Friday, June 30, 2006
Lookalikes
Sir,
Could you re-print that marvellous lookalike from a few years back showing the remarkable resemblance between the World Cup trophy and Munch’s ‘The Scream’? I think we should be told again.
Yours,
K.E. HUGHES
Prague
Source: Private Eye
Merck - Vioxx: Scolnick "not aware" of negative trial results
Merck did not inform the FDA about two clinical trials in which users of the painkiller Vioxx were more likely to die than people given a placebo, jurors in the first Vioxx liability case to go to trial in California were told Wednesday.Dr. Edward Scolnick, the former head of Merck's research laboratories, said in a videotaped deposition that he did not believe the numbers were coincidental.
''It's not likely due to chance,'' he said.
Scolnick testified that people who took Vioxx died at a rate four times higher than those who didn't receive the drug in one of the clinical trials, and 2 times higher in the other.
Both trials were done in 2001 in Alzheimer's patients.
Merck, however, did not turn over trial results to the FDA when company officials met with agency representatives in April of that year.
Scolnick said he was not aware of the clinical trial results at the time.
Why was he unaware? Was he not doing his job as head of research properly?
Insider wonders if there is an email out there that might help Ed refresh his memory?
link
Also see this very helpful NPR Vioxx timeline.
The name's Friday, Jack Friday
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Some people have asked why I picked the name "Jack Friday".
It comes from an old US TV cop series.
Detective Sergeant Joe Friday was a fictional character created and played by American actor, television producer, and writer Jack Webb (1920-1982) on the radio and television series Dragnet.
In 1987, actor Dan Aykroyd starred as Joe Friday, supposedly the original Joe Friday's nephew, in the comedy film Dragnet.
Friday's catchphrase was; "Just the facts, ma'am, just the facts".
And thus Jack Friday (aka Insider) was born.
Irony - will Crestor's "success" be AstraZeneca's downfall?
The pharmaceuticals giant AstraZeneca hit a four-year high yesterday despite reports that it will not increase the price of its "superstatin" Crestor now that the competitor Zocor has gone off patent.
Some traders remain convinced that recent strong newsflow on Crestor will lead to a bid for the company, and the shares surged 111p to 3,242p. Dresdner Kleinwort became the latest broker to increase its forecasts for AstraZeneca and also upped its target price on the stock to 3,315p and its recommendation from "sell" to "add".
Since the UK rival GSK lost out in the auction for Pfizer OTC to J&J, takeover talk has intensified.
GSK are thought to be keen to do a big deal this year.
Although there would be regulatory issues to be overcome in the event of a GSK bid for AstraZeneca, traders said there would be a long queue of buyers for the parts of AstraZeneca that GSK would be forced to sell. GSK, a long-term underperformer in comparison to many of its rivals, added 33p to 1,500p.
Insider's view: the fact remains that Crestor has failed to get anywhere near the 20% market share that was forecast by the last two CEO's.
It is a "dog" in marketing terms.
None the less, it would be ironic if Crestor's latest PR "successes" helped fuel AZ's ultimate demise.
Source: The Independent
Thursday, June 29, 2006
Merck - Gardasil: score Big Pharma 1: Big Jesus 0
Looks like Merck have taken the lead over religious groups in the cervical cancer wars .
A US government advisory committee is recommending that all 11- and 12-year-old girls get a new vaccine to prevent the sexually transmitted virus that leads to most cases of cervical cancer.
Conservative groups, including the influential Family Research Council (FRC), had voiced concerns that immunising young girls against the virus that most regularly causes cervical cancer, Human Papilloma- virus, may lead to sexual promiscuity. "We would oppose any measures to legally require vaccination or to coerce parents into authorising it," wrote to the FRC in a recent letter to the US government. "Our primary concern is with the message that would be delivered to nine- to 12-year-olds with the administration of the vaccines. Care must be taken not to communicate that such an intervention makes all sex 'safe'."
Moreover, the vaccine will get federal funding under the Vaccines for Children program.
Additionally, the vaccine could be given to girls as young as 9.
More here at Forbes.
"Hope I die before I get old"
Roger Daltrey's final preparation for The Who gig at Bristol this week?
A cup of camomile tea!
Ahh, bless.
Hat tip: popbitch
Big Pharma clinical trials - "endemic untrustworthiness"
Big Pharma cannot be trusted to safely run clinical trials without outside regulation, a UK healthcare expert has claimed.
An article published in today's Journal of the Royal Society of Medicine by Sir Iain Chalmers argues that the untrustworthiness of clinical health trials has reached endemic proportions in the UK.
Sir Iain, editor of treatment monitoring organisation the James Lind Library, also criticises doctors who he claims "collude" with the drugs industry by collaborating with "scientific misbehaviour driven by the marketing departments of pharmaceutical companies".
"Research undertaken by pharmaceutical companies cannot be trusted," Sir Iain writes. "Their systematic under-reporting of negative results and lack of transparency is blatant scientific misconduct and unethical. Without radical change this will continue."
Insider's view: sad but true. This adds to the Paul Dieppe "complicity theory" post from the same journal.
Time for a radical change? Insider hopes so, but is realistic about the chances.
An article published in today's Journal of the Royal Society of Medicine by Sir Iain Chalmers argues that the untrustworthiness of clinical health trials has reached endemic proportions in the UK.
Sir Iain, editor of treatment monitoring organisation the James Lind Library, also criticises doctors who he claims "collude" with the drugs industry by collaborating with "scientific misbehaviour driven by the marketing departments of pharmaceutical companies".
"Research undertaken by pharmaceutical companies cannot be trusted," Sir Iain writes. "Their systematic under-reporting of negative results and lack of transparency is blatant scientific misconduct and unethical. Without radical change this will continue."
Insider's view: sad but true. This adds to the Paul Dieppe "complicity theory" post from the same journal.
Time for a radical change? Insider hopes so, but is realistic about the chances.
Sanofi Aventis - Acomplia: KOL quotewatch
Prof Anthony Barnett, a diabetes specialist from Birmingham University, who took part in the UK launch, said: "There is a distinct possibility that there will be some limitations on its use, which will be a great shame. The real question is, can we afford not to treat?"
OK Tony. Your quote is noted.
Merck - Vioxx: complicity theory
In the past, when things have gone badly wrong, Insider has subscribed to the idea that it's either due to a "cock-up" or a "conspiracy".
Now Paul Dieppe, from Bristol University has another possibility "complicity theory".
He relates this theory to the Vioxx/coxibs issue:
"Complicity works like this.
All those with a vested interest in an enterprise get sucked into the rhetoric associated with it, and they soon `believe' in everything that is going on within that enterprise. If personal financial gain is involved, corruption may also occur. So, in the case of drugs such as anti-inflammatory agents, researchers and prescribers work with the industry to promote the development, testing and use of these drugs.
Personal financial gains come through company shares, consultancies and free trips to exotic locations (for those who do research or actively promote the drugs), trips to educational meetings (for specialists), or `just' free lunches (for just about everybody—does any doctor still buy his/her own lunch?).11
If this goes on for long enough (and it has), everyone starts to believe that they are doing the right thing when they accept company largesse, and to believe in the drugs. And they do not realize that their ability to look at data critically, and at drug use objectively, has been compromised. So, when data comes along that says that rofecoxib causes heart attacks, lots of people say `wait a minute, rofecoxib is wonderful, so maybe the explanation for this is that the NSAID comparator (naproxen) is also a wonder drug and is protecting people against heart attacks'.12
The marketing pressures make all of this worse, of course. So when a paper gets published that says that celecoxib is wonderful, it gets distributed to everyone (as they attend the free lunch event). And when it turns out that the data are flawed (fraud?) the papers still go on being distributed to everyone.13
The pharmaceutical industry has developed a position of extraordinary power over governments, medical research and medical practice.14,15
But complicity theory makes it clear that this would not have been possible without others going along with their story. Doctors have been terrible in that regard; we now work in an industry where companies who stand to profit from our activities sponsor most of our postgraduate education.
Politicians are also to blame. For example, Gordon Brown is campaigning to keep the pharmaceutical industry in Britain, to help `UK plc', and one result of that is that all of us (including Medical Research Council scientists like myself), are being encouraged to work with the industry.
The complicity of politicians and health professionals with the pharmaceutical industry agenda, driven by the profit motive, has made us all blind to data and to common sense. For example, there is now widespread use of drugs (including NSAIDs and coxibs) for problems that are largely social, behavioural or mechanical in origin and the prevention and treatment of which is more logically approached through behavioural interventions than by the use of drugs.16
Most current medical research, as well as medical practice, is dominated by the vested interests of the multi-national pharmaceutical industry, which is now busy inventing diseases for which it can find drugs.17
We now live in a medical culture that appears to have become completely drug dependent—because of money.
How bad is that? "
Now Paul Dieppe, from Bristol University has another possibility "complicity theory".
He relates this theory to the Vioxx/coxibs issue:
"Complicity works like this.
All those with a vested interest in an enterprise get sucked into the rhetoric associated with it, and they soon `believe' in everything that is going on within that enterprise. If personal financial gain is involved, corruption may also occur. So, in the case of drugs such as anti-inflammatory agents, researchers and prescribers work with the industry to promote the development, testing and use of these drugs.
Personal financial gains come through company shares, consultancies and free trips to exotic locations (for those who do research or actively promote the drugs), trips to educational meetings (for specialists), or `just' free lunches (for just about everybody—does any doctor still buy his/her own lunch?).11
If this goes on for long enough (and it has), everyone starts to believe that they are doing the right thing when they accept company largesse, and to believe in the drugs. And they do not realize that their ability to look at data critically, and at drug use objectively, has been compromised. So, when data comes along that says that rofecoxib causes heart attacks, lots of people say `wait a minute, rofecoxib is wonderful, so maybe the explanation for this is that the NSAID comparator (naproxen) is also a wonder drug and is protecting people against heart attacks'.12
The marketing pressures make all of this worse, of course. So when a paper gets published that says that celecoxib is wonderful, it gets distributed to everyone (as they attend the free lunch event). And when it turns out that the data are flawed (fraud?) the papers still go on being distributed to everyone.13
The pharmaceutical industry has developed a position of extraordinary power over governments, medical research and medical practice.14,15
But complicity theory makes it clear that this would not have been possible without others going along with their story. Doctors have been terrible in that regard; we now work in an industry where companies who stand to profit from our activities sponsor most of our postgraduate education.
Politicians are also to blame. For example, Gordon Brown is campaigning to keep the pharmaceutical industry in Britain, to help `UK plc', and one result of that is that all of us (including Medical Research Council scientists like myself), are being encouraged to work with the industry.
The complicity of politicians and health professionals with the pharmaceutical industry agenda, driven by the profit motive, has made us all blind to data and to common sense. For example, there is now widespread use of drugs (including NSAIDs and coxibs) for problems that are largely social, behavioural or mechanical in origin and the prevention and treatment of which is more logically approached through behavioural interventions than by the use of drugs.16
Most current medical research, as well as medical practice, is dominated by the vested interests of the multi-national pharmaceutical industry, which is now busy inventing diseases for which it can find drugs.17
We now live in a medical culture that appears to have become completely drug dependent—because of money.
How bad is that? "
Insider's view: this all rings so true.
Complicity theory explains the venality of medicine today.
This is both a seminal idea and thought provoking piece.
Wednesday, June 28, 2006
Muddy Waters AND Johnny Winter
The previously posted Stevie Wonder Sesame Street video has been pulled by its owner due to it going viral and being abused by some people.
Shame......it was hot!
Lets hope it comes back (please Shuck, please).
UPDATE: Its back up! Hurrah!
In the meantime, how about some Muddy (plus Johnny Winter!!!)?
The previously posted Stevie Wonder Sesame Street video has been pulled by its owner due to it going viral and being abused by some people.
Shame......it was hot!
Lets hope it comes back (please Shuck, please).
UPDATE: Its back up! Hurrah!
In the meantime, how about some Muddy (plus Johnny Winter!!!)?
Sanofi Aventis - Acomplia: UK Patient Information Leaflet and Summary of Product Characteristics
Go here.
Type "Acomplia" into the search box, hit go and Bob's your uncle!
The UK indication is:
As an adjunct to diet and exercise for the treatment of obese patients (BMI greater or equal to 30 kg/m2), or overweight patients (BMI > 27 kg/m2) with associated risk factor(s), such as type 2 diabetes or dyslipidaemia.
Type "Acomplia" into the search box, hit go and Bob's your uncle!
The UK indication is:
As an adjunct to diet and exercise for the treatment of obese patients (BMI greater or equal to 30 kg/m2), or overweight patients (BMI > 27 kg/m2) with associated risk factor(s), such as type 2 diabetes or dyslipidaemia.
Sanofi Aventis - Acomplia: just as PharmaGossip predicted
The cost of a month supply of Acomplia for the National Health Service in Britain, where one in five adults is obese, will be 55.20 pounds ($100.5) per month per patient, a spokesman said, and Sanofi itself would get 2.50 euros ($3.14) per pill.
Reuters - more
BUT, Dear Readers..............
You heard it here first!
Reuters - more
BUT, Dear Readers..............
You heard it here first!
Takeda - TAP 'd for back taxes
Poor Takeda. They have denied they failed to declare 122.3 billion yen (US$1.05 billion; euro0.84 billion) in taxable income over six years to March 2005, rebuffing claims by tax authorities and saying it will fight an order to pay back taxes.
The Osaka Regional Tax bureau on Wednesday said it would impose back taxes worth 57 billion yen (US$491 million; euro390.61 million) because Takeda's stated profits did not accurately reflect revenue from transactions between Takeda and TAP Pharmaceutical Products Inc., which Takeda operates jointly with the U.S. company Abbott Laboratories.
TAP have had a few mentions on PharmaGossip (here, and here, for example)!
Who to believe............ that's the question!
More here.
The Osaka Regional Tax bureau on Wednesday said it would impose back taxes worth 57 billion yen (US$491 million; euro390.61 million) because Takeda's stated profits did not accurately reflect revenue from transactions between Takeda and TAP Pharmaceutical Products Inc., which Takeda operates jointly with the U.S. company Abbott Laboratories.
TAP have had a few mentions on PharmaGossip (here, and here, for example)!
Who to believe............ that's the question!
More here.
Beta blockers for hypertension - RIP
Guidelines issued today by the UK's NHS drugs watchdog (NICE) have given new advice on which medicines should be used to treat high blood pressure.
They now recommend that beta-blockers should no longer be routinely used.
The Guideline recommends using ACE Inhibitors as first line in all patients under the age of 55. It also suggests using CCBs or thiazide diuretics for patients aged over 55 or black patients of any age.
The BBC produced quite a nice Q and A piece.
They now recommend that beta-blockers should no longer be routinely used.
The Guideline recommends using ACE Inhibitors as first line in all patients under the age of 55. It also suggests using CCBs or thiazide diuretics for patients aged over 55 or black patients of any age.
The BBC produced quite a nice Q and A piece.
How Merck stacked the Vioxx deck
This was written by Robert Burton MD and published in Salon in March 2005.
Given the recent shennanagins over Vioxx, Insider re-read the piece and re-discovered what a great piece of both perceptive and analytical writing it is!
Settle back and enjoy:
------------------------------------
The same week that drug manufacturer Merck pulled its highly profitable painkiller, Vioxx, from the market last September, acknowledging that it was linked to heart attacks and strokes, a Las Vegas legend dropped into our local poker game. Ray is one of poker's few long-term success stories. A math wiz, highly praised author of several authoritative books on game theory and high-limit poker, and a practicing Buddhist, Ray was reminiscing about his early days in Las Vegas.
"Cheating was rampant," he said. "Stripped decks, wired hands, coolers, seconds, holdouts and marked cards. You name it, they did it -- the dealers and the players."
Ray had been able to make a great living in poker because he assumed the games might be rigged and acted accordingly. He studied the players and dealers, even watched videos of how card dealers dealt off the bottom of the deck or from the middle. He always expected the worst and was prepared.
"You weren't bothered playing with a bunch of crooks?" I asked.
Ray laughed. "You got to play with someone. We all have cheat in us, given the right circumstances." He smiled slyly. "But even cheats don't cheat all the time. The trick is to know when and how."
With its spectacular medical advances, Big Pharma is the only game in town. We cannot walk away; we must play. But unlike Ray, we are reluctant to assume that drug companies are rigging the outcome. Without this requisite skepticism, we are at their mercy -- in this case, with fatal consequences. The U.S. Food and Drug Administration has linked Vioxx, since it was released in 1999, to more than 27,000 acute heart attacks and sudden cardiac deaths. What the agency didn't report was its own culpability in the debacle.
Even the disclosure of tragic deaths, though, won't stop the same malfeasance from happening again. In order to protect ourselves as patients, we need to know how the game might be fixed.
Dissecting the way that Merck developed Vioxx gives us a perfect opportunity.
I was initially reluctant to write another piece on the Vioxx scandal. The mainstream press has more than adequately pointed the finger of blame at Merck for knowing the cardiovascular risks of Vioxx and yet minimizing them to reap huge economic rewards.
The medical literature has been equally damning. Two months after Vioxx was recalled, Dr. Richard Horton, editor in chief of the British medical journal Lancet, wrote: "With Vioxx, Merck and the F.D.A. acted out of ruthless, short-sighted, and irresponsible self-interest."
But the medical literature related to Vioxx suggests an even more onerous possibility, which is that Merck intentionally designed its studies to avoid discovering the truth about the potential C.V. risks of Vioxx. I have not been privy to the company's private staff meetings and internal documents. But it has been my experience that undertaking any major research study involves extensive consultation between experts in all pertinent fields, including pharmacologists, epidemiologists, statisticians and business managers. Given the enormous intellectual investment in the design of a drug like Vioxx, it is reasonable to presume that all potential outcomes were seriously entertained. I must presume that Merck would factor in what might happen to Vioxx sales with each study result.
And so it's hard to escape the sadly cynical conclusion that the company consciously crafted its tests to avoid exposing the risks of Vioxx to the public.
After all, the stakes of new drug development are enormous. Only a fraction of new drugs submitted to the FDA for approval make it to market; the average cost per approved drug is over $800 million. Any drug that makes it into the marketplace is a potential bonanza to be coddled, cherished and protected. A drug patent lasts 17 years, and then the drug is thrown to the generic manufacturers. The FDA approved Vioxx for sale in May 1999. By 2004, 20 million Americans had taken the painkiller and its annual sales exceeded $2.5 billion. Is it any wonder that Merck sought to present Vioxx to the public in the best possible light?
To understand Merck's approach, we need a crash course in biology. COX (cyclooxygenase) is an enzyme in the body that produces an inflammatory response -- swelling, fever and pain. Drugs that reduce COX activity are called NSAIDs, and traditionally include aspirin and ibuprofen. But COX is present throughout the body and has a host of other effects, some of which are beneficial. For example, it helps protect the lining of the G.I. (gastrointestinal) tract from ulceration and bleeding.
Approximately 1 in 1,200 patients taking traditional NSAIDs for at least two months will die from G.I.-related complications. A conservative estimate: 16,500 NSAID-related deaths occur every year in the United States, approximately equivalent to the number of deaths from AIDS.
The holy grail of anti-inflammatories would be a COX inhibitor without this side effect. This became a real possibility in 1990, when COX was shown to exist as two chemically distinct enzymes -- COX-1 and COX-2. COX-1 protects the G.I. tract, while COX-2 is responsible for the inflammatory response. The obvious answer to the G.I. complications: develop a drug that inhibits COX-2 but not COX-1.
Give Merck credit. It developed Vioxx, a drug with the same degree of anti-inflammatory and anti-pain response as NSAIDs, but with a significant reduction in G.I. complaints and complications.
But medicine rarely comes in such neat categories. As far back as 1984, Garret FitzGerald and his colleagues at the University of Pennsylvania, writing in the New England Journal of Medicine, showed that the COX enzyme might prevent arterial blood clot formation. FitzGerald suggested that this side effect might mean little in healthy persons but could be dangerous to patients with severe atherosclerosis. Which sounds reasonable -- a high level of an anti-clotting enzyme wouldn't be necessary in normal vessels, but would be necessary in damaged vessels in which clot formation was more likely.
In 1997, with Vioxx still in clinical trials, FitzGerald himself consulted with Merck. According to Merck's position statement, recently filed in a U.S. District Court in Louisiana, in response to a class-action lawsuit, FitzGerald warned the company that COX-2 had a possible anti-clotting benefit. He expressed concern that suppression of this mechanism by a "coxib" drug such as Vioxx might increase the risk of blocked arteries.
Merck responded to FitzGerald's research by re-analyzing all of its Vioxx clinical data, and included FitzGerald's potentially worrisome lab data in its FDA application. (This data was published in 1999 in the Journal of Pharmacology and Experimental Therapeutics.) Merck also declared that it had adopted the standard procedure for "facilitating rigorous scientific analysis, on an ongoing basis, of all competing hypotheses about potential CV risks or benefits from Vioxx."
Was this a sufficient evaluation of a potentially serious side effect of Vioxx? Or should more have been done? Given that it is standard practice to assess all serious potential risks of new drugs, FitzGerald's concern should have been directly addressed.
But rather than design a study focused on the C.V. risks of Vioxx, Merck created the VIGOR (Vioxx Gastrointestinal Outcomes Research) study in 2000. It compared the incidence of G.I. complications of Vioxx to naproxen, another conventional NSAID, whose most popular brand is Aleve. The goal was to prove that Vioxx was an equally effective but safer drug than an over-the-counter NSAID. Unfortunately, the study, published in the New England Journal of Medicine, revealed a twofold increase in C.V. risk for patients who took Vioxx. Of course, Merck acted surprised. What Merck didn't tell us is that it had stripped the deck of patients at high risk for heart disease.
In the VIGOR study, 80 percent of patients were women with an average age of 58, with Merck being well aware that women, on average, develop C.V. disease 10 years later than men. Only 4 percent of the total subjects had a prior history of C.V. disease and were felt to be at high risk for further C.V. events. It was no surprise, then, that 38 percent of the heart attacks in the group of patients who took Vioxx came from this small 4 percent subgroup.
Ironically, it was Merck's failure to eliminate these few high-risk patients that allowed the C.V. effects of Vioxx to be detected. According to a review of coxibs in the New England Journal of Medicine, published in 2001, if these few high-risk patients had been excluded from the VIGOR study, the difference between Vioxx and naproxen would not have been significant. Therefore Vioxx may have never been taken off the market.
But there's more.
Anyone who's gambled in a casino knows that the key to winning is to get lucky initially and quit before the odds catch up with you. Get in and get out before the odds get a chance to declare themselves.
To understand the risks involved with a coxib, it is necessary to conceptualize risk as a function of time. The risk of electrocution is immediate. You don't grab a hot wire and get electrocuted next year. It's now or never. Similarly, a fatal allergic reaction to a penicillin injection happens within minutes, not in six months. In assessing risk factors with a predictable time of occurrence, it is easy to determine the study period. But other risks can take years or decades to manifest themselves.
It took many years to recognize the detrimental effects of hormone replacement therapy, or the time lag between sun exposure and the subsequent development of a malignant melanoma. Such correlations require following large groups of patients for extended periods of time. A major source of our understanding of cholesterol levels and the development of C.V. disease came from large-population longitudinal studies such as the Framingham Heart Study, which began in 1948 and is still ongoing.
It is self-evident that risk factors can be present for many years before becoming clinically observable. Although elevated levels of cholesterol increase the risk of a heart attack, the rate of heart attacks in teenagers with high cholesterol is far less than that of middle-aged adults with similar cholesterol levels. The cholesterol effect is cumulative; atherosclerosis takes time to become manifest.
If we wanted to minimize or negate the apparent effect of cholesterol on heart disease, we would study the youngest patients we could, and for the shortest period of time. If we ran a nine-month study to compare the incidence of heart attacks in a group of 10-year-olds with high cholesterol vs. normal controls, it is highly unlikely that we would see a difference.
The Framingham study has been ongoing for more than 50 years. Merck's VIGOR study followed its patients for an average of nine months. Even this short period revealed a very disturbing trend.
During the first six weeks of the study, there was no significant difference between the two drugs. As the follow-up period continued, the patients taking naproxen clearly were having fewer heart attacks than those taking Vioxx. But between months 8 and 11, the naproxen rate was relatively constant, while the Vioxx rate appeared to be accelerating. It was at this critical point that Merck concluded its trial.
When asked why it concluded its VIGOR study at this key juncture, a Merck spokesperson replied with a terse e-mail: "VIGOR was an endpoint-driven study and it ended when it was designed to end."
Merck repeatedly contended that it was actively investigating possible reasons for the adverse findings in the short VIGOR study. One of them was that the difference between Vioxx and naproxen could be best explained as a cardio-protective benefit of naproxen as opposed to an untoward side effect of Vioxx. Most researchers disagree. To date, no large-scale study has demonstrated more than a possibly small protective effect of naproxen, and certainly not of the magnitude that would explain the VIGOR difference. In fact, a recent study of naproxen and prevention of Alzheimer's disease was halted because of an apparent increase in C.V. events.
Listen to Peter S. Kim, president of Merck Research Laboratories, explain why Vioxx had a higher C.V. complication rate than naproxen. "Because the VIGOR study compared two drugs -- Vioxx and naproxen -- and did not contain a placebo arm, it was not possible to conclude, based on this study alone, whether naproxen was having a beneficial CV effect or whether Vioxx was having a detrimental CV effect."
When I asked Merck why it didn't include a placebo group in the study, which would have underscored the C.V. effects of Vioxx, it referred me again to its court statement: "For ethical reasons, Merck could not conduct a placebo-controlled study in a population that required pain medicine (because patients in the placebo arm would receive no pain relief)."
Yet placebo control studies are commonly used to study anti-pain medications. Indeed, many peer-reviewed osteoarthritis and rheumatoid arthritis studies of NSAIDs and coxibs, including Vioxx, have included a placebo group for comparison. (Unfortunately, these studies were of too short a duration -- 6-12 weeks -- to assess any long-term C.V. effect. Merck, nevertheless, cites the data to show no evidence of C.V. effect of Vioxx.)
In an August 2001 article in the Journal of the American Medical Association, Drs. Mukherjee, Topol and Nissen from the Cleveland Clinic compared rates of heart attacks in trials performed with selective COX-2 inhibitors, including Vioxx, to heart attack rates compiled from a large number of studies on aspirin for heart disease prevention. Their review included 48,000 patients; the Merck VIGOR trial had 8,000.
The authors concluded: "The available data raise a cautionary flag about the risk of cardiovascular events with COX-2 inhibitors." Even more compelling, they stated: "We believe that it is mandatory to conduct a trial specifically assessing cardiovascular risk and benefit of these agents. Until then, we urge caution in prescribing these agents to patients at risk for cardiovascular morbidity."
Merck did make a motion in that direction. According to an article in the New York Times earlier this year, the company planned to initiate a major C.V. risk study called VALOR in 2002. But just days before company researchers were to submit the study's protocol to the FDA, the project was abruptly halted. Merck did not explain why. It issued a general statement, saying that as it was designing the study, "we continued to ask ourselves and our consultants whether this was the right way to definitely answer" the question of whether Vioxx posed C.V. risks. "We ultimately decided not to conduct that particular study."
In 2002, with Vioxx selling extremely well, Merck was no doubt convinced that the odds of keeping the painkiller on the market remained in its favor. After all, when the VIGOR study revealed that patients who took Vioxx showed a twofold increase in heart attacks, Merck must have figured that it could face potential lawsuits. Just as all Big Pharma companies do, Merck must have calculated that profits from sales would outweigh losses from lawsuits.
In fact, as a study in the Archives of Internal Medicine would later show, Merck, through heavy promotion, sought to create as wide a market as possible for Vioxx. (The study revealed that 73 percent of people who took Vioxx did not need a coxib, that a standard NSAID like aspirin would have been sufficient.) Apparently, selling Vioxx as a niche drug for people who really did suffer G.I. problems from NSAIDs, and who were at low risk for heart disease, did not meet Merck's profit-and-loss forecast.
Merck initiated several more studies of Vioxx, all primarily intended to uncover further potential markets for the drug. In each case, it avoided delving specifically into possible C.V. complications. Most notable was the APPROVe study, which looked toward the prevention of colon polyps, as well as other studies for possible treatments for colorectal and prostate cancer.
In September 2004, when the APPROVe trial revealed the same twofold increase in C.V. complications as the VIGOR study, Merck recalled Vioxx.
Even then, Dr. Alise Reicin, vice president of clinical research at Merck, reiterated that this was a puzzling finding. She said that Merck has so far been unable to identify a mechanism behind the increased risk.
The fact is that Merck avoided initiating studies to find one.
To further distance Merck from any responsibility for those who had recently begun taking Vioxx, Kim added, "While the cause of these results is uncertain at this time, they suggest an increased risk of confirmed CV events beginning after 18 months of continuous therapy."
No, the risk didn't begin after 18 months. This would be analogous to saying that daily sunbathing for 18 months poses no risk for melanoma if no melanomas are detected during that time, and that the risk doesn't begin until the melanomas are first discovered. The risk is present from the beginning but only evident at 18 months.
Finally, Merck is asking us to believe that it didn't suspect from the outset that Vioxx might increase the risk of heart attacks and strokes. It's telling us that its studies were adequately designed to detect both the incidence and possible underlying mechanisms of cardiovascular risks. It wants us to accept that a nine-month study, abruptly concluded, was insufficient evidence for the withdrawal of Vioxx because it was reasonable to presume that naproxen had a cardio-protective effect.
For me, the sad but inescapable conclusion is that Merck made an informed decision to avoid knowing the full extent of Vioxx's potential risks for heart attacks and strokes.
And the FDA was either extraordinarily lax or frankly complicit. In April 2002, the federal agency did state that Merck must affix a new label to Vioxx, advising doctors to use caution when prescribing it to patients with heart disease. But it didn't rule that the drug be withdrawn from the shelves.
Based upon their review of available data about Vioxx, a team of medical scientists from the University of Berne, Switzerland, published this summary in a December 2004 issue of Lancet: "Our findings indicate that Vioxx should have been withdrawn several years earlier. The reasons why manufacturer and drug licensing authorities did not continuously monitor and summarize the accumulating evidence need to be clarified."
This situation is not likely to change. On at least three occasions, Congress has voted to approve partial FDA funding by pharmaceutical companies. Beginning in 1992 with the passage of PDUFA -- the Prescription Drug User Fee Act -- pharmaceutical companies have been paying up to $500,000 for each new drug application. Currently, greater than 50 percent of drug reviewers at the FDA are funded by the pharmaceutical industry.
According to the Center for Science in the Public Interest, 10 of the 32 FDA advisory board members who, in 2005, recommended the continued sale of coxibs, had previously consulted for Merck, Pfizer or Novartis. (Pfizer and Novartis have not withdrawn their coxibs, Celebrex and Prexige, respectively, from the market.) To be fair, this isn't entirely damning, as many top researchers have ties with pharmaceutical companies yet maintain unbiased positions. Dr. FitzGerald, one of Merck's harshest critics, has received research funding from Merck.
When Merck withdrew Vioxx, the FDA responded: "The risk that an individual patient taking Vioxx will suffer a heart attack or stroke related to the drug is very small."
This is both true and profoundly misleading.
A truly independent agency for the evaluation of new drugs is essential. But the unfortunate truth for the foreseeable future is that we are dependent upon the pharmaceutical industry and its hired security guards -- the FDA -- to police itself.
We are not helpless. We do have one ace in the hole -- the simplest and most difficult of questions. Do I need this medication? Or, as Ray would say, is this the only game in town and do I need to play?
If you have rheumatoid arthritis and can barely dress and feed yourself, a doubled chance of a heart attack on Vioxx might be an acceptable trade-off for increased mobility. A disabling stroke, no matter how unlikely, doesn't seem like a reasonable risk for a twinge of tennis elbow.
The decision to take any medication is highly personal, a reflection of everything from genetic predispositions to cultural values to the loftiest of metaphysics. It cannot depend exclusively upon statistics. An honest and thorough medical system can provide the information, but the old saw, know thyself, is essential to such choices.
So is know thy playing partner.
And the key to making the right personal decision is that we need transparency of data. We need to get our hands on the deck and look for ourselves. There are plenty of smart and independent folks who could sift through the information and give us an informed opinion. We must demand that study data be made publicly available to those without a vested interest.
The best place to start is with your own family doctor. If you and your physician had adopted Ray's approach to medication, you would have known in August 2001 that leading cardiologists such as Dr. Topol had major concerns about possible Vioxx C.V. effects. And you would have carefully discussed the labeling change ordered by the FDA in 2002. Unless you are an Internet health letter, medical journal junkie, only your doctor would have received this news in a timely fashion.
However, the problem of post-approval drug side effects will not go away. After 30 years on the market, it is still unclear as to the C.V. effects of the allegedly "safe" NSAIDs such as Aleve. We have to anticipate the unknown, accept certain knowledge limitations, and trust someone to be our advocate in an ever more confusing medical landscape. And we need to balance a well-deserved skepticism with an equal appreciation of what modern medicine has accomplished.
In the big picture, Merck has had an outstanding reputation. It offers a variety of formidable drugs that both improve and save lives. As a niche drug, prescribed to those unresponsive to the older NSAIDs, or to those with unacceptable G.I. complaints or at high risk for ulcers or bleeding, Vioxx would have been a good alternative.
If the properly designed studies had been carried out, and we had been given full and prompt access to the data, we could have made our own smart choices.
It's a tragedy that Vioxx led to fatal heart attacks and strokes. And it's a sad irony that those who were clearly benefiting from the drug no longer find it available to them.
Given the recent shennanagins over Vioxx, Insider re-read the piece and re-discovered what a great piece of both perceptive and analytical writing it is!
Settle back and enjoy:
------------------------------------
The same week that drug manufacturer Merck pulled its highly profitable painkiller, Vioxx, from the market last September, acknowledging that it was linked to heart attacks and strokes, a Las Vegas legend dropped into our local poker game. Ray is one of poker's few long-term success stories. A math wiz, highly praised author of several authoritative books on game theory and high-limit poker, and a practicing Buddhist, Ray was reminiscing about his early days in Las Vegas.
"Cheating was rampant," he said. "Stripped decks, wired hands, coolers, seconds, holdouts and marked cards. You name it, they did it -- the dealers and the players."
Ray had been able to make a great living in poker because he assumed the games might be rigged and acted accordingly. He studied the players and dealers, even watched videos of how card dealers dealt off the bottom of the deck or from the middle. He always expected the worst and was prepared.
"You weren't bothered playing with a bunch of crooks?" I asked.
Ray laughed. "You got to play with someone. We all have cheat in us, given the right circumstances." He smiled slyly. "But even cheats don't cheat all the time. The trick is to know when and how."
With its spectacular medical advances, Big Pharma is the only game in town. We cannot walk away; we must play. But unlike Ray, we are reluctant to assume that drug companies are rigging the outcome. Without this requisite skepticism, we are at their mercy -- in this case, with fatal consequences. The U.S. Food and Drug Administration has linked Vioxx, since it was released in 1999, to more than 27,000 acute heart attacks and sudden cardiac deaths. What the agency didn't report was its own culpability in the debacle.
Even the disclosure of tragic deaths, though, won't stop the same malfeasance from happening again. In order to protect ourselves as patients, we need to know how the game might be fixed.
Dissecting the way that Merck developed Vioxx gives us a perfect opportunity.
I was initially reluctant to write another piece on the Vioxx scandal. The mainstream press has more than adequately pointed the finger of blame at Merck for knowing the cardiovascular risks of Vioxx and yet minimizing them to reap huge economic rewards.
The medical literature has been equally damning. Two months after Vioxx was recalled, Dr. Richard Horton, editor in chief of the British medical journal Lancet, wrote: "With Vioxx, Merck and the F.D.A. acted out of ruthless, short-sighted, and irresponsible self-interest."
But the medical literature related to Vioxx suggests an even more onerous possibility, which is that Merck intentionally designed its studies to avoid discovering the truth about the potential C.V. risks of Vioxx. I have not been privy to the company's private staff meetings and internal documents. But it has been my experience that undertaking any major research study involves extensive consultation between experts in all pertinent fields, including pharmacologists, epidemiologists, statisticians and business managers. Given the enormous intellectual investment in the design of a drug like Vioxx, it is reasonable to presume that all potential outcomes were seriously entertained. I must presume that Merck would factor in what might happen to Vioxx sales with each study result.
And so it's hard to escape the sadly cynical conclusion that the company consciously crafted its tests to avoid exposing the risks of Vioxx to the public.
After all, the stakes of new drug development are enormous. Only a fraction of new drugs submitted to the FDA for approval make it to market; the average cost per approved drug is over $800 million. Any drug that makes it into the marketplace is a potential bonanza to be coddled, cherished and protected. A drug patent lasts 17 years, and then the drug is thrown to the generic manufacturers. The FDA approved Vioxx for sale in May 1999. By 2004, 20 million Americans had taken the painkiller and its annual sales exceeded $2.5 billion. Is it any wonder that Merck sought to present Vioxx to the public in the best possible light?
To understand Merck's approach, we need a crash course in biology. COX (cyclooxygenase) is an enzyme in the body that produces an inflammatory response -- swelling, fever and pain. Drugs that reduce COX activity are called NSAIDs, and traditionally include aspirin and ibuprofen. But COX is present throughout the body and has a host of other effects, some of which are beneficial. For example, it helps protect the lining of the G.I. (gastrointestinal) tract from ulceration and bleeding.
Approximately 1 in 1,200 patients taking traditional NSAIDs for at least two months will die from G.I.-related complications. A conservative estimate: 16,500 NSAID-related deaths occur every year in the United States, approximately equivalent to the number of deaths from AIDS.
The holy grail of anti-inflammatories would be a COX inhibitor without this side effect. This became a real possibility in 1990, when COX was shown to exist as two chemically distinct enzymes -- COX-1 and COX-2. COX-1 protects the G.I. tract, while COX-2 is responsible for the inflammatory response. The obvious answer to the G.I. complications: develop a drug that inhibits COX-2 but not COX-1.
Give Merck credit. It developed Vioxx, a drug with the same degree of anti-inflammatory and anti-pain response as NSAIDs, but with a significant reduction in G.I. complaints and complications.
But medicine rarely comes in such neat categories. As far back as 1984, Garret FitzGerald and his colleagues at the University of Pennsylvania, writing in the New England Journal of Medicine, showed that the COX enzyme might prevent arterial blood clot formation. FitzGerald suggested that this side effect might mean little in healthy persons but could be dangerous to patients with severe atherosclerosis. Which sounds reasonable -- a high level of an anti-clotting enzyme wouldn't be necessary in normal vessels, but would be necessary in damaged vessels in which clot formation was more likely.
In 1997, with Vioxx still in clinical trials, FitzGerald himself consulted with Merck. According to Merck's position statement, recently filed in a U.S. District Court in Louisiana, in response to a class-action lawsuit, FitzGerald warned the company that COX-2 had a possible anti-clotting benefit. He expressed concern that suppression of this mechanism by a "coxib" drug such as Vioxx might increase the risk of blocked arteries.
Merck responded to FitzGerald's research by re-analyzing all of its Vioxx clinical data, and included FitzGerald's potentially worrisome lab data in its FDA application. (This data was published in 1999 in the Journal of Pharmacology and Experimental Therapeutics.) Merck also declared that it had adopted the standard procedure for "facilitating rigorous scientific analysis, on an ongoing basis, of all competing hypotheses about potential CV risks or benefits from Vioxx."
Was this a sufficient evaluation of a potentially serious side effect of Vioxx? Or should more have been done? Given that it is standard practice to assess all serious potential risks of new drugs, FitzGerald's concern should have been directly addressed.
But rather than design a study focused on the C.V. risks of Vioxx, Merck created the VIGOR (Vioxx Gastrointestinal Outcomes Research) study in 2000. It compared the incidence of G.I. complications of Vioxx to naproxen, another conventional NSAID, whose most popular brand is Aleve. The goal was to prove that Vioxx was an equally effective but safer drug than an over-the-counter NSAID. Unfortunately, the study, published in the New England Journal of Medicine, revealed a twofold increase in C.V. risk for patients who took Vioxx. Of course, Merck acted surprised. What Merck didn't tell us is that it had stripped the deck of patients at high risk for heart disease.
In the VIGOR study, 80 percent of patients were women with an average age of 58, with Merck being well aware that women, on average, develop C.V. disease 10 years later than men. Only 4 percent of the total subjects had a prior history of C.V. disease and were felt to be at high risk for further C.V. events. It was no surprise, then, that 38 percent of the heart attacks in the group of patients who took Vioxx came from this small 4 percent subgroup.
Ironically, it was Merck's failure to eliminate these few high-risk patients that allowed the C.V. effects of Vioxx to be detected. According to a review of coxibs in the New England Journal of Medicine, published in 2001, if these few high-risk patients had been excluded from the VIGOR study, the difference between Vioxx and naproxen would not have been significant. Therefore Vioxx may have never been taken off the market.
But there's more.
Anyone who's gambled in a casino knows that the key to winning is to get lucky initially and quit before the odds catch up with you. Get in and get out before the odds get a chance to declare themselves.
To understand the risks involved with a coxib, it is necessary to conceptualize risk as a function of time. The risk of electrocution is immediate. You don't grab a hot wire and get electrocuted next year. It's now or never. Similarly, a fatal allergic reaction to a penicillin injection happens within minutes, not in six months. In assessing risk factors with a predictable time of occurrence, it is easy to determine the study period. But other risks can take years or decades to manifest themselves.
It took many years to recognize the detrimental effects of hormone replacement therapy, or the time lag between sun exposure and the subsequent development of a malignant melanoma. Such correlations require following large groups of patients for extended periods of time. A major source of our understanding of cholesterol levels and the development of C.V. disease came from large-population longitudinal studies such as the Framingham Heart Study, which began in 1948 and is still ongoing.
It is self-evident that risk factors can be present for many years before becoming clinically observable. Although elevated levels of cholesterol increase the risk of a heart attack, the rate of heart attacks in teenagers with high cholesterol is far less than that of middle-aged adults with similar cholesterol levels. The cholesterol effect is cumulative; atherosclerosis takes time to become manifest.
If we wanted to minimize or negate the apparent effect of cholesterol on heart disease, we would study the youngest patients we could, and for the shortest period of time. If we ran a nine-month study to compare the incidence of heart attacks in a group of 10-year-olds with high cholesterol vs. normal controls, it is highly unlikely that we would see a difference.
The Framingham study has been ongoing for more than 50 years. Merck's VIGOR study followed its patients for an average of nine months. Even this short period revealed a very disturbing trend.
During the first six weeks of the study, there was no significant difference between the two drugs. As the follow-up period continued, the patients taking naproxen clearly were having fewer heart attacks than those taking Vioxx. But between months 8 and 11, the naproxen rate was relatively constant, while the Vioxx rate appeared to be accelerating. It was at this critical point that Merck concluded its trial.
When asked why it concluded its VIGOR study at this key juncture, a Merck spokesperson replied with a terse e-mail: "VIGOR was an endpoint-driven study and it ended when it was designed to end."
Merck repeatedly contended that it was actively investigating possible reasons for the adverse findings in the short VIGOR study. One of them was that the difference between Vioxx and naproxen could be best explained as a cardio-protective benefit of naproxen as opposed to an untoward side effect of Vioxx. Most researchers disagree. To date, no large-scale study has demonstrated more than a possibly small protective effect of naproxen, and certainly not of the magnitude that would explain the VIGOR difference. In fact, a recent study of naproxen and prevention of Alzheimer's disease was halted because of an apparent increase in C.V. events.
Listen to Peter S. Kim, president of Merck Research Laboratories, explain why Vioxx had a higher C.V. complication rate than naproxen. "Because the VIGOR study compared two drugs -- Vioxx and naproxen -- and did not contain a placebo arm, it was not possible to conclude, based on this study alone, whether naproxen was having a beneficial CV effect or whether Vioxx was having a detrimental CV effect."
When I asked Merck why it didn't include a placebo group in the study, which would have underscored the C.V. effects of Vioxx, it referred me again to its court statement: "For ethical reasons, Merck could not conduct a placebo-controlled study in a population that required pain medicine (because patients in the placebo arm would receive no pain relief)."
Yet placebo control studies are commonly used to study anti-pain medications. Indeed, many peer-reviewed osteoarthritis and rheumatoid arthritis studies of NSAIDs and coxibs, including Vioxx, have included a placebo group for comparison. (Unfortunately, these studies were of too short a duration -- 6-12 weeks -- to assess any long-term C.V. effect. Merck, nevertheless, cites the data to show no evidence of C.V. effect of Vioxx.)
In an August 2001 article in the Journal of the American Medical Association, Drs. Mukherjee, Topol and Nissen from the Cleveland Clinic compared rates of heart attacks in trials performed with selective COX-2 inhibitors, including Vioxx, to heart attack rates compiled from a large number of studies on aspirin for heart disease prevention. Their review included 48,000 patients; the Merck VIGOR trial had 8,000.
The authors concluded: "The available data raise a cautionary flag about the risk of cardiovascular events with COX-2 inhibitors." Even more compelling, they stated: "We believe that it is mandatory to conduct a trial specifically assessing cardiovascular risk and benefit of these agents. Until then, we urge caution in prescribing these agents to patients at risk for cardiovascular morbidity."
Merck did make a motion in that direction. According to an article in the New York Times earlier this year, the company planned to initiate a major C.V. risk study called VALOR in 2002. But just days before company researchers were to submit the study's protocol to the FDA, the project was abruptly halted. Merck did not explain why. It issued a general statement, saying that as it was designing the study, "we continued to ask ourselves and our consultants whether this was the right way to definitely answer" the question of whether Vioxx posed C.V. risks. "We ultimately decided not to conduct that particular study."
In 2002, with Vioxx selling extremely well, Merck was no doubt convinced that the odds of keeping the painkiller on the market remained in its favor. After all, when the VIGOR study revealed that patients who took Vioxx showed a twofold increase in heart attacks, Merck must have figured that it could face potential lawsuits. Just as all Big Pharma companies do, Merck must have calculated that profits from sales would outweigh losses from lawsuits.
In fact, as a study in the Archives of Internal Medicine would later show, Merck, through heavy promotion, sought to create as wide a market as possible for Vioxx. (The study revealed that 73 percent of people who took Vioxx did not need a coxib, that a standard NSAID like aspirin would have been sufficient.) Apparently, selling Vioxx as a niche drug for people who really did suffer G.I. problems from NSAIDs, and who were at low risk for heart disease, did not meet Merck's profit-and-loss forecast.
Merck initiated several more studies of Vioxx, all primarily intended to uncover further potential markets for the drug. In each case, it avoided delving specifically into possible C.V. complications. Most notable was the APPROVe study, which looked toward the prevention of colon polyps, as well as other studies for possible treatments for colorectal and prostate cancer.
In September 2004, when the APPROVe trial revealed the same twofold increase in C.V. complications as the VIGOR study, Merck recalled Vioxx.
Even then, Dr. Alise Reicin, vice president of clinical research at Merck, reiterated that this was a puzzling finding. She said that Merck has so far been unable to identify a mechanism behind the increased risk.
The fact is that Merck avoided initiating studies to find one.
To further distance Merck from any responsibility for those who had recently begun taking Vioxx, Kim added, "While the cause of these results is uncertain at this time, they suggest an increased risk of confirmed CV events beginning after 18 months of continuous therapy."
No, the risk didn't begin after 18 months. This would be analogous to saying that daily sunbathing for 18 months poses no risk for melanoma if no melanomas are detected during that time, and that the risk doesn't begin until the melanomas are first discovered. The risk is present from the beginning but only evident at 18 months.
Finally, Merck is asking us to believe that it didn't suspect from the outset that Vioxx might increase the risk of heart attacks and strokes. It's telling us that its studies were adequately designed to detect both the incidence and possible underlying mechanisms of cardiovascular risks. It wants us to accept that a nine-month study, abruptly concluded, was insufficient evidence for the withdrawal of Vioxx because it was reasonable to presume that naproxen had a cardio-protective effect.
For me, the sad but inescapable conclusion is that Merck made an informed decision to avoid knowing the full extent of Vioxx's potential risks for heart attacks and strokes.
And the FDA was either extraordinarily lax or frankly complicit. In April 2002, the federal agency did state that Merck must affix a new label to Vioxx, advising doctors to use caution when prescribing it to patients with heart disease. But it didn't rule that the drug be withdrawn from the shelves.
Based upon their review of available data about Vioxx, a team of medical scientists from the University of Berne, Switzerland, published this summary in a December 2004 issue of Lancet: "Our findings indicate that Vioxx should have been withdrawn several years earlier. The reasons why manufacturer and drug licensing authorities did not continuously monitor and summarize the accumulating evidence need to be clarified."
This situation is not likely to change. On at least three occasions, Congress has voted to approve partial FDA funding by pharmaceutical companies. Beginning in 1992 with the passage of PDUFA -- the Prescription Drug User Fee Act -- pharmaceutical companies have been paying up to $500,000 for each new drug application. Currently, greater than 50 percent of drug reviewers at the FDA are funded by the pharmaceutical industry.
According to the Center for Science in the Public Interest, 10 of the 32 FDA advisory board members who, in 2005, recommended the continued sale of coxibs, had previously consulted for Merck, Pfizer or Novartis. (Pfizer and Novartis have not withdrawn their coxibs, Celebrex and Prexige, respectively, from the market.) To be fair, this isn't entirely damning, as many top researchers have ties with pharmaceutical companies yet maintain unbiased positions. Dr. FitzGerald, one of Merck's harshest critics, has received research funding from Merck.
When Merck withdrew Vioxx, the FDA responded: "The risk that an individual patient taking Vioxx will suffer a heart attack or stroke related to the drug is very small."
This is both true and profoundly misleading.
A truly independent agency for the evaluation of new drugs is essential. But the unfortunate truth for the foreseeable future is that we are dependent upon the pharmaceutical industry and its hired security guards -- the FDA -- to police itself.
We are not helpless. We do have one ace in the hole -- the simplest and most difficult of questions. Do I need this medication? Or, as Ray would say, is this the only game in town and do I need to play?
If you have rheumatoid arthritis and can barely dress and feed yourself, a doubled chance of a heart attack on Vioxx might be an acceptable trade-off for increased mobility. A disabling stroke, no matter how unlikely, doesn't seem like a reasonable risk for a twinge of tennis elbow.
The decision to take any medication is highly personal, a reflection of everything from genetic predispositions to cultural values to the loftiest of metaphysics. It cannot depend exclusively upon statistics. An honest and thorough medical system can provide the information, but the old saw, know thyself, is essential to such choices.
So is know thy playing partner.
And the key to making the right personal decision is that we need transparency of data. We need to get our hands on the deck and look for ourselves. There are plenty of smart and independent folks who could sift through the information and give us an informed opinion. We must demand that study data be made publicly available to those without a vested interest.
The best place to start is with your own family doctor. If you and your physician had adopted Ray's approach to medication, you would have known in August 2001 that leading cardiologists such as Dr. Topol had major concerns about possible Vioxx C.V. effects. And you would have carefully discussed the labeling change ordered by the FDA in 2002. Unless you are an Internet health letter, medical journal junkie, only your doctor would have received this news in a timely fashion.
However, the problem of post-approval drug side effects will not go away. After 30 years on the market, it is still unclear as to the C.V. effects of the allegedly "safe" NSAIDs such as Aleve. We have to anticipate the unknown, accept certain knowledge limitations, and trust someone to be our advocate in an ever more confusing medical landscape. And we need to balance a well-deserved skepticism with an equal appreciation of what modern medicine has accomplished.
In the big picture, Merck has had an outstanding reputation. It offers a variety of formidable drugs that both improve and save lives. As a niche drug, prescribed to those unresponsive to the older NSAIDs, or to those with unacceptable G.I. complaints or at high risk for ulcers or bleeding, Vioxx would have been a good alternative.
If the properly designed studies had been carried out, and we had been given full and prompt access to the data, we could have made our own smart choices.
It's a tragedy that Vioxx led to fatal heart attacks and strokes. And it's a sad irony that those who were clearly benefiting from the drug no longer find it available to them.
TGN 1412 - last man out
Back story links here.
Ryan Wilson, one of six volunteers who suffered devastating side-effects from drugs trials in March, spoke of his ordeal last night, showing amazing resolve.
"Every doctor said, 'I didn't think you'd live.' Most of the nurses said they didn't think I'd live. They had a look of amazement on their faces - they thought I was going to die, and I didn't.
"I'm not a weak person, and anyone who knows me knows that, so I'm not going to give up yet. At the moment my goal is to have my operation, come through it successfully and walk."
Source: Daily Telegraph
P&G - Actonel: "The Blumsohn Files" uncovered
Go here to get all the links to the back story.
But wait! What's this?
This site appears to be still under construction.
From what Insider can make of it, it appears to be the last year or so's emails and correspondence between Dr Aubrey Blumsohn and the editor of the Journal of Bone and Mineral Research, Professor John A Eisman.
There is a lot to get through!
But it gets more and more "interesting" as it progresses.
Make of it what you will! Insider is still digesting it all.
But wait! What's this?
This site appears to be still under construction.
From what Insider can make of it, it appears to be the last year or so's emails and correspondence between Dr Aubrey Blumsohn and the editor of the Journal of Bone and Mineral Research, Professor John A Eisman.
There is a lot to get through!
But it gets more and more "interesting" as it progresses.
Make of it what you will! Insider is still digesting it all.
Merck - Vioxx: first west coast trial kicks off
Merck knew of potential harmful side effects of its drug Vioxx and failed to notify doctors, a lawyer for a man who claims the painkiller caused his heart attack said Tuesday in opening statements of the first Vioxx liability case to go to trial in California.
"Merck knew of these potential side effects and never told a soul," said attorney Thomas Girardi, who represents plaintiff Stewart Grossberg.
Grossberg's lawsuit is one of more than 13,000 such claims against Merck nationwide. Some 2,000 of the lawsuits were filed in California and consolidated in Los Angeles Superior Court by Judge Victoria G. Chaney.
The outcome is expected to serve as a guide for navigating through other California cases involving Vioxx, which was put on the market in 1999 as a treatment for arthritis and acute pain in adults and was pulled two years ago amid concerns it increased the risk of heart attacks and strokes with long-term use.
Girardi said that testing inadequacies such as excluding patients with a history of heart disease clouded the experiments and that the company had a "careless disregard" for patients for not warning doctors of the potential for heart attacks and strokes.
Company memos dating to 1996 showed that Merck was aware of the potential side effects, he said.
The company nevertheless hired 3,000 sales people and trained them to downplay the risks when talking with doctors, Girardi said.
More here.
"Merck knew of these potential side effects and never told a soul," said attorney Thomas Girardi, who represents plaintiff Stewart Grossberg.
Grossberg's lawsuit is one of more than 13,000 such claims against Merck nationwide. Some 2,000 of the lawsuits were filed in California and consolidated in Los Angeles Superior Court by Judge Victoria G. Chaney.
The outcome is expected to serve as a guide for navigating through other California cases involving Vioxx, which was put on the market in 1999 as a treatment for arthritis and acute pain in adults and was pulled two years ago amid concerns it increased the risk of heart attacks and strokes with long-term use.
Girardi said that testing inadequacies such as excluding patients with a history of heart disease clouded the experiments and that the company had a "careless disregard" for patients for not warning doctors of the potential for heart attacks and strokes.
Company memos dating to 1996 showed that Merck was aware of the potential side effects, he said.
The company nevertheless hired 3,000 sales people and trained them to downplay the risks when talking with doctors, Girardi said.
More here.
Tuesday, June 27, 2006
Are Pfizer buying Sepracor?
You tell me!
That $16.6 billion they got for their OTC business might be burning a hole in their pockets.
Forbes speculates.
That $16.6 billion they got for their OTC business might be burning a hole in their pockets.
Forbes speculates.
Consumers International Report - Branding the Cure
Big Pharma are accused today of endangering public health through widescale marketing malpractices, ranging from covertly attempting to persuade consumers that they are ill to bribing doctors and misrepresenting the results of safety and efficacy tests on their products.
In a report that charts the scale of illicit practices by drug companies in the UK and across Europe, Consumers International - the world federation of consumer organisations - says people are not being given facts about the medicines they take because the companies hide the marketing tactics on which they spend billions.
"Irresponsible marketing practices form a serious, persistent and widespread problem among the entire pharmaceutical industry," says the report, which analyses the conduct of 20 of the biggest companies, two of which are British. It calls for tougher government controls and for the companies to put their house in order.
Scandals such as the withdrawal of Vioxx, a drug to relieve pain and inflammation in arthritis, show that unethical drug promotion is a consumer concern, says the report. Merck withdrew the drug in September 2004, but allegedly knew it could increase the chances of heart attacks and strokes from 2000 and has been accused of manipulating study results to play down the risk. More than 6,000 lawsuits have been filed against the company in the United States by people who claim they suffered heart attacks as a result of the drug, or by their families.
Despite regulatory action against drug companies, the malpractice continues, says CI. Many people in the UK may feel they are secure because they trust their doctors to tell them which drug to take, but CI says there is no room for complacency when drug companies spend twice as much on marketing as on research - $60bn last year (£33bn) - but do not publish information on their drug promotion practices. Of the 20 companies, only Bristol-Myers Squibb provides a marketing code of conduct to consumers.
"One obvious area of concern is about how the promotion of drugs by the pharmaceutical companies to doctors can lead to irrational drug use," says Richard Lloyd, CI's director general. "There is a lot of evidence around of malpractice. This report has found that it is still going on and in a big way and it must be stopped."
More than half the companies looked at were implicated in controversies regarding their relationships to healthcare professionals between 2001 and 2005, says the report.
The British company AstraZeneca, for instance, has been criticised by regulatory bodies: it allegedly organised an event to promote its drug Crestor which included tickets for a musical, and provided flights and hotels for doctors to attend a conference on bipolar disorder on the French Riviera.
AstraZeneca says all employees must now pass an exam on its code of conduct.
GlaxoSmithKline, Britain's largest drug manufacturer, is under investigation by German and Italian authorities for alleged corruption of doctors - at least 1,600 in Germany and more than 4,000 in Italy, where the illegal gifts were said to amount to €228m (£156m) from 1999 to 2002.
GSK says it has since established marketing codes. New staff have to pass a test on the code of practice. The report points out that in 2004, 87 employees were dismissed or agreed to leave the company voluntarily as a result of breaches of the codes, and that sanctions such as written warnings were imposed in 109 cases.
Source: Grauniad
In a report that charts the scale of illicit practices by drug companies in the UK and across Europe, Consumers International - the world federation of consumer organisations - says people are not being given facts about the medicines they take because the companies hide the marketing tactics on which they spend billions.
"Irresponsible marketing practices form a serious, persistent and widespread problem among the entire pharmaceutical industry," says the report, which analyses the conduct of 20 of the biggest companies, two of which are British. It calls for tougher government controls and for the companies to put their house in order.
Scandals such as the withdrawal of Vioxx, a drug to relieve pain and inflammation in arthritis, show that unethical drug promotion is a consumer concern, says the report. Merck withdrew the drug in September 2004, but allegedly knew it could increase the chances of heart attacks and strokes from 2000 and has been accused of manipulating study results to play down the risk. More than 6,000 lawsuits have been filed against the company in the United States by people who claim they suffered heart attacks as a result of the drug, or by their families.
Despite regulatory action against drug companies, the malpractice continues, says CI. Many people in the UK may feel they are secure because they trust their doctors to tell them which drug to take, but CI says there is no room for complacency when drug companies spend twice as much on marketing as on research - $60bn last year (£33bn) - but do not publish information on their drug promotion practices. Of the 20 companies, only Bristol-Myers Squibb provides a marketing code of conduct to consumers.
"One obvious area of concern is about how the promotion of drugs by the pharmaceutical companies to doctors can lead to irrational drug use," says Richard Lloyd, CI's director general. "There is a lot of evidence around of malpractice. This report has found that it is still going on and in a big way and it must be stopped."
More than half the companies looked at were implicated in controversies regarding their relationships to healthcare professionals between 2001 and 2005, says the report.
The British company AstraZeneca, for instance, has been criticised by regulatory bodies: it allegedly organised an event to promote its drug Crestor which included tickets for a musical, and provided flights and hotels for doctors to attend a conference on bipolar disorder on the French Riviera.
AstraZeneca says all employees must now pass an exam on its code of conduct.
GlaxoSmithKline, Britain's largest drug manufacturer, is under investigation by German and Italian authorities for alleged corruption of doctors - at least 1,600 in Germany and more than 4,000 in Italy, where the illegal gifts were said to amount to €228m (£156m) from 1999 to 2002.
GSK says it has since established marketing codes. New staff have to pass a test on the code of practice. The report points out that in 2004, 87 employees were dismissed or agreed to leave the company voluntarily as a result of breaches of the codes, and that sanctions such as written warnings were imposed in 109 cases.
Source: Grauniad
Merck - Vioxx: NEJM corrects itself
Poor Merck. Their contention that its Vioxx painkiller raised the risk of heart attack or stroke only after 18 months' usage was contradicted Monday by the New England Journal of Medicine.
Correcting the results of the Merck-sponsored APPROVe study it previously published, the Journal suggested the increased health risk started earlier for Vioxx patients, but didn't specify a time frame.
The correction escalated the debate about Vioxx, the drug Merck pulled off the market in September 2004 after the study found the elevated health danger. The company faces more than 11,500 lawsuits over the drug, and has won half of the six cases in the court trials completed so far.
The Journal reported that the original article about the study used a faulty statistical analysis, which Merck itself disclosed earlier this year. But while company experts contended the mistake didn't affect conclusions about when the danger risk begins, the Journal disagreed.
"Therefore, statements regarding an increase in risk after 18 months should be removed," from the article that reported the study results, the Journal said.
Lawyers suing Merck on behalf of Vioxx patients or their survivors argued that the Journal correction significantly undercut Merck's legal contentions.
"I think that judges are almost required now to grant new trials in the cases where Merck has won, because the linchpin of Merck's defense has always been the 18-month argument," said "Hotshot" Mark Lanier, a Texas attorney who won a $253 million Vioxx verdict against the firm last year. "It turns out that 18 months is bogus, and it's bogus because of Merck's own internal mistakes."
Christopher Seeger, a New York attorney who last year lost a Vioxx case in which shorter-term usage of the drug was an issue, said he plans to add the Journal correction to his legal arguments seeking a new trial.
"This removes a major hurdle to getting verdicts against Merck," Seeger said.
Source: USA Today
Thanks to jimbo for this link.
Correcting the results of the Merck-sponsored APPROVe study it previously published, the Journal suggested the increased health risk started earlier for Vioxx patients, but didn't specify a time frame.
The correction escalated the debate about Vioxx, the drug Merck pulled off the market in September 2004 after the study found the elevated health danger. The company faces more than 11,500 lawsuits over the drug, and has won half of the six cases in the court trials completed so far.
The Journal reported that the original article about the study used a faulty statistical analysis, which Merck itself disclosed earlier this year. But while company experts contended the mistake didn't affect conclusions about when the danger risk begins, the Journal disagreed.
"Therefore, statements regarding an increase in risk after 18 months should be removed," from the article that reported the study results, the Journal said.
Lawyers suing Merck on behalf of Vioxx patients or their survivors argued that the Journal correction significantly undercut Merck's legal contentions.
"I think that judges are almost required now to grant new trials in the cases where Merck has won, because the linchpin of Merck's defense has always been the 18-month argument," said "Hotshot" Mark Lanier, a Texas attorney who won a $253 million Vioxx verdict against the firm last year. "It turns out that 18 months is bogus, and it's bogus because of Merck's own internal mistakes."
Christopher Seeger, a New York attorney who last year lost a Vioxx case in which shorter-term usage of the drug was an issue, said he plans to add the Journal correction to his legal arguments seeking a new trial.
"This removes a major hurdle to getting verdicts against Merck," Seeger said.
Source: USA Today
Thanks to jimbo for this link.
Monday, June 26, 2006
sanofi aventis - disinterested in Altana
Sanofi-Aventis SA "definitely" has no interest in Altana AG's pharmaceuticals business, head of Sanofi, Jean-Francois Dehecq said, according to the pre-release of an article to appear in Monday's WirtschaftsWoche.
Who has!?
Who has!?
Pfizer OTC - cash sale
Johnson & Johnson today agreed to buy rival Pfizer's consumer healthcare business for $16.6 billion (£9.1bn) in cash.
Well, Pfizer probably need the reddies to pay for Hank's pension!
Well, Pfizer probably need the reddies to pay for Hank's pension!
Bad boys, bad boys, what'cha gonna do
Four Big Pharma companies have been ruled to have brought the pharmaceutical industry into disrepute following recent complaints that they broke the UK Association of the British Pharmaceutical Industry's code of practice.
Serono brought discredit on the industry by paying 30 neurologists to prescribe one of its drugs. The company has been ordered by the Prescription Medicines Code of Practice Authority, which enforces the code, to ask for its money back.
The doctors were paid £700 each to cover administrative costs associated with an audit of a project to transfer multiple sclerosis patients from low-dose interferon treatment made by Serono, Biogen or Schering Health Care, to a high-dose treatment made only by Serono and to monitor its effect.
A PMCPA inquiry panel ruled that the project was not a bona fide audit and the arrangements amounted to paying doctors to prescribe Serono’s Rebif (interferon beta-1a). A PMCPA appeal board subsequently ordered the company to ask for its money back in case the doctors concerned got the impression that payment in such circumstances was acceptable.
Boehringer Ingelheim and Pfizer brought discredit on the industry by paying for a night out for a GP, three nurses and some practice administrative staff. The two companies provided conflicting accounts of whom they took to a restaurant and wine bar, what the purpose of the event was and who paid for what.
A PMCPA appeal board ruled that the discredit was heightened by the involvement of two companies together and that the event could give outsiders the impression that such practices were commonplace.
Sankyo Pharma brought discredit on the industry by failing to comply with an undertaking it gave after being found in breach of the code on a previous occasion. The company had repeated a claim that Olmetec (olmesartan) was unbeaten at reducing hypertension. Its behaviour also reduced confidence in the industry.
Source: Pharmaceutical Journal
Pfizer - McKinnell: because I'm worth it
"In my business, pharmaceuticals, the medicines we build this year will not make it to market for 12 to 15 years. So what is performance? Is it current share price? I don't think so. It's long-term value," Pfizer's CEO Hank McKinnell said, speaking at Stanford University's Directors' College.McKinnell became the target of complaints about excessive executive compensation when Pfizer disclosed a retirement package under which he can he can choose from an annual pension of more than $6.5 million, or a lump sum payment of $83 million. He also earned nearly $16 million in 2005.
More here.
The Listerine Cup - " and as they round the final turn it's J&J in the lead by a head
Johnson & Johnson is close to reaching a deal to buy the consumer products unit of Pfizer, which includes brands like Listerine and Sudafed, for more than $16 billion, The New York Times online edition reported on Sunday.
If true, J&J will beat GSK and Reckitt Benkeiser to the prize.
Citing people involved in the deal, the newspaper said the transaction could be announced later on Sunday or Monday morning.
Pfizer first announced in February it was weighing a sale or spinoff of the business.
Go here for the back story.
If true, J&J will beat GSK and Reckitt Benkeiser to the prize.
Citing people involved in the deal, the newspaper said the transaction could be announced later on Sunday or Monday morning.
Pfizer first announced in February it was weighing a sale or spinoff of the business.
Go here for the back story.
Sunday, June 25, 2006
Serono to "tilt" at Shire?
Swiss biotechnology group Serono is gearing up its $10bn (£5.5bn) acquisition drive, which could include a tilt at pharmaceutical giant Shire.
"Management has a clear, renewed sense of urgency to do a deal," said ABN Amro fund manager Arnoud Diemers, who recently spoke with management. Investors have been pressing the company to deliver on the pledge it made in April to hit the acquisition trail after it failed to sell itself.
Let's hope they dont end up tilting at the wrong target.
More here in The Independent.
Saturday, June 24, 2006
Sanofi Aventis - Acomplia; a hundred bucks a month!
That's what Insider understands the UK price will be!
Friday, June 23, 2006
Big Pharma's Big Problem contd.
Forbes show it nicely in this year by year breakdown.
And remember, new drugs are, at best, coming on line at half this rate.
And remember, new drugs are, at best, coming on line at half this rate.
Merck's anti-Parkinson's drug no great shakes
Poor Merck KGaA. They lost a key product in its late-stage development pipeline today, after deciding there was no longer any point pressing on with development of sarizotan as a treatment for Parkinson's disease.
Merck made the decision after taking a look at the results of two Phase III studies of sarizotan in advanced Parkinson's disease patients suffering from dyskinesia.
The Phase III studies did not confirm earlier Phase II findings or the results from preclinical studies, said Merck in a statement. "Merck does not plan to pursue further development of this compound," it said. The company had earlier said it hoped to file for approval of the drug in both Europe and the USA later this year.
The decision leaves a hole in Merck's near-term pipeline as sarizotan was one of just two new drugs in later-stage testing at the company, the other being cancer vaccine Stimuvax, which it acquired from Biomira earlier this year. The latter product is just starting a Phase III programme.
The failure also adds to the disappointment Merck suffered after failing to complete a takeover of fellow German drugmaker Schering AG, which now look set to complete a favoured merger with Bayer. Merck had hoped to join forces with Schering to boost its specialty pharmaceutical portfolio and become more competitive in the global pharma industry.
News of sarizotan's demise had sparked a 5% fall-off in Merck's shares to 70.28 euros in early morning trading today.
Source: PharmaTimes
Merck made the decision after taking a look at the results of two Phase III studies of sarizotan in advanced Parkinson's disease patients suffering from dyskinesia.
The Phase III studies did not confirm earlier Phase II findings or the results from preclinical studies, said Merck in a statement. "Merck does not plan to pursue further development of this compound," it said. The company had earlier said it hoped to file for approval of the drug in both Europe and the USA later this year.
The decision leaves a hole in Merck's near-term pipeline as sarizotan was one of just two new drugs in later-stage testing at the company, the other being cancer vaccine Stimuvax, which it acquired from Biomira earlier this year. The latter product is just starting a Phase III programme.
The failure also adds to the disappointment Merck suffered after failing to complete a takeover of fellow German drugmaker Schering AG, which now look set to complete a favoured merger with Bayer. Merck had hoped to join forces with Schering to boost its specialty pharmaceutical portfolio and become more competitive in the global pharma industry.
News of sarizotan's demise had sparked a 5% fall-off in Merck's shares to 70.28 euros in early morning trading today.
Source: PharmaTimes
Sanofi Aventis - Acomplia: Ronaldo signed up for celebrity endorsment deal
Clause in contract stipulates he changes his name for the rest of the World Cup to "Rotundo".
If you played for Brazil what would your football name be? Go here to find out.
Zocor - now a branded generic
This is the day that Merck — and Pfizer — have long dreaded.
Today, Merck's cholesterol-lowering drug Zocor loses its United States patent protection, becoming the largest-selling drug yet to be opened to cheap generic competition.
That change will cost Merck billions of dollars a year. But it could be nearly as damaging to Pfizer, whose rival cholesterol drug, Lipitor, is the world's most popular medicine, with global sales last year of $12 billion. Now insurers are hoping to convince patients and doctors that cheap clones of Zocor will make full-priced Lipitor an unnecessary luxury.
More from Alex Berenson at the NYT here.
Today, Merck's cholesterol-lowering drug Zocor loses its United States patent protection, becoming the largest-selling drug yet to be opened to cheap generic competition.
That change will cost Merck billions of dollars a year. But it could be nearly as damaging to Pfizer, whose rival cholesterol drug, Lipitor, is the world's most popular medicine, with global sales last year of $12 billion. Now insurers are hoping to convince patients and doctors that cheap clones of Zocor will make full-priced Lipitor an unnecessary luxury.
More from Alex Berenson at the NYT here.
"Whistleblower" - the movie: Clooney to play Rost
George Clooney to play Peter Rost in a movie about whistleblowing.?
Well, it could happen!
If it does then Insider wants a cut for having had the idea.
Hell, he would even help write the script!
It's not such an outlandish idea.
Rost and Clooney seem to have a connection: they both have had recent beefs with The Huffington Post. They are both men of substance and conscience.
And Big Pharma will become more of a hot movie topic given the recent success of The Constant Gardener and the upcoming Michael Moore documentary "Sicko".
Peter Rost's blog is moving along at a fair old pace since he left both Pfizer and The Huffington Post.
Catch up on the latest twists and turns there.
Thursday, June 22, 2006
MDs and seeding studies - some harsh words, but true
"If big pharma may have corrupted the Evidence Based Medicine process, how should the physicians who take part in them be characterized?
Two nouns come to mind; dupes and co-conspirators and I wish I could think of some less pejorative words as alternatives. Some are simply naive and do not understand what is really going on. Some of the academics, however, probably cannot plead ignorance. They either know better or at least in recent years should know better."
So says Dr James Gaulte in his blog, which is rapidly becoming one of Insider's faves!
Two nouns come to mind; dupes and co-conspirators and I wish I could think of some less pejorative words as alternatives. Some are simply naive and do not understand what is really going on. Some of the academics, however, probably cannot plead ignorance. They either know better or at least in recent years should know better."
So says Dr James Gaulte in his blog, which is rapidly becoming one of Insider's faves!
Merck - Vioxx: VIGOR's Michael Weinblatt; well done, good and faithful servant
In 1999, Merck appointed rheumatologist Michael Weinblatt of Brigham & Women's Hospital in Boston to head the safety panel for the Vioxx VIGOR study.
When he became chair of the safety panel, Weinblatt and his wife owned $73,000 of Merck stock.
David Bjorkman, now dean of the University of Utah School of Medicine, also served on the five-member safety panel.
In 1999, he participated in the Merck speakers bureau and gave presentations in the summer of that year.
In addition, the panel meetings had a Merck employee present. The employee attended all the panel's meetings -- including its private deliberations. She even wrote the meetings' minutes.
At its last meeting, in December 1999, when the safety panel decided the heart problems weren't serious enough to stop the study, it also said that the problems merited analysis. The panel asked Merck to do that as soon as possible.
Merck sent back word that it wanted to wait.
When the safety panel's chairman Michael Weinblatt insisted, Merck proposed a plan.
The company would analyze heart problems it was told about by a "cutoff" date -- one month before the study ended.
Weinblatt agreed.
As a result of that cut-off date, three of the 20 heart attacks among Vioxx patients weren't included when Merck wrote up the study in the New England Journal of Medicine.
And, Vioxx looked safer than it really was.
Soon after agreeing to Merck's plan, Weinblatt signed a new consulting contract to sit on a Merck advisory board. Merck agreed to pay him $5,000 a day for 12 days over a two-year period.
Weinblatt received an initial check for $15,000 a few weeks later.
Research published in the medical journal The Lancet estimates that between 1999 and 2004, when Vioxx was withdrawn from the market, 88,000 Americans had heart attacks from taking the drug, and 38,000 of them died.
Source: npr.org
Merck - Vioxx: first trial in "the city of LA"
California (california)...knows how to party (knows how to party!)
California (west coast)...knows how to party (yes they do)(that's right)
In the city of L.A. (city of L.A.)
In the city of good ol' Watts (good ol' Watts)
In the city, the city of Compton (city of Compton)
We keep it rockin! We keep it rockin! (come on, come on, come on...)
Thus spake Tupac.
Meanwhile, jury selection began on Wednesday in a lawsuit by a California man who claims he suffered a heart attack after taking the painkiller Vioxx; one of more than 13,000 such claims brought against Big Pharma Merck in the US.
The SoCal man, Stewart Grossberg, claims he took Vioxx for more than two years before he had a heart attack at 66.
His case is the first to go to trial in California and one of some 2,000 filed in the state and consolidated in Los Angeles Superior Court by Judge Victoria Chaney.
More here.
Sanofi Aventis - Acomplia: July launch for UK
French Big Pharma Sanofi-Aventis will soon begin selling its anti-obesity drug Acomplia.
A 20-mg per day version has been authorized for all 25 EU member states, with the first launch set for the UK in July.
Launches in Denmark, Ireland, Germany, Finland and Norway will occur by the end of this year.
But what of the biggest market?
Sanofi-Aventis hopes to receive full approval for Acomplia in the US by year-end. But they have never revealed what was in their FDA approvable letter though!
Merck - Vioxx; "Hotshot" Mark Lanier - a profile
In the second Vioxx trial that W. Mark Lanier tried, he turned to a different approach in his closing arguments.
Lanier spun the case like four episodes of "Desperate Housewives," the popular prime time soap opera several jurors had indicated that they watched. Between each story, he paused for a "commercial break," playing a Vioxx advertisement for emphasis.
As a prop, he used a poster with the women of the television show, with pictures of Merck & Co. executives' faces superimposed over the characters' faces.
It worked.
Lanier represented the plaintiff on general liability issues, while Robert Gordon and Jerry Kristal of Weitz and Luxenberg represented the plaintiff on all case-specific issues at trial. Their client won a $13.5 million verdict against Merck in Atlantic City, N.J., McDarby v. Merck & Co., No. ATL-L-1296-05 (Atlantic Co., N.J., Super. Ct. 2006).
Lanier's first Vioxx win was a $253 million verdict in Texas in 2005, Ernst v. Merck & Co., No. 19961-BH02 (Brazoria Co., Texas, Dist. Ct.). Both cases are being appealed by Merck.
"If you tell stories, jurors will remember it better, and relate to it better," said Lanier.
The Atlantic City trial was Lanier's first jury trial outside of the Texas area. To prepare, Lanier used more pretrial focus groups than for any of his previous trials, and spent countless hours preparing.
"I walked the streets in Atlantic City," he said. "I went through stores, casinos, I struck up conversations with people and asked what made them tick."
As a young Texas trial lawyer, Lanier has enjoyed remarkable success. He founded The Lanier Law Firm in 1990, which recently opened a New York office. He has verdicts of $417 million and $118 million under his belt, in addition to the recent Vioxx wins.
He's earned a reputation for his high energy, Southern accent and theatrical flair in the courtroom.
"He is passionate. He's funny without being inappropriate, and the whole time he's trying a case it's as if he's just having a conversation," said Lisa Blue, a close friend of Lanier's who is also a psychologist, a jury consultant in the Vioxx cases, and of counsel at Baron & Budd in Dallas. "He talks to a witness as if he's talking to a friend at a cocktail party. It's a very relaxed and real style for him."
Lanier, a part-time Baptist preacher, scoffs at being deemed "theatrical."
"I had one case where the bad guys -- that's what I call the opposing side -- would stand up and say 'objection, your honor, argumentative and theatrical,' and the judge sustained it. ... But there's no such thing as a theatrical objection," Lanier said. "I like to think I'm high-energy and demonstrative."
The key to his success is his hard work, he said, and his creativity. For every trial, "I try to do one thing that will improve my trial skill set," said Lanier. Before the Ernst case, he worked on his PowerPoint presentation skills, and brought in additional lawyers to counsel him on trial tips.
Lanier is always looking for "nuggets of information," by filing advertisements in newspapers to attract witnesses or hiring private investigators to locate extra witnesses. In the Ernst trial, Lanier hired a private eye to find a coroner who had relocated to the United Arab Emirates.
Lanier scoured the auction Web site eBay for paraphernalia, buying a plastic heart that Merck had made in the 1950s to use as a prop in trial.
"His mantra in life is to always improve and kick it up a notch," Blue said. "He'll do whatever it takes -- focus groups, mock juries, elaborate questionnaires. He's all about being prepared.
"Jurors love the way he explains things to them so they can retain it," she added.
Merck lawyers declined to comment on Lanier. An opponent with more success against Lanier, Peter Bicks, the managing partner of Orrick, Herrington & Sutcliffe's New York office and a litigation defense attorney, characterizes Lanier as an attorney with "considerable charms."
"Mark is a great trial lawyer, a skilled examiner, and will entertain a jury," said Bicks. "A steady, even-keeled and passionate approach provides a nice counterbalance to Mark's animated, theatrical and preacherlike style."
Bicks handed Lanier one of the worst losses of his career in an asbestos case in 2004, Kelly-Moore Paint Co. Inc. v. Union Carbide Corp., No. 19785-BH02 (Brazoria Co., Texas, Dist. Ct.). In the six-week jury trial, Lanier's client Kelly-Moore sought nearly $6 billion.
"You know if you defeat Mark Lanier ... you have beaten one of the best trial lawyers," Bicks said.
Source: Law.com
Wednesday, June 21, 2006
Dr. Peter Rost - now "fired" from the Huffington Post!
Dear Jack,
Arianna Huffington’s online newspaper, the Huffington Post, terminated my access to the site late yesterday after I wrote an investigative article about an anonymous heckler who had been stalking my blog (who had actually challenged me to write about him). The heckler turned out to be Huffington Post’s own technology manager.
In the article I had stated, “In order for the Huffington Post to maintain its credibility, the site needs to avoid even the appearance of a conflict of interest or rigged rankings.”
The Huffington Post first shut down access to my blog post; later in the day allowed the post to be viewed again, and then terminated my access to the site. The full article with reader comments can be viewed here: http://peterrost.blogspot.com/2006/06/troll-inside-huffington-post.html. You can also view the HuffPo post with comments here, (unless it has been shut down again): http://www.huffingtonpost.com/dr-peter-rost/a-troll-inside-huffingto_b_23387.html
The Huffington Post wrote in a letter to me, “You have not been "fired" but rather asked to refrain from posting as our editorial staff felt that your recent blogs were not in line with the mission of our site.” HuffPo added, “this was not an Arianna call. Ultimately, the decision was an editorial one - not one person to be held responsible -- really.”
I was terminated without any investigation of the statements in my blog post, all of which were referenced using independent sources on the net. Arianna Huffington’s newspaper decided to shut down the whistleblower and proved that her online magazine is no more ethical than the people and organizations she criticizes on a daily basis. This is a sad day for online journalism.
I will continue to blog on: http://peterrost.blogspot.com/
Regards,
Peter
Arianna Huffington’s online newspaper, the Huffington Post, terminated my access to the site late yesterday after I wrote an investigative article about an anonymous heckler who had been stalking my blog (who had actually challenged me to write about him). The heckler turned out to be Huffington Post’s own technology manager.
In the article I had stated, “In order for the Huffington Post to maintain its credibility, the site needs to avoid even the appearance of a conflict of interest or rigged rankings.”
The Huffington Post first shut down access to my blog post; later in the day allowed the post to be viewed again, and then terminated my access to the site. The full article with reader comments can be viewed here: http://peterrost.blogspot.com/2006/06/troll-inside-huffington-post.html. You can also view the HuffPo post with comments here, (unless it has been shut down again): http://www.huffingtonpost.com/dr-peter-rost/a-troll-inside-huffingto_b_23387.html
The Huffington Post wrote in a letter to me, “You have not been "fired" but rather asked to refrain from posting as our editorial staff felt that your recent blogs were not in line with the mission of our site.” HuffPo added, “this was not an Arianna call. Ultimately, the decision was an editorial one - not one person to be held responsible -- really.”
I was terminated without any investigation of the statements in my blog post, all of which were referenced using independent sources on the net. Arianna Huffington’s newspaper decided to shut down the whistleblower and proved that her online magazine is no more ethical than the people and organizations she criticizes on a daily basis. This is a sad day for online journalism.
I will continue to blog on: http://peterrost.blogspot.com/
Regards,
Peter
In the wrong business - richest celebs of 2005
Steven Spielberg - $332,000,000 Howard Stern - $302,000,000 George Lucas -$235,000,000 Oprah Winfrey - $225,000,000 Jerry Seinfeld - $100,000,000 Jerry Bruckheimer - $84,000,000 Tom Cruise - $67,000,000 Bruce Springsteen - $55,000,000 Donald Trump - $44,000,000 The Olsen Twins - $40,000,000 Michael Jordan $32,000,000 Tom Hanks - $29,000,000 Johnny Depp - $29,000,000 LeBron James - $26,000,000 Brad Pitt - $25,000,000 Larry the Cable Guy - $19,000,000 Ryan Seacrest - $12,000,000 Paris Hilton - $7,000,000 Adriana Lima - $4,000,000
FDA management - quick, lets do somthing!
U.S. regulators are re-evaluating clinical trials for medicines and plan changes that include a proposal to force drugmakers to promptly inform them if companies believe a researcher has committed fraud during a study.
The Food and Drug Administration is expected to launch an effort to standardize the forms used to collect information in studies and adjust the rules on how patients access experimental treatments, The Wall Street Journal said.
The FDA also will seek to clarify which adverse events in trials have to be reported to review boards that monitor studies to protect patients, the newspaper said.
FDA Deputy Commissioner Janet Woodcock will discuss the initiative on Wednesday at an industry conference.
Insider's view: about time!
This particular knee jerk comes hot on the heels of the Ketek affair and study 3014!
The Food and Drug Administration is expected to launch an effort to standardize the forms used to collect information in studies and adjust the rules on how patients access experimental treatments, The Wall Street Journal said.
The FDA also will seek to clarify which adverse events in trials have to be reported to review boards that monitor studies to protect patients, the newspaper said.
FDA Deputy Commissioner Janet Woodcock will discuss the initiative on Wednesday at an industry conference.
Insider's view: about time!
This particular knee jerk comes hot on the heels of the Ketek affair and study 3014!
Dont get me wrong. The FDA is full of good people. In fact, it's an organisation of lions led by donkeys!
Pfizer - Exubera: you dont have to be mad to take it
But it helps!
Only patients with a proven needle phobia or severe problems with injection sites should get Pfizer's inhaled insulin product Exubera, Britain's cost-effectiveness watchdog, NICE, said on Wednesday.
The National Institute for Health and Clinical Excellence (NICE) had already said the treatment was not worth the money in April.
That initial decision provoked a storm of protest and Andrea Sutcliffe, deputy chief executive at NICE, said the revised guideline showed flexibility.
This means some patients would have to prove mental illness to get Exubera as under the NICE proposal, injection phobia would have to be diagnosed by a psychiatrist or psychologist.
Source: Reuters
Only patients with a proven needle phobia or severe problems with injection sites should get Pfizer's inhaled insulin product Exubera, Britain's cost-effectiveness watchdog, NICE, said on Wednesday.
The National Institute for Health and Clinical Excellence (NICE) had already said the treatment was not worth the money in April.
That initial decision provoked a storm of protest and Andrea Sutcliffe, deputy chief executive at NICE, said the revised guideline showed flexibility.
This means some patients would have to prove mental illness to get Exubera as under the NICE proposal, injection phobia would have to be diagnosed by a psychiatrist or psychologist.
Source: Reuters
Big Pharma drug trials - a GOTBO moment
Physicians who participated in Big Pharma-sponsored clinical trials involving asthma medications maintained adherence to treatment guidelines but were more likely prescribe the sponsor's drugs, according to a new study in JAMA.
Morten Andersen, M.D., Ph.D., and colleagues from Denmark investigated the effects of physicians participating in company-sponsored clinical trials aimed at improving patients' use of asthma medicine.
The researchers found the prevalence of inhaled steroid use in asthma patients increased from 68.5 percent to 72.9 percent. The study also revealed participants in the trail did not impact the physicians' adherence to international treatment guidelines.
Researchers say pharmaceutical companies are often involved in clinical trials in general practice, and this may trigger an increase in the use of the sponsoring companies' products because physicians become familiar with them. The researchers suggest this effect may be further strengthened by close physician-company cooperation, which they say may create physician loyalty toward the company.
"Our study confirms the hypothesis that physician involvement in clinical trials is a powerful tool for influencing company-specific drug preferences. Several mechanisms may be responsible, including setting up a gift relationship by payment to a trial conducting physician."
GOTBO = glimpse of the bleeding obvious
Morten Andersen, M.D., Ph.D., and colleagues from Denmark investigated the effects of physicians participating in company-sponsored clinical trials aimed at improving patients' use of asthma medicine.
The researchers found the prevalence of inhaled steroid use in asthma patients increased from 68.5 percent to 72.9 percent. The study also revealed participants in the trail did not impact the physicians' adherence to international treatment guidelines.
Researchers say pharmaceutical companies are often involved in clinical trials in general practice, and this may trigger an increase in the use of the sponsoring companies' products because physicians become familiar with them. The researchers suggest this effect may be further strengthened by close physician-company cooperation, which they say may create physician loyalty toward the company.
"Our study confirms the hypothesis that physician involvement in clinical trials is a powerful tool for influencing company-specific drug preferences. Several mechanisms may be responsible, including setting up a gift relationship by payment to a trial conducting physician."
GOTBO = glimpse of the bleeding obvious
Tuesday, June 20, 2006
Sweden
Honours even. Cole's goal was the best individual effort of the tournament to date. We finish top of the group and avoid Germany, for the moment!
Pictured are two healthy young Swedish fans (possibly drug reps) celebrating.
Zocor RIP, Lipitor on life support?
Link for pic.
A report in the British Medical Journal says that England's NHS could save in excess of £2 billion over a five year period if prescriptions were switched to generic statins.
Report authors, James Moon and Richard Bogle, both senior doctors, say statin prescriptions have gone up by 30% every year in England for several years - they cost the NHS £738 million in 2004.
Statins now represent the largest part of the NHS drug bill.
40% of all statin prescriptions are for atorvastatin, followed by simvastatin.
85% of prescriptions are for 10 and 20 mg atorvastatin doses, the lower doses.
Simvastatin is much cheaper than atorvastatin as its patent expired. Atorvastatin's patent expires in 2011.
By switching from the lower dose atorvastatin prescription to the cheaper statin the NHS would save £1 billion (pounds sterling) over the next five years.
Another £1 billion will be saved anyway because of the fall in price of simvastatin.
pdf. here
Recordati - bribes, in Italy! Never!
Three executives of Italy's biggest Big Pharma Recordati were arrested on Monday as part of an investigation into possible bribes to doctors to encourage them to prescribe the firm's drugs, triggering a slide in its shares.
Tax police did not name the three executives in a statement, but Recordati said separately the general manager of the pharmaceuticals division, Vittorio Bonazzi (pic), was among them, adding he had resigned from his job.
"The issues in question have no impact on the continuity of the company's business, nor do they affect the outlook in respect to the previously announced targets," the company said.
Recordati, Italy's biggest listed pharmaceutical firm with sales of over 570 million euros in 2005, is known for its lercanidipine drug, used for the treatment of hypertension.
Tax police said another 31 people -- company employees, doctors and a pharmacist -- were also under investigation and that they were considering including Recordati in the probe.
Doctors were offered cash or gifts such as mobile phones, computers and laptops if they agreed to prescribe selected drugs to a large number of of patients, according to the investigation's findings.
Insider's view: Italian Big Pharma will be sweating. It all now depends upon whether Vittorio sticks to the rule of omerta!
Source: Reuters
Big Pharma falls out of the workplace rankings
At one time Big Pharma featured highly in the the rankings for "great places to work".
With one exception - not any more.
With one exception - not any more.
GW - losses rise, getting tense
GW Pharmaceuticals, which develops cannabis and other controlled drug-based medicines, reported widening losses and reiterated that research spending is set to rise 30 per cent this year.
Its leading product Sativex, an under-the-tongue spray for the treatment of muscle spasms, stiffness and pain associated with MS, and neuropathic cancer, is on the market in Canada. But a series of setbacks means the regulatory process has taken longer than expected in the UK.
Pre-tax losses widened to £7.1 million from £6 million in the six months to the end of March as research and development expenditure rose by £1.5 million £6.5 million.
Insider's view: dont worry about a 'ting! Email me if you need something to help you relax.
Source: The Times
Statin Wars - anything you can do, I can do better
On this special week it's all hotting up nicely.
At this weeks beanfeast, the International Symposium on Atherosclerosis meeting in Rome, AstraZeneca is battling both Merck and Schering-Plough as the rivals seek to prove each has the best medicine for lowering cholesterol.
New clinical data presented at the weekend showed the U.S. drugmakers' two-in-one pill Vytorin (Inegy in the UK), which combines the ingredients ezetimibe and simvastatin, reduced "bad" cholesterol more than AstraZeneca's Crestor.
AstraZeneca hit back on Monday, however, with another trial showing that a combination of Crestor and ezetimibe reduced LDL cholesterol even more.
At this point Insider will stifle a yawn and ask the following question:
So what? Who should really be treated?
DB's Medical Rants has a post that might just be able to help here.
"The challenge to doctors is not to become so enamored by numbers that they strive for some theoretical advantage that may not in fact exist.
The hard part is not to write the prescription. "
Exactly! Now please pass the generic simvastatin.
Monday, June 19, 2006
BMS - Erbutex: not for Ca in CA
One of the world's most costly cancer drugs will not be marketed in Canada because of a price dispute between the drug's distributor and the federal government.
The colorectal cancer drug Erbitux, which was approved by Health Canada nine months ago, will not be launched after distributor Bristol Myers Squibb Canada could not agree on a price with the federal Patented Medicine Prices Review Board., The Globe and Mail reports.
Marc Osborne, director of public relations for Bristol-Myers Squibb Canada, refused to say how much the company wants to charge for the drug, but it's believed the federal board has found it to be too high.
In Europe, Erbitux sells for less than half of what it does in the United States, a spokeswoman for Merck KGaA, the company that licenses Erbitux in Europe, told The Globe.
Erbitux typically costs the equivalent of $5,677 Cdn monthly.
More here.
The colorectal cancer drug Erbitux, which was approved by Health Canada nine months ago, will not be launched after distributor Bristol Myers Squibb Canada could not agree on a price with the federal Patented Medicine Prices Review Board., The Globe and Mail reports.
Marc Osborne, director of public relations for Bristol-Myers Squibb Canada, refused to say how much the company wants to charge for the drug, but it's believed the federal board has found it to be too high.
In Europe, Erbitux sells for less than half of what it does in the United States, a spokeswoman for Merck KGaA, the company that licenses Erbitux in Europe, told The Globe.
Erbitux typically costs the equivalent of $5,677 Cdn monthly.
More here.
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