The tale of an Afib Device, Novelty and the FDA

Here is the link to the story:
http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/13882

Atritech
Atritech (and not Artritech as mentioned in the Med Page article, as of this blog's publication time) is the manufacturer of the "Watchman" device, dubbed to be a "novel AF" device that the FDA has marginally approved as comparable to Warfarin.

The novelty:

The novelty part seems to be partly in the parachute shape and maybe in its implantation and somewhat in it's function? The article is quick to endorse the "novelty", yet lends no explanations to where the roots of this novelty lie.

The device:

Here is some information about the device:

1. The device is approved for "warfarin-eligible" patients with nonvalvular atrial fibrillation. (We will discuss what all this song and dance means shortly)

2. In terms of size, it appears that the device is about an inch in maximum diameter.

3. Placement: Left atrial appendage.

The idea behind the placement apparently is to block off the left atrial appendage, because it is assumed that the left atrial appendage is the major source of blood clots in patients with Atrial Fibrillation.

For evidence, look up this review of the Left Atrial Appendage Occlusion Study (LAAOS). (It's free by the way):

http://stroke.ahajournals.org/cgi/content/abstract/38/2/624

"Warfarin-enabled patients with nonvaluvular atrial fibrillation"

Based on their relationship to other valvular diseases, such as mitral stenosis, there are two types of atrial fibrillation: valvular (in the presence of valvular disease such as mitral stenosis) and nonvalvular atrial fibrillation.

For a good reference and review:

http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1022771&blobtype=pdf

Because valvular diseases are better controlled in developed nations such as the US, about 70% of all Atrial Fibrillation is nonvalvular. And, because the good news is that people now tend to live longer, the bad news is that we see more people suffer from conditions such as Atrial Fibrillation, as people live longer.

There is a need to make sure that we treat people with atrial fibrillation. Warfarin is the most common medication used as a blood thinner for patients prone to thromboembolisms (blood clots, but we all love fancy names, don't we?). As with most medication, not everyone is eligible to take Warfarin, and even those who are on Warfarin need to take it on a regular basis.

Are there issues with warfarin?

It is somewhat stupid to state that there is necessarily a problem with warfarin, as much as with all forms of medication (or devices for that matter). The central focus of the issue seems to be that since people will be taking warfarin and since you can't risk slow releases or anything of that sort (too much blood thinner ain't good for you either), people will have to take warfarin on a regular basis for the rest of their lives. Naturally, this is a problem. This is where Watchman is supposed to come in.

What can Watchman do and why wasn't there a 12-0 approval?

There are a few things to think about:

1. The FDA may have finally been acting cautiously about approvals, or maybe the committee was doing the right thing after all...

2. For one, it is "assumed" that most of nonvalvular atrial fibrillation can be controlled by occluding (shutting off) the left atrial appendage. Since there are assumptions and belief systems are involved, there is no certainty that this device can replace warfarin.

3. Looking at the data submitted to the committee, we can note that there were 14 ischemic strokes (approximately 3%) compared to the 2% of ischemic strokes in Warfarin patients. There is no clear winner here, so the committee decided that the device was at best comparable to warfarin and is not better than warfarin.

4. Physician Training - seems to be a somewhat steep necessity. Apparently higher rates of pericardial effusion were seen in the device. Pericardial effusion is termed the high accumulation of fluids outside the heart in the pericardial region. The heart likes to be efficient about space use, and excessive fluid can cause increases in pressure, leading to a stressed heart. A small note - the article doesn't hint at exactly how many incidents were reported, something worth digging up (see conclusion below).

5. Words of Wisdom: There is one really scary thing - personally for me. That is, any device compared to "drug eluting stents". (If you want to know why, read the blog's archives).

Here is a quote and a repeat from Dr. William Maisel MD, stolen verbatim from the Medpage Today article:

"He said the Watchman has some of the same issues that the drug-eluting stent advisory panel -- which he chaired -- grappled with: a potentially huge patient population, trials with low rates of very serious events, and a lack of postmarketing data.

"I think the lessons from that are that it may sound like a great idea to roll it out quickly, but I hope the sponsor will be careful about where the device goes," Dr. Maisel said. "

The Conclusion:

I am still not clear on the presence of novelty in this device, but it may follow from a device that seems to have the potential to fit well with a large patient population well in need of relief.

The numbers reported so far don't look bad either: a 32% reduction of total risk in terms of stroke, embolic events and death related to cardiovascular events. In terms of mortality alone, there is a total reduction of 39%. All this looks very good.

However, I would agree with the committee. The approval is a boon for the company. They don't have to go back to the drawing board and get more data. Now, they can do a few things:

1. Train surgeons, so that the outcome issues such as pericardial effusion can be avoided. There may be opportunities here for the company to offer a next generation device that either reduces the possibilities for effusion, or helps easy implantation.

2. Collect long post-marketing data and report adverse events promptly to the FDA, unlike other companies that tend to wait for about six to n months.

3. Try to understand where the ischemic strokes are coming from. It seems like something to investigate and contain.

Since PLAATO, a device made by Appriva Medical, Inc. is veritably the first-in-class device and WATCHMAN is the second, if you are a competitor or a potential one, there are two things to note - you could use some time waiting for more data (or planning in your budget to generate more data) and also watch for lessons to learn, before jumping and starting the umpteenth stent, I mean appendage occluding device company....

AdvaMed: Hey if we reeeally want to scare them away we need to throw around the word "innovation"

Here is the article link:

http://online.wsj.com/article/BT-CO-20090415-716238.html?mod=dist_smartbrief

Nothing outside this statement can be farther from the truth about pre-emption:

""Nothing chases away advanced medical device innovation like uncertainty" about whether a company is going to get sued for its product, said Stephen J. Ubl, AdvaMed's president."

What is innovation?

For one, it has nothing to do with the fear of being sued. That would be "AdvaMed-artifically-generated-phobia".

Here is what the paragon of truthisms, Wikipedia has to say on innovation:

"The term innovation means a new way of doing something. It may refer to incremental, radical, and revolutionary changes in thinking, products ..."

Reference: en.wikipedia.org/wiki/Innovation

Innovation would be saying, "Let's not start another drug eluting stent company, only to lay off 111 out of 121 folks after a few years. Let's either prove that drug eluting stents work or let's find a new way to cure disease."

Innovation could also be innovation in cost restructuring, outside of keeping the devilishly under-performing CEO, handing him out bonuses and laying off 20% of your workforce (amounts to 4,300 employees. Very hard to find out which "innovative" company I am talking about).

Innovation could be steps taken in shorter time to establish Design Validation, better designs, better manufacturing, Design for Manufacturability and so on.

What else could innovation be?

Surprisingly, it could be some of this:

1. When patients die because of your device, report them, promptly! No "the dog ate my adverse reaction reports".

2. When patients' hips start squeaking and their ICD batteries die out, start investigating.

3. When your product is the result of some bad "fitting round pegs into square holes", apologize - no medical device company has done that before. It would count as one heck of an innovation!

4. Do post-market follow up, not because the FDA weakly grunts about it, but because it is something you ought to do!

5. Stop subscribing to AdvaMed and it's opinion pieces.

Are innovation and torts related?

Absolutely not. Here is how a typical medical device gets to market:

1. Doctor and couple of engineers get together in a garage. They sit on the device for a while, think of and do all kinds of crazy things. They then double mortgage their house and go present in West this conference and East that conference.

2. After several failures and crazy ideas, some random thing works. Then a couple of years down the line they get funding and muck about sleeplessly for a few more.

3. They start selling the first generation, possibly first-in-class device. They are about to hit the IPO.

4. Really fat company rolls (lumbers and sometimes huffs and puffs) in and purchases them. Wants to impose it's "culture". Brings strange looking aliens (managers, change agents, transfer managers and such are their taxonomic guises) who want to change everything from the coffee machine to the CAD program.

5. All the "good" folks leave or are kicked out. The people who are left are still well meaning people staring at designs they don't understand. New people replace yet another layer of skimmed off people. Eventually, no one knows what's going on where.

6. The second in class device based on "marketing driven product development" and other wonders of nature gets to market.

7. Hips squeak, leads break, stents fail, meters dole out improper readings and patients, of course, die or become otherwise greviously injured!

In this whole mess innovation can only possibly happen from step 1 to 3. Torts happen after step 7. The FDA is a thematic black comedy that spans all these steps, but really doesn't affect anything, at least positively.

So, are torts and innovation related? No!

But don't we still need pre-emption?

Nope.

First of all, the Supreme Court Judges are acting like a bunch of txting teenagers. On the one hand they say that devices are subjected to pre-emption but on the other hand they say that the same iconic government agency (I mean the F, D and A) is ill-equipped to regulate drugs pre-emptively.

What gives?

Secondly, "the fear of lawsuits is the mother of many things". If these companies walked off on a permanent basis from responsibility (helped by the likes of the Federal Judge "Kyle" from Minnesota), then consumers, in this case patients, dead, dying or a loved one, have absolutely no respite.

A parting word for AdvaMed

So, let's not abuse the word innovation please. Let's start with listing your "donors" and "Corporate Members" somewhere easily accessible on the home page. That would make it so much easy for us to separate reality from Kool Aid and find out who really is going to be chased away from innovation and if that indeed is an ironic oxymoron...

Madit-CRT - forcing proof to expand usage works, but at what price?

[Click on Post Title for Link to External Article]

Implanted automatic defibrillators, known and described by several confounding names, have been in the market for a few years now. Essentially, just like all implanted devices, they have always been high risk devices. CRT is more riskier and expensive than implantable AF devices.

Every company involved in the manufacture of implantable defibrillators has been involved in expensive recalls and patient deaths:

1. Medtronic:
http://www.medtronic.com/product-advisories/

2. St. Jude: (I wasn't able to find any fatalities related to St. Jude's device)
http://www.schmidtandclark.com/St-Jude/

3. Boston Scientific/Guidant: (The most famous one)
http://www.fda.gov/bbs/topics/NEWS/2005/NEW01185.html

Whither logic?

Given the very risky nature of defibrillators themselves, CRT should naturally only be recommended and restricted to patients severely afflicted with atrial fibrillation(AF). Of course, device makers have never concerned themselves with such aberrations one would call logical.

Why bother, especially when it can be claimed that because it is highly likely that patients with mild to moderate conditions of AF may progress to severity over the years, implanting them with the defibrillators is essential. This is why you see Medtronic's competitor, Boston Scientific prop its CEO Jim Tobin to "cautiously" suggest that MADIT-CRT will succeed.

After all, if it's good for the goose (and the officious FDA is easily pleased) then it will be good for the gander too...

It is in fact, quite true that patients with mild to moderate heart disease may progress in disease severity. But..., well, let's first look at the positives.

The Positives

While the study did not show progress in the first year, of the 262 patients carried over to the second year of MADIT-CRT (based on the assumption that one year wasn't sufficient because of the pace at which the disease spread), 180 had the device turned on in the second year. Of the 180 with the device turned on, only 19% had disease progression compared to the 82 in the other arm where a device was implemented but not turned on. In the second arm, 34% worsened in disease condition. This means that the device itself has a statistically significant chance at success in the patient group.

Why the rant?

1. For one, the devices are very risky, even for patients with severe disease conditions. These risks have not been mitigated to the extent that we can be confident that someone without a severe prognosis should risk having these implanted.

2. I haven't read the original study's details and I plan to do so, but I haven't seen the extent to which aggressive medical treatment was indeed pursued in this study. What about pursuing medical management aggressively in the future? Will that offset the need for a CRT device?

3. Is there a scientific technique by which the risks vs. benefits of CRT can be compared, and in turn, compared with respect to medical management? We don't know, and of course, no one is going to try hard.

4. Competition - No matter what the shiny press releases and the glossy pamphlets tell you, no one really understands AF and failure all too well to the extent of treating it, and none of the medical treatments/device treatments have had what can be termed "remarkable" success. Companies such as Hansen Medical are developing robotic mapping catheters that may have a better effect than implantable devices. If a procedure tends to work better (of course, we have no clue as of now) than an implantable device, then the patients who did have the devices implanted would be at an unfortunate and unnecessary risk...

5. Implantable Devices - With Implantable Devices, "Houston tenemos un problema"! It is always a high-risk option to consider implantable solutions. While, cardiac risk represents one of the highest echelons of risk, they have found in-roads much easier than with other diseases.

Remember all the apnea implantables? They competed with the ugly monstrosities that CPAP masks are! Easy to bring an implantable that gets rid of the CPAP mask to market, right?

Wrong!

Okay, so procedures and surgeries always win, right?

Wrong again! Years ago, I worked with a company on an RF procedure to treat migraines by closing the Patency of Foramen Ovale, shortly and sweetly abbreviated to PFO. Well, many other reasons aside, one big question never went answered - Hey, I get migraines, but will I let you poke around my heart with a catheter? Well, the device failed due to ineffectiveness, but once someone like NMT (if they can stop suing all the independent researchers who disagree with them, an excellent PR exercise by the way) has to actually answer that.

However, the point remains. If insulin pumps can deliver insulin shots from the outside into the inside, and can be easily removed and replaced in case of malfunction, then that is a good way to brainstorm the next AF device! So, yes, my doubts remain. I don't think any of Medtronic, Boston or St. Jude have a winner and probably ever will (innovation is different from market share grabbing), unless they buy someone out.

Really, can you have a wearable CRT device? Maybe, who knows? And in any case, if you are not afflicted with severe heart failure, would you really want something implanted? At this expense, given where our healthcare systems are?

What next?

I am predicting, if this is not carefully watched, and if the "big 3" (if you will) do not start forcing Doctors' arms and implant the patients willy-nilly, two things will happen:

1. Defibrillator style CRT tort suits:

Oh don't worry about Riegel and Pre-emption. It is going to go away, sooner than later. It won't be long before Congressional legislation finds a way to bring injury lawsuits back. Which means, the next time there is trouble with one of these implanted defibrillators, there is going to be a lot of unnecessary diversion.

2. NEJM, JAMA or some agent of sanity will come through, just like NEJM did in 2007, clearly demonstrating that Drug Eluting Stents are disappointing when compared to medical management of coronary disease. Since then, DES has only seen misery and collusion. Now, the drug manufacturers and the device makers have gotten together to perform a study to "prove" DES superiority. Hmm, Good Luck.

Oh yes, I know, HHS sponsored a study and proved that DES is better than bare metal stents - but, really, who cares? How do stents do by themselves?

A note on "Business Development and Medical Device Case Study Authoring"

All said and done, such cockamany elegant solutions are the kind of thing I love to call "entrenchment". It is the result of essentially being a "sad one trick pony" well masked with "product diversity", the kind of thing that Intel and AMD are doing to their industry. Grow, grow, grow and then try to stifle competition.

The end result?

You are stuck with heavy investments in technology, manufacturing, intellectual property and everything else, going in one direction. And now, it becomes your business to stifle and possibly shut down competition, compromising on patients and customers.

Once down this path, you have to keep going down, you cannot make turns and you will have to keep spending money on diminishing returns, both in profits and in PR. Of course, the solution is not to hire more MBAs to cover this up and muddle reality :). Leave that to the technology industry and Microsoft.

Medical Device Companies cannot stifle innovation and get away with it. Yes, it is difficult to start a company, do the trials and bring the device to market, but companies can and will do it.

What can you do?

To start with, cut down on the ppts, the seamless integrations, the fitting of the round pegs in the square holes, innovateuring, inventeuring - in short, BS! Don't limit strategies to "industry experts", and "Business Development" or "Marketing Driven Product Development".

"Marketing Driven Product Development"

I once had an amusing interview with a Marketing Director who asked me what my opinion towards "MDPD" was.

You want to know what happened right?

Well, I didn't take up the job and about a few million dollars later, the MDPD failed and the project was scrapped. A failed engineering student could have pointed them that, if they had developed the ability to listen.

Another MDPD situation I was involved in included sitting and making the shape of a device look "safe". And no, it didn't look unsafe to begin with. Moreover idiots and Joe Shmoes don't get to become coronary surgeons...

So, should engineering departments drive design?

Wrong Question. Competitiveness, Innovation and an undying flair for cutting-edge products that "save patients lives" and "do not, absolutely, do not compromise patient safety" should drive design.

Don't shut off your "strategy" and "business development" activities to Powerpoint experts. Let everyone play. Do constant reality checks. Make everyone go to the operating table and observe...Hey, you should really be paying me for this. :D

Conclusion

I think Madit-CRT is good news, but caution needs to be exercised in how it is introduced into standard treatment practices. I would also surmise that smaller start-ups designing the right CRT solutions can do with some extremely cost-effective marketing - "Hey, we have an indication for moderate to mild heart failure risk, and guess what, we don't leave anything in your body"..oops, did I say that out loud?