Blog Brief: Medical Technology Funding - relaying good news

I first saw this posted on the sfmedengineers group, and on searching, found out that Mediligence had this blog on medical technology funding. It appears that amidst all the bad news and coerced good news, medical device companies seem to be enjoying the cliched "green shoots".

Amidst shying VCs and dried up funding wells, $300mn for a month appears to be quite a sum for 2009. Hopefully, this also means there is some sanity to the ideas that are being funded. A cursory glance does show that it is not a bunch of stent companies that received money.

So, here's to hoping we are in for a period of rationality. One easy way to find out if irrationality has returned, obviously would be a good count of highly ambiguous device ideas, companies that don't even have device ideas, ideas or even an i, and of course, my favorite, stent companies.

Till then, let's hope we see some real medical needs be solved, as opposed to the future Madit-CRT in waitings. (Madit CRT - the act of "If at first you don't succeed or obtain a large population size, simply say everyone has a disease and implant a potentially volatile shock device close to their hearts".)

Here is the link to the companies that received funding in the past month:

http://mediligence.com/blog/2009/06/30/medtech-financings-total-300-million-in-june/

India's own agents of shame - Her own Doctors and "Government" Hospitals...

Women and children tend to be the worst affected victims of HIV and AIDS for the most part. It is disgusting when people take the women and children and demonize them for being HIV+. This is not new for India. When the children of HIV+ patients turned out to be HIV+ in Kerala, the parents of other children in the school took up a disgusting approach to the whole issue. The idiots acted just like the adjective I chose to describe them.

This recent incident, which happened in a Government Hospital in Jamnagar is extremely disturbing to say the least. There was once a time when I used to think that Doctors who practiced medicine commanded the highest echelons of respect and admiration. Disillusionment, as they say, can be a bitch. What with physicians and surgeons faking data and research, and now this...

A plan of action

The Indian Government needs to be very affirmative and strict about this. Unnecessary, misplaced belief systems and activism cannot be luxuries India can afford. Before the Indian medical practice also becomes infested with religious beliefs and other nonsense (yes, it's nonsense if you bring Jesus, Krishna or your favorite anti-abortion god to work with you) in the US, it is possible to stem the flow:

1. Medical practice must come with a strict licensing. If the license is suspended, then the physician/surgeon cannot practice. Of course, only the judiciary system and the medical board should be allowed to touch the licenses.

2. Religious beliefs and other systemic/cult based moral beliefs should not be permitted to allow a physician/surgeon/healthcare professional violate basic tenets, principles, guidelines and required acts of practice.

3. Licensing for practice should not be the burden of Doctors alone. Nursing, hospital administrators and others alike need to be held to appropriate licensing standards.

4. "Government" Hospitals need to lead by example. The Indian public has never received what can be deemed "Quality" care from Government Hospitals as such. In this day and age when India wants it's footprint recognized as a Global leader, this is simply not acceptable. These hospitals need to strive to the highest International standards of care. This is very much un-Utopian and achievable if acts like those that occured in Jamnagar are punished such that no sane person would try to repeat them if they wish to safeguard any professional future to their careers.

5. With specificity to HIV and AIDS, what the Indian Government does is criminal enough that we should let everyone currently in Parliament go... A paradigm shift (and no, I am not an MBA, so this phrase is being used with meaning) needs to take place. Nonsensical protests by parents against HIV+ children, any form of derision and parading must be met with fines and jail time alike. Wherever possible, if such protests and parading are performed by Government officials, they need to be unemployable by the Indian Government from that point forward automatically. If private firms act in a complicit manner to such acts of parading and disparagement, to the degree that they were complicit, their legal and physical existence must come into paucity.

Without such well marked moves, the Indian Government will be achieving nothing. If the "activists" really want to achieve something, they need to take this act to the Indian Parliament for attention - yesterday!

To throw up, visit:

http://www.indianexpress.com/news/Hospital-puts--HIV-positive---tag-on-pregnant-woman/479364

Health Insurance Companies to senate: Sorry, and screw you too!

At a time when health insurance is such a well debated and turbid issue in the United States, Health Insurance Companies out there seem to be acting in the most childish way possible - this in an effort to prove that they are better off left as they are --> in charge of our death and demise in the name of health!

Isn't it amazing? If you have acne or if you gain or lose a few pounds, you could lose health insurance.

The idea behind insurance is all wrong, and of course there is no intelligent fix for a bloated system in which MBA Jockeys earn more than the actual Doctors and Nurses that help you.

I will tell you what we need to do - force health insurance companies to do severe cost cutting. Here are a few suggestions on how to regulate the industry. I am sure not one of them will ever be implemented:

1. The Chief this and Chief that officers of any health insurance company should have been employed for at least 5 - 10 years as either Doctors and Nurses only. No MBAs with Oil Baron dads or Social Anthropology backgrounds permitted.

2. Device and Pharmaceutical reimbursement should be tightly regulated. Increases of over 10% in the reimbursement in any category must be audited.

3. On the subject of audits - one or the other of the hundreds of gobbledygook Federal Agencies should audit every one of these companies - their mechanisms to accept or reject 'surance.

Of course, none of this will happen. In any case, read 'em and weep:

http://edition.cnn.com/2009/POLITICS/06/16/health.care.hearing/

This, as it where, is the state of affairs...

Generic Pharma: Why India should stop babbling and rambling and start acting like the world leader it wants to be

The Premise

Very quickly: Stung by the fact that it is not just IT that India has a stereotypical leadership in, but also in generic pharma, Europe has resorted to shoddy tricks such as "customs seizures" on India's shipments of generics drugs.

The Rant

The 21st century is here. While a large portion of the world would like to look forward, Europeans would like to use "monopoly" and "copyright" to try and re-live the centuries past (and Australians will kill Indian students in merriment and no, of course they are not a racist nation, God forbid!).

You only have to pick up the paper to find out that Europe has issues with federal bailouts, Intel, Microsoft and anything with a remote chance of working. Why not? After all, it must be too hard to actually do work, right? Other than extremely expensive cars (whose manufacturers are also being bought up by Indians), what, if anything has Europe made by way of real global contribution in the recent past?

Or what, if anything is Europe going to be able to contribute by way of scientific progress or economic prowess? In a tiny continent where every island and street likes to call itself a country, they have joined forces to become a cabal of backward looking nonsense.

On to India

Of course, we all know that. But what is wrong with my fellow country men and women? We continue to launch "protests" while British Airways or the French Airports would treat us like dirt and Australians come out and kill us straight.

The days of groveling before the "master" are long gone my dear dinosaur-mother-land!

We need to wake up to a new Indian reality. Do we need motivation?

Just look at China. Ask one of the geniuses, anyone from the Clintons to Merkel to point a finger at China, which now wants to tell its folks what websites they can browse. We don't have to get to that level of ridiculousness, but we definitely need to start making a lot of noise - you know, like how we drive those Elephants off our streets.

If the Dutch seize our shipment or Frankfurt wants to sit on our pills for a month, how about suing them?

How about calling their Ambassadors and demanding an explanation?

How about summoning their Kings (the Dutch still have a King, go figure) and asking them some intriguing questions on discrimination?

How about holding up the next round of "World" "Trade" ""Talks"" till the European countries explicitly promise to stop nonsense-mongering?

Hey, how about a long, cold and slow investigation on Dutch and German shipments to India for "copyright violations"? Remember, the British taught us bureaucracy. How about using it other than on someone Indian?

The Congress got re-elected and Rahul Gandhi appointed "young and old" politicians to various ministries. Fine. How about appointing some aggressive and assertive folks that will push India out of the "East India" mentality into the 20-frigging-first-century.

It is so tired to be one among 1.08 billion (and counting) people with truck loads of market potential, a land size and definitely a population that is probably larger than Europe's and having to watch this unravel on a daily basis.

Of what use are Indian organizations and Associations if they cannot be alert and act assertively? We shouldn't become the catch-all filter for the West to harass us!

Whither the necessary spirit?

Reference:

http://economictimes.indiatimes.com/News/News-By-Industry/Pharma-firms-continue-to-face-patent-violation-charges-in-Europe/articleshow/4629307.cms

May the BPA Wars begin....An FDA review, an Industry cabal and the sweet smell of nexus

The FDA has never been one to stick to it's goals, objectives, responsibilities or duties in the last eight years or so. In the same spirit, last year, despite growing "concern" from scientists and consumer groups, it went ahead and approved BPA as safe for use in "baby food" nonetheless. If you ever wanted to recruit for a party that need people with no scruples or self-doubt, I guess you had to look at last year's FDA staff. Now which party would look to hire folks with such characteristics, eh?

The FDA's approval cannot be taken lightly, in wake of the following facts (Washington Post linked at the bottom):

1. BPA has been shown that BPA can be linked to a variety of cancers, infertility and other fun diseases.

2. BPA was found to leach into bottles even when used in cold temperatures.

3. Apparently, Harvard found out that people who drank regularly from BPA bottles had a 69% increase in BPA in their urine...

And, the FDA says it was safe for baby food.

The Present

Of many of the federal government's gambling hobbies, the FDA is becoming prime. Ignoring the nonsensical ruling, a few local governments started pressing on their own restrictions on BPA use. The strange bedfellows included Minnesota and Chicago. Apparently, yesterday, the California senate did the same thing. We may have no money left in my state, but even we think baby food needs protection!

Finally, Congress wanted to get into the game. It's amazing how fast Congress can act given it's dinosaurial origins...Waxman and Stupak, remarkably both Democrats (you should talk to your local Republican representative about what they think of your babies' health and future voting potential), wanted to know what the "new" FDA was going to do about it.

Progress or not, the one thing the new Obama FDA wants to review everything it's predecessor version did. At best, this is all the progress we can expect over the next eight years.

So, you think the party's over? Think not....

The Battle Ground

Nope, no Fallujah or Kabul here. This battle ground is the industry. I guess it consists of the American Chemistry Council (if you buy your kids a chemistry set, buy them an ethics set too..) and a host of guess-who's...

So what is their strategy? Apparently according to notes obtained by the Washington Post and confirmed by the people who were apparently in the meeting:

1. They would like to use fear tactics: "Would you like your babies to not have access to food?" as opposed to, I guess, urinating plastics.

2. Raising prices! You gotta pay more for BPA-free food. You now have a choice between using your food stamps or staying away from cancer and infertility. Rock and Hard Place, meanwhile, were reported to have lost most of their stock value.

3. Parade "pregnant young mothers" to talk about the safety of BPA. Never in the history of mankind have we relied on the public relations skills or the scientific progress of young pregnant mothers or pregnant young mothers (whatever the differnce is) on learning us the nice things babies urinating plastic can do for you...

Are there no alternatives?

You bet! There are alternatives. Apparently Japan has managed to throw BPA out of it's bottles and I guess lead out of its paints...

What is the war being fought over?

Brace yourself. The war is being fought over: "How foolish are Americans today"

1. If the FDA simply reviews last year's recommendations, and walks off with a ban on BPA - the story doesn't end there. Why did the recommendation change? If so, does it prove the old recommendation was indeed unscientific, politically motivated and does it reek of nexus? If so, who, if anyone, is going to pay?

2. If the industry wins, well...

Articles for review:

1. http://www.washingtonpost.com/wp-dyn/content/article/2009/05/30/AR2009053002121.html?hpid=topnews

2. http://www.foodproductiondaily.com/Quality-Safety/FDA-announces-BPA-safety-review/?c=hZd7lm1eoKjsNCZ8t7IWvg%3D%3D&utm_source=newsletter_daily&utm_medium=email&utm_campaign=Newsletter%2BDaily

Whither Chronic Tinnitus...

[Click on the following for Link to External Article]

As I was ambling along the western edges of the internet, I came across this post:

http://langhout.wordpress.com/

Since this is 2009, many a promising medical device company has had to wait on the sidelines because Venture Capitalists would rather react than act. This particular company called Silere Medical Technology, Inc. seems to be one of the many affected by the paucity of funding this year. However, it is always useful to dig a little deeper. So, I went digging...

The preface:

Silere seems to be in the process of developing a medical device, specifically an implantable neurostimulating prosthetic to cure chronic tinnitus. So, let's look at the dissection one by one.

What is tinnitus?

Tinnitus is a condition in which the patient experiences a ringing sensation of sound in the ears, even though a sound is not actually present. There are many types of Tinnitus - depending on sound type, body position etc. I do not wish to convert this into a pathology/epidemiology. Here is a brief, well written article on Tinnitus:

http://brneurosci.org/tinnitus.html

There are many pathological and non-pathological causes that lead to Tinnitus, and Chronic Tinnitus is the condition where the ringing can persist for long periods of time, and if untreated or if treatment is ineffective, can lead to significant problems, including cognitive decline, according to this ScienceDaily article:


http://www.sciencedaily.com/releases/2006/03/060310101636.htm

Treatments for Chronic Tinnitus

As such my research into medical devices specific to Chronic Tinnitus led me to a few interesting results:

1. This looks most promising - an agreement between Durect and Neurosystec:

http://www.newsrx.com/newsletters/Medical-Devices-and-Surgical-Technology-Week/2004-07-25/0725200433350QW.html

Durect is a publicly traded company and while Neurosystec's website is furtive about what they are working on, a patent search has revealed that as late as 2006, they had a drug delivery device for the inner ear on file.

2. The second result, is more direct at least, given that it deals with "electromagnetic stimulation of the inner ear with a weak electrical signal":

http://www.steinbeis-europa.de/index.php5?file=195&show=17546

3. This of course seems to be what is directly in line with Silere's objectives ( This is purely speculation on my part):

http://clinicaltrials.gov/ct2/show/NCT00876720

This particular clinical trial concerns itself with Transcranial Magnetic Stimulation for Tinnitus and other disease conditions. Apparently, low-frequency stimulation has been successful in the past, and based on that, the University is now turning to high-frequency stimulation. Given that this therapy is externalized, I am guessing Silere's implantable will be either a low-frequency or high-frequency stimulation device...that is, if at all, I am anywhere close to the real Kahuna.

What does competition mean?

Competition is always good, for a start-up, and all around for customers. Especially, for the start-up, it is a method to convince Venture Capitalists that this is not a hare-brain mad-scientist scheme, but a legitimate business model. It further allows the start-up to present its case and why it is better positioned to succeed and so on. This convinced me that Silere must be on the right path.

Whither the numbers?

This is the part that gets a little confusing for me. According to wrongdiagnosis.com and the NIH (slightly outdated numbers I guess), there are 13 million people suffering from Chronic Tinnitus in the United States. However, Silere states that there are over 50 million suffering from the condition, and about 13 million seek treatment.

http://www.wrongdiagnosis.com/t/tinnitus/stats-country.htm

Even if my data is outdated because it is from the '90s, it can't be that 37 million people developed Tinnitus in the median... So there is some confusion here that needs to be resolved. Still, Silere claims they are looking at a market of about 2.7 million folks. For an implanted device, that is a huge market. Even if Neurosystec, the existing drug therapies and others were to offer stiff competition, Silere, from a pure market standpoint, can hold its own.

Implantable Devices

The one fly in the ointment for me are implantable devices. Call me old fashioned, but it is not just me. I wonder if this has even a minor part to play in the reluctance of VCs. While a PMA regulatory path is always excellent for a company to stave off direct competition for a while, the pathway itself is expensive and may hold off VCs. Mixed in with the risk of recalls and such, this may be a drag on a device.

Of course, one could present some counterarguments:

1. In the most debilitating condition, (especially if you played the YouTube Videos linked on Silere's website), you would see that the noise can be hell to live with.

2. Drug delivery may not be effective and may bring with it, side effects of it's own.

3. A less invasive therapy, even surgery may not be the option for many patient populations with this disease. Surgical treatment does exist, however, the first one microvascular decompression is actually recommended for another condition and only provides add-on benefits for Tinnitus. The second procedure is specific to Meniere's Disease, and also involves the surgical injection of drugs - not spectacularly innovative.

All said and done, if Silere sticks to the implantable pathway, both FDA approval and capturing the attention of surgeons and the patient population represent a long pathway, which may deter some, if not all VCs.

On the other hand, it is quite clear that for companies such as Medtronic and St. Jude that already compete in the neurostimulation space, rather heavily, Silere may represent an attractive future acquisition target, especially in a rather lateral industry, adding to the acquirer's sales and revenue stream.

Software Sales

While reading up on Silere's strategy, I saw how they plan to allow these devices to adapt to new software to allow for modulating the stimulation program, and how they plan to sell it. I am not sure, but some VCs may see this as a digression rather than a branching sales stream. It would appear that if the software that provides stimulation were to improve, it would only make sense to make it available to all patients free of upgrade costs. Regardless of whether or not this makes for an acceptable strategy, there remains another question - how much of it's development efforts will Silere have to devote to software development and what margins of profit will it realize from this stream.

Alternative Funding?

Apart from grant applications, companies such as Silere could look into In-Q-Tel. A few days ago, there was a press release touting the fact that In-Q-Tel, a non-profit funding arm of the CIA had funded Sonitus Medical because it's products would be useful to the CIA and the military. Given how Tinnitus might have at least some of it's origins in the military, DARPA, CIA and such should only be more interested than not in what they are proposing, especially since it appears that they are able to layout how much the treatments would cost the VA system.

Conclusion

All said, I like what Silere is trying to do. There is a clear market, a well defined disease condition (unlike Fibromyalgia or PAD and other make-it-up-as-you-go diseases), a large patient population, competition and pre-existing clinical proof. They may also have to look into some of their development and sales strategy. And, yes, they seem to fall into the bracket of companies that have to struggle as the VCs wait it out.

Personally, I have felt the economy may start recovering sooner than later, and given how our doomsday conspirators are being quelled one way or another, maybe the VC market will pick up and a lot of firms can begin their process again...

A small business tip - credit under tight circumstances

[Click on the following for Link to External Article]

http://www.inc.com/magazine/20090501/loans-you-pay-every-day.html

This may not necessary apply to your medical device company, but it may apply to small businesses anyway. After having caused the financial "crisis", and been mildly punished, credit card companies are now pouting, raising interest rates, and in many cases simply shutting down credit to small businesses and individuals alike.

On Deck Capital is not necessarily your knight in shining armor, but at least it is a better alternative when capital runs dry.

I am not planning to re-hash the article here, because this is not that kinda blog :)

Go ahead and read the article, and be aware of the pitfalls, but do not take it from the banks - look for alternatives.

May your business live long and prosper....

Radiofrequency may be a way out for Barrot's Esophagus after all...

[Click on the following for Link to External Article]

http://www.medpagetoday.com/Gastroenterology/GERD/14401

What is Barret's Esophagus?

Here is a simple and easy-to-follow web page on the disease:

http://digestive.niddk.nih.gov/ddiseases/pubs/barretts/

The esophagus has a sphincter which should technically allow passage of food (bolus) from the mouth to the stomach and prevent the motion backwards. Gastro-esophageal reflux (GER) is a condition where the sphincter stays open longer. This allows the acid from the stomach to rise, and causes heart burns, the ability to taste food near the back of the mouth etc.

When this condition happens more frequently, like more than 2 times a week, it is called GERD, a more serious condition, now qualified as Gastro-esophageal Reflux Disease.

In about 20% of people who have GERD, the lining of the esophagus, typically muscular, is now replaced with lining from the stomach. This is when the disease becomes Barret's Esophagus.

Barret's Esophagus and Dyslpasia

In a very small percentage of patients with Barret's Esophagus, (less than 1% according to the reference above), develop a rare form of cancer called esophageal adenocarcinoma. Carcinomas are cancers of tissue linings and walls.

Before this happens though, the tissue develops pre-cancerous cells leading to a tissue condition called dysplasia. As a result, regular biopsies are recommended. Usually though, the disease is noticed in later stages, and treatments are not very effective at that point. There is no indication that the current radiofrequency ablation technique would help those patients either.

Barrx Medical and their treatment

Barrx was started sometime in the year 2000 and has made this product commercially available since 2005. However, it looks like this particular study shows a lot of promise for the device.

Analyzing the study

Please read the Medpage article at the beginning of the blog for specific details. I want to discuss the key points of interest here:

1. The study was not the world's best - still, producing great results. The high-grade and low-grade nature of dysplasia in the patients randomized to be treated as opposed to the sham treatment was somewhat unnecessary. This is the first large trial with the device/treatment modality. Nothing significant can be gained from splitting patients up. It could have waited for a second study, and yes I know, they are expensive. They could have still noted down the grades and sought some sort of meaning. Right now, we don't really know of a big difference the treatment has on the grades. Plus, it only makes it harder for the device's reimbursement strategy, which I guess is not short of an uphill task.

2. The second point is somewhat moot, but worth a throw - we still need to wait for long term follow up.

3. The treatment was not a large scale energy wash - in patients that were randomized to be treated, dsyplasic and metaplasic (irregular, but not fully differentiated) lesions alone were treated. That is this was not a "paint" type of ablation procedure delivered over a large region.

I like the idea of a localized treatment. However, there is the confounding factor - do we know we got everything? In a preventive treatment setting, wouldn't being more conservative indicate higher value? This of course, needs to be balanced with factors such as anticipated side-effects.

3. As reported by the researchers themselves, the results are on somewhat of a fragile trend, at least right now. Of the patients that were treated, if one more patient had developed cancer or if one less person in the sham procedure group had not developed cancer, things would have been very different.

Of course the striking thing is, unlike our friendly, neighborhood stent trials, researchers and companies, this word came from the researchers themselves.

4. This treatment could definitely become first-in-line for patients with dysplasic or metaplasic Barret's.

5. What of course, would be the state with patients who have early stages of the disease?

This of course, is where the commercial challenges lie.

Will the physician community accept this as a reasonable preventive measure and recommend it?

Will the same significance persist in a larger patient population with longer follow up?

Will insurance reimbursement come through, especially for patients with the early stages of the disease?

What about the competition from medical management and others trying to play in this device/therapy space?

6. The most important thing helping anyone playing in the Colon cancer space for example, tends to be the large scale motivation for biopsies. How about Barret's and GERD? Will routine biopsy be recommended given the small percentage of folks developing cancer? If they do become routine, then Barrx will be in a great position. If not, no harm done, except there will be some missed opportunities in the white space.

Conclusion

Of course, challenges always lie ahead, but right now, things are looking good for Barrx and the treatment. Time will have to tell if everything that exists will hold and other things that are necessary will fall into place.

If the company continues to play it right, they could win over surgeons, reimbursement and find themselves on line for a good chunk of change.

The Post Script (P.S.) - Radiofrequency Ablation

Radiofrequency Ablation is a tired old horse that has been beaten to death quite a bit. Dozens of companies out there have done to radiofrequency what has been done to stents. Given a chance people would try stenting for everything from migraines to mania. In a similar fashion, for every conceivable disease radiofrequency/energy based destruction, albeit in many cases, without much attention being paid to rhyme, reason or scientific thought. It is one thing when when Google throws sphagetti on the wall, it is another when people try that with disease conditions.

Of course, the point there is that if some company X tried an energy delivery modality and failed, it doesn't mean much. At least, it does not always mean they failed for the right reasons, as has been demonstrated by several third-in-class, fourth-in-class devices and so on.

Based on the study's results, it is not too presumptuous to note that Barrx may at least be on the right path...

The Democrats plan to fix the FDA: Give them more responsibilities...

[Click on the following for Link to External Article]


http://www.reuters.com/article/healthNews/idUSTRE54J7R420090520?feedType=nl&feedName=ushealth1100

Okay, this is going to be a much shorter post. In the last few months, we have all had the wonderful opportunity to realize:

1. The FDA did not have any clear plans for device or pharmaceutical regulation and on top of that wanted to retain "status quo" by preventing anyone else but itself to continue the bungling via "preemption".

2. The FDA never actually bothered to really regulate the food industry, and stood by watching as people became infested with disease or worse, died.

3. The FDA also let go of it's responsibilities to monitor DTC - Direct to Consumer ads. This is where the new tobacco nonsense comes in. Let's get back to point 3 in a bit.

4. The FDA engaged in very poor device review process, and is now re-reviewing some of the same devices that it approved...

5. The FDA threatened it's employees when they complained about their voicing protests of its questionable track record.

Given that there are so many examples to prove points 1 through 5, you would think the Democrats and the Obama Administration would do one of the following:

1. Perform a thorough review of device/drug approvals and streamline the process.

2. Not pass up an excellent opportunity to split up the FDA into two, possibly three organizations so that there will be no more excuses for the lack of efficiency with which they have been doing things.

3. Not load the FDA with new responsibilities as they continue to struggle through failure to perform the most basic of their existing functions...

Instead, of course, they want the FDA to regulate tobacco ads, just not tobacco. I am not going to go into an extended diatribe about what this entails, because it is quite evident:

Neither President Obama nor the rest of the Democrats have much of an idea or clue about what to do with the FDA. They will do one thing to fix the problem though - throw more money and responsibilities at it...

Got a patent for drug combinations on cardiovascular disease? How about "proving" everyone needs the drug...

[Click on the following for Link to External Article]

Click here for the Medscape Article

The actual study is here:

Click Here

The Premise

Call me a skeptic, call me rude, call me anything you want..But having seen and known too much about conflicts of interest and bias in clinical trials and studies, I become suspicious, especially so when I see small studies and more importantly "meta analyses" make broad stroke recommendations.

Thus when I saw a study that said "Feed all old people anti-hypertensives", I became wary. Alright, the title of the article was a little less crude, I admit. But, nevertheless, it did not please me. Let's examine some quick facts:

Some notes on the study

1. The study examined data from 147 clinical trials conducted over 40 years.

2. The study concluded that all 5 major classes of anti-hypertensives seemed to reduce the risk of cardiovascular events regardless of the patients' history with respect to either prior cardiovascular events/risk or hypertension.

3. How much of a reduction in pressure where they looking for? A 10mm mercury reduction in systolic and 5mm in diastolic pressures.

Results, Conclusions and Recommendations

The study results do look good, just like they do in meta-analyses. After all, you are not directly studying something, just looking for what you would like to see.

People with hypertension are definitely on their path to cardiovascular events. The real difference comes from a combination of hypertension and other factors.

What is the real gripe?

The studies should have focused on reducing hypertension, and consequentially, cardiovascular events in patient populations pre-disposed to hypertensive and cardiac disease. If the 22% reduction in coronary artery disease and 44% reduction in stroke was comparable in both groups, how can we actually assume that patients who we consider not pre-disposed to CV/hypertensive were indeed not actually pre-disposed to the disease?

Well, there can only be one of three answers:

1. That, in these studies, at a broad level, folks who were not considered "at risk" were indeed at risk, and 147 studies were designed poorly. Okay, that is an extreme position to take, but at least some of the studies should be wrong, right?

If not, shouldn't you see a comparable decrease in CV events in patients/controls considered not "at risk"? Well, let's consider the other possibilities.

2. It is quite possible that the controls who were not considered "at risk" would have not really taken good care of their health. They let their life styles slip and as a result, ended up with cardiovascular disease.

3. Since at least some of these studies were treating patients for other factors, such as cholesterol, it is possible that they had a role to play in disease mitigation and the 22% and the 41% might have been influenced by the study population being treated for other conditions - see the problem with "large" and "comprehensive" meta analysis?

The Conclusion and a Side Note

Anyway, at the end of it all, when I came down to the article's end, I found out that the scientists involved in the study, who recommended (albeit with warnings on the fringe about drug combinations) that every "older adult" should be asked to take anti-hypertensive medicine actually own patents on drug combinations...

You can conclude the rest for yourself, but I am no Doctor, and still, I am going to try the "lifestyle change". I really think the idea of popping anti-hypertensives after I reach my "older adult" stage sucks. If that is what I am looking for, I might as well harm my already poor lifestyle a tad bit more...

Other problems?


1. What about people prone to low blood pressure? What if some company thinks it is a great idea to make blood pressure medicines to be a "dietary supplement" and someone prone to lower blood pressure accidentally takes it?

2. Hmm, have you thought about side effects of blood pressure meds before telling the world to take 'em?

A side note: Was aspirin also gold-standardized in a similar manner for all "older adults"?

You know, with the new wave of recommendations on hypertension coming from the old world on the basis of some extremely strong metanalysis, I got to wondering if Aspirin was also pushed on us in a similar manner. Remember when Bayer wanted to call Aspirin a "Dietary Supplement"?

Well, it does not appear to be as flimsy as the anti-hypertensives:

http://circ.ahajournals.org/cgi/content/full/96/8/2751

The AHA seems to have done a fair job, with 22,071 male physicians testing themselves with aspirin as an alternate therapy, resulting in a 44% reduction in MI. Of course, given they are physicians and knew about hypertension, hyperlipidimia (fancy for High Cholesterol) and smoking, maybe, just maybe some of them made "lifestyle changes".

Somewhat comforting, eh?

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?

Sparky, Phaky and Trooper, the medical device manufacturer!!!

[Click on Post Title for Link to External Article]

Conducting sting operations can be boring sometimes, apparently! So, some of the following names were used (I made up Sparky, but how would you know?)

1. Device Med-Systems (okay, that's for warm up)
2. Adhesiablog (apparently, titled to be a surgical adhesive. So, the blog did not raise any eyebrows?)
3. April Phuls
4. Timothy Witless
5. Alan Ruse, and to top it off,
6. Chetesville, Ariz

It is not like Grassley was suffering from want of material, you know. Or we. No one was going to miss this, but now that we have it, it is time to frolic on the floor..unless of course, you forget the fact that these people are supposed to examine and approve trials on humans...

The IRB and its function

Amidst the laughter that April Fool's Day was subsumed with March Madness, we may have forgotten what IRBs are supposed to do. IRBs can be part of large institutions, such as teaching hospitals, University hospitals, etc. or they can be independent.

They ensure that studies performed on humans meet the medical and ethical standards and are within reason - simply put, Frankenstein doesn't get to build his/her monster in the name of research.

Want to dig deeper than the primary school level mention here?

Knock yourself out on this link!

One bad apples = IRB dead?

No, not really. There are several IRBs across this country. Many of them would have caught this, maybe..Many actually function just to satisfy the local needs of the communities they serve.

Remember, most countries don't have the faintest notion of an ethics review board that goes beyond what can be termed as "eye wash". (This, based on the personal experience of yours truly!)

Then, do we just stand by and defend this?

No! Obviously, the FDA, the HHS and Congress have failed again. And so has our friendly, neighborhood administration (by failing to split the FDA in a timely manner). The FDA itself has existed for too many years in a very brazen, devil may care environment. The organization, and its guidances have become toothless (and now we are on a pistachio scare, for nuts' sakes...).

Whither Grassley?

Yes, he loves to hit the roof. However, where was he all these years? And why is Grassley the only contestant in a letter-writing contest to the FDA, IRBs and the biotech companies in Congress? Is everyone else already bought out, or do they not care enough?

What we really need:

What we really need is a thorough washing, rinsing and drying (saw that with a nice regional drawl..).

A thorough examination of "trust" based systems that also includes a plan on how to manifest and maintain this trust, while ensuring that they system has checks, balances and inspections that allow people to scrutinize and perform their functions well. Systems need to be modernized as well - with electronic record keeping and sleuthing tools, IRBs may just be able to catch Chetesville, Az. off the map.