Wasted Medicine: A Mantra

A report in the June 7 issue of the Journal of the National Cancer Institute (see article in Medical News Today):

Screening for cancer can find tumors that might not otherwise have been diagnosed in a person’s lifetime, a situation called overdiagnosis. Overdiagnosis wastes health care resources. Tests and treatment resulting from overdiagnosis can lead to substantial toxicity and even premature death in patients.

I find this interesting, unsurprising and largely irrelevant. First, I have to note that I was struck with the use of the term “overdiagnosis”, which I would expect to be a term used to describe an exhausted physician. I’m certain the authors intended to mean something akin to “false positives”.

It is unsurprising in that I expect clinical practice to occasionally result in instances where there appears to be a problem that, under further evaluation, turns out not to be a problem. The alternative is to miss the problems, resulting in pain and/or death.

It is largely irrelevant because, in lieu of technology or clinical practice that is perfectly accurate and precise by never missing pathology and never mistaking normal tissue from abnormal, we must err on the side of false positives — excuse me, overdiagnosis. Do we want to minimize the wasted use of our precious healthcare dollars? Are these non-trivial differences between accurate and inaccurate diagnoses? Who can argue against these questions?

A marketing manager was questioned by a new boss about a promotion to get registrants to a conference, and the boss questioned why the brochures were sent out to so many people. The manager responded, “Tell me who will attend the conference, and I’ll only send brochures to them.”

How is cancer really any different?

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Guidant Warning Letter Never Sent Over Concern of “Undue Alarm”

The New York Times reported today that in January 2005 Guidant drafted a letter warning doctors about a short circuiting defect in its Contak Renewal and Contak Renewal 2 defibrillators, but never sent the letters to doctors over concerns the letter would cause “undue alarm” and result in procedures to remove potentially faulty devices, and that such procedures would be associated with higher risk than simply leaving the debrillators in place. The letter and other documents were unsealed by a Texas judge overseeing a product liability lawsuit.Of course hindsight is 20/20. With what Guidant (now Boston Scientific) knows now, there is no question (at least in my mind) that failing to send the letter, and instead sending the “product update” letter, was ill-conceived. The subsequent recalls and class action lawsuits caused a reveral of fortune for Guidant, knocking billions off the price tag of its sale to Boston Scientific.

If there was indeed real concern about the risk of explantation being higher than the risk from faulty defibrillators, then that is precisely what should have been communicated. It is difficult to conceive that Guidant calculated the potential fallout from the letter and deemed it to be greater than the fallout of not disclosing the defibrillator defects. In this day and age, in which every misstep by manufacturers is magnified with crystal clarity, it is an absolute obligation to understand the impact of product liability.

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MEMS and Nanotech in Medicine

In initiating our report on “Micro- and Nanomedicine“, which details the full spectrum of products, technologies and markets in the application of MEMS and nanotech to medical use, I elected not to approach this as an update of the report we did in 2003, for several reasons. First, I was able to draw on very qualified resources for the current report, and was particularly interested in the analysis capitalizing on this by having an “unbiased” view of the market. Second, the market continues to be driven heavily by R&D, which by its nature results in a rapid flux in the players, the nature of their nanotech/MEMS initiatives and the actual status of development.Since our prior analysis, a very great deal has changed in the fields defined by those corporate, academic and government entities pursuing medical development of nanotech and MEMS. We currently profile about a 100 companies, but there are easily 4-fold more that one might consider for profiles given the number of companies and their current or potential involement in micromedicine or nanomedicine.

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Unnecessary Surgery and Throwing the Baby Out with the Bathwater

Here’s another reference from BusinessWeek today, “Bypass that Operation”, on the same vein about doctors who don’t know what they are doing, including performing unnecessary surgery.   It suggests that many if not most of 400,000 bypass surgeries and 1 million angioplasties are unnecessary. 

While I find fault with the general tone of this article, glorifying Dr. David Eddy, his brilliance and his blunt challenge to healthcare that it needs better proof for the efficacy of its treatments, because the tone of this article blithely understates the fact that there is a clinical basis for the decisions doctors make, some patients actually do get better by the treatments prescribed, and wholesale dismissal of physicians’ education and training may have less to do with the facts than it does with Dr. Eddy’s ego and BusinessWeek’s need to make brash statements to gain attention.  This is not to say that I do not believe there are flaws in the process, but there is little justification for the kind of criticism that the BW article. What bothers me most about this article is that its sensationalistic approach to the subject and its flippant consideration of clinical practice on a grand scale trivializes the benefits of medicine and medical technology to patients.

By the way, in 2003, I was diagnosed with coronary artery disease, with blockage at 90% in one artery. While Dr. Eddy may thrive on the debate challenging the value of angioplasty and stenting (“mesh tubes” are not angioplasty, BusinessWeek), I know that however true it may be that some “cheaper alternative” might have done as well as angioplasty/stenting, there was no such alternative at the time. I am alive now. Replicate my experience with all others similarly diagnosed and that is precisely the reason for the high utilization of angioplasty/stenting. BusinessWeek’s cursory analysis failed to consider such an obvious driver.

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“Medical Guesswork” Exposing the Ugly Truth

I have always had a rather sanguine understanding of medicine, having been sensitized to its practical limitations for most of my life. Having been the son of a general surgeon and the nephew of a pediatrician, I saw many aspects of medicine that have tempered my thinking about treatment alternatives in the medical device industry. For this reason, when I came across the article in the May 29, 2006, issue of BusinessWeek Online, asserting that healthcare professionals really know little about which treatments actually work, I found agreement with the idea, and in some cases strongly so, but in other cases I felt the premise misses a few big boats.

From BusinessWeek: “The problem is that we don’t know what we are doing,” says Dr. David Eddy (the“mathematician and health-care economist” who coined the term “evidence-based medicine”), arguing that, bluntly, there isn’t very much of this in healthcare today. Further, according to BusinessWeek, “even today, with a high-tech health-care system that costs the nation $2 trillion a year, there is little or no evidence that many widely used treatments and procedures actually work better than various cheaper alternatives.”

The point at which I agree with this is that physicians have always been given wide latitude in determining therapeutic choices, by virtue of their education, their consideration of many different variables affecting patient condition and the suitability of any given treatment. What drives the physician’s decision-making is the availability of a reimbursible therapeutic option that specifically addresses the clinical problem to address the medium term need of the patient. By “medium term” I mean the need to solve the problem now, get the patient back on their feet and keep them that way not in any permament sense, but in a medium term sense. Does any cardiothoracic surgery think CABG is a permenent solution? Perhaps long term, but not permanent. Does any interventional cardiologist believe even a drug-eluting coronary stent is a permanent solution? Perhaps more likely to be permanent than bare stents or angioplasty alone, but certainly not permanent. So, doctors are applying the available therapeutic option for the longest solution that is viable. There are many stakeholders interested in the more expensive option — medical product manufacturers, physicians, even patients (who want the high-tech quick-fix). There are not many stakeholders advocating for cheaper options — perhaps HMO’s — but who is listening to them?

However, medical devices and drugs are already aggressively evaluated for their efficacy against controls, so the premise of this article, however well-founded, overstates the case when it comes to the use of medical products. The upshot of this article otherwise is to suggest that the upward spiraling U.S. healthcare costs are attributable to expensive treatments alone, when indeed the focus should be on clinical decisions themselves. Physicians are the ones who have been given the latitude to apply them or not, and until they have a different incentive system or until the evidence is much stronger for alternative treatments, absolutely nothing will change.

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Endoscopic GERD Treatment

Market shares for key players supplying GERD devices in the U.S. are shown in the chart at right.

Gastroesophageal reflux disease (GERD) is a growing problem affecting approximately 5% of the population. An estimated $10 billion is spent on GERD in the United States each year. It is primarily treated with medical therapies (e.g., proton pump inhibitors, or PPIs) for the majority of patients who present. For the remainder of the patient population (approximately 20%) who do not respond satisfactorily to PPI therapy, surgery or one of a variety of innovative endoscopic therapies that treat GERD are the next best alternatives. For some patients, neither palliative drug regimens nor major surgery are attractive options. Trends indicate that this market is moving towards GI endoscopic therapies as less invasive therapies continue to evolve and enter clinical studies. In 2006, the GI endoscopic anti-reflux device market is expected to be $10 million and by 2011 the market is expected to reach $50 million.Related Tags: , , , ,

Nanotech Hype versus Actual

The potential for nanomedicne, the medical application of nanotechnology, is vast, as has been pronounced almost endlessly since it was conceived. However, already on the market in the United States are wound dressings that exploit the antimicrobial properties of nanocrystalline silver, and nanotech-based products for drug delivery, materials technologies and other nanomedical applications are indeed real and in clinical trials now. Many ompanies are developing a diverse range of nanotechnology types for applications including biopharmaceuticals, drug delivery, materials uses, and sensors & diagnostics. These select applications represent just a small sample of the possibilities being pursued, but also represent uses that have made noteworthy progress toward commercialization, a very elusive aspect of the often overstated nanotechnology industry. The unique traits of nanoparticles, fullerenes and other nanoscale structures that either represent novel types of biopharmaceuticals or allow coupling to therapeutic agents for more effective (e.g., localized) drug delivery have lended themselves to development by many companies. Here are examples:

  • Avidimer Therapeutics
  • Introgen Therapeutics
  • BioSanté Pharmaceuticals
  • ImaRx Therapeutics

One very common use of nanotechnology, under development at many companies and institutions, is as a means to develop unique materials with properties similar to, or even identical to, other naturally occurring or synthetic materials, but with distinct advantages afforded by the materials. Examples:

  • Angstrom Medical
  • MIV Therapeutics
  • …many others

Nanotech-based sensors and diagnostics represent a middle ground, in development terms, between nanotech-as-materials and therapeutic nanotech devices, and many companies are focusing efforts in this area, including:

  • Biophage Pharma
  • Orion Integrated Biosciences
  • …more

We adddress the nanotechnology/MEMS industry, reviewing the technologies, applications and their status for companies in a range of applications of nanomedicine and micromedicine in the May 2006 MedMarkets. Related Tags: , , , ,

Organ Printing

The process of engineering tissues is advancing to the point where researchers actually consider such possibilities as organ printing. The formation of organs proceeds, at least in principle, on the formation of tubes, which then fuse after incubation in a bioreactor. It was described this way in Wired.Of course, organ complexity in terms of differentiated morphogenic function, shape, etc., will complicate the ability to produce organs that can even be considered for clinical trial. Hence, exceedingly optimistic assessments of when organ printing may reach trials are at least five years away (ten years is probably pushing it).

However, the ability to form the simple structures like sheets in bioengineered skin grafts or fill voids for regeneration of bone through extracellular matrices is already an established skill (see Tissue Engineering, Cell Therapy & Transplantation).

There are many, many questions to be answered, and many hurdles crossed, before bioartificial organs can be produced at the push of a button, but the possibility of success is just the sort of stimulant that feeds entrepreneurs (and drains VCs).

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Diabetes complications

Long term studies, performed with the goal of capturing more data that will enable more confident conclusions, sometimes become moot when more recent studies eclipse their premise.In the May issue of the Journal Diabetes, researchers at the University of Pittsburgh Graduate School of Public Health reported on the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study’s findings (see press release) that long term complicatons including heart disease and eye disease have not improved over the past 25-30 years for type 1 diabetes juveniles and adolescents treated at Children’s Hospital of Pittsburgh between 1950 and 1980.Now, I certainly respect long term studies, because arguably there are far too few of them and far too many studies that are not only too short term, but also too narrowly focused to reveal all the implications of treatment options. Short term data is awfully compelling, especially if you are a manufacturer seeking marketing approval or just a market edge.

But long term data can lose much of its relevance when it is eclipsed by more recent research that also passes the “long-term” test. Clearly, the EDC study is undercut by the Diabetes Control and Complications Trial conducted from 1983 to 1993, which showed very clear improvement in the risk and severity of complications associated with eye, kidney and nerve disease when Type 1 diabetes had their glucose more tightly controlled:

  • Eye disease
    76% reduced risk
  • Kidney disease
    50% reduced risk
  • Nerve disease
    60% reduced risk

Now, even though patients in the DCCT trial were not expected to have heart-related problems at the beginning of the trial, since they were on average only 27 years old, cardiograms, BP and blood fat were assessed during the trial, revealing at the end of the trial that those with tight glycemic control had significantly lower risk of developing high cholesterol, a significant indicator of risk for developing heart disease.

Therefore, one must seriously question findings of a type 1 study that did not specifically factor the level of glycemic control in a consideration of heart disease or eye disease risk. Almost as significantly, the patients included in this study were type 1 individuals who, at the latest, were patients 13 years before the end of the DCCT trial.

Further, in discussion of the findings, it is noted that “many of the guidelines currently used for managing type 1 diabetes are derived from what we know about people with type 2 diabetes. We need to recognize that they are two different conditions with different processes involved. Therefore, some of the complications we see in type 2 diabetes do not occur in type 1 and vice versa.”

I am struggling to not be harshly critical of statements like this. Type 1 and Type 2 are well known to be starkly different, the only common denominator being a problem of one sort or another with insulin and therefore the need to keep an eye on blood glucose (again, the omission of the level of glycemic control being a glaring omission).

Fast forward to today (read “modern technology”). A type 1 diabetic diagnosed in 2006 faces an order of magnitude difference in treatment than one diagnosed between 1950 and 1980. Research should therefore focus on what we know now, and how we can enhance treatment, rather than what we knew almost 60 years ago.

As a matter of obligation, I must note that my 11 year old daughter has type 1 diabetes, having been diagnosed over four years ago. So yes, maybe I’m biased, but I’m also extremely well informed on this topic. Her most recent HbA1c was 7.4.

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Cardiovascular Drug-Eluting Stent Developers, Products, Status

Developers of Cardiovascular Drug-Eluting Stents

Company Stent Drug Status
Abbott Vascular Devices ZoMaxx Zotarolimus In clinicals; ZOMAXX II trial approved 6/05
Avantec Vascular (Goodman) Duraflex Pimecrolimus In development
Biosensors International BioMatrix Biolimus A9 In trials; Expects CE Mark in 2006
Boston Scientific Taxus Express2 Paclitaxel CE Mark 1/03; FDA approval 3/04
Boston Scientific Taxus Liberté Paclitaxel CE Mark 9/05 (launched 1/05); FDA approval expected mid-2006
Conor Medsystems CoStar Paclitaxel CE Marked 2/06
Conor Medsystems (Next-generation CoStar) Pimecrolimus Pimecrolimus licensed from Novartis in 3/06; Testing two devices: one loaded with pimecrolimus and another with both pimecrolimus and paclitaxel
Cordis (J&J) Cypher Sirolimus CE Mark; FDA approved, U.S. launch 4/03
Cordis Cypher Select Sirolimus CE Mark in 2003
Cordis Cypher Neo Sirolimus In development
CorNova (Undisclosed) (Undisclosed) In development
Devax Axxess Plus (bifurcated) Biolimus A9 In clinicals (positive first-in-man data reported 11/05)
DISA Vascular Stellium Paclitaxel In development
Estracure/Medivas/Picarus (Undisclosed) 17-(beta)-Estradiol In development
Guidant Xience V Everolimus CE Mark 1/06; European launch pending
Medtronic Endeavor Zotarolimus CE Mark 7/05; U.S. launch planned in 2007. RESOLUTE trial began 12/05
Occam International (subsidiary of Biosensors International) Axxion Paclitaxel CE Mark 7/05
Relisys Medical Devices (Undisclosed) Paclitaxel In clinicals
Sahajanand Medical Technologies (SMT) Infinnium Paclitaxel CE Mark 12/05
Sorin Biomedica Cardio Janus Flex Tacrolimus CE Mark; launched in Europe 2/06
Terumo Nobori Biolimus A9 Clinical trial launched 6/05
X-Cell Medical Ethos 17-(beta)-Estradiol In clinicals
Xtent Xtent Biolimus A9 In clinicals; European launch planned in 2007, U.S. in 2009

Note: CV Therapeutics and MIV Therapeutics (among others) are developing coatings for coronary drug stents.Source: MedMarket Diligence, LLCRelated Tags: , ,