Monday, February 22, 2010

The Avandia beatup

I would normally cover this on my FOOD & HEALTH SKEPTIC blog but as it seems to be part of a political war against the drug companies designed to shore up support for Obamacare, I am covering it here. It is a huge crock, as I will point out at the foot of the article below. Politicians faulting the super-cautious FDA on drug safety really is a laugh

A Senate report that revives concerns about a GlaxoSmithKline PLC diabetes drug's link to heart attacks is putting pressure on the Food and Drug Administration to make changes to its drug-safety program. People familiar with the situation say agency leaders held calls over the weekend to discuss how to address complaints from Sens. Max Baucus (D., Mont.) and Chuck Grassley (R., Iowa), who released a new report Saturday on the Glaxo drug, called Avandia.

The FDA is trying to assemble a timeline of what the FDA knew of risks associated with Avandia, these people say, and plans to call a meeting of an outside advisory committee in the next few months to look at recent information on the drug, which Glaxo reported as having global sales of £771 million ($1.2 billion) in 2009.

According to a two-year investigation by the Senate Finance Committee, Glaxo knew about data linking Avandia to elevated risk of cardiovascular events for several years, but played down the information and tried to suppress doctors who raised concerns. Starting in 1999, Glaxo executives complained to superiors about researchers who questioned Avandia's safety, the report says.

Glaxo rejected those conclusions. It said in a statement that the increased risk of heart attacks hasn't been proven and noted that the FDA "has ruled that Avandia remain available." The company says it never tried to suppress doctors' views but sought to correct what it considered misinformation.

Internal FDA reviews included in the Senate report show that in 2008, longtime FDA scientists David Graham and Kate Gelperin urged the FDA to get Avandia off the market. They analyzed data on side effects in dozens of Avandia studies, but their recommendations were rejected by FDA chiefs. The senators want to know why.

Avandia is still on the market, but it has a strong warning label about cardiac risks. Its sales dropped after a widely publicized study in May 2007 by the Cleveland Clinic's Steven Nissen that linked Avandia to a 43% greater risk for heart attack.


Below is a meta-analysis of the data upon which the FDA based its decision. The meta-analysis appeared in the prestigious "Journal of the American Medical Association"

Long-term Risk of Cardiovascular Events With Rosiglitazone: A Meta-analysis

By Sonal Singh et al.

Context: Recent reports of serious adverse events with rosiglitazone use have raised questions about whether the evidence of harm justifies its use for treatment of type 2 diabetes.

Objective: To systematically review the long-term cardiovascular risks of rosiglitazone, including myocardial infarction, heart failure, and cardiovascular mortality.

Data Sources: We searched MEDLINE, the GlaxoSmithKline clinical trials register, the US Food and Drug Administration Web site, and product information sheets for randomized controlled trials, systematic reviews, and meta-analyses published in English through May 2007.

Study Selection: Studies were selected for inclusion if they were randomized controlled trials of rosiglitazone for prevention or treatment of type 2 diabetes, had at least 12 months of follow-up, and monitored cardiovascular adverse events and provided numerical data on all adverse events. Four studies were included after detailed screening of 140 trials for cardiovascular events.

Data Extraction: Relative risks (RRs) of myocardial infarction, heart failure, and cardiovascular mortality were estimated using a fixed-effects meta-analysis of 4 randomized controlled trials (n = 14 291, including 6421 receiving rosiglitazone and 7870 receiving control therapy, with a duration of follow-up of 1-4 years).

Results: Rosiglitazone significantly increased the risk of myocardial infarction (n = 94/6421 vs 83/7870; RR, 1.42; 95% confidence interval [CI], 1.06-1.91; P = .02) and heart failure (n = 102/6421 vs 62/7870; RR, 2.09; 95% CI, 1.52-2.88; P < .001) without a significant increase in risk of cardiovascular mortality (n = 59/6421 vs 72/7870; RR, 0.90; 95% CI, 0.63-1.26; P = .53). There was no evidence of substantial heterogeneity among the trials for these end points (I2 = 0% for myocardial infarction, 18% for heart failure, and 0% for cardiovascular mortality).

Conclusion: Among patients with impaired glucose tolerance or type 2 diabetes, rosiglitazone use for at least 12 months is associated with a significantly increased risk of myocardial infarction and heart failure, without a significantly increased risk of cardiovascular mortality.

JAMA Vol. 298 No. 10, 1189-1195, September 12, 2007

In other words, a survey of the strongest data available showed that taking Avandia increased your risk of having a heart attack from 1.05% to 1.46%, an increase in risk of less than one half of one percent -- which is vanishingly trivial compared to the risks we take in most things we do. Given the large sample size, however, the result is statistically significant, if not significant in any other sense. If we were to reject such small risks as that we would have NO drugs on the market because all drugs have some adverse side-effects.

But here's the real kicker. Read the last clause in the abstract above. What it means in plain English is this: Although Avandia takers had a minutely greater risk of having heart attacks, the "extra" heart attacks DID NOT KILL THEM. Avandia takers were no more likely to die from a heart attack than anybody else! And THAT is the drug that is so evil that the Senate Democrats are making a huge fuss about it! It's just the usual search for evil in the world about them that IS Leftism. See the article immediately following this one.


Grassley is a Republican but he was an easy target to get sucked into this affair as he has in the past made something of a career of exposing researchers who had failed to declare payments received from drug companies. His interest is clearly in the possibility of corruption rather than in the science.


The Perpetual-Crisis Machine Of The Apocalyptic Left

The left is in crisis-overdrive. Imminent disaster is its rallying cry. The world will end, if we don’t appropriate billions, launch another massive government program, shower condoms on 6-year-olds, socialize another sector of the economy, cede more of our freedom to Washington, and venerate the polar bears.

Since at least the early 1960s, the left has been in a constant state of agitation, prophesying doom at every turn. Any who question its hysteria-mongering are labeled anti-science, a tool of corporate interests, insensitive or just plain Republican.

The refrain is always the same: Don’t question. Don’t examine the evidence too closely. Don’t debate the proposals. Whatever you do, don’t read the legislation before you vote. Just give us what we want, or civilization, as we know it, will cease to exist, millions will die horrible deaths – and it will be your fault.

Like its progenitor, Karl Marx, the left is always wrong – often hilariously so. On September 24, 2008, Robert F. Kennedy Jr. (to speak of a Kennedy scion from the low end of the gene pool implies there’s another end), in a commentary for the Los Angeles Times, pointed to recent mild winters in the D.C. area (“anemic” he called them) as conclusive evidence of global warming.

Junior disclosed, “Once, my father, Atty. Gen. Robert Kennedy, brought a delegation of visiting Eskimos home … for lunch. They spent the afternoon building a great igloo in the deep snow of our back yard.” Yet, in the face of irrefutable evidence of lack of igloo-building, “Exxon Mobil and its carbon cronies continue to pour money into think tanks whose purpose is to deceive the American public into believing that global warming is a fantasy.” Kennedys know a lot about deceiving the American public.

Meanwhile, the blizzard from which Washingtonians just dug out surpassed the record snowfall of 1899. At one point, Dulles Airport reported that 72 inches had fallen. The response of the apocalyptic left? Well, we told you global warming will result in extreme weather conditions. You see, mild winters prove global warming – as do severe winters. Any questions?

Karl Marx was the original progressive doom-and-gloomer. In the mid-19th century, Marx (who never set foot in a factory or met a blue-collar worker) confidently predicted the “crisis of capitalism” – the rich would keep getting richer, while the proletariat would have children, until, on the verge of starvation, the latter would throw off their chains in a worldwide revolution.

Instead of poverty, the proletariat got collective bargaining, employer-paid health insurance, and comfortable pensions. Workers of the world unite! You have nothing to lose but your 401-k plans.

It wasn’t quite a straight line from “The Communist Manifesto” to Rachel Carson’s “The Silent Spring” (1962). The Al Gore of her day, Carson warned of environmental catastrophe from the widespread use of DDT to control the mosquitos that spread malaria. Considered the mother of the environmentalist movement, Carson was responsible for the 30-year ban on DDT, finally lifted by the World Health Organization in 2006. Her book claimed the compound caused cancer in humans and genetic damage to birds and beneficial insects – all based on anecdotal evidence and rats doing laps in vats of DDT.

In 1981, Rachel Carson got a commemorative U.S. postage stamp. Millions in the Third World – especially pregnant women and children – got early deaths from malaria, which DDT had largely eliminated by the mid-60s.

From “The Silent Sprint” to “An Inconvenient Truth" and beyond, it’s been a steady march of hysteria, manufactured statistics and speculation totally detached from reality. Stroll down memory lane and meet the ghosts of liberal crises past.

• The Homeless – The “homelessness crisis” suddenly appeared in the early ‘80s, conveniently, just as the left was looking for an emotional way to indict Reaganomics. Supposedly, millions of homeless wandered the streets of our cities, pushing shopping carts, sleeping on heating grates and mooching change. Shelters were filled to capacity. Rising unemployment, lack of affordable housing and the disappearance of the proverbial safety net were to blame, liberals charged. We were all just a few steps away from the streets, they told us.

Mitch Snyder, self-anointed advocate for pavement people (Martin Sheen played him in a made-for-T.V. Movie – “Samaritan: The Mitch Snyder Story”), informed an ever-credulous media that there were 3 million homeless, a statistic he later admitted making up. In a campus address, Snyder, who committed suicide in 1990, tearfully told us that in America, 45 homeless people die every second. That would mean 1.4 billion (four times the total U.S. population) expire annually, and then are resurrected to die again the following year.

P.J. O’Rourke once wrote that if you put all of the homeless in affordable housing, half are so crazy they’d jump out the windows and the other half would sell the plumbing for drugs or booze. According to one study, between 65% and 85% of the homeless are mentally ill, alcoholics, addicts, or a combination thereof.

We were all just a few cases of Thunderbird or a psychotic episode away from the streets.

• The AIDS Epidemic – Discovered about the same time as the homeless crisis, the dread contagion wasn’t a gay disease, we were assured – on the theory that, if it was, we wouldn’t care enough. Everyone was susceptible. If we didn’t spend billions pronto, AIDS would sweep the nation like wildfire.

“Now No One Is Safe From AIDS,” screeched the cover of Life magazine. It was worse than the Black Plague, a Joe Biden speech and daytime television combined. Then-Surgeon General C. Everett Koop (who was co-opted by the AIDS lobby) forecast a “heterosexual AIDS explosion.” Oprah said that by 1990, 20% of all heterosexuals would be dead from AIDS. Clinton’s HHS Secretary Donna Shalala said AIDS may leave “nobody left.”

These projections were delusional, to put it mildly. According to The Centers for Disease Control, in 2007, 14,561 died from AIDS – not much of a mega-plague, when compared to 631,636 deaths from heart disease, 559,888 from cancer and 137,119 from stroke in the same year.

A 1988 New York Times story (“Researchers List Odds of Getting AIDS in Heterosexual Intercourse’) gave away the game. According to the paper, which never misses a chance to proselytize for the gay agenda, the chances of contracting AIDS from a single act of heterosexual intercourse – with an infected partner and without a condom -- were 1 in 500. No one was safe from AIDS – no one who was gay, bisexual or into sharing (needles).

• The National Epidemic of Hate Crimes – The late Sen. Edward Kennedy called hate crimes “domestic terrorism” – thereby suggesting that they were just as much a threat to our nation’s security as al-Qaeda, Taliban, Hezbollah and every jihad-preaching imam around the world. Neo-Nazis, Ku-Kluxers and freelance haters were roaming our streets looking for victims on which to inflict their vile animus. The alleged epidemic led to the passage last year of The Matthew Shepard and James Byrd, Jr. Hate Crimes Prevention Act, which added “sexual orientation” to the category of protected classes.

Just how much of a hate-crimes crisis there is may be seen from the FBI Uniform Crime Reports. (The FBI is required to compile statistics of so-called bias offenses.) According to the UCR, in 2007, there were 16,929 murders and over 855, 000 cases of aggravated assault in the United States. There were also a grand total of 7,624 hate crimes of all kinds – motivated by race, religion, ethnicity, sexuality, whatever.

Of that number, 78% involved either intimidation (words alone), or simple assault (no serious injury occurred), which included pushing and shoving. In 2007, 9 murders were classified as hate crimes – which constituted .0005 % of total homicides. Your chances of being the victim of a hate crime – any hate crime – are comparable to being struck by lightening twice while bungee-jumping on Groundhog Day. For this, we abrogated the First Amendment’s Free Speech clause.

• Global Warming—To justify spending trillions of dollars, drastically altering our way of life and wrecking our economy with idiocies like Cap and Trade, in “An Inconvenient Truth,” Gore forecast that the sea level could rise by as much as 20 feet, due to melting polar ice caps. Even, the U.N.’s Intergovernmental Panel on Climate Change, run by the global-warming alarmists, was more modest – predicting that sea levels would rise 17 inches by 2100.

Besides his Oscar, Gore deserved a Nebula Award for science fiction writing. Dr. Nils-Axel Morner, a Swedish geologist and physicist who formerly headed the International Commission on Sea Level Change, says that, despite fluctuations, the sea level “has not risen in the past 50 years.” And if there is any change in this century, it will “not be more than 10 cm (4 inches), with an uncertainty of plus or minus 10 cm.” The mainstream media would call Dr. Morner a “global-warming denier.”

Still, Gore’s forecast could come to pass. If the 1.4 billion homeless who die in America every year each had a burial at sea … .

• Over-population – The world was “overpopulated” in 1798, when Thomas Malthus wrote “Principles of Population” and planet earth contained less than a billion people. In his tract, Malthus predicted mass starvation in the coming century. Instead, we got the Industrial Revolution and the greatest expansion of material well-being in history.

The world was overpopulated in 1968, when there were 3.63 billion on earth and Paul Ehrlich wrote “The Population Bomb,” in which he predicted mass starvation in the 1970s – and thus joined the ranks of Malthus and Marx as a prophet of dumb. Today, the world’s population is 6.8 billion. It’s been said that you could fit everyone currently on earth into Texas, and they’d have 1,000 sq. feet of living space. If those quarters are too tight, you could send them all to Brazil, where they'd each have three acres.

If starvation and overcrowding won’t do the trick, how about climate change? Now, it’s argued that a growing population increases carbon fuel consumption, depletes the ozone layer and – aaaaarah! We’re all going to die! Thus, the left has one of its newest myths (global warming) driving one of its oldest myths (overpopulation).

• The Health Insurance Crisis – In his State of the Union address, Barack Obama warned, “By the time I’m finished speaking …. more Americans (45 a second?) will have lost their health insurance.” “Millions will lose it this year.” Plus, (you guessed it) we’re all just a job away from being one of the health insurance-less.

Obama and the Democrats are wedded to the figure 46 million for the number of uninsured in America. For a change, the stat comes from a reliable source, the U.S. Census Bureau. But this is a snapshot of a point in time. It does not mean that 46 million Americans are uninsured over the course of a year. It also doesn’t tell us why they’re uninsured. (Some are between jobs.)

The same data shows that 38% of the uninsured earn more than $50,000 a year and 9.1 million earn more than $75,000. They could afford health insurance. Many are young and healthy and willing to gamble the cost of insurance against the prospect of a serious illness. Another 14 million qualify for government programs that they’re not currently using. And almost 10 million aren’t U.S. citizens. Obama swears on a stack of Korans they’ll never get federally mandated health insurance.

The chronically uninsured are about 8 million, in a population of 305 million. For this we’re expected to turn the best health-care system in the world over to the politicians and bureaucrats who gave us sub-prime mortgages, $1,000 toilet seats and the U.S. Postal Service – and get rationing, death panels, and federally funded abortion in the process.

If they were honest, liberals would confess: “There’s a severe power crisis in this country. When it comes to power over your own life, you have too much and we have too little. Please help us to rectify this situation.”

Of course, that would get them nowhere. Hence, the left’s perpetual-crisis machine – apocalypse now. ”Unless you let us do something drastic right away, you could get AIDS, end up homeless, lose your health insurance, see your beachfront property under 20 feet of water, and watch as beach towels are airlifted to the Eskimos." Goebbels wouldn’t have the gall to concoct the lies they’ve been peddling for half a century.

But more than a power grab is involved. The left hates the middle-class, hates private property and hates limited, constitutional government. It wants to make us feel guilty for what we have. Whatever the crisis, ultimately, it’s our fault – it’s our greed, stupidity, callousness or bigotry that fuels the catastrophe.

In the movie “The Invention of Lying,” Ricky Gervais lives in a world where everyone tells the absolute truth. The protagonist becomes the first person to intentionally tell a lie. (Could the invention of liberals be far behind?) To see how much he can get away with, in one memorable scene, Gervais approaches a beautiful woman on the street and tells her, “If we don’t have sex right now, the world will end.” She responds, “Do we have time to go to a motel, or do we have to do it here?”

That's the way liberal crisis-mongers operate – Let us screw you, right now, or the world will end.




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The Big Lie of the late 20th century was that Nazism was Rightist. It was in fact typical of the Leftism of its day. It was only to the Right of Stalin's Communism. The very word "Nazi" is a German abbreviation for "National Socialist" (Nationalsozialist) and the full name of Hitler's political party (translated) was "The National Socialist German Workers' Party" (In German: Nationalsozialistische Deutsche Arbeiterpartei)



Ed Darrell said...

Hmmm. You said: It wasn’t quite a straight line from “The Communist Manifesto” to Rachel Carson’s “The Silent Spring” (1962). The Al Gore of her day, Carson warned of environmental catastrophe from the widespread use of DDT to control the mosquitoes that spread malaria.

No. Carson, a dedicated free-marketeer, warned against overuse of DDT on things not necessary, instead of conserving DDT to use against serious threats, like mosquitoes carrying malaria.

I understand from your piece that you did not read Carson's book and you know nothing about her, and not much about DDT, either. Is that right?

Considered the mother of the environmentalist movement, Carson was responsible for the 30-year ban on DDT, finally lifted by the World Health Organization in 2006.

Carson didn't call for a ban on DDT. She called for "integrated pest management," which is the policy now used to fight malaria where malaria is still a serious problem. Give her credit where credit is overdue, will you?

WHO never was bound by the ban on DDT use on agricultural crops in Sweden, nor the later ban on DDT use in agriculture in the U.S. WHO never banned the use of DDT.

In the middle 1960s, when Carson's prophecies unfortunately became real, DDT stopped working well against malaria-carrying mosquitoes. WHO had to abandon its DDT-based campaign to eradicate malaria from Africa and Asia, with added complications from unstable governments in central Africa, unable to attain the discipline in public health delivery necessary to fight malaria. WHO didn't lift a ban in 2006 -- they put out a press release in late 2005 that reiterated their stand: Use DDT where appropriate.

DDT has never been banned in Africa. WHO does not have authority to ban any chemical for anything. You should get the history and facts straight, to prevent wrong conclusions.

[More next post]

Ed Darrell said...

[Continued from previous post]

Her book claimed the compound caused cancer in humans . . .

No, she never claimed DDT as a carcinogen -- though it is now listed as a "probable carcinogen for humans" by every cancer-fighting agency on Earth.

. . . and genetic damage to birds and beneficial insects – all based on anecdotal evidence and rats doing laps in vats of DDT.

Wrong on all counts. She didn't claim genetic damage. She noted studies that showed that birds with DDT in their tissues were unable to bring eggs to pubescent birds. The eggs didn't hatch, or the chicks died soon after hatching, or in the rare cases where the young actually survived and fledged, they could not breed successfully.

We now know this is from DDT's powerful endocrine disruption powers. It mimics estrogen, making eggs unviable, and screwing up the reproductive organs of birds, fish, lizards, amphibians, and mammals including humans. DDT shrinks the testes of young boys and men, and gives them swollen mammaries, among the more obvious problems.

Genetic damage was never alleged. Probably not so. At least a hundred studies show the thinning of eggshells, however, which results from the overdose of estrogen-like substances.

Carson provided more than 50 pages of citations to scientific studies on birds, none on rats. None of those studies has ever been contradicted by any subsequent research.

Rat studies show carcinogenicity, but again, Carson didn't claim that.

In the ban on DDT use on crops, EPA cited the destruction of ecosystems by DDT. Carcinogenicity is the concern of the FDA, and they banned DDT residues on food crops much earlier. FDA lacked the authority to ban use of DDT, however. You're confusing agencies and actions covering more than a decade of increasing knowledge of the harms of DDT.

The National Academy of Science published a book calling DDT one of the most valuable chemicals ever. Then they called for a ban on DDT as soon as possible, since its harms outweigh its benefits.

You could look it up.

In 1981, Rachel Carson got a commemorative U.S. postage stamp. Millions in the Third World – especially pregnant women and children – got early deaths from malaria, which DDT had largely eliminated by the mid-60s.

If millions died unnecessarily, it's because too many policy makers listened to ill-informed screeds like this one of yours, and they failed to act to save the kids and mothers because they thought poisoning Africa would do the trick.

I think you packed at least two errors of history or science into each of those sentences, maybe more. If you're that wildly inaccurate on this one issue, which is easy to research, how wildly off the mark are you on all the other issues you race through?

Aristotle The Hun said...

Ed, Dr. Ray didn't write that article. Had you followed your own advise and read before you commented you wouldn't look so foolish now.


Ed Darrell said...

I'm not sure how the source of the piece makes any difference in its manifold errors of history and science.

Nor do I see any criticism of the errors here.

Can you explain why I should be embarrassed? Are you defending the errors?

Ed Darrell said...

"To kill an error is as good a service as, and sometimes better than, the establishing of a new truth or fact" -- Charles Darwin

Do we believe that?

JR said...

Herr Darrell seems to have missed the point of the post: Carson undoubtedly generated a scare

Detailed criticisms should however be directed to the author concerned.

I have not specialized in the matter but I note that African authors attribute many deaths to the Carson-inspired restrictions on DDT

The development of immunity problem is, from recollection, mainly an Indian problem