for three to six months”?

And now we’re thinking, “If a customer responds, do we offer them the opportunity to fill out another survey?” Really testing the waters first and not just continuing to send surveys out looking for a response.

Action Plan #3 – Program Focus

We’ve also focused on different programs. And we came up with a really interesting idea for this recent survey that we just completed in August 2018.

Research said if we offer a small incentive or chance to win, it would increase the response rate. And it sure did. Our net promoter score went up.

I don’t think that’s because of the gift card. Really, it’s that our products services, our solutions consulting, our success management are becoming more and more streamlined.

We’re leveraging the tools and technology we’ve invested in to deliver a positive experience that’s driven by data. We offer executive summaries that are guided by triggers and calls to action to show us where we need to course correct a customer’s experience.

And we’ve started to really drive internal product training, internal services training, to ensure when someone says, “Hey, but my device does this or my mask is causing a mark on my face or my nose is really dry in the morning,” any of these types of questions or concerns or comments, we’ve really started to drive the creation of playbooks that are validated internally that can be utilized and sent to customers who drive that outcome.

Our response rate in this case was 30%. We not only took an improvement into the industry benchmark, but we actually did a fantastic job.

Customer Effort Score

And what was really a positive indicator for us in all of the change we’ve done over the last year is 87.6% of our customers felt their interaction with us is effortless.

  • Continue to Survey in Agreed Upon Frequency

You may hear of customer effort score as being an indicator that people look at. Customer effort score is around “how hard is it for you to work with us on things? If you have a problem, did you have to troubleshoot it for multiple hours, wait on hold, talk to us once, call back, check the status of your ticket?”

You may have actually resolved the issue. But if you had to put in four hours of your time and three phone calls, it’s resolved but you’re not happy. It should have been easy.

And that’s another key indicator that we’ve started to really pay attention to.

What we’ve started to do and what we’re in the process of doing is taking these insights and now benchmark against the contact center.

So we’re saying, “Hey, what are our patients saying?” The feedback you saw on the last slide is our home medical equipment providers – how happy they are. They interface directly with success managers.

When we start to look at these results, what’s very interesting is the feedback they’re giving us in some cases is regarding the order flow and what it was like to talk to someone about that order. But more often than not, the information being shared with us is feedback on the health of that patient and their home medical equipment provider relationship.

So this is now being fed back into success to say, “Wait a second, we’re seeing trends.”

If you have patients calling our support center because we answer the phone and when they call their branch, no one answers, that’s a problem.

When they call us and they say, “I’m so frustrated. Every time I order something different, they mix the order up. My order doesn’t come. I’m really getting frustrated. I’m looking somewhere else.”

We can start to indicate there’s potentially a churn risk before a patient leaves. And so, we’re aggregating this feedback, feeding it back into our success teams and ensuring they can put it into that customer conversation.

It shows that we’re not just delivering the adoption rates, the platform use, your typical success conversation. Instead, we want them to be successful. We want our customers to drive maximum revenue potential, and we want to be a partner. We don’t just want to be someone whom they buy equipment problem.

Support Services Provide Actionable Business Insight

Don’t underestimate the power of data collected at any input within the company that you work for.

Oftentimes, people think the data that comes into a support center to a success manager, to a solutions consultant, to a salesperson is siloed and a one-time experience.

Oftentimes there’s a story if you stitch all of those instances together and, then, take those learnings and broadly share them across your company.

  • Support Services Provide Actionable Business Insight

It can inform how we market products. It should inform how we prioritize feature enhancements. And it should also be a call to action internally when we see a release and it drives up the call to support, it drives down satisfaction.

If you put out a net promoter score survey and it’s bad, it’s a starting point. Don’t see it as a failure. Engage with your detractors.

Have that conversation. You’ll be shocked.

All of our detractors, we always engage with them. Since this is new for us, we also engaged with our neutrals just this time. But our detractors will always be a call to action for us because we want to see what we can do to really change that conversation and ensure that they feel like a satisfied customer.

Thank you.

Medical Device Change Management Best Practices

19 min reading time

Best Practices for Medical Device Change Management

Presented by Michael Drues and Jon Speer at 10x for Design and Manufacturing – San Diego 2018

Reading Time: 19 minutes


Michael Drues: I want to have a little bit of a discussion. And I want to invite all of you to participate as well because I genuinely believe this is a very important topic and a topic that, quite frankly, so many companies screw up.

Does anybody know what one of the most common reasons why companies get warning letters and 483’s from the FDA?

Response #1: Not following design change rules?

Michael Drues: Yes, not following design change rules, assuming the rules make sense. I’ve never made the assumption that rules make sense.

But, not doing what makes sense when it comes to changing a product. And we’re going to talk about that this afternoon.

For those of you in the audience, how many of you have been involved with bringing a medical device onto the market?

[Audience Signals]

Okay. How many of you have been involved, once your product has gotten onto the market, changing it in some way? Most of you.

Now, this is not a drug audience. But if I were doing this presentation at a drug audience and asked the same question, how many people do you think would raise their hands to that second question?

Zero.

Should you do a letter-to-file? It might allow you to make a change without notifying the FDA.

But having “avoid FDA notifications” as a motivating factor is a bad idea, says regulatory expert Michael Drues.

He said, “Several medical device companies tell their R&D engineers, “If you’re going to change a device, only change it to the point we can handle that change internally, doing a letter-to-file. Don’t change it to the point we have to notify the FDA.”

Can you think of any better way to prevent or hamstring development than putting a limitation on your R&D engineers?

Medical Device Companies Are Paranoid About Changes to a Product on the Market

One of the many interesting differences between drugs and medical devices is medical devices, by their nature, are very iterative and companies make changes.

On the other hand, when it comes to drugs, drug development is not very iterative. Although, that’s going to change in the future.

But, more importantly, drug companies are absolutely paranoid to make a change to a product once it gets onto the market. To some extent, medical device companies can be paranoid as well.

I’ve worked with several medical device companies – including some of the largest medical device companies on Earth – that have said, as a matter of company policy, to their R&D engineers, “If you’re going to change a device, only change it to the point that we can handle that change internally, doing what we call a letter-to-file. Do not change it beyond a certain point where we have to notify the FDA via either a special 510(k) or a PMA supplement.”

Now, perhaps as a biomedical engineer, you understand that’s what makes my blood pressure just shoot through the roof.

Can you think of any better way to prevent or hamstring development than putting a limitation on your R&D engineers?

Change Management Is a Key Role for Any Engineer in the Medical Device Space

So, Jon, when we talk about change management in the context of medical device development, what does that mean to you?

Jon Speer: Well, first of all, I felt like I should have done the intro for the global medical device part.

Anyway, I started my career as a product development engineer. And to your point, changes happen.

The moment you launch a product, something happens. You’re going to change the material or a supplier. Manufacturing is going to find a better way or something you forgot.

And so, change management is really a key role for any engineer working in this space. So, you really have to analyze.

Those of you who know me or read anything I’ve written, I’m a huge design control nerd. And so, design control isn’t just a design and development activities. It’s not just something you do while something is prior to market launch. Design control is pervasive throughout.

So, anytime you make a change, you have to assess and evaluate – How does this impact the form, fit, and function? What are the V&V implications of that? What are the risk implications of that?

Design control is something that should be living throughout the entire product lifecycle as well.

Michael Drues: I could not agree more, Jon. Thank you for sharing that.

Why Many Companies Get in Trouble When They Change Products

And I want to come back to the question I asked a moment ago – why do so many companies get in trouble because of change management?”

And I don’t think it’s a matter of following the rules.

Scott Phillips: I think the post-market changes in my study of these numbers say that’s the big bucket, right? It’s a different team.

Michael Drues: So the reason why companies get in trouble is they’ve made changes to the product?

Scott Phillips: They make a post-market change; they don’t update the risk file; they don’t update their specifications; they don’t validate that the training was affected; it’s all these sorts of secondary things that are normally required.

And the original team would have done them, but the sustaining team doesn’t do anything.

Michael Drues: Okay. I think that’s part of the answer. That’s a good start. Anybody else want to add to what Scott said? Or, Jon, what would you add?

Jon Speer: I would just build on what Scott was offering.

In my experience, what happens during the design and development process is the product development team does, usually, a pretty decent job of documenting design controls and risk management activities. And the moment design transfer happens, that file gets archived and buried, and those are not the people who will continue to maintain that product once it’s in a manufacturing environment.

Now, you have a sustaining team or manufacturing team or some other group of people that did not design and develop the product whose responsibility it is to author these changes.

And they’re making changes blindly because that design history file, that risk management file oftentimes is buried somewhere in archive, and they don’t go back to that design history file and those design controls to see if the change they’re making has any impact upstream or downstream to the decisions that were made when that product was originally launched.

We have another opinion here.

Christine Zomorodian: Jon is going to probably smack me when I say this, but it depends. And what it depends on is a couple of things.

First of all, we talked about a situation with a contract manufacturer where the 510(k) holder is not doing the manufacturing. There tends to be some drift, in my experience, once you turn it over to the contract manufacturing organization. And, sometimes. management doesn’t want to even know what that drift looks like. So, that’s one reason.

The other reason is fear of questioning or the risk of questioning when they make a submission to FDA.

They don’t want to face that. They don’t want to take the risk of making a new submission and face questions about their product.

Michael Drues: So, I think all of the comments people have shared have been very good. They’ve all been part of the answer. But I think we’re still dancing around on the surface.

As engineers, we like to think in terms of root cause. But, oftentimes, when I hear people talk about root cause, they don’t get anywhere close to the actual root cause. They’re talking about the superficial manifestations of a much deeper problem.

And I think, quite frankly, the root cause to a lot of the problems we’re talking about here and a lot of the reasons why companies get in trouble when they change products is because of what’s up here [points at his head] or the lack thereof – the thinking, the analysis that goes into it.

What are the Administrative Options When Changing a Medical Device?

So let me, as my attorney friends like to say, lead the witness – if you’re going to change a medical device in an administrative way, you have two options to handle that.

What are the two options? Let me give you a hint –

  • you can either notify the FDA; and if we notify the FDA, how do we do that?
  • Or we cannot notify the FDA; and if we don’t notify the FDA, how do we do that?

So, with that big hint, what are those two options?

Jon Speer: So, if you’re going to notify the FDA, what are some forms that you might communicate a change you’re making to the FDA?

Response #4: Special 510(k).

Jon Speer: Special 510(k). Are there any other examples you can think of?

Michael Drues: How about if you’re a Class III device?

Response #4: PMA supplement.

Michael Drues: All right. So those are ways we can notify the FDA. What if we choose not to notify the FDA?

Response #5: Letter-to-file.

How Does a Company Decide Whether or Not to Notify the FDA?

Michael Drues: Letter-to-file. How does a company make that decision on whether or not they should notify the FDA?

Response #6: Follow the flow chart.

Michael Drues: Yes, you can follow it if you want to but – let’s be honest – does that happen in most companies? What’s the point of having a discussion if we’re not going to be candid?

So, at least in my experience, most people just don’t do that. And even if they do follow the flow chart – for those of you that heard my talk on substantial equivalence yesterday – give me any flowchart from FDA, I will make the result come out any way you want it – backwards, sideways, this way, that way.

So, talk about reality. How do you, in a company, make that decision as to whether or not you need to tell the FDA?

Scott Phillips: If it’s a new indication.

Michael Drues: If it’s a new indication, now the question becomes, what does “new” mean? How different from your original indication can your new indication [be]?

Scott Phillips: If your indication means now you’re [in the heart?], then it’s a new indication.

Michael Drues: But what if it’s not quite that extreme?

So, labeling changes, that’s one possibility. Yes, Sri?

Sri Punnamaraju: It automatically triggers an update to the risk management and the new risk is escalated. That is a quantitative way to say, “We assess the risk as high now, and we need to update that.”

Michael Drues: So I would agree some companies will get to that eventually, but that’s not usually where the conversation starts.

Jon Speer: Do you see what I have to deal with whenever we do a podcast?

[Laughter]

Michael Drues: Because I talk about reality, and Jon talks about theory.

Jeff Gable: If they don’t notify, they think the FDA will say no.

Michael Drues: That’s an interesting spin, Jeff.

Of course, that could never happen in the real world, right? (sarcastically)

Jon Speer: In my experience, I think what, oftentimes, happens is we go through the FDA guidance document on deciding when to submit a 510(k). We follow the flowchart. We pick the path of least resistance.

We may or may not document that decision. But more times than not, we choose not to communicate changes to the FDA because we can justify it through whatever means.

And we may or may not document “the letter-to-file,” which is interesting to me because I see a lot of companies say, “Oh, that’s a letter-to-file,” and, then, they never document the decision. There is no letter in a file.

Michael Drues: There are, actually, some advantages to not documenting things down. When it comes to product liability, that’s a huge advantage. If we have time, we can come back to that.

The Industry-Wide Misconception About Letter-to-File

But again – let’s be honest here –

How many people have a friend who told us the perception in their organization is, if the company chooses to do a letter-to-file, that’s somehow less work than if they were to notify the FDA via special 510(k) or PMA supplement? How many people have heard of this?

I think I’m being facetious here. Most, if not all, medical device companies believe it is less work to do a letter-to-file. And this is where I believe the industry standard is flat out wrong.

Jon Speer: 100%. We go through the decision tree. If we choose to document it, we may print out that flow chart; we highlight or circle the items; we may write a paragraph or a memo and document it and check the box. And we’re done. That’s the most common practice.

Michael Drues: That’s a very common practice. And that is, in fact, the industry standard.

And the industry standard is 100% wrong.

Because, typically, the way that decision is made, we’re going to make this change, let’s decide first – letter-to-file or special 510(k) – and, then, do the other stuff that go into it.

I think that’s 100% backwards.

I work with companies all the time. I say,

“Whether you’re going to do a letter-to-file or a special 510(k), it makes absolutely no difference. The amount of work you have to do in terms of thinking, in terms of analysis, in terms of literature search, in terms of benchtop testing, maybe additional other kind of testing, is exactly the same.”

The only question is, “What do you do with that information?”

In some cases, you will take that information and literally put it into a file folder and put it in your three-drawer file cabinet. For those of you that don’t remember what a three-drawer file cabinet is, you can Google it. You’ll see a picture. That’s what we used in the olden days. That’s why we call it a letter-to-file.

Or you take that same information and you put it into a different package – we call it a special 510(k) or a PMA supplement – and we send it off to the FDA. The information is exactly the same. It’s just a matter of what we do with it.

And here’s another reason why I write a letter-to-files that way. If you make a change to a medical device and you choose, for whatever reasons, not to notify FDA and, in the future, some knock on your door comes – it’s the FDA – they say, “Hey, we’ve noticed you’ve made a change to this device. We don’t remember you ever coming and talking to us about it? What the heck is going on?”

I don’t want to be in a situation where I say, “Oh, gee, we forgot,” or worse, “Darn. You caught us.” I don’t want to say that at all.

I would say, “Oh, Mr. or Mrs. FDA reviewer, come on in. Sit down. Have a cup of coffee.”

Jon, are we allowed to give them coffee anymore?

Jon Speer: No.

[Laughter]

Michael Drues: “Let me pull out my letter-to-file where we have completely documented the change we made, why we made it, all the testing we’ve done to support it. Oh, by the way, here is a list of other companies that have made similar changes and they didn’t notify you either.”

I work as a consultant for the FDA, so I see this from both sides. I want to make it painfully obvious to my friends at the FDA that we know what the heck we’re doing, that we’re not forgetting something, we’re not hiding something. We made a business decision that, based on the following reasons, we decided not to notify you.

The reason why I like that strategy is very simple. It is because – worst case scenario – if the FDA says, “Well, gee, thank you for sharing all this information with us. We think you should have let us know.”

“Fine. Not a problem,” I take all that info from my letter-to-file; I repackage it; I put special 510(k) on it, “You’ll have it next week.”

What do you think of that approach, Jon?

Jon Speer: Well, a lot of companies simply do this letter-to-file path to minimize the work.

And this is the key thing Mike is illustrating here – the letter-to-file is not a substitute for the work.

We still have to do the analysis. We have to make a decision as to – when we make a change – what is the impact of that. We may have to update design control activities. We may have to update risk activities. We may have to do additional testing and analysis.

“It’s just good, prudent engineering.” [To Drues] I’m stealing one of your phrases.

Michael Drues: They say if you’re going to steal, steal from the best. So, I’m flattered, Jon.

Jon Speer: But I think this is where companies get themselves in trouble because, “We’re in a rush; we have to hurry; we got to make this change. We got new components that came in from the supplier and they are a different color, but let’s just do a letter-to-file and let’s push on without doing the appropriate amount of work and effort that goes into that.”

So, that’s a problem. And if you do that on one change and, then, you make another change and, then, you make another change, and you handle all these things the same way, what does that look like?

What does this product – two or three changes down the road – look like when compared to the product you originally got clearance or approval for?

Michael Drues: Now, what Jon is talking about is what I call “change creep.” So, for those of you that are familiar with predicate creep, the idea here is exactly the same.

Change creep: You make a change to a device. That change is not significant enough to let FDA know. You make another change to the device. That change is not significant to let FDA know. You make a third change.

Each of those individual changes, considered one at a time, might not be significant. But over a long enough period of time, when your device is on the market, now those changes become significant.

At What Point Do We Notify the FDA? And How?

At what point do we notify the FDA? And, if so, how? Some of you are probably familiar with the phrase in the vernacular, the catch-up 510(k).

Officially, there is no catch up 510(k). There are only three types of 510(k)s. That’s not one of them. I’ve suggested to FDA many times we need to create one, but we don’t. At least, not yet.

But I refuse to use regulation as an excuse to hold me back. If the regulation does not have a way to notify FDA of these changes, we need a way.

What I will do is I will use a special 510(k) which has a significant change in it. But I will embed, into that special 510(k), the previous changes.

In other words, I will say, “As a matter of professional courtesy, I’m going to use this opportunity to notify you of all these other changes we’ve made to our device.” If FDA kicks that back on administrative reasons, I will fight them to the tooth because that defeats the entire purpose of being able to work together.

Jon Speer: So, question, Mike.

I do the analysis; I do the work; I do the testing; the effort to properly evaluate and analyze my change. And after I do that work and I’m stuck, I go through the decision tree and I’m not sure if I should do a letter-to-file or if I should do a special 510(k). Should I just go ahead and submit a special 510(k)?

Michael Drues: Some companies will take that approach. Some companies will be more conservative and, if they’re in that gray area, go ahead and file anyway. Other companies will be a little more – I’m not sure if aggressive is the right word – and decide to do the other way.

But most important to me, Jon – and I don’t want to put words in your mouth, but I think you agree – that decision can only be made once we’ve done all of that work first, right?

Jon Speer: Absolutely. So what about a pre-submission? I know you’re a big fan of pre-submissions. is this scenario where, if we’re on the fence, we might consider a pre-submission?

Michael Drues: You could. I am a huge fan of the pre-sub process. Like the catch-up 510(k), we don’t have an official pre-sub type to notify FDA of a change to an existing medical device. But there are ways.

Again, it’s a matter of perception here. I refuse to use regulation as an excuse to do prudent engineering. I want to be able to proactively notify FDA of my changes whether I do it in a submission, whether I do it in a pre-sub, however. I don’t care as long as we get it done.

Downsides to Making a Robust Letter-to-File

We made a joke, a moment ago, about documentation. And Jon was saying documentation, from a regulatory perspective, is a good thing. But there are some downsides to having documentation.

To illustrate the point we were trying to make here – I’m not going to ask for your own experience, your own company – how many people think or have heard of companies where, if they choose to do a letter-to-file, that letter-to-file is built out to the extent it would be if they were submitting something to the FDA? How many people would do that? How many people would not do that?

Some of you are not being honest. I’ve seen letter-to-files that are a paragraph long. A letter-to-file is a legitimate path, but it is not an excuse to not do what we should do as engineers. That’s what gets people into trouble.

So, what’s the downside of making a more robust letter-to-file?
I’ll give you a huge hint – product liability.

I spend a fair amount of my time working as an expert witness in medical device product liability cases. And one of the cool things I like about working with my attorney friends is, they don’t limit me to what FDA may or may not require.

They want to know from me, as a professional biomedical engineer, did the company do what they should have done? Who cares if it was required by FDA or not? That’s not an excuse.

Did the company do what they should have done, from an engineering or biological perspective? That’s the litmus test here.

Now, the problem with that, when I write letter-to-files – and I do these a lot – I want to write them from a regulatory perspective to cover my you-know-what, but I also want to write them from a product liability perspective to not expose my you-know-what.

There’s sort of a fine line. Maybe, Jon, you can describe it a little bit more?

Jon Speer: Well – all of us who have been in this space – sometimes we don’t even think about the potential litigation aspects. We have a healthy fear or maybe unhealthy fear of regulation i.e. the FDA.

And it seems like, a lot of times, what we’re doing is jumping through hoops to satisfy the regulator.

And, sometimes, that lends us to maybe going a little bit overboard and thinking of every single use case or mis-use case and documenting that in our risk assessments or documenting that in our testing.

And, from one perspective, you can say, “Well, I’m being thorough.” But, from the other perspective, if there were an adverse event or something happened to the product, that may come back to bite you.

So, this is totally gray. How do you know when it’s too much or not enough? Because you get it wrong in either scenario, you could have regulatory issues or you can have legal issues.

Michael Drues: Or, maybe, both.

So, to illustrate in a slightly different way, a lot of people I work with in companies, they tell me they fear the FDA and I say, “No, no. You should not fear the FDA. You should have a healthy respect for the FDA.”

After all, as one of my friends who used to be a senior reviewer was fond of saying,

“Physicians can kill patients one at a time, but an FDA reviewer can kill patients thousands at a time.”

And that’s something that, quite frankly, more people in our industry need to remember.

So, you should not fear the FDA. Whom should you fear?
You should fear product liability attorneys because they can impose a heck of a lot more damage than the FDA ever could.

And let me tell you – I’m being deposed in one of my cases in just a couple of weeks – the product liability attorneys are much better at finding documentation that the FDA ever will be.

I’m constantly amazed because – remember, I work as a consultant for the FDA. A lot of reviewers are personal friends of mine. Some of them go back to graduate school, before some of you in this room were probably born – they’re flabbergasted when I tell them about changes.

And FDA says, “Well, we don’t know. We weren’t notified.” Well, duh. How would you ever know about a letter-to-file unless something bad happens?

So, quite frankly, the agency has not a clue as to how many letter-to-files actually are done.

I don’t have a problem with the fact that they’re done. I have a problem with the way a lot of people do them. In other words, they use it as an excuse to not do what we should do.

Jon Speer: So I’ve gotten the signal there are just a few minutes left. What do you think about opening the floor to–?

Michael Drues: I was just going to say the same thing, Jon. Let’s do that.

Jon Speer: Who has questions about change management in medical device?

Hitesh Mehta: I’ve never worked on a drug side but, on the drug side, you said changes never happen?

Michael Drues: Let me qualify that.

Changes happen but you, typically, have to notify the FDA. I’m simplifying here, but there isn’t really an analogy to letter-to-file in the drug world.

Hitesh Mehta: So, there’s always a supplement which they have to submit?

Michael Drues: Of some kind, yes.

Hitesh Mehta: Okay. That makes it clear.

Michael Drues: Yes. Sorry about that. Thank you.

Jon Speer: Any other questions? All right.

Christine Zomorodian: Hi. I appreciate the discussion we’re having. But, for my money, this is really about risk management.

If you have an adequate and robust risk management system and you’ve identified, adequately, your product risks, when you have a change and you’re considering a change, you’re looking at your risk assessment and you’re making a determination if the changes you’re making are affecting requirements that are high risk.

Michael Drues: I could not agree with you more. You and I are singing the same song, just in a slightly different key.

But here’s my point – Do we need any guidance? Do we need FDA to tell us that?

To me, that’s basic engineering. To me, that’s what they used to teach in engineering school back in the day. I’m not sure they still do.

And to me – and I’m going to set the bar very high here purposely –

Anybody that changes a medical device without considering risk, as you just suggested, should not be in this business. To me, that is such common sense.

I’m sorry. I get frustrated with the amount of micromanagement that we have with regulation telling people to do things that, quite frankly, they should know to do anyway.

Jon Speer: And I’m just going to build on that. Back in the day, design control used to include risk management and human factors and usability. When did that go away?

It’s like we keep creating these other “disciplines.” Not that they’re wrong, it’s just that they were always there the entire time. When design control regulations were rolled out 20 years ago, and even before that, if you’re doing prudent engineering and good design and development work, risk is part of that process. It’s not a separate thing.

Michael Drues: And just to take that a tiny bit further, I agree 100% but we have to be careful about overgeneralizing.

I happen to be a subject matter expert for FDA in a few different areas, one of them being risk. So we can say “to take, into account, risk management,” but what the heck does that mean? What kind of risk and what detail and so on?

So, the devil’s in the details. And I would love nothing more than to be sitting in a court being able to say, “Well, this company followed the guidance.” The new change control guidance does specify risk in it now, which I think is a no-brainer for me. But if there were aspects of risk that they did not consider, you know where I’m going with that.

What’s the Typical Timetable for Approval of a Special 510(k) or PMA Supplement?

Jeff Gable: I’ve never dealt with either one of these special 510(k) or PMA supplement. What’s the typical timetable for clearance or approval of that additional information?

Michael Drues: Good question. We’ve got a lot of real-world evidence sitting in the room. Anybody want to share your own experiences? If you’ve submitted a special 510(k) or a PMA supplement, how long did that process take?

Hitesh Mehta: Correct me if I’m wrong, but the special 510(k), there is no notification back. You just send it and it goes into a black hole and it never comes out.

[Laughter]

There’s no response back.

Michael Drues: Whew. I’m glad that it is 4:30 in the afternoon. We’ll continue that discussion at the pub, maybe. Anybody else want to give a little more quantitative number?

Response #10: … the special 510(k) does not require three months [inaudible 00:26:30]

Michael Drues: Now, we’re getting into some regulatory minutiae. But, bottom line, it depends on what product code you’re in, and it depends on your device.

We’re talking about a couple of months. We’re not talking about a huge amount of time here. But here’s the most important point, Jeff. In many ways, a special 510(k) is much easier than a traditional 510(k).

I don’t care what the contents or requirements are. I don’t care what the RTA Checklist is. The only important thing, to me, in a special 510(k) comes down to one and only one thing – to demonstrate that whatever change you’ve made, regardless of reasons, is not going to impact safety, efficacy, performance.

To me, that’s the only part of a special 510(k) worth reading. All the other stuff is pretty much copied and pasted from the traditional 510(k).

Jeff Gable: I’m a software engineer. And you can change software a lot faster than you can change hardware, which is one of the subjects of my talk tomorrow.

Say you can make software improvements, and you do the risk analysis; you do the testing; all that to make sure it’s safe, how fast can you feasibly push software updates and so forth?

Michael Drues: I’m not sure, Jeff, if you’ll like this answer or not.

Philosophically, to me, it makes no difference if you’re changing a hardware, if you’re changing a software. The mental process, the investigation isn’t exactly the same.

I’m not a programmer, but you have to go through that testing, Okay. You make this change in this part of your software. How do you make sure that’s not going to have impacts on other parts of your software or your hardware and so on?

It’s the law of unintended consequences, right. But there are zillion mechanical equivalents to that.

Let’s be honest, when the special 510(k) was created, we weren’t talking about software-based core products.

So, this is another example of how we’re taking newer technologies and trying to fit older regulatory models. I’ve never really thought about this before but, maybe, in the software world, we need a different mechanism to update FDA on those changes.

Regardless of what change you’re talking about; the most important thing is that we have that communication.

Joe Hage: Highly engaging. Highly interactive.

Michael Drues: And I’m sorry if I threw you a curveball.

Joe Hage: They don’t want to leave.

And so, you get to speak last from now on.

[Laughter]

Dr.Michael Drues and… Jon.

[Laughter]

How To Use Human Factors To Mitigate User Risk

7 min reading time

Managing the Big Risk – The User

Presented by MaryBeth Privitera, PhD FIDSA – October 11, 2018

Reading Time: 7 minutes


MaryBeth Privitera:: I like to take pictures of things. I observe people for a living, and I observe the surroundings I live in.

These are just some of the funny pictures I take along my travels.

  • Funny Pictures on MaryBeth Privitera Travels

Things are odd, but you have to look at them. We’re so busy going through life that, sometimes, you need to stop and just take a look around.

What I’m here to talk to you is about managing the big risk. And that is the user.

I work at HS Design. It is a certified design firm. I teach at the university. I like both worlds. Both worlds give me insights into a whole host of things, and given that I like to observe the world around me, that’s pretty prime.

MaryBeth Privitera is impressive.

She co-chairs the AAMI human engineering committee, is the Human Factors and Research Principal for HS Design, and teaches biomedical engineering at University of Cincinnati.

Naturally, she gave an excellent talk at 10x in October, here for your education.

About HS Design

HS Design is 40 years old. We do full service; we have engineers, designers that work there. I just wanted to give you the context of my world.

Overview

I’m here to talk about:

  • the role of the user in risk management;
  • how to uncover the users’ abilities, their actions and attitudes in the design process; and then,
  • the application of human factors.

One of my other jobs is I co-chair the AAMI human engineering committee. Human factors and usability are near and dear to my heart. I’m an industrial designer by training, even though I teach biomedical engineering.

Role of the User in Risk Management

First and foremost, if you don’t have any use risk, you don’t have any problems.

The Lowly Scalpel

Think about a plain scalpel. Would a scalpel get approved today with our current methods of risk analysis?

No, it would never get approved because you could never get rid of all the associated risks.

Users are unpredictable, and that is the point. You don’t know how a user will behave, but you can predict it.

When we do our risk and our use-risk analyses, we consider all the various ways a user could behave, but we’re very creative as individuals.

The best example of our creativity is if I were to open up everyone’s cell phone: the apps you selected, the organization … we like to customize; we like to do things on our own. That is true in every person’s being in their way of life.

This is a really good question – If a user performs the task incorrectly or fails to perform a task, could it cause serious harm?

That’s really what the agency is looking for – Could it cause harm?

Definition of Harm – CDRH vs CDER

When I look at the discussions between CDRH and CDER – for those that are in the pharma versus the device world – their definition of harms varies.

So the definition of harm according to CDER is, “Yes. You know what, a little bit is okay.”

And that’s why the scalpel stays on the market – there’s no possible way I can do surgery without doing some level of harm.

Whereas the pharma world says, “Nope. No harm. No harm at all.”

So when we get into the combination device, it gets increasingly complex, which means that you must pay attention to our use-base risk.

Know Your Users: Apply Human Factors

So what does that mean? The first and fundamental thing about assessing the user-end risk is that I have to know my user in and out.

  • Know Your Users – Apply Human Factors

If I don’t know my user, I can’t actually do an adequate risk analysis. It’s just fundamental, and that means everyone.

So good design is going to start with knowledge of the user – What are their capabilities, their education? What’s their training? What’s their bias? How long have they been there? Is there a difference between somebody that has been working in the hospital for six months versus 10 years?

Yes, of course, there is. What are they, and how does that information impact the design? How can I bring in some of the disciplinary bias?

So let me give you an example of what I mean by disciplinary bias. And we all have them.

If you were to spend a day with an anesthesiologist, you’d notice they have an entire box that they will mix and, then, they will administer their medications. If I give them an infusion pump that automates it, they don’t like it. They like to mix it. That’s a fundamental tenet of who they are.

So they (disciplinary bias) exist in everything, and it’s about control because we like control.

Hence, that’s why all of our cell phones are different. So you get to the element of creativity; you get to the element of how we go ahead and execute our life, how we execute our daily life and our daily practice. And it’s true for all of our users.

Why Apply Human Factors?

I have these two pictures from my academic world, and I think they are two really telling pictures.

  • Why Apply Human Factors?

And the reason is, someday, God forbid, we may encounter the fact that we could be that person or a loved one could be the person in that bed, in the ICU over there.

And if you look at the number of screens that are available and the amount of information that’s coming to that critical-care physician team – which is the picture on the left that is a group of critical care physicians, residents, nurses, pharmacists on rounds – the amount of information going to these people is overwhelming. and they’re going to make the decisions that impact their life.

So the way we need to think about human factors is really just making it easier for them to make the right decisions; harder for them to make the wrong decisions; and making sure that, when we consider the patient at the end of the day, they’re doing the right work for their patients.

I’d like for them to not really look at a screen but, actually, look at the patient. Those are my thoughts.

It’s true throughout the hospital. This is an example of the amount of screens that you would find in anesthesia, and you can find complexities everywhere.

  • All Devices For Anesthesia

If you look at the practice of medicine, it’s abundant. Even when we bring devices to the home care, they’re also complex. We’re not following the IKEA model of instructions for use. You’d find them to be pretty elaborate.

But this is just an example of some of the world in which we have developed.

One of the challenges that we have as device developers is, we look at our own device in isolation. We don’t look at our devices as part of an overall system, which is where we need to take a look at it from – a very specific “Here’s my user, but here’s the context with which it’s used in.”

So when we design in context, it becomes a little bit easier, a little bit better for us to consider how that user is going to make that clinical decision.

And we know, from a business perspective, if it doesn’t lead to clinical decision making, we don’t actually have a product to sell. So we have to be involved in that clinical decision and on the onset.

Uncover User Abilities, Actions & Attitudes

Someone’s going to prescribe our device; someone’s going to use our device; someone may be the recipient of that device. So how do we uncover our user’s abilities, attitudes, actions?

When we talk about considering capabilities and limitations, we’re talking really about –

  • how big they are,
  • their age,
  • their dexterity,
  • training and education,
  • their experience,
  • and their culture.

When I talk to physicians, they could be trained in a specific organization, and that is why they do what they do. It’s based on that training. They’ve always done it that way. If it’s not broke, don’t fix it.

And then, with more and more devices coming into the home healthcare, age becomes something we must consider. It could be a child that uses the device.

It could be something as simple as “how does the color go?” Color and design go beyond brand guidelines and preferences. We have to consider – are they going to be colorblind? How do we distinguish elements for one thing or another?

And that means we have to get the user feedback and asking them questions and how do they respond to the designs we put forward with them.

Physical and Sensory Characteristics

So physical and sensory characteristics include vision, hearing, manual dexterity, strength, and reach.

If you’ve ever designed a hand tool, one of the things with hand tools is “how do I actually reach all of the controls I need to reach and in what order?”

I had the fortunate experience of working for Ethicon. It was Ethicon Endo-Surgery back in the early 1990s. We did pistol grips, and it was pointed out that pistol grips for laparoscopic surgery were really ergonomically incorrect.

So, ergonomically incorrect meaning, I am like this when I do my cases.

  • Image Showing the Ergonomically Incorrect Pistol Grip

And the edict was, “Why don’t you just lower the table then, doctor?”

Well, they’re used to it. Now they’re accustomed to holding it up.

If I went into laparoscopy today, I can demonstrate very easily that, biomechanically, this is the worst position that I want my physician to stay in for 45 minutes. But it doesn’t matter because that’s how they’re trained.

And if I showed them something that wasn’t a pistol grip, they probably would balk at it, and I would negatively change it.

So there’s very much to learning manual dexterity and strength.

When I go like this, the reason that’s so bad is, every time I have a joint deviation, I have negated my ability to provide the strength in pulling that lever.

So how does that translate into the real world? Let’s just say I’m back at Ethicon, and I’m designing a linear stapler. And in order to get the linear stapler to fire two lines of staples and cut in the middle, I need to produce 75 pounds of force coming on this lever.

So, all the engineers in the room can think about the math. It’s inputs to outputs, when I think about it from an engineering perspective.

Well, I’m not physically able to do that if I’m a 50th percentile female. The reality is most people going to medical school are becoming increasingly women. So it was designed for men, but now it’s for women.

So that’s when gender size, all of the biomechanics come into play to impact the overall usability of a design. So it’s important to pay attention to that.

I find that element of design to be the easiest. There’s a great standard. It’s called AAMI HE75. It has all of that in there. Those are the easy wins.

What’s more difficult are knowledge-based tasks, cognitive task, where we are having to remember something.

And that gets to the legibility and the discrimination – How do I hear an alarm? Can I hear an alarm over the top of what else is going on in the room? And I just demonstrated for you all of the complexities of the devices that are in the room. So how does one alarm sound versus another alarm? Can I provide more cues to those alarms? Can there be a visual with that auditory signal?

Building a Better Wearable Device and Getting it Cleared Through FDA

< 1 min reading time

Building a Better Wearable Device and Getting it Cleared Through FDA

Presented by Walt Maclay, President, Voler Systems – October 12, 2018

Reading Time: < 1


How To Bring Medical Device Software Development Out Of The Dark Ages

13 min reading time

Continuous Integration: Bring Medical Device Software Development Out of the Dark Ages

Presented by Jeff Gable, Founder and Principal, Gable Technology – October 12, 2018

Reading Time: 13 minutes


Jeff Gable: Most medical device companies develop embedded software like it’s 1995. Let’s learn from modern DevOps practices to drastically improve software quality and reduce development time. If you agree, let’s get started.

Jeff Gable: Hello, everyone. My name is Jeff Gable and I am embedded software consultant. I help companies develop embedded software for critical applications, like medical devices. I have also done some work for the aerospace and automotive industries.

The topic of my talk today is continuous integration. This is a software development practice that’s kind of taken the web development world by storm, and I want to evangelize it and bring it to medical device software development because I think it can help us a lot.

Putting medical devices to the side for a second, let’s talk about traditional IT organizations that would make web applications for their internal business processes. You know, circa 2005, you have lots of engineers working on different features, you have these development branches running in parallel. Merging them together is very, very painful so people avoid it. They keep going longer and it gets more and more painful.

There was very much a “throw it over the wall” attitude from the software developers to the IT operations people. You would often see that marketing has set a deadline for this application – to be released on Monday. It gets thrown to the IT operations people at 5pm on a Friday and, “Have fun deploying this over the weekend.”

There were a lot of manual error-prone developments, probably poorly written instructions, and people didn’t have much of a process how to get applications to deployment.

The Results

That results in what you think it would: very low-quality software. The iteration time was measured in months. A lot of these applications are on a release schedule where every nine months they come out with a new version of the software. That means that if someone in marketing or the business side has an idea that they want to test with the customer, they must wait months to get an answer.

Arlen was talking yesterday about getting answers: He wanted to do simulations to get answers faster on the technical side. Likewise, on the business side, if you have a hypothesis you want to test with the customer, you want to get answers quickly. This very slow, high-latency software development process just kills that effort.

There are a lot of people who’ve done work in the manufacturing industry on speeding up the manufacturing process and reducing the latency of the manufacturing process. You can respond to the market needs more quickly.

If there are any MBAs in the room, you may have heard of these books. There’s the Toyota Way. Toyota was a company that really espoused lean manufacturing methods and developed a lot of groundbreaking efforts.

There was the Theory of Constraints. These principles from lean manufacturing have been applied to great effect in the manufacturing world to increase the responsiveness of the manufacturing process to the market, and some very smart people looked at that and said, “Hey, why don’t we start applying these principles to software development?”

This revolution that came out, you may have heard of the term DevOps – that’s development and operations smashed together.

I’ve heard a lot over the course of this conference about breaking down silos, trying to get people from regulatory and development to work together. One of the tenants of systems engineering, as Martin said, is getting these different stakeholders in the room and having them all contribute to the process. That’s the core of this DevOps revolution that has taken the web development world by storm.

The Three Principles

One is to apply systems level thinking, and the system I’m talking about is the business system. You have ideas that for the business that you want to test in the marketplace. And you want to reduce the amount of time that it takes for that idea to get in front of a customer, so that you can validate that hypothesis.

Second is to improve the feedback loops. So again, getting it to the customer. You can test that hypothesis, getting that feedback back up to the business, but also various stages in the process that there any defects that are passed down stream, you want immediately to, to flow back upstream that information to fix the process and not allow this to continue.

Third is to foster a culture of continuous improvement. This last one is doing things like prioritizing the flow of daily work almost as much as the daily work. A lot of people think, we’re too busy, we’re late on our projects, we’re behind, we don’t have time to invest in making our process better.

There are some good rules of thumb in the software world, that you invest 20% of your effort in every development cycle to improving your process. So that’s kind of a good metric to follow.

That way 80% of your time is spent getting work done, so you’re not, you know, completely ignoring that. But every development cycle, you’re investing 20% your effort into improving your process.

Let’s get concrete.

At least from the software development and operations side, when a software developer has written code for some feature, and they commit it to version control, there are a lot of steps to happen before that’s deployed to the customer.

You may need to provision a server, they need to install a bunch of software packages, they need to configure the network settings, whatever it is.

There needs to be a unit test or acceptance tests. It needs to go to staging for a little while for testing, and then go to the production servers.

These different steps that go there and again, back in the day most of them were manual and error prone.

What people have started to do is just automate that. All of it. And it’s surprising how much of the process you can automate.

Particularly you might think that something like provisioning a server is hard to automate.

Well, nowadays, there are software tools that people have developed as part of this effort where you describe your infrastructure as code, you have human readable text configuration files that say, “I want this server and I want it to have these libraries, and they better have this minimum version.”

And nowadays, with all the servers being in the cloud, you almost must do it that way. These configuration files that describe your infrastructure, again, they’re stored in version control with your application code.

You really can’t say, “I have an application and there’s some dependencies such that if they’re not there, the application doesn’t run right, so I’m going to have some written instructions…” No, those should actually be stored in text right along with the source files for code. What this gives you is repeatable, guaranteed deployments of applications.

As a result, what you get is high quality software, and if you can automate all this, your iteration time can be measured in hours. Going back a few years at a typical enterprise, you would have this deployment frequency of every nine months, you would get a new version of software.

If there were an urgent business need, you had to go through all of those manual steps over months. Because you had this very slow feedback time, you had low quality, low responsiveness, low reliability. You couldn’t get quickly get fixes to the application if you discover them in the field.

This chart is from a book I’ll show you later called the Phoenix project. But this was, I think in 2012, Amazon was doing 23,000 deployments a day. What that really means is that each deployment is extremely small. I see a bug, I fixed it, I kick off this process, and a few minutes later, it’s done, it’s live, it’s going to users.

Now, in order to do that, you must have really, really solid testing. But that’s part of your responsibility as engineers, is to make sure that all the testing that would you would do to do your due diligence to make sure that your code is okay to go in front of customers, that all of that is built into this automated process.

You can imagine what that does for the business in terms of enabling new experiments to be run. A marketing person come up with an idea and you can have code in front of customers the very next day testing that out to see if it works. It really changes the business side of things, speeding up software deployment so quickly, and it’s now the industry standard in web development. If you’re developing a web application, and you’re not doing this, you are way behind the times and you’re going to go out of business because you can’t keep up.

I’m on a mission to take these lessons and apply them to software development for medical devices. I want to evangelize how we can apply these lessons to solve a real demand for medical devices, because I’ve rarely seen it done.

Prerequisites for continuous integration

One, your software has to be in version control. If you’re not version controlling your software, you’re in big trouble and you’ve got bigger problems, so please come see me afterwards.

All version control is not alike. There are more modern version control systems that are much less painful to work with for developers. Git is the most popular one in the world right now. It’s been popularized by sites like GitHub.

The second prerequisite is that your build process – building your executables that actually get flashed onto your device – that build process has to be fully automated.

You can’t be working in an IDE (an integrated development environment) where someone uses their mouse pointer to click build and then configuring things… No, you type in a command and it goes and does the rest. Once you have that, you can start having little robots on the internet do that for you all the time. And it’s wonderful.

The next thing you do is to start adding automated testing. There’s a couple of different levels of this. There are unit tests, where you’re testing low level functions of your code, and you can run them on host computer rather than on the target device that maybe is running a different processor with a different architecture.

I’ve heard a lot of people complain, essentially, no, no, my code runs on this device only. It’s dependent on the hardware and it’s just not unit testable.

To which I say: bullshit. It can be done. It is worth the effort and going through that exercise really forces you to have good modular software architecture.

I’ll show you the book “Test-Driven Development for Embedded C” later. It walks you the process. I don’t know that many people in this room are going to go through that exercise themselves, but if you hear these excuses from your software engineers, have them call me.

Then, there are integration tests, which are maybe more common these days. This is where you’re running code on the actual device.

You can still apply a fair level of automation to that, especially if you build in scripting and data instrumentation capability into your embedded code.

At that point, you can have something running on the host, communicating with the device, saying, “Run this command and give me the data back,” and you can verify that. It gets to be a little messier in the real world because hardware sometimes fails. It’s not as predictable, but it can be done, and you can create special test images of the software with very limited capability to exercise the hardware in a certain way.

We see, again, that principle of infrastructure as code. It’s a very common problem in software development for different engineers to say, “Well, it builds on my machine, I don’t know why it’s not building on yours.”

There again, you can create your build and development environments by describing them with configuration files. These could create a virtual machine that would have the compiler, the flashing tool, and probably your development environment with your debugger, and everything else. I’ve been working this way for five or six years now, where I do my software development in virtual machine, and it’s fast enough to where it works.

At that point, you’re guaranteed that everyone who’s working on this project has the same development and build environment, and then you reuse that on your build server. This automated build that takes place uses that same configuration.

Putting this into practice

Now, this next part may be getting a little too in the weeds, but at least I’ll give you an overview. If you’re in an organization, and you say, “Hey, that sounds great. I actually want to get started with continuous integration.”

First, you buy build server, and don’t skimp. You make it really, really fast. Lots of RAM, lots of processor speed.

There is continuous integration software out there. For open source options, there is one called Jenkins, and there’s another good option called GitLab. There are several others that are paid.

The very first thing is to have it run your builds automatically, every single time you check into version control, and email you if there’s a failure. All of these tools come with nice, pretty dashboards, which show you the latest status. Then you slowly, over time, invest 20% of your effort into adding tests, defining more of your infrastructure, and just improving everything that you’re capturing there.

This is an example of a dashboard of a continuous integration build. I stole this from someone’s talk on the web [“Microcontrollers in Micro-increments” by Mike Ritchie, CppCon 2017].

This is checking out the latest version of code, and then you have different unit tests and you’re running it with the debug configuration and the release configuration. If any one of these steps fails, it immediately stops the build and lets you know. Your highest priority is to fix that issue, and only then move on. This way, your code is always in a working state.

And you can see that there’s a lot of things you can put in here to do very robust checks of your software, and know that if you check in software, and it passes all these tests and you’ve done your due diligence, and you’ve done this properly, by definition, then it is suitable for deployment.

At this point, I have an open question for the group.

Medical devices are not web applications. We are highly regulated. The FDA is an important part of the deployment chain. So, an open question is: How fast can you make that process?

This is all predicated on the fact you did your due diligence and you’re comfortable. I’ve made a software change. I’ve tested it and analyzed it well enough so that if my spouse or my child were using this medical device, I would be comfortable with the software change.

At that point, and only once you satisfy that condition, what’s the fastest you can deploy to your device? If that involves the FDA, what are the steps you could do? Again, it’s an open question for the audience. What can you do to speed that process up?

Walt McClay: So, not all deployments require FDA approval. If it’s a simple deployment, you can deploy it immediately. Of course, if your device is somewhere out in the field, you have to find it and update it.

Maren Nelson: I’m Maren Nelson, and I have done a little bit of medical device software in my past. As Walt mentioned, there is a straightforward assessment you can do on the software, even before you get to the point of deployment, to know whether you’ve got to bring the FDA into that or not.

The other part of the deployment chain is the end user. Because if you’re making a change that impacts user interface or anything like that, you may have training and other things to address. So, I think it’s important to keep the user as part of the deployment chain as well.

Jeff Gable: Absolutely. I wanted to bring up the FDA part, because inherent in that is the assumption that you have done all the analysis that that you were doing the right thing and that you’ve checked all the boxes for the right reasons, not just to check boxes for compliance.

Walt, you mentioned updates over-the-air updates.

These days, web applications have continuous delivery. The engineer checks in code, and a few minutes later it is deployed live to real users. Maybe it’s in a staged fashion where they’re looking for problems and would automatically roll back if there were problems. But instead of continuous integration, that’s the next logical evolution. That’s continuous delivery.

I don’t think that’s feasible for medical devices. I’m not suggesting that it is, but you can certainly greatly increase the cadence, the frequency of your releases. What can that enable?

Tesla does a lot of things that I disagree with, but Tesla has shown the automotive world what’s possible in terms of, they just push something to your car and now your shocks ride differently, or they’ve solved an issue in the field.

They are getting reports of a problem and a week later, they have pushed a fix and it is running on everyone’s cars.

So again, just use that as inspiration to spark your imagination for what’s possible and whether that enables you to work differently, to test business hypotheses in a different way that maybe was not feasible before. All that requires the engineering of over-the-air update. But it’s doable, and people are doing it a lot.

Joe Hage: What about legacy systems? I mean, it would be ideal to be able to change everything everywhere. But we’ve had a system in the field for the last 10-15 years. Does it mean we’ll just have to wait till the next generation of product? Because it’s just too much to reverse and …

Jeff Gable: A lot of those have no means for updating. Some of them do, but you have to ship USB sticks to your customers. So, what I’m what I’m advocating for is a new way of engineering new products.

Christine Zomorodian: This is happening. There are legacy products in the field for large device manufacturers are already receiving remote service. This is already happening. They do it usually through the hospital it. They’re connected to the network.

There are huge issues around cyber-security. Joe and I were present for a presentation in Washington on this topic where we had the manufacturing side and the hospital institution side.

It’s happening though, because these guys, especially in imaging systems, they have to get the software out there and they can’t afford of when servicing it to deliver a USB stick and they can’t hand it to anybody else. It’s already happening.

Jeff Gable: Sure, it’s just very painful.

You deal with legacy systems the best that you can. What I’m advocating is, for your new products, use this process. Even if you don’t worry about the deployment, the increasing the cadence of release, using continuous integration during the development, until release, speeds up the process so much.

It’s breaking down the silos, like in the web world between development and operations, and in the medical device world, it’s been between development and QA.

So, involve your QA people’s creativity to automate these tests. How can we describe in computer code how you are testing this device, and let’s code that up and then we can automate it.

You don’t have to run the same manual test every time you do a release. Tests can get run automatically. It’s definitely useful during development.

Ryan Carpenter: I thought I’d point out, it’s not only software, I’m seeing several hearing aid companies delivering firmware updates via apps.

And, well, I know the old way too; I worked with a product manager in Sydney that at the time, it was shipping CDs for updating firmware.

At any rate, I’m seeing that happen, where several new manufacturers are delivering firmware updates over the air through apps. Many of the legacy devices don’t have the same full capability as the most current wireless hearing aids, but they do have older wireless technology, so some of them will use a streaming device to connect to a phone for example.

Jeff Gable: I would say this about over-the-air updates. So, to anyone who is selling a connected medical device.

FDA has issued guidances on post-market cyber security. A lot of those connected medical devices are using open source libraries. Security researchers are pounding those libraries all the time and finding new vulnerabilities.

If you don’t have a list of what libraries are on your device, and you’re not monitoring the central worldwide database for new vulnerabilities, and you’re not getting latest versions, and then patching your device… It’s the reason you get updates on your iPhone and your Android phone all the time.

They are constantly finding and fixing new vulnerabilities.

People are still designing medical devices with no way to patch, and so now you have medical devices on hospital networks that are completely vulnerable. It used to be, well, if it’s on the hospital network, it’s the hospital’s problem. The FDA is starting to change their tune, so they expect you to be able to patch for security reasons.

Joe Hage: I know this is a terrific layup for you. But let’s say they employed you as their consultant. What are you going to do about it?

Jeff Gable: My role is, I help people develop embedded software better. I have two sides to my consultancy – I do coaching where I help clients improve their process, and also help them early in the product design process, to flush out their development plan.

I bring the technical side to systems engineering, where I have enough knowledge of all the different engineering areas to be able to intelligently spot problems.

Then, on the development side, I specialize in firmware development and control algorithms. Not as much the cyber security, but I know enough to be to be dangerous, and at least spot the problems.

Resources

I’ll close by adding, if your software engineers are giving you the excuse that they can’t do unit testing on their embedded hardware, give Test-Driven Development for Embedded C by James Grenning. It’s wonderful.

The Phoenix Project is a business novel that describes the revolution of DevOps. Like most business novels, it’s cheesy, but it is a little bit easier to read than, say, this one [The DevOps Handbook] which is the same information presented in textbook form.

Even not working on web applications, working on firmware, these two books were really eye opening for me, showing me this whole world of capability that’s possible.

Thank you!

A New Take on Prototyping that Could Save You Millions

17 min reading time

A New Take on Prototyping that Could Save You Millions

Presented by Doug Fankell, PhD, Structural Integrity Associates, Inc – October 12, 2018

Reading Time: 17 minutes


Dr. Fankell: Arlen is much more in the energy tissue interaction world. So hitting it with lasers, hitting it with ultrasound, things like that. I’m much more in the looking at the structural mechanics’ side of things.

Editor’s Note: Doug gives a fantastic presentation. At its conclusion, a lively conversation breaks out about predictive modeling versus simulation (from Arlen Ward’s presentation the day before) in bringing your medical device to market in the most efficient and cost-effective manner.

Doug Fankell: I’m going to talk about a “new” take on prototyping that could save you millions. It’s not necessarily new. And it’s going to be following up on some of Arlen’s presentation yesterday as well.

So just to give you a little bit of background about me, I’ve sort of been all over the map for school. I did my undergrad and master’s at the University of Wyoming, and UC Berkeley in structural engineering. So I have a weird roundabout path to how I ended up in biomedical device design.

I actually worked as a structural engineer for about a year and a half, decided I didn’t like it, and so I ended up at the University of Colorado in the Advanced Medical Technologies Lab working on both device design and then, more specifically, I was working on using analysis and finite element analysis to actually inform how we design these devices.

I graduated there a little over a year ago, I guess, and then started at Structural Integrity Associates where they’ve been doing finite element analysis of really hard nonlinear problems for a long time.

We have kind of 250 highly technical staff all over the country. We have some material testers, some material scientists, and they specialize in advanced nonlinear mechanics and FEA in highly regulated industries.

So they started in the nuclear power plant world which is very regulated and, since then, have expanded into different industries, such as aerospace; we’ve done a little bit with automotive, but I’m kind of their first foray into the biomed world.

They had all these tools, but they didn’t have anyone that really liked working on tissue and devices and things like that. So that’s where I came in.

So just to give you a background, I’m going to tell you a bunch of numbers that you guys probably have more understanding of and a better idea of than I do – about how much it costs to bring a device to market. And then hopefully, I’ll open your eyes on some benefits of using predictive computational modeling and then give you a couple of examples of projects that I work on that I can sort of talk about, and then just talk about where I think this is leading as well.

Background – Cost of bringing a surgical device to market

So here’s a general study that was done by Stanford in 2010 where they say it costs an average of $31 million to take a 510(k) product to market from initial concept, and an average of $94 million to take a PMA product to market.

So if we can reduce these numbers, I’m sure people would be very happy. And so where I’m really going to talk about how you can use computational modeling to help this is in the concept development and proof of concept areas, and then also how we can use it to inform our clinical tests and things like that.

Let’s make experiments better; let’s make our tests better so we actually know what we’re looking for before we spend all this money and then realize we have to reduce that.

Background – Time to bring a product to market

This talks about the time it takes to do this. So you see, on average, it takes a 510(k) product about 20 months just in that concept development and proof of concept phase.

I know that’s pretty widely varying depending on the type of product you have and what you’re doing, but just to give you a general idea. We’re going to hopefully help you reduce that time.

Background – Estimated costs of delays for a 30-person company

And then lastly, it comes down to money. Estimated costs of delays for a 30-person company, so eight-week delay. Sheldon et al. estimates that it costs a company about $1.8 million; 20 animal study, $5.5 million. I think that was for a year of work as well and a year of delay, and same with the additional hundred patients’ study.

So these are big numbers. So if you can avoid doing additional studies and reduce your amount of delays– I’m not exactly reinventing the world. That’s what everyone’s been talking about throughout this whole conference – let’s do things better to save money and make better products.

How Advanced Predictive Computational Modeling Can Help

So how can we use predictive computational modeling to help us? Well, you can reduce your time to market. You can speed up the design iteration process, so you can do more iterations. You can build a better device.

Again, I think there was a talk earlier today that was talking about, we need to get back to focusing on people and focusing on what’s our ultimate goal when we’re designing these medical devices.

We want to help the patient. We want to build better products, and a byproduct of that is hopefully we’ll also be making more money with these better products.

You can foresee potential errors that you might not have thought of as obvious before you actually are building these devices, and reduce experimental testing, and then also improve what you’re looking for in these tests, improve how you conduct these tests and the likelihood for FDA approval.

My boss asked me to summarize this in one concise statement. And it’s “I want to help produce safer, more effective products faster.” That’s the end goal. I know that’s very general but, again, I think if we don’t look at the end goal, we are going to get bogged down in the details and lose that.

Predictive Modeling

Arlen touched on this yesterday. Until recently, modeling of medical devices, I felt like it fit into one of two categories.

  • We’ve either looked at the device itself – but then how do you model it in vitro? With all the soft tissue that’s acting on it, how do you actually model those boundary conditions? That’s really hard. And then what’s it doing to the body? You’re putting something foreign into the body;
  • or we’ve looked at the tissue itself.

A lot of people have struggled at actually combining those two – looking at how medical devices interact with the tissue and how they actually work. So that’s what my PhD was focused on, and then also what I’ve been working to do now.

So predictive modeling, now it not only models the device but also the physics within the tissue when it’s acted on by the device.

So this could be simple like:

  • Deformation. If you have a needle and you’re poking it through the skin, what’s going on in the skin? What stresses do you need to reach to push it through the skin?
  • Fluid flow through the biological tissue. My thesis was developing a thermoporomechanics model of biological tissue I won’t bore you with. That’s a lot of math. If you ever want to see it, I can send it to you. It was like 2000 equations or something in my thesis.
  • Within the biological tissue. We can look at temperature, chemical reaction, tissue remodeling within the biological tissue.

And honestly, most of the time, we have to do many of these things and explain how they affect one another.

The Design Iteration Process

So again, this is a very simplified slide but I think it really hammers home the point of – this could be a device; this could be even just a little portion of your device – “You have some need that you have to meet, right? You come up with ideas of how you’re going to solve that need, you design a prototype.” Only, most of the time, I swear I spend half of my time in SolidWorks.

But you come up with the design, you come up with ideas for this design, then you produce. You’d say, “Okay, this is the best one. We want to produce this prototype.” Or maybe you come up with a simple prototype of three different designs, then you test it, and you go through this loop over and over and over again until you get down to the design that works the best in what you want.

Well, I’m proposing that we want to speed up that design. So you still have your need; you come up with a bunch of ideas; you prototype this digitally in SolidWorks or in whatever you feel like you want to prototype it in; and then we simulate the design performance.

Now, this could be as simple as doing stuff that we already have the tools to do. Or maybe we have to do some laboratory benchtop testing to validate the computational models.

A lot of the times, even just doing simple computational models, you discover new needs or you’re like, “Oh, this might not actually do what we want it to do.” So then you go back, come up with new ideas, come up with new designs, but you’re not having to build any physical prototypes and take that time to build those prototypes.

From that, you can also say, “Well, this one looks like it is the best design.” But now, instead of coming up with 10 designs and then narrowing it down to one, maybe you can come up with 100 or you can do an optimization study and narrow down on what you think the best design, produce that, test that. And then lastly, you get additional experimental input or you can look at what you might really want to focus on with your testing. It just helps inform that testing as well.

Example I – Arterial Cutting and Fusion

So now, I’m going to take you through a couple of examples because this is all great theory, but unless you actually see how it’s applied, it doesn’t really matter. Right?

So during my Ph.D., ConMed Electrosurgery was really interested in developing a model to inform and speed up their design process. So this was taken a while and it was of their tissue fusion devices which they used to both cut and fuse arteries.

And the goal was to develop a predictive FEA model – we knew we were going to use experimental data, but they didn’t want to use a ton of experimental data. And most of the data that we used was stuff that they were collecting anyways as they went along – and then use that to inform device design.

So I came up with a model. This I ran on my desktop computer with six gigs of RAM. It was back four or five years ago.

And this is kind of what it looks like. The top, you’re looking at the Isochoric Strain Energy, which is a fancy way of comparing things to stress and strain. It was a more informative value, I guess, and then temperature at the bottom.

And from this and then from a little bit more experimental testing, we were able to actually take these terms and come up with a way of measuring the damage in the tissue. And then actually I wrote a little user subroutine that modeled how the tissue was mechanically being damaged.

And we didn’t care if the cells were staying alive, we just cared if there was actually a mechanical strength left in the tissue or if it was being cut all the way through.

And we were able to predict pretty well. This is my favorite picture. I always have to put this caveat of “Not all the pictures lined up exactly like this,” but this test actually ended up doing that. We were able to say, “We’re going to predict the outcome of this surgery.” We were able to do it almost 90% of the time. And we were also able to put bounds on “you have to press this hard with this device, and you have to get it this hot, or you’re not going to see cutting or you might only see it 50% of the time.”

And we ran a whole parametric study on different artery sizes, on different temperatures and different pressures, and all kinds of different things that really provided some insight.

You see on the right side there, there’s sort of this little ridge. They wanted to get rid of that ridge, and I ran several simulations and said, “If you get rid of that ridge, you’re not going to be able to cut the tissue.” And one of the more experienced people there was like, “Oh, yeah. 30 years ago, we tried to do this without that and they were like, ‘No, we couldn’t cut the tissue.’” So little insights like that into the job design are pretty interesting.

So, really, these FEA models were used to iterate the jaw shape and the control parameters. We could run tens or hundreds of optimization simulations in the time it took them to build one physical prototype of these jaws.

And then we were able to do parametric studies. And there were still some upfront V&V experimental tests, but they were doing these anyway. But now they have these tools and this understanding of the tissue to where they just have to go back and validate their models. That’s a big thing in the nuclear world.

We have lots of good ways of validating models because they don’t really let you test anything nuclear anymore [laughs]. Or it’s very small scale. So just the statistics behind that as well.

Example II – Tubes

And then another example. I can’t talk too much about this one. That first one was more of a big picture – how does this affect our whole device. This was just a very simple part of their design process but it was causing pretty significant delays.

They needed a composite tube casing, and they needed special holes within the tube in order to house their tooling. And this casing needed to be able to be pushed through an artery, but if it crimped at all, it just damaged their tools pretty significantly.

And it was taking them six to eight weeks to get these special custom tubes. So they’d have to get the tube, they’d go test it in the lab, be like “Oh, it’s not as stiff as we need,” or, “It’s too flexible. It’s not what we need,” as they’re trying to push it through some pulsing arteries.

Including the initial benchmarking of the material which they had already done – they’d gone through several iterations of this – we were able to come up with numerous design ideas and run simulations of them in the amount of time it took them to get one. Or a lot of the time, my colleague over there said that they would order 10 different types because it was taking six to eight weeks for them to get these tubes in the [case?? 00:13:04].

So this is just one very small part of a design that was causing pretty significant delays in them moving forward with producing their product, where it was something we could really help them out with and say, “Yes, let’s run through several iterations on a computer and come up with the best design. And then you can have that produced instead of having to wait six weeks just to get a product that wasn’t working how you wanted it to do.”

Summary

So just summarizing everything, what can we do with predictive computational modeling? Well, we can come up with faster design; you can iterate more quickly; you can iterate more so you can converge on a better solution, and you get additional insight into the performance. Then you get a better design product. You hopefully see better performance during testing, and you see less testing or what you need of less testing. And then lastly, hopefully, you get a better product; it gets to market faster; and it costs less.

That’s the ideal world. And this is just one way that we’re helping companies do that.

Future

And then lastly, looking at the future, Arlen touched on the ASME V&V 40 that’s supposedly coming out with guidelines this year.

And then, one of my favorites, he also touched on the high computing performance scene, like if you have a laptop, you can run these hundred-core simulations now. And it’s a million degrees or 10 million or 100 million degrees of freedom. And the simulation is not a problem anymore.

And then lastly, my favorite quote was from a paper that just came out from the FDA, where they say they believe computational modeling is poised to become a critical tool for accelerating regulatory decision making and adopting this will be essential for advancing their mission.

So that’s speaking to where this field is going and how important being able to use these tools effectively is. And with that, I’d love to answer any questions.

Joe Hage: I’ll start. Dr. Fankell?

Doug Fankell: Mhm?

Joe Hage: Respect, man.
[laughter]

Most of what you said went over my head, but that’s when I know it’s really good. And I never really thought about the parallels between the structural work that you used to do and the structural work that goes into making a medical device. It’s just, I don’t think everyone in TV Land, certainly I, would have made that intuition.

You referred to Dr. Ward’s work yesterday. And both of you are on different planes as it relates to simulating. He talked a lot about as it relates to clinical trials and animal testing, and you talked about it from another angle. Where do you see your work overlapping and where is it quite different?

Doug Fankell: I would say mostly, it’s different in our expertise. So we both got our Ph.D. looking at these vessel-sealing devices.

It was kind of funny, but I’ve been meeting with him. We’re both in Denver as well. But we hadn’t met until about six months ago.

Joe Hage: Oh, you knew one another.

Doug Fankell: Yes, we do.

Joe Hage: Okay. Go over one another’s houses at all or…?

Doug Fankell: [laughs] We have coffee every now and then.

But he’s much more in the energy tissue interaction world. So hitting it with lasers, hitting it with ultrasound, things like that. I’m much more in the looking at the structural mechanics’ side of things.

And honestly, they do overlap some. Very rarely are we looking at one physics anymore. My Ph.D. thesis was looking at the fluid flow, and the water becoming vapor, and how it was expanding the tissue, and what was going on as far as the deformations of those tissues. So there is some overlap, but I would say I’m much more of the structural mechanics’ side of thing, looking at structural damage, not necessarily thermal damage, Arlen Ward: I think the last time that we met for coffee, this was one of the things that we talked about quite a bit because it’s easy to say, “Oh, we both work in simulation so we’re natural competitors, right? People that would work with me would work with him. So one of us will be losing out between that.”

But really, in the conversation, what we realized is, there’s a lot of different areas of expertise that people outside of the simulation world may not really have an appreciation for.

And looking at it more as “we have a network of people that each are focused in different areas,” it helps when a device company comes to me and says, “We have a problem.” A good example of that is insertion forces for needles. My response to that is, “I know someone you should be talking to.” Could we do it? Yes, probably, but I know somebody that can do it a lot better than we could, and point them in that direction.

And being that connector like you and I talked about before, I think, is going to be necessary in the simulation world as it relates to medical devices because we can’t expect medical device companies to have that knowledge of the entire area.

Joe Hage: One more thing and I’ll come right to you, Tor and Hilary.

Because I don’t understand the discipline like you doctors can, I think about design and development firms as “I’m going to delegate that. They’re going to design and develop it for me.”

And this term about structural integrity and all of these things, they never even occurred to me. I don’t know, – and Torey, you are a great person to hand the mic to – should I think most design and development companies have this expertise or do they typically need to find someone like Doug or Arlen?

Tor Alden: Sure. We talked about this a little earlier. So as product development firms, we have simulators or some of the lower-end ones. We get in trouble when we start working with non-Newtonian fluids and other things.

Even though we have these capabilities and we rush to make prototypes and prototypes, – you mentioned the needles puncturing through tissue. That was one of the issues that we had – the challenge for us was really to convince the client of the importance of getting the simulation versus going into actual [?? 00:19:00] testing.

And so we ran into trouble when we actually tested on animals because after one or two needle punctures, the needle dulled slightly and the whole instrument blew up in our hand. So we had to go back to the drawing board, and the needle became the issue. But if we had earlier involvement with companies like yourselves, we probably could have avoided that.

But again, the challenge is, how do we sell your services to our clients?

Joe Hage: So I’m curious, because I know time is a premium, you want to get the market. And I guess in most cases, time is more valuable than money.

But I wonder, if I were in this business and I had to make these decisions, I have a certain cost associated with you, but I might be able to avoid it if the testing goes fine and I didn’t have the dulled needle, so I saved. But when it didn’t work out that way, how much money did it cost to do it again, not to mention the time? And would that be exactly how much he charges or a fraction of it? Do you have a perspective on that? Or you, Tor?

Doug Fankell: I would say that’s exactly the argument that I’m making. You can avoid all these delays.

I’m trying to remember who was talking yesterday where they were talking about the cost of finding out these errors later on in the process. I mean, it’s 500-fold or a thousand-fold or 100-fold. It’s much more expensive.

And then also, just coming up with these computer models, while it’s expensive, animal testing can get really expensive really fast if you’re not careful. And so I would say you can both look at it from a time aspect. I mean, I can set up 15 simulations and run them overnight. I can press go on Friday and have an answer Monday morning.

Joe Hage: Do you think it would be a fair parallel to say that hiring someone like your firm for simulations is like an insurance policy, like I’m paying a certain premium to mitigate risk?

Doug Fankell: I would say, “Yes, that’s one way of looking at it.” Maybe not necessarily the whole way of looking at it. We also can help drive innovation by being able to test your crazier design ideas and things like that.

Tor Alden: I think we actually ended up using more finite element analysis to our advantage when we started looking at the different needle tips, whether or not it was a single probe or a trilobe. As we worked through it, we let the simulation do the work. And then we were able to optimize prototype, then go back and take that prototype and optimize it again.

But it wasn’t a clear yes or no answer, where I think in our world as prototype or product developments, if you CNC something out of ABS, you’re 98% sure it’s going to work. Where in a finite element analysis, it’s a little bit more fuzzy, I think, to people that are untrained in it.

Doug Fankell: Yes. It can be–

Joe Hage: I want to follow up with Tor and ask, “You have a better sense of your competitive set. As I said immaturely a few moments ago, design and development firm, you know, they’re going to design and develop. How many design and development firms typically have functional expertise like Doug’s in-house? Would you say quarter, half or third?

Tor Alden: So I think everybody will say they have it, but I think whether or not you’re using SolidWorks simulator versus ANSYS or whatever you’re using, there’s a different level of functionality and capability.

And then it’s also who’s developing the parameters of the test to make sure the test is actually working. So yes, we can say we have it, but are we doing it efficiently and correctly?

Doug Fankell: I have a whole soapbox about SolidWorks simulation because it’s making things easy [laughter]. But as Arlen was saying yesterday, unless you’re doing a good job validating and verifying A. that it’s doing what it should be doing, and B. that it’s actually simulating the physics that’s going on in the world–

Joe Hage: The reason I’m going a little beyond time on this is I think this issue is probably something that the folks in TV Land face a lot. Because I know, as I said, I would be clueless about that.

If my design and development firm says they can do that, they can do that. So what kind of questions would I ask to even know that “well, could ya?”

Because I’m thinking – and correct me if I’m wrong – most of your clients are companies like Tor’s that do design and development instead of the manufacturer themselves because they don’t even know that they should really be asking you. Is that true?

Doug Fankell: Yes. That’s definitely been the people who have been most interested in working with us.

Joe Hage: Is that the same for you, Arlen?

Arlen Ward: Yes.

Doug Fankell: I would say asking a simple question like “how are you validating this model? How are you proving to me that the model is doing what you say it’s doing?”

That was what I spent a big portion of my thesis on. Great, I developed this crazy mathematical framework. Now, actually, is it doing what I hope it’s doing?

Joe Hage: At the end of the day, I’m going to talk a bit about medicaldevicesgroup.net – this site that I lead and I want it to be extremely useful.

Just talking with you, I’m thinking it would be great. I think everyone in this room can contribute to it. What is the compendium of questions that you didn’t even know to ask, you didn’t even know it was going to be on the test? Because I’ll meet physician entrepreneurs who have a great idea, and they’re like, you know, does hmm. And they won’t know to ask these questions in the first place.

If we could put together a resource of– It’ll be exhausting and it’ll be intimidating, but if you show it to the right people, did you ask these questions? If you have electricity running through it, did you ask these questions? Does it have IoT? Put it. How will it interact? All these things.

So, a group effort is really the spirit of the community that I attempted to build. And Hillary, you have a question?

Hillary Sweet: Yes.

So I’m just wondering if you have anyone that comes to you, not on the large manufacturing side, but with an idea of “we have this problem and we don’t know where to start?” Do you have anyone who comes to you and says, “What material or what thickness?”

I’m thinking of a particular application with someone who’s working on a urethral stent that continues to clog. I’m just thinking this could be really helpful for something like that.

Doug Fankell: Oh, definitely. We definitely have had some of that. You get people that are again, like you said, almost sort of clueless – I have this idea, but I have no idea what to do.

I used to deal with it. I’m an adjunct advisor of a grad design team, and they came up to me and they were like, “Oh, we have this great idea and this great design.” And I looked at it. I was like, “Well, you have to make that three times thicker, otherwise it’s just going to break every single time you even–“

Just little things like that.

Joe Hage: Were they like, “What do you mean?”

Doug Fankell: Yes, exactly. And I asked them, “You are engineers. Have you done any mechanical analysis on this?” And they were like, “Oh, no.” I was like, “Don’t be scared of equations. It’s okay.”

Joe Hage: Well, you have 2000 in your paper. So where can we read 2000 equations in case we—

Doug Fankell: Uhm… I can—

Joe Hage: I’m joking. I have no interest whatsoever in reading that document.
[laughter]

Ladies and gentlemen, Doug Fankell. Thank you very, very much.

Doug Fankell: Thank you.
[applause]