Whither Chronic Tinnitus...

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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

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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 Barret's Esophagus after all...

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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...

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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?