Rita Rubin On the Nissen Trial

06/07/2007 08:43 AM |

Here's Rita Rubin about the chain of events leading up to the black box warning about congestive heart failure and PPARs at the FDA:

"Grassley, whose office released the letter Wednesday, asked von Eschenbach to respond to allegations that Johann-Liang had been reprimanded for agreeing with her staff's recommendation that Avandia needed a black-box warning about congestive heart failure and stronger warnings about macular edema, a serious eye condition."

Let's be clear about who Johann-Liang is and her history. She is the same person who was selectively leaking stuff to Grassley on Ketek and recommended pulling the drug altogether. Her actions and dalliance with Grassley's staff have led delays and increased costs in antibiotic research. Her demand for a black box was in advance of both the Glaxo meta analysis, the DREAM results and the RECORD study. And both Takeda and Actos had previously sent out letters to prescribers warning about the elevated risks of their drugs to patients with a history of heart failure.

"The FDA, which had received data from Glaxo last August suggesting a 30% increased risk of heart attacks in Avandia users, did not alert patients and doctors about that possibility until Steven Nissen, chair of cardiovascular medicine at the Cleveland Clinic, reported a similar finding, posted May 21 on The New England Journal of Medicine's website."

The facts are that the FDA had been working on this issue well in advance of the NIssen article -- as Nissen himself admitted in his testimony. Nissen's article was timed to pre-empt a pending FDA decision.

Rita again: " Glaxo should have begun enrolling high-risk diabetes patients in a large, long-term study when Avandia was approved in 1999. By now, Nissen said, the results would be in."

In fact, Glaxo did begin enrolling "high-risk diabetes patients in large long term study when Avandia was approved in 1999." It was called the DREAM study. It looked at heart problems as a secondary endpoint and was expected to have it's data blended with other studies looking at heart safety since the sample size alone was considered to be underpowered to determine RARE risks.

That's how safety signals are validated today in the absence of new IT and genomic tools. We could do it faster, better, more personalized and predictive.

Which is why Andy Von E kept on calling for more resources, not more authority to improve post market surveillance.

That's the rest of the story.  Read More & Comment...

PDUFA Passes the Senate Intact ... Barely

06/06/2007 06:16 PM |

From the Food and Drug Letter...

Senate Passes PDUFA Reauthorization Bill

The Senate passed a bill to reauthorize the Prescription Drug User Fee Act (PDUFA) after adding an amendment to increase penalties for noncompliant drugmakers and narrowly rejecting two amendments that would have augmented other safety regulations in the bill.

We will see if certain senators have the stomach for their own show trial after Dr. Nissen's embarassing performance today.  Read More & Comment...

Meta-Analysis Mess

06/06/2007 01:33 PM |

Nissen's entire approach is a case study of how to use statistical tools to manufacture biased results. In “Why Most Scientific Research Findings Are False” John Ioaniddis, a professor nstitute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts-New England Medical Centera notes that a study relying on meta-analytic finding from inconclusive studies where pooling is used to “correct” the low power of single studies, is probably false and biased.

Research findings from underpowered, early-phase clinical trials would be true about one in four times, or even less frequently if bias is present. Epidemiological studies of an exploratory nature perform even worse, especially when underpowered, but even well-powered epidemiological studies may have only a one in five chance being true. Nissen’s research which combines small clinical trials to conduct a epidemiological study of an exploratory nature that deliberately excludes patients without heart attacks, that does not independent confirm if one took place and does not have access to patient level data, to find a risk he believes is there may or may not be true but it is certainly biased and likely to be false.

Indeed, stating that there is a increase of 40 percent risk in heart attacks relative in Avandia users compared to others raises two other troubling questions. First, it is generally true that, as Ioannidis claims that independent of molecular or genetic confirmation of a cause and effect, “too large and too highly significant effects may actually be more likely to be signs of large bias in most fields of modern research.”

They should lead investigators to careful critical thinking about what might have gone wrong with their data, analyses, and results.

For instance, in the 1980s a Swedish epidemiological study found that people with hip and knee replacements had a 30 percent greater increase of kidney cance than those who had no surgery. That study did not cause the authors to run to Congress and the media with results at a politically sensitive time. Instead, it suggested further epidemiological analysis and observational analysis which lead to the conclusion that the ‘relationship’ between orthopedic implants and kidney cancer was “noise” as opposed toa signal of something going wrong.

The proper response to the Avandia exercise would be to conduct further research and to put the general risk of heart events in context, Nissen, the authors of the editorials supporting his claim and the NEJM have not done either. Instead Nissen ran to the media and Congress with a highly speculative report. The NEJM gave the article prominence and failed to run a cautionary editorial.  Read More & Comment...

Nissen Agonistes

06/06/2007 01:02 PM |

"I provided a preliminary analysis to congressional staff" prior to giving it the FDA and NEJM..

Dr. Nissen regards this as moral and ethical.  Read More & Comment...

DTC = Direct to Congress

06/06/2007 11:44 AM |

Today's hearing was supposed to be Steve Nissen and Henry Waxman's grand unveiling of a new master plan for FDA reform. Instead it was an embarassing examination of how Nissen's effort to explain away why he went to Congress (rather than the FDA) with a preliminary analysis of Avandia.

Now of the more zealous critics of the FDA are now left hanging out to dry by Nissen's own measured statements about not recommending that any doctor stop prescribing or not prescribe Avandia on the basis of his study. Of course to say that totally contradicts his claim that Avandia was "worse than 9/11" is an understatment. Too bad the head of GSK research didn't have the chance to take him head on. CMPI will try to offer him that opportunity as well as the researchers of the RECORD study.

That did not stop Bruce Psaty from waving the bloody shirt of safety at the hearings, though he was reduced to irrelevancy by the end.

One by one the safety extremists are marginalizing themselves. Dr. Nissen was alternately defensive, evasive and hesitant.  Read More & Comment...

Headline Acts

06/06/2007 10:53 AM |

One of these things is not like the other ...

Analysis of Avandia Finds
No Increased Risk of Death

-- Wall Streeet Journal

Glaxo: Diabetes pill does not raise heart risk

-- USA Today

Avandia No Riskier Than Other Diabetes Drugs Says Interim Study

-- Medical News Today

Diabetes Drug Still Has Heart Risks, Doctors Warn

-- New York Times  Read More & Comment...

Regulatory Accountability

06/06/2007 07:54 AM |

Here's the Washington Times editorial page on the subject of Waxman and Nissen (along with Furberg and Psaty) as a defacto FDA:

"Dr. Nissen thus used his prominence and ties to Mr. Waxman and the media in order to engage in what one pundit has called drug safety vigilantism. So, while the media and Mr. Waxman have put Avandia, the FDA and drug companies on trial (once again) the real question is: Do we want Mr. Waxman and those he has anointed to usurp the authority of the FDA and scuttle proposed improvements to the current approach to regulation?

The Waxman-Nissen approach is clear: Come up with possible safety problems with questionable statistical approaches; share them with friendly members of Congress and editorialists who will use the findings to attack the FDA; hold hearings in order to put companies on the defensive and generate more lawsuits. "

Here's a link to the entire editorial:

http://washingtontimes.com/op-ed/20070605-092645-7468r.htm  Read More & Comment...

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...