Lately, the Food and Drug Administration has been receiving increased numbers of reports describing  problems with insulin pumps, those small devices used by diabetics to deliver insulin without the need for injections.

The FDA noted that various hardware and software issues have resulted in 18 device recalls during the last 5 years.

“Device problems…exist across manufacturers,” the agency noted. 

In response, FDA has convened an advisory panel to recommend actions to “minimize risks associated with the devices in these recall situations,” according to its Web site.

Insulin pumps are typically used by patients with Type I diabetes, in which the pancreas produces little or no insulin. Type 1 diabetics rely on exogenous insulin for survival.

According to the FDA, the number of people in the US who used insulin pumps increased from 130,000 in 2002 to 375,000 in 2007.

The FDA requires pump makers to report problems and potential problems associated with the devices. The agency received 17,000 such reports in the 3-year period ending September 30, 2009. Such reports don’t necessarily mean the pump caused a problem but usually merit further investigation. Patients can misuse a properly functioning pump, for example.

Roughly 12,000 reports to the FDA were associated with a patient injury (which typically involved gyrating blood glucose levels). Deaths occurred 310 times.

In these instances, the FDA said information provided by pump makers “was typically incomplete.” In 225 of these reports, the manufacturer listed the device problem as “unknown.” In many of these cases, the device wasn’t returned to the manufacturer for follow-up investigation.

In 41 reports involving a patient death, the circumstances included diabetic coma and other problems typically associated with severe abnormalities in blood-sugar levels, which suggests possible device malfunctioning.

Boston Scientific Corp. has agreed to cut a $716 million check to Johnson & Johnson to settle more than a dozen patent infringement lawsuits, including one in which a judge had already ruled in favor of J&J.

The settlement wraps up all but 3 stent-related lawsuits involving the two companies. Stents are cage-like metal struts that prop open partially blocked arteries.

Stents are most frequently used in the coronary arteries, but they can be used in other arteries as well.

The market for cardiac stents now exceeds $4 billion. Boston Scientific leads the pack in this field, but J&J owns the original patents on the medical devices after acquiring them from Julio Palmaz, the radiologist who invented them.

Nine years ago, a judge ruled that a Boston Scientific stent known as the NIR infringed on one of J&J’s patents. Boston Scientific appealed, but announced last year that it expected to fork over more than $700 million to settle the claim. That includes interest dating from the original verdict.

Boston Scientific announced it will pay the settlement from cash holdings, which amounted to $1.2 billion as of last June.

The market for stents has leveled off in recent years after studies showed they weren’t that effective in many instances, and other studies raised concerns about bleeding from the anti-platelet therapy that is normally prescribed after stents are placed.

The J&J settlement comes shortly after Boston Scientific settled separate stent-related claims with Medtronic. For its part, Medtronic recently paid $400 million to Abbott Laboratories to settle a patent infringement case regarding…you guessed it, stents.

Not long ago, FDA deputy commissioner Joshua Sharfstein criticized the process his Agency used to approve ReGen’s Menaflex knee device,  claiming that “extreme” pressure from New Jersey Congressmen had compromised its integrity.

He added that the skullduggery was a factor in prompting his decision to review the FDA’s 510 (k) program, which fast-tracks approval of medical devices by requiring less rigorous clinical testing than the standard process.

“It’s autumn, and change is in the air. This is particularly true for our 510k program,” echoed Donna-Bea Tillman, head of the device evaluation office, in an email to her staff that was obtained by The Wall Street Journal.

The very thought of change to 510k goes over like a lead balloon for device makers like Johnson & Johnson, who warn that tampering with it would end up robbing the public of rapid access to a stream of live-saving, quality improving (not to mention money making) instruments.

J & J spokesperson Carol Goodrich said that 510k streamlines clearance for devices deemed “substantially equivalent” to those on the market, “builds on ever-expanding knowledge,” and accelerates innovation.

Tighter approval standards, she said, “would raise development costs substantially while also creating barriers to market entry that would reduce competition.”

About a third of J & J’s $64 billion in annual world-wide revenues derives from the sale of medical devices and diagnostic equipment.

The FDA’s move was just the latest bad news for the device industry.

Congressional Democrats for example, are pitching a tax on device makers to help pay for  health reform. If passed, the proposal could cost the industry $40 billion over 10 years.

To be sure, the Advanced Medical Technology Association, a lobbying group that represents device makers, is working overtime in Washington to set things straight on both counts.

The new deputy commissioner of the Food and Drug Administration has criticized his Agency’s approval of ReGen’s Menaflex knee device last December in a report claiming that “extreme” pressure from New Jersey Democratic Congressmen compromised the integrity of the process.

In his report, Joshua Sharfstein asserted that the Congressional heat was “the most extreme (the FDA’s Congressional liaison) had seen. In addition, “the FDA’s acquiescence to (ReGen’s) demands was unprecedented.”

The events undermined the Agency’s ability to “counter the suggestion that lobbying on behalf of ReGen affected the decision,” according to the report which was obtained by the Wall Street Journal.

The Congressmen, Senators Robert Menendez and Frank Lautenberg, and Representatives Frank Pallone Jr. and Steve Rothman apparently encouraged the Agency to hasten its review of New Jersey-based ReGen’s device, which is a collagen meniscus implant designed to guide new tissue growth following surgical repair in patients with tears or loss of meniscus tissue.

Sharfstein added however, that his report does not constitute grounds for Menaflex recipients to panic and that the device remains on the market. The Agency, he said, will begin a review to determine whether that continues to be the case.

The 4 Congressmen countered that their involvement was a simple case of helping a constituent get fair treatment from the FDA.

The case could have far-reaching implications for the medical device industry. It is one reason why the FDA has undertaken a comprehensive review of the 510 (k) program which fast-tracks approval of medical devices by requiring less rigorous clinical testing before approval is granted.

ReGen claims that its product is safe and effective. Former FDA Commissioner Andrew von Eschenbach wasn’t available to comment.

Here’s an idea that might not be too hard to swallow. Proteus Biomedical, a Silicon Valley start-up has developed a tiny microchip that can be attached to pills and signal caregivers when patients have swallowed them.

At the same time, sensing devices on the skin can relay information regarding the patients vital signs using wireless technology.

The combo technology could help physicians monitor compliance with prescribed dosing, assure the patient takes the proper dose, and provide early warning about untoward physiologic effects.

The chips have been shown to be safely digestible. In commercial production, they would cost less than a penny per pill.

Proteus is one of many companies using micro chips and wireless technology to create new medical tools. Triage Wireless, for example is testing a wearable device that can transmit continuous blood pressure readings in hospitalized patients, while Corventis has a sensor that measures respiration, fluid status and movement.

The potentially huge health care market for wireless devices has prompted larger companies to enter the fray as well. Qualcomm for example, is developing chips that can be used in various wearable medical applications.

Similarly, Intel is developing “magic carpet” devices to be deployed in the homes of senior citizens to track movement and prevent falls, a major cause of morbidity in the elderly.

Wireless networks, of course, are already in widespread use to support the 4 billion cell phones sold to date. The same networks can be used to transmit medical data.

According to Eric Topol, a Scripps Institute cardiologist, remote monitoring devices could save $10.1 billion in the care of patients congestive heart failure alone.

Republican Senator Charles Grassley has been all over the medical device industry for years.  Why just a month ago he called out the University of Wisconsin in the Zdeblick-Medtronic debacle.

“I am concerned that Wisconsin’s reporting requirements do not go far enough to fully capture a physician’s potential conflict of interest,” he said a moment after revealing the surgeon had pocketed $19 million, most of it undisclosed from Medtronic, the nation’s largest spinal device producer.

That was quite a performance, but now Grassley is movin’ in for serious carcass. Last week, he and Herb Kohl, who ironically is a cheesehead, reintroduced legislation that would require device makers and Big Pharma to list all financial ties with physicians on a .gov Web site.

The public is clamoring for transparency,” Kohl said of the Physician Payments Sunshine Act.

And other parts of the government are providing precision support for the senators on multiple fronts. 

In 2007 for example, the Justice Department forced knee and hip makers to accept its oversight as a quid pro quo for not looking further into allegations they bribed physicians to use their stuff.

In fact Justice already requires knee and hip makers to disclose all payments to physicians on corporate Web sites and has capped per-day consulting payouts to physicians at a measly $500.

Even some hospital systems are getting into the act. Kaiser Permanente for example does not permit its physicians to accept income from the private sector and requires that device makers compete for contracts on price, perish the thought.

Abbott Laboratories announced last week it has acquired Advanced Medical Optics of Santa Ana, California for $2.8 billion.

The deal valued the Lasik eye surgery supplier at $22 per share, which had to open a few eyes since the company had been trading under $9 and Lasik isn’t thought to be a recession-proof procedure.

Not only that, Advanced Medical’s contact-lens solution was pulled off the market 2 years ago after it was linked to a potentially sight-threatening infection known as Acanthamoeba keratitis. 

But even the most vociferous critics would have to agree, Abbott’s recent track record on acquisitions is above reproach. The device maker has dropped $21 billion in the last 10 years on acquisitions beginning with a $680 million purchase of Perclose in 1999.

That represented a jaw-dropping 60 times earnings but in time most came to evaluate that buy as smart, even frugal.

Two years later Abbott acquired Knoll Pharmaceuticals from BASF for $6.9 billion. At the time Knoll was a sleepy producer of thyroid hormone-replacement drugs but then wouldn’t you know it?

It developed Humira, a blockbuster monoclonal antibody used for rheumatoid arthritis, Crohn’s disease, psoriasis and other conditions. Now, Abbott receives 70% of its earnings per share from drugs, and most of that comes from Humira. 

Abbott then acquired Guidant’s interventional cardiology business, and it too turned to gold. Guidant’s Xience drug-eluting stent recently whipped Boston Scientific’s Taxus in head-to-head trials. 

“We note ABT’s solid track record of timing, executing and integrating transactions,” understated Leerink Swann in a written statement picked up by the Wall Street Journal.

And remember, Advanced Medical traded in the mid-20s before the Feds played Russian roulette with Lehman Brothers and the chamber turned out to be loaded.

Each year between 2003 and 2007, University of Wisconsin spine surgeon Thomas Zdeblick told the school he received $20,000 or more from Medtronic, the nation’s largest producer of spinal devices.

His disclosure was consistent with university policies which do not require scientists to specify the amount received if it exceeds $20,000.

But Republican Senator Charles Grassley, who has raised exposing conflicts of interest in health care to an art form, just informed the University that Zdeblick raked in an astounding $19 million from Medtronic over that period.

“I am concerned that Wisconsin’s reporting requirements do not go far enough to fully capture a physician’s potential conflict of interest,” Grassley understated in a letter obtained by the Wall Street Journal.

Robert Golden, the medical school dean had no choice but to come clean. He agreed the University’s disclosure policies were “indefensible,” and vowed to toughen them up.

“Clearly there is a big difference between $20,000 and $20 million,” Golden told the Journal. 

Charles Rosen, a spine surgeon who is president of the Association for Medical Ethics, said Wisconsin’s disclosure policies were in line with other medical schools, for whatever that’s worth.

“When you are advocating devices or procedures, it can’t be said this is a private matter and that no one should know how much this company is paying me,” he told the Journal.

Zdeblick maintains he doesn’t take royalties for products he uses, and that he has informed patients of his relationships with Medtronic. 

Years ago, Medtronic employees accused the company of inducing surgeons to use its spinal devices with perks and payoffs. In 2006, Medtronic paid $40 million to settle the allegations. As part of the settlement, employees dropped their claims and Medtronic denied unlawful behavior.

The Great Economic Crisis of 2008 has cast a pall over public offerings in general, but in health care it’s been surreal. There have been 3 measly new stock offerings the whole year and that includes pharmaceutical, biotech and medical device companies combined.

That’s down from 38 in 2007 according to Dealogic.

And the ones that made it, MAKO Surgical Corp., CardioNet Inc, and Bioheart, Inc., went forward in QI. There hasn’t been a single health-care IPO since March.

“It’s very troubling,” says Steve Brozak, a medical devices and biotech expert and the president of WBB Securities LLC. “These companies are like the farm team for large pharmaceutical makers to buy novel technology and drug discoveries,” he added in the Wall Street Journal.

The famine represents a reversal of fortune for the sector which outpaced all others between 2004 and 2006 and finished second to tech offerings in 2007, according to Renaissance Capital’s IPOHome.com.

But the spigot did not close as suddenly is it appears. In the 6 months before MAKO went public in February, 13 health care deals were yanked before the big day. Twenty-four have been withdrawn since.

Maurice R. Ferré, MAKO’s CEO believes his company succeeded in part because its IPO made it out just before the roof collapsed.  “We faced a huge amount of headwind going into the deal,” he told the Journal.

No doubt they did, but it’s a Cat 5 hurricane out there now.

We’ve deployed nanoparticles (that is, particles measured in billionths of a meter) in the war on cancer for awhile now. For example, Abraxane packages the breast-cancer drug Taxol with albumin, a tiny blood protein that improves drug delivery and reduces side-effects.

Now, scientists have begun testing a new generation of nanoparticles that attack malignancies in a different way. By focusing energy from external sources, the new nanoparticles destroy cancers physically rather than chemically.

Jennifer West at Rice University for example, has developed gold- and silicon-based nanoparticles that absorb infra-red light and then heat up. If we can deliver these nuggets exclusively to the site of a cancer and turn on the juice, the tumor cooks while normal tissue remains unharmed.

It turns out this is quite possible because the pores of tumor capillaries are many nanometers larger than normal. It’s just a matter of creating nanoparticles exactly the right size to exploit the difference.

West’s nanoparticles have proven effective and safe in mice and dogs. Her team has begun testing them in humans with head and neck cancer.

Other teams are deploying nanoparticles of their own. The privately held German company MagForce Nanotechnologies for example, injects iron-containing particles directly into tumors and heats them with magnetic fields.

And the Taxol/albumin vehicle is only the first of what will likely be many cancer-fighting, drug-based nanoparticles. CytImmune Sciences of Rockville, Maryland has initiated a study of another gold nanoparticle that delivers tumor necrosis factor, while Calando Pharmaceuticals of Pasadena, California has enclosed camptothecin in a protective nanoparticle made of sugar.

The particular nanoparticles mentioned here may or may not prove effective, but those leaky tumor capillaries provide an opening big enough to drive a truck through.

People who are old enough will remember the 1966 flick Fantastic Voyage, in which scientists are miniaturized and sent into the body of a man dying of a brain clot. The scientists run a gauntlet of biological obstacles before saving the man’s life.

It may not be long before we’re doing that for real and in one sense, we already are. Given Imaging for example markets Pillcam, a 1.1 cm by 2.6 cm capsule that contains a camera. Once Pillcam has been swallowed, the camera transmits images that can identify causes of GI bleeding, abdominal pain and diarrhea.

Pillcam relies on peristaltic contractions to whisk it along, but what if we could design one that moves on its own or rejigger it to perform biopsies?

Paolo Dario and his group in Pisa have already designed prototype robots that have retractable legs which allow the capsule to go where no capsule has gone before (sorry). His and other European teams are also designing modular robots in which individual pieces assemble themselves inside the stomach and the resulting devices can perform surgery “inside-out.”

The big hurdle is powering the devices. While they wait for battery technology to improve, scientists believe the most effective work-around is to build the robots using magnetic material which can be manipulated with magnetic fields produced by MRI machines.

Scientists reported in Nature this week that monkeys could overcome a temporarily paralyzed wrist in order to continue playing a computer game, a finding that could point towards new treatments for people that have sustained spinal cord injuries or a stroke.

Amazingly, the animals pulled off the feat by controlling the activity of a single cell in their brains.

Chet Moritz and colleagues at the University of Washington tested two pigtail macaques (see picture) in their study. The monkeys had learned to play a game in which they manipulated their wrists up and down in order to move a cursor towards a target on a computer screen.

The scientists then implanted probes to track firing patterns in the monkeys’ brain cells and observed as the monkeys played the game. They noted that certain brain cells fired at different frequencies when the monkeys raised or lowered their wrists.

The researchers then used anesthetic to temporarily block nerves that normally activate wrist the monkeys’ wrist muscles, and connected the brain cell probe directly to an electrical stimulator affixed to the monkeys’ wrist muscles.  In no time, the monkeys learned to use the artificial bypass tract to move their wrists so they could continue playing the game.

The finding is, “an important step forward.” Case Western Reserve scientist Dawn Taylor told the Associated Press. Taylor works in the field but was not involved in this study.

But Moritz cautioned that human applications are at best a decade away. “There’s no way to say with confidence that it will work,” he added.

Four stent makers and 4 drug companies have agreed to fund a $100 million study to determine how long vigorous but risky anti-platelet therapy should be continued in patients who receive stents following balloon angioplasty.

Anti-platelet therapy with aspirin and Plavix helps prevent blood clot formation around the stent (pictured), an event which can be serious, even fatal. The downside of anti-platelet therapy is an increased risk of bleeding and stroke. 

In patients receiving stents, physicians typically prescribe aggressive anti-platelet therapy for about one year, but many patients have developed clots after that time. The study will randomize patients to receive one year versus 2 ½ years of aggressive anti-platelet therapy.

The global market for stents, particularly the more profitable drug-eluting variety, has diminished to about $5 billion per year primarily due to concerns about blood clots and bleeding from anti-platelet therapy.

Four of the study’s funding companies are stent-makers: Johnson & Johnson, Boston Scientific Corp. Abbott Laboratories, Inc. and Medtronic, Inc.

The other four are drug companies. They include Sanofi-Aventis and Bristol-Meyers Squibb, which co-market Plavix, and Eli Lilly & Co. and Daiichi Sankyo, which co-developed prasugrel, a Plavix competitor that is edging toward FDA approval.

Plavix by the way, is the world’s second largest selling drug with $5.9 billion in annual sales. It has patent protection until November, 2011. It is anticipated that the current study will take 4 years to complete.

Medtronic’s spinal devices unit has been in bunker mode since the FDA alerted surgeons about serious complications associated with off-label use of its products. Yesterday, the medical device giant received more bad news when sealed documents from a 2002 lawsuit were leaked to the Wall Street Journal.

The suit was filed by a former Medtronic lawyer. It alleges that the spinal devices unit provided surgeons incentives to use its products. The incentives included entertainment at a Memphis strip club, fishing expeditions to Alaska, free rides on Mardi Gras parade floats and royalties on inventions they didn’t develop.

The federal government does not allow companies to provide incentives that encourage physicians to use products covered by Medicare and Medicaid.

The spinal devices unit is already under investigation by Sen. Charles Grassley (R-IA) who wants to know whether incentives like the ones alleged in this lawsuit have driven widespread off-label use of Infuse, a growth factor that promotes healing following lower back surgery. Medtronic had refused to provide documents from the case to Sen. Grassley’s staff.

Medtronic denies engaging in improper behavior of any kind and added that it is “committed to reform and transparency in the industry.”

The Senate Committee on Aging will soon hold a hearing about direct-to-consumer ads for medical devices.

Herb Kohl (D-Wisc), Chairman of the committee, indicated the hearing was necessary to decide whether the FDA ought to ramp up its oversight of device promotions to match what it already does for drug ads. “The medical device industry is just beginning to get into the game,” he said.

DTC advertising for medical devices nearly doubled between 2005 and 2007, to approximately $193 million. This is peanuts compared to the $5 billion spent annually on prescription drug promotions, but some people believe medical device advertising can have a disproportionately large impact on consumers. Surgery is after all usually required to implant medical devices and the devices remain in situ for years.

Currently, TV promos for medical devices are not required to address risks and benefits as are those for pharmaceuticals.

Johnson & Johnson promotes its artificial hips with ads featuring iconic Duke basketball coach Mike Krzyzewski. The ad shows people jumping rope and surfing, among other things. In spots for its competing product, Biomet features former Olympic gold medalist Mary Lou Retton.

In Pune, India this summer a judge relied on evidence from a brain scan to convict a woman, Aditi Sharma, of murder. Sharma insists she is innocent.

The controversial machine is named the Brain Electrical Oscillations Signature test or BEOS. It was developed by Champadi Mukundan, the former Chief of Clinical Psychology at Bangalore’s National Institute of Mental Health.

BEOS is based on preliminary observations by several American scientists including J. Peter Rosenfeld, a psychologist at Northwestern, yet Rosenfeld was quick to denounce the verdict. “Technologies which are neither seriously peer-reviewed nor independently replicated are not…credible,” he said. “The fact that an advanced, sophisticated democratic society…would …convict persons based on unproven technology is…incredible.”

Apparently, BEOS software interprets patterns derived from a conventional electroencephalogram (EEG) recorded while the suspect listens to details of the crime she supposedly committed. Mukundan asserts that certain areas of the brain respond when experiences are relived, and that BEOS can differentiate between memories of witnessed events and memories of deeds they committed.

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