The Patron Saint of Drug Safety

06/06/2007 12:57 AM |

If sunshine is the best disinfectant -- then let the sunshine in.

Here's our op-ed that appears in today's edition of the Washington Times:

Plaque problem
By Peter J. Pitts and Robert Goldberg

Dr. Steven Nissen, head of cardiovascular medicine at the Cleveland Clinic, by running to Congress and the media about the heart risks of Avandia, has positioned himself as the nation's de facto drug regulatory czar. Today, he will tell Rep. Henry Waxman, California Democrat and the chair of the House Committee on Oversight and Government Reform, that he had no choice but to bypass the Food and Drug Administration, because the agency (in both appearance and reality) is too cozy with industry to move in a timely fashion.

But Dr. Nissen, who has often said, "Even the appearance of bias can damage trust as actual impropriety," has his own credibility gap to deal with. As Dr. Nissen admitted to The Wall Street Journal, he was in touch with Mr. Waxman -- but not with the FDA -- well before his study was even published in the New England Journal of Medicine. FDA Commissioner Andy von Eschenbach received a letter about Avandia from Mr. Waxman and Dr. Nissen. That means Dr. Nissen was strategizing with Mr. Waxman well before rushing to save the public from cardiovascular Armageddon. Or at least that is how it appears. But "even the appearance of bias can damage trust as actual impropriety," so says the self-appointed and media-anointed Patron Saint of Drug Safety.

Indeed, avoiding the appearance of bias is why Dr. Nissen tells anyone with a pulse that he donates all "drug industry consulting fees offered to me to a philanthropic charity run by the American College of Cardiology ACC." Saint Steven the Pure.

Except the "charity" was the Steven E. Nissen Healthy Heart Fund, and it subsidized such philanthropic activities as gym memberships for the staff of the American College of Cardiology. In 2005 the $1 million in the Healthy Heart Fund was folded into the ACC Foundation. In 2006 the ACC elected a new president: Dr. Steve Nissen.

"Even the appearance of bias can damage trust as actual impropriety." Dr. Nissen regularly claims that the pharmaceutical industry hypes the value of new medicines while soft-pedaling or not publishing safety problems. Yet he has hawked early clinical results of several drugs such as ones he had been paid to study, including some that ended up causing heart attacks and kidney failure.

And then there's the question of scientific consistency. In his hotly debated New England Journal of Medicine Avandia article, he questioned the FDA's "use of blood glucose measurements as a surrogate endpoint in regulatory approval." Yet, the cornerstone of Dr. Nissen's approach to drug evaluation -- the intravascular ultrasound (IVUS) study of plaque in the wall of heart arteries -- is itself a surrogate endpoint for regulatory approval of cardiovascular and diabetes medications.

Is hypocrisy too strong a word? Or maybe the word is self-promotion. In 2004 Dr. Nissen was involved in the evaluation of AGI-1067, a drug designed to reduce the level of fatty plaque deposits (atherosclerosis) in a person's arteries. The company that developed the compound, Atherogenics, predicted the drug would positively influence many different types of serious heart problems. But the original results were unclear.

Enter Dr. Nissen, who did an IVUS re-analysis of the Atherogenics trials. Suddenly, AGI-1067 was a breakthrough. As Dr. Nissen told Forbes Magazine, "There is no other interpretation." Actually there was. A 2007 study of AGI-1067 showed that it not only failed to reduce plaque but actually increased bad cholesterol levels, decreased good cholesterol and increased the overall number of heart failures. When the negative results of the study were published, Dr. Nissen's name was not among the authors. Nice touch for a guy who beats up on drug companies for hiding safety problems.

Coincidentally, in the wake of Dr. Nissen's hit piece on the FDA and Avandia, AGI-1067 was reintroduced. And, coincidentally, Atherogenics wants to see if it treats glycemia, the same condition treated by... Avandia. Another coincidence: glycemia may contribute to arterial plaque -- a substance measured by (yes, you guessed it) Dr. Nissen's IVUS.

Dr. Nissen also worked on a drug called ETC-216, made by the company Esperion. ETC-216 was a synthetic version of good cholesterol. Dr. Nissen did an IVUS study on 47 people and claimed ETC-216 reversed plaque by 4 percent in 5 weeks. He gave several interviews in the press calling it "liquid Drano for the coronary arteries." (He's always had a good ear for media soundbites. On Nightline he called Avandia "worse than 9/11.") Though Dr. Nissen's presentation about ETC-216 figured in Esperion being acquired for $1.3 billion, there has been no additional study of the drug. Coincidentally, Esperion's former CEO, Roger Newton, is a friend of Dr. Nissen's and Delos Cosgrove, CEO of the Cleveland Clinic, is a limited partner of Canaan Partners, a firm that had a stake in Esperion.

For someone who is concerned about the appearance of impropriety, Dr. Nissen's conduct is characterized by a series of uncomfortable coincidences. Most involve putting his career ahead of the safety of patients. Members of Congress -- especially those that exalt him as the unimpeachable savior of the public health -- should use today's hearing to ask Dr. Nissen tough questions about his methods and motives.  Read More & Comment...

New England Journal of Manipulation Retreats When Confronted With RECORD

06/05/2007 06:20 PM |

Though you wouldn't know if by the defiant tone of the editorials...

Link

Nissen did a meta-analysis looking at the increased risk of myocardial infarction and death from cardiovascular causes from Avandia and found a 41 percent greater risk and his analysis excluded anyone with a high risk of or a prior MI. The RECORD team released interim results showing that there was little difference in the risk of MI or death of all people on the drug with or without a history of MI... "As compared with the control group, the rosiglitazone group had no evidence of an increased risk of death, either from any cause (hazard ratio, 0.93; 95% CI, 0.67 to 1.27) or from cardiovascular causes (hazard ratio, 0.80, 95% CI, 0.52 to 1.24). The primary end point included all first hospitalizations or deaths from cardiovascular causes and as such included myocardial infarction and congestive heart failure. "

NEJM changes the goal post and definition of safety by demanding that Avandia show that it is cardioprotective...to wit; David Nathan's unctuous editorial comment: "Considering the low power of the study and the trend for more adverse cardiovascular outcomes in the rosiglitazone-treated group, it is highly unlikely that the study will ever establish a cardiovascular benefit for rosiglitazone." Thanks David and maybe it will be a source of renewable energy too.

Nathan goes on to write: "It is reasonable to ask whether physicians should feel comfortable using a drug that might have an 8% excess risk of severe cardiovascular disease or death from cardiovascular causes. " And as we all know, there are subpopulations that will carry about 80 percent of that risk.



In patients that have a 50 percent greater chance of having a stroke, heart attack or heart failure if they stop taking the medcine? No one is doubting that there are other tools out there for controlling diabetes but the last time I checked the incidence of the disease was increasing as was the prevalence. More people are dying from the disease and if a PPAR can reduce that a 50 percent increase in absolute risk of stroke with a drug that carries a 2 percent or less risk of MI and other treatments are not working....  Read More & Comment...

Provenge Protesters Should Pay Attention to New House FDA Bill

06/05/2007 05:03 PM |

because it will seal the fate for thousands of others who will die hoping for a chance at life. The House bill makes safety superior to drug approvals and makes the pseudo analysis of Steve Nissen -- which gives the meta-reality of danger -- pre-eminence in the drug approval process. Given this additional hurdle more drugs that show a targeted benefit will be pulled because all fear mongers will have to do is lump all the questionable safety risks into one sample to create a signal of danger.

Provenge protesters interested in getting access to the new drug should direct their phone calls to the following individuals who now constitute the new drug regulatory regime in America

Congress Henry Waxman (202) 225-3976
Dr. Steve Nissen (216) 445-6852
Senator Charles Grassley 202.224.3744
Gardiner Harris, The New York Times 212-556-1234  Read More & Comment...

Doctor of Torts

06/05/2007 11:13 AM |

While it's very nice to have Dr.Goldberg recognized as one of health care's most influential bloggers (see Boston Globe article in previous blog) -- it's downright frightening to see one of our nation's most aggressive tort lawyers supporting Dr. Steve Nissen as the next Commssioner of the FDA.

As the Globe article states,

"To W. Mark Lanier , an attorney nationally known for representing patients in cases against drug companies, such positions would make Nissen a fine candidate for FDA commissioner."

Thus the King of Torts dubs Steven Nissen, Doctor of Torts.  Read More & Comment...

The Defacto Drug Regulator Responds

06/05/2007 09:14 AM |

Diedtra Henderson interviews Steve Nissen who responds -- sort of-- to my blog calling him "small and craven" as he shifts positions and engages in self promotion in a campaign to become defacto FDA commissioner....

Just remember these words from St. Steven the Pure because they will come back to haunt him and those who have annointed him the savior of drug safety in the weeks ahead:

“Even the appearance of bias can damage trust as actual impropriety"

Watchdog draws growls in return
Cardiologist-FDA adviser says his goal is drug safety; critics say he's bucking to run agency

By Diedtra Henderson, Globe Staff | June 5, 2007

WASHINGTON -- Vioxx . Ritalin. Drug-eluting stents .

Those popular drugs and medical devices are on a growing list of therapies used by millions of people that have shown up on the radar of Dr. Steven E. Nissen , a prominent heart specialist.

Leveraging his power as a federal adviser, tapping the reach of medical publications, and whispering in the ears of key members of Congress, the Cleveland Clinic cardiologist has questioned the heart safety of each product. In doing so, he's chipped away at the credibility of the Food and Drug Administration as the nation's top drug safety watchdog.

Avandia , the world's best-selling oral diabetes treatment, is the latest drug targeted by Nissen. In a New England Journal of Medicine article last month, he said it increases the risk of heart attack. Avandia's manufacturer, GlaxoSmithKline , called Nissen's analysis flawed. But Nissen is scheduled to testify tomorrow at a congressional hearing on Avandia , again commanding the media spotlight.

Nissen, son of a physician and husband of a journalist , calls himself the "point on the end of the spear" during drug safety debates, raising awareness on matters he says the FDA has overlooked. Time magazine last month included the 58-year-old among 100 people "whose power, talent, or moral example is transforming the world."

Others say his motivation has more to do with wanting to run the FDA. And that worries the drug industry. If a Democrat is elected president next year and Nissen -- or someone like him -- becomes FDA commissioner, they say it could make the FDA more cautious, slowing new product approvals to a crawl and stifling innovation.

Nissen, who joined the Cleveland Clinic in 1992 , now chairs its department of cardiovascular medicine . He is immediate past president of the board of trustees of the American College of Cardiology . He has been published more than 250 times, including books and journals, and has been an early leader in the development of a type of imaging that spots artery damage at its earliest stage and can determine whether anti cholesterol medicines are effective.

But on Capitol Hill and in pharmaceutical company boardrooms, those achievements are trumped by his role as a drug-safety watchdog.

Years before Vioxx was pulled from the market in 2004, Nissen pointed to its heightened heart attack and stroke risks. In 2005, as the FDA was on the verge of approving Pargluva, a diabetes drug known generically as muraglitazar that works like Avandia , Nissen pointed out cardiovascular problems, effectively killing the drug's development. And he also rallied other federal advisers to prod the FDA to put its harshest warnings on attention- deficit hyperactivity disorder drugs, like Ritalin and Adderall , due to cardiovascular risks.

Such public stands have unleashed a firestorm of criticism. FDA spokesman Douglas Arbesfeld , in an e-mail to reporters days after Nissen's Avandia analysis was published by the New England Journal -- derisively dubbed him "St. Steven ," and wondered whether his feet were made of clay.

Arbesfeld, responding to a Boston Globe question about the e-mail message, said the correspondence -- sent using his FDA e-mail address -- reflected his personal views and not the agency's.

After the Avandia news broke, Robert Goldberg , a conservative pundit and vice president of the Center for Medicine in the Public Interest New York, posted a message on his blog, DrugWonks.com, that said Nissen is campaigning to become FDA commissioner in a way that "makes him look craven and small."

Told of Goldberg's blog entry, Nissen asked, "Who would say such a thing?"

"I'm not running for anything," Nissen added. "I've got a great job here, and I'm not going anywhere."

Goldberg, however, does have more clout than the average blogger. As a senior fellow at New York's Manhattan Institute , he once wrote that a front-runner to become FDA commissioner would so stymie the drug-approval process that the shorthand message to patients would be: "Drop dead." The candidate, Dr. Alastair J.J. Wood, foundered in the face of stiff industry opposition.

In an interview, Goldberg said the cardiovascular risks of such drugs as Vioxx have been highlighted by others, but Nissen is "the most aggressive in promoting himself, whether he is accurately depicting the risks and benefits of products."

Nissen's word carries weight with influential members of Congress intent on FDA reform, including US Representative Henry A. Waxman , a California Democrat, whose assistance Nissen sought when he had difficulty obtaining details about Avandia, and US Senator Charles E. Grassley , an Iowa Republican, who wants to create a separate drug safety center at the FDA.

In a key switch, Nissen now agrees with Grassley on the need for such separation.

Nissen has also earned the praise of US Senator Hillary Rodham Clinton of New York , a Democratic front-runner in the 2008 presidential race.

Like other FDA critics, he says the agency is so reliant on drug industry funding that it is reluctant to swiftly tamp down on drug-safety problems. He seeks to reduce the number of FDA advisers with financial ties to drug and device companies, and wants more and larger clinical trials conducted after drugs are approved for sale. He favors restricting advertising for products that have questionable safety records. And he champions public access to results of the clinical trials that drug makers conduct to gain FDA approval for their products.

To W. Mark Lanier , an attorney nationally known for representing patients in cases against drug companies, such positions would make Nissen a fine candidate for FDA commissioner.

"The current FDA commissioner is, at best, a passivist before a ravenous beast named Big Pharma. At worst, he is their actual lap dog," Lanier said.  Read More & Comment...

Avoiding the Media's Avandia Trap

06/04/2007 04:08 PM |

The media tried to turn John Buse into another Nissen, but he wouldn't bite. The scuffle he had about Avandia back in 2000? Old history, not a open sore that will fester and explode like a bombshell against Glaxo when he testifies June 6

Rather he said the patients should stay on Avandia until all the data was in and that Nissen's article was just one of many.

He devotion is to patients, not to the press or to Congressman Waxman. His unwillingness not to be manipulated has left the Stephanie Saul's perplexed.

Again, in the wake of the media's shoddy handling of the SSRI and Vioxx issues who would have thought it would have reached new lows on Avandia?  Read More & Comment...

pandemics, mild and moderate

06/04/2007 01:45 PM |

Hallmark had an interesting movie on pandemics a week ago. Here's my take, published in my LA Times column, the Unreal World. It is interesting to note that at least the last 3 flu pandemics have been caused by low path avian viruses H1, H2, H3, which transformed to human killers, rather than by highly pathogenic AI, like H5N1

Marc Siegel:
The Unreal World
Killer flu may not be the one we've feared
'Pandemic' points out that H5N1 bird flu isn't the only danger to public health.
June 4, 2007


"Pandemic," the Hallmark Channel, May 26.

The premise: On an island off the north coast of Australia, as surfer Charley Williams begins to cough, he is unaware that several dead seagulls and a dead dog lie near him. They are infected with a new form of flu virus, later determined to be an H3N7 mutated variant named "Riptide." Fellow surfer Ames Smith leaves the island and boards a plane to Los Angeles. While on board, he develops a high fever, coughs up blood and dies. The plane and its passengers are quarantined by the Centers for Disease Control and Prevention. A passenger escapes and spreads the virus. Five days later, as several more passengers escape, L.A. has 154 dead and 1,400 sickening. Schools and shops are closed, paper masks are everywhere, mass graves are dug. The city is placed under quarantine. The anti-viral drug "Tana-Flu" is found to be largely ineffective, and a more useful newer drug, "CoToxil," is in short supply. As Riptide spreads, the governor declares martial law and brings in the National Guard. The CDC finally determines that antibodies against tuberculosis bacteria prevent this virus from attaching to the lung, so the blood of TB survivors can be used as a vaccine. The world is saved.



The medical questions: Isn't the H5N1 bird flu our greatest risk for a massive pandemic? What is the typical incubation period for a deadly influenza? Are masks or quarantine effective? Is coughing up blood (hemoptysis) characteristic of a highly virulent influenza such as the devastating, 1918 Spanish flu or this new Riptide virus? Does a sudden "antigenic shift" (as a scientist suggests) bring about the pandemic because the public lacks immunity to the new virus? Can TB antibodies protect against a deadly flu?

The reality: Though the H5N1 highly pathogenic avian influenza strain has been much publicized and has worried many scientists, it is still primarily a disease in birds, and may not mutate sufficiently to cause the next human pandemic. "If we put all our eggs in this one basket, we can easily miss a mutation in a different virus which becomes the next pandemic strain," says flu researcher Dr. Jeffrey Taubenberger of the National Institutes of Health. The movie sends an important message to the public when it shows a non-H5N1 influenza transforming into the pandemic virus.

The incubation time — or period between exposure and the onset of symptoms — for influenza is two to four days, sometimes longer. The film depicts this waiting period fairly accurately. In real life, scientists are not always sure exactly how influenza is transmitted, and it is unlikely that paper masks would provide much of a barrier to infection. More sophisticated N-95 respirator masks are only occasionally shown in the movie and must be fitted properly to be effective. The movie correctly illustrates the significant downside to quarantining whole regions (as opposed to the more effective strategy of isolating sick patients and their contacts), where people under suspicion become fearful and may take fewer precautions and thereby may spread the virus more widely.

The imagined Riptide virus, like the Spanish flu of 1918, kills a high percentage of older teens and young adults. Some scientists have theorized that this phenomenon is due to a hyperinflammatory response, which causes victims (often young and healthy) to drown in their own respiratory secretions. But Taubenberger believes that the high mortality in young adults in 1918 was likely due to an absence of immunity to the flu strain in those ages as compared to the older population who may have been exposed to a related virus earlier in life.

Coughing up blood is commonly associated with a virus that damages lungs so severely and quickly. But this doesn't happen as commonly as shown in the movie, where practically everyone infected is experiencing hemoptysis.

A virus experiencing a sudden antigenic shift or significant mutation is believed to be the cause of all pandemics. Bringing up this genetic term to explain the suddenly deadly Riptide" virus is a fine bit of scientific detail.

Less believable is the movie's optimistic portrayal of cooperating government officials, or the science-fiction contention that antibodies against tuberculosis can somehow prevent Riptide from attaching to lungs of potential victims. True, some immunity can be provided by extracting antibodies from the blood of survivors. In Asia, the blood of bird flu survivors has just been shown to protect mice from the disease. But TB is an entirely different disease. You wouldn't expect antibodies of TB sufferers to help fight flu.

Finally, viewers should know that the next flu pandemic may be mild, not massive. Not all pandemics kill many millions like the 1918 Spanish flu.  Read More & Comment...

PS to the No Comment Comment

06/04/2007 11:12 AM |

Nissen and others wants to make Avandia the poster child for wants wrong with the FDA and their approach as the right way....

Do Nissen's supporters believe that regulation by meta analyses, by end-run to Congress and the media is an appropriate substitute. Should those who push such analyses be unaccountable -- as Nissen, Furberg, Psaty, Avorn have thus far -- to scrutiny by the media which is the current and only conduit for their warnings?  Read More & Comment...

Incomplete? "No comment."

06/04/2007 07:43 AM |

Here's the latest Avandia/Nissen article from today's edition of the Newark Star-Ledger (Pharmaland's hometown newspaper):

Link

Unlike most coverage of this story, reporter Robert Cohen presents both sides of the story and carries this crucial sentence near the top of the story (in paragraph 6 ):

"The data was already available on Glaxo's Web site, and Nissen acknowledged he did not have access to all the information needed for a definitive conclusion."

Cohen continues, "Alternatives include Actos, a similar drug made by Takeda Pharmaceutical, which did not show a link to heart attacks and strokes in a 2005 study. Nissen has consulted for Glaxo and led a small clinical trial on Actos for Takeda, but insists this has not affected his view on Avandia."

Heavens no.

And then, curiously, Cohen reports that the usually media-friendly Nissen "... was unavailable for comment but plans to testify at the hearing Wednesday."

No doubt.  Read More & Comment...

Elementary Dear Watson? Hardly

06/01/2007 10:50 AM |

From the New York Times ...

Genome of DNA Pioneer Is Deciphered

By NICHOLAS WADE

The full genome of James D. Watson, one of the discoverers of the structure of DNA in 1953, has been deciphered, marking what some scientists believe is the gateway to an impending era of personalized genomic medicine.

Here's the rest of the story.

http://www.nytimes.com/2007/05/31/science/31cnd-gene.html

Pay particular interest to the bit about Watson's apolipoprotein E gene.  Read More & Comment...

The Critical Path for Vaccine Development

06/01/2007 10:01 AM |

One more time -- here's why the Critical Path is so critical.

FDA Finalizes Guidances for Pandemic and Seasonal Influenza Vaccines

The U.S. Food and Drug Administration (FDA) today issued final recommendations to increase the supply of safe and effective influenza vaccines for both seasonal and pandemic use.

FDA's goal with the guidances is to outline the regulatory pathways for the rapid development and approval of these products.

"FDA continues its commitment to help increase the supply of influenza vaccines and support the development of new approaches to vaccine production," said Jesse L. Goodman, M.D., M.P.H., director of FDA's Center for Biologics Evaluation and Research (CBER). "Having additional manufacturers of licensed influenza vaccines will enhance the capacity to produce more doses of seasonal influenza vaccines, as well as contribute to the nation's pandemic preparedness, one of our top priorities."

In March 2006, FDA issued two draft guidance documents for public comment — one for seasonal influenza vaccines and another for pandemic influenza vaccines. The draft documents outline specific approaches for manufacturers to develop new vaccines that are safe, pure, and potent. The final guidances reflect public input, including vaccine companies and public health officials.

Both guidances recommend using recent technologies such as cell culture and recombinant manufacturing to enhance the development and evaluation of vaccines. They also recommend adding substances that improve the immune response from the vaccine (novel adjuvants).

The guidances describe conventional and accelerated approval pathways to vaccine licensure. Companies selecting the conventional pathway must provide clinical evidence that the vaccine prevents influenza. Adequate and well-controlled clinical trials are also required for accelerated approval but companies may use a biological indicator — such as immune response to the vaccine — to predict effectiveness, an approach that may reduce the vaccine's development time. Further clinical studies are then required to verify the vaccine's clinical benefit.

The guidances indicate that manufacturers should submit a new Biologics License Application (BLA) for the initial licensure of a pandemic or seasonal influenza vaccine to ensure that each pandemic and seasonal vaccine has its own trade name and labeling.

For companies with U.S. licensed seasonal influenza vaccines, the pandemic guidance outlines the regulatory pathway for obtaining licensure for a new pandemic vaccine in which the manufacturing process is the same as for the seasonal vaccine. For manufacturers developing vaccines using a new manufacturing process, both guidance documents explain the process for obtaining licensure using the accelerated approval pathway.

The guidance documents represent the FDA's ongoing efforts under its Critical Path Initiative to translate scientific advances, such as cell-culture derived and recombinant vaccine technologies, into new medical products with shorter approval timeframes.  Read More & Comment...

Nightline's Late Night Romp With Nissen

06/01/2007 08:45 AM |

Steve Nissen says he got physically sick to his stomach when he saw the results of his Avandia "study." I felt the same way after seeing Nightline's Chris Burri do everything but kiss Nissen on air during this tribute to St. Steven. Somehow Nissen's irresponsible remarks and behavior regarding ADHD drugs never made it on air and Nightline never checked out the accuracy of the claim that Nissen was a critic of Celebrex (untrue).

For my money I would have loved to have seen how much time Nissen spent and was paid for flying around the country talking about Viagra back in the 1990s. How does that square with his rabble rousing image.  Read More & Comment...

Chinese Checkers

06/01/2007 08:18 AM |

The FDA has determined that not only did tainted heparin from China infiltrate the US drug supply -- it did the same to 11 other nations as well. The facts are indisputable -- 12 different Chinese companies supplied contaminated heparin not only to the United States but to Australia, Canada, Denmark, France, Germany, Italy, Japan, the Netherlands, New Zealand -- and China.

The response from China -- denial there even were any impurities and then to imply that the problem stems from contaminated vials used in the United States. And, get this, the Chinese authorities won't allow FDA officials to inspect any Chinese facilities unless they can, in turn, inspect the American plants where the product was prepared for distribution.

How do you say "chutzpah" in Mandarin?

It's hard to say what these Chinese Checkers might discover -- but it's likely they'd find that the GMPs in place in the United States are the global gold standard. Whether the tainted ingredients were used in error or to save money doesn't matter. What matters now is that the problem must be identified -- and that means that our trading partners in the Middle Kingdom must allow FDA inspectors in now -- and allow them to inspect plants that produce API or other ingredients bound for US shores.

It's not a question of national sovereignty -- it's a matter of responsibility and public health.

What does all this say about the realities of drug importation? It points out, once again, that it’s nothing other than a dangerous political charade. And when you look at the list of nations impacted by this crisis, they're many of the same countries on the "approved" list for many ill-conceived drug importation bills.

So much for eastern promises.  Read More & Comment...

Chinese Checkers

06/01/2007 08:18 AM |

As any assistant district attorney will tell you, the "some other guy did it" defense generally means "guilty."

Now, it seems, China is blaming Panama for the deaths of 51 people caused by cough syrup containing Diethylene glycol -- a chemical commonly used in antifreeze and brake fluid. But, it seems, there is plenty of blame to go around.

This is just the latest example of China-as-hub for the international trade in counterfeit API (Active Pharmaceutical Ingredient). And connecting the dots to the issue of "safe" drug importation is pretty obvious.

Here's the story off the AP wire:

China blames Panama for deadly tainted drugs

Papers altered to say glycerin was for medical use, Chinese official claims

BEIJING - Businesses in Panama, not China were "mainly responsible" for passing off an industrial chemical as a medical ingredient leading to the deaths of at least 51 people, a senior official in China's product-inspection agency said Thursday.

Wei Chuanzhong, vice minister of the Administration for Quality Supervision, Inspection and Quarantine, said Chinese companies sold the industrial solvent called 'TD glycerin' to Spanish companies who then sold it to Panamanian companies. The product was then used to make cough syrup and other medicine.

"The Panamanian business people are mainly responsible because they changed the scope of use and shelf-life of this product," Wei said.

The deaths in Panama, which began last year, have dramatically added to a growing international alarm about the safety of food and medicines exported by China.

Wei acknowledged that the Chinese manufacturer, Taixing Glycerin Factory, and the Chinese distributor, CNSC Fortune Way, "engaged in some misconduct," because they used the name TD glycerin for a mix of 15 percent diethylene glycol and "other substances."

Diethylene glycol is a chemical commonly used in antifreeze and brake fluid.

Misleading name

"They used the very confusing name of TD glycerin, which will mislead people to think it's glycerin," said Wei. "The markings on the package also used the name glycerin instead of TD glycerin."

But he said the Panama traders bore the brunt of the responsibility for the deadly substance ending up in medicine.

"The Panama trader changed or altered the paperwork to say the substance was medical glycerin that met U.S. standards for use in medical products and changed the shelf life of the already expired product from one year to four years," Wei said. "The responsibility here is very clear."

He said the Chinese investigation found that the Chinese side made it clear in their export paperwork that the material they were selling was for industrial, not medical, use. Wei said Taixing had been punished for its misbehavior but when pressed for details, he said the company was still being investigated. He said China would not continue to allow the use of the name TD glycerin, but no ban has been formally announced.

Glycerin, which is often processed from animal fats and occurs naturally in the human body, is a sweet liquid that can give cough syrup and other remedies thickness while preventing them from dissolving in water. It is used in many kinds of medicines all over the world.

The first documented poisonings were reported in October, but Panamanian authorities said there may have been earlier cases that went undetected. Fifty-one people died after taking the tainted medications and 68 were hospitalized.

Why isn't Senator Bernie Sanders asking, "Where are the dead Panamanians?  Read More & Comment...

Osama ben Nissen

05/31/2007 02:57 PM |

Woke up this morning to the New York Times quoting Curt "No Brainer" Furberg saying, "Safety is just not a high priority for them."

"Them" being the FDA.

That statement is untrue, unjust, and unfair to the staff of the FDA who put their heart and soul into their jobs -- and could walk out the door tomorrow for much better paying, lower stress jobs. And yet they stay.

And this is what people say about them. For shame.

I will go to bed this evening after the Nightline feature on Avandia. Curious to see how ABC edits the interviews they did with Scott Gottlieb and Steve Galson.

In fact, I am more than curious considering the clip of Steve Nissen that ABC has on their web site:

http://abcnews.go.com/Nightline/story?id=3225419&page=1

Dr. N. compares Avandia to 9-11.

Fearmongering at its worst.

And his you-know-what eating smile should tell you all you need to know about how much he's enjoying himself.

For shame.  Read More & Comment...

Nissen Hissy Fit

05/31/2007 01:08 PM |

"Nissen points to his outspoken criticism of Cox inhibitors including Celebrex -- a Pfizer product -- at the time he was the principal investigator for a Pfizer clinical trial."

Can anyone find any criticism of Celebrex by Nissen? Here is the full extent of Nissen's whining in advance of his Nightline puff piece tonight....

http://www.abcnews.go.com/Nightline/Story?id=3225419&page=2

Here is a contemporary account of who was outspoken and when:

"Following the decision to pull Vioxx from the market three years later, Topol continued to publicly criticize Vioxx-maker Merck for its slow response and for its decision to put the dangerous drug on the market in the first place. Dr. Nissen, however, was less vocal.

Subpoenaed in the first federal Vioxx trial in November 2005, Dr. Topol gave a three-hour videotaped deposition attacking Vioxx and accusing Merck of scientific misconduct. Less than a week after that deposition, Topol lost his position at the Cleveland Clinic.

There is one other important point to note here: At the same time Dr. Topol was being demoted, his past partner in protest, Dr. Nissen, was being asked to lead the $100 million study into the safety of Celebrex. "

http://www.newstarget.com/019333.html

Nissen has also voiced support for Pfizer's new ad campaign for Celebrex (we do too!)

I guess silence is golden.  Read More & Comment...

Can You Be Half Conflicted?

05/31/2007 08:52 AM |

Dr. Nissen talks about how he donates all his drug industry honoraria to a private charity -- more on THAT later -- but no much later since he didn't start becoming pure until 2004. As Dr. Nissen wrote in his inaugural letter as Pres. of the American College of Cardiology -- which runs his private charity -- " you will sleep better at night and your favorite charity will be grateful for the support. "  Read More & Comment...

St. Steven? Saints Alive!

05/30/2007 05:09 PM |

Dr. Nissen, it seems, can dish it out. But when it comes to "taking it," that's another thing entirely.

According to the man himself, "While I did spend a sleepless night about this, I'm not backing down."

What's causing Dr. Nissen to lose his zzzzs? An e-mail from an FDA spokesman to reporters challenging Dr. N's motives and credibility.

Yep -- he's losing sleep over a nasty e-mail.

In the correspondance in question, entitled "What are St. Steven's feet made of? Clay, perhaps?," FDA spokesman Doug Arbesfeld forwarded to reporters critical news articles, including an anonymous blog accusing Nissen of playing favorites among drug companies.

It's nice to share, right? Well not if you don't agree with Dr. Nissen.

According to The Man, "I'm a pretty tough guy, but I'll tell you, having this kind of an e-mail that questions my motives, broadcast to the major journalists with whom I work and have established a reputation, is -- it's an outrage."

Mommy!

Dr. Nissen, have you heard this one: Do unto others as you would have them do unto you.

This from the same guy who says he donates all his consulting fees to charity -- except that the "charity" resides within the American College of Cardiology -- an organization over which he holds tremendous sway. (Although, in fairness, it is certainly not the same as depositing the money into one's own piggy bank.)

As Mark Twain said, "The rule is perfect: in all matters of opinion our adversaries are insane."

An outrage indeed.  Read More & Comment...

Initial Concepts

05/30/2007 01:27 PM |

Whether it's EBM or HTA or RUM or RUD ... it means the same thing ... putting cost before care. You can tell when this is happening when health ministers begin to act like junior finance ministers. Unfortunately it's happening all the time across the EU and it's pennywise and pound foolish. Oh yes -- it's also bad for patient care. Details. Details.

Don't let the alphabet soup of acronyms fool you -- it all spells care denied.
But you already know that.

Now this dangerous medicine threatens US health care policy with the current phrase de jour, "comparative effectiveness."

No matter how you cut it, evidence-based medicine based on bad evidence is bad medicine.

But you know that already too.

Here's a new paper (published jointly via the Center for the New Europe and the Center for Medicine in the Public Interest) authored by Jacob Arfwedson (a leading European thinker on this topic) and yours truly. The paper discusses where this variously named and initialed concept came from and where it's going not only in Europe but also, via our buddies at the WHO, into the developing world.

http://www.cne.org/pub_pdf/2007_05_arfwedson_pitts_ebm.pdf

And, if you're listening carefully to the rhetoric from inside-the-beltway and from the various presidential campaigns, you'll see that the concept of comparative effectiveness is entering into the general parlance.

But it's more than just another simplistic answer to a complicated question -- it's a signal that we had better start paying attention and offering real, long-term solutions -- like personalized medicine via the Critical Path.

Like we keep saying -- it ain't called "critical" for nothing.  Read More & Comment...

Obviousness-Based Medicine

05/30/2007 12:49 PM |

Smokin!

The National Institute for Health and Clinical Excellence (NICE) in the United Kingdom has recommended Champix (varenicline) for use on the National Health Service for adult smokers who have expressed a desire to quit. This gives smokers across England, Wales and Northern Ireland access to another important treatment option to help them quit smoking.

In its Final Appraisal Determination, NICE concluded that varenicline was “superior to NRT [nicotine replacement therapy] and bupropion in achieving continuous abstinence” and that its use in smoking cessation was “likely to be a cost-effective use of National Health Service resources.”

“This guidance means that smokers who are serious about stopping have another choice from a good range of clinically proven treatments, said Professor Robert West, Professor of Health Psychology at University College London. “Smokers who combine treatments with the right support – for instance from smoking cessation services - could significantly increase their odds of successfully quitting for life.”  Read More & Comment...