DTC² and Vytorin

01/21/2008 08:36 AM |

Should Vytorin continue to advertise? What impact, if any, will this question have on the larger issue of DTC regulation? These and other questions are discussed in a worthwhile article in this week’s edition of Advertising Age.

Here’s a link to the article:

http://adage.com/article?article_id==123228

And a few paragraphs to whet your appetite:

"Unlike Merck's Vioxx, which in 2004 was found to contribute to heart attacks in some patients and was pulled off the market, Vytorin is safe and can still be sold. It does, the study found, reduce the levels of LDL in patients. It just doesn't, according to the study, live up to its claim of reducing plaque build-up. That's why Peter Pitts, a former associate commissioner for the FDA and now the president of New York-based Center for Medicine in the Public Interest, says this won't be the death knell for DTC that some think it is.

Just because a congressman sneezes doesn't mean pharmaceutical companies will catch a cold, Mr. Pitts said. DTC is heavily regulated and the question becomes 'What does the study tell us and how is it relevant to DTC?' It's a small study and a study based on certain genotypes. If you're currently on Vytorin, you don't have to stop taking it.

But even Mr. Pitts, a strong advocate for DTC, admits drug companies need an image boost. The industry should absolutely explain to the general population where drugs come from and how they're made," he said. “It's going to be hard. It's going to be a long-term proposition. But it's important for the viability of its image with consumers, not to mention the people on Capitol Hill."

That being said, it’s good news that, in yesterday’s edition of the New York Times (and elsewhere) there was a Vytorin ad that tried to put the current study into perspective.

Nice start – but more needs to be done. Vioxx was a missed opportunity to talk (soberly and sensibly) about safety (risk/benefit). Let’s not let Vytorin be a missed opportunity to talk about what clinical trials can tell us – and what they cannot.

This is an important teaching moment -- and can show the potency of DTC advertising and, more broadly, DTC² (direct to consumer communications) as a way to educate the public (yes -- politicians too) about the urgency of personalized medicine and 21st century clinical trial design.

Tough and complicated topics? You bet. But (as Tom Hanks said in A League of Their Own) "If it was easy, anyone could do it."  Read More & Comment...

Sunday Best

01/20/2008 10:12 AM |

Have a look at today’s New York Times editorial,“The Real Price of Fakes.”

Here’s a link:

http://www.nytimes.com/2008/01/20/opinion/20sun3.html?_r=1&ref=opinion&oref=slogin

And here’s the concluding paragraph:

“Some people in Congress want to tighten penalties on counterfeiters, a good but modest move. More to the point, the Consumer Product Safety Commission and the Food and Drug Administration need more money. And businesses that often avoid acknowledging the fake trade, for fear of damaging their brand, should be more open with consumers about how to tell the difference between real and unreal. Until then, buyer beware.”

A few points. First is that, absolutely, penalties must be significantly enhanced. Today the risks are too low and the rewards too high – and that will only lead to exponential growth in the counterfeiting of prescription medicines. According to the WHO, “The US based Centre for Medicine in the Public Interest predicts that counterfeit drug sales will reach US$ 75 billion globally in 2010, an increase of more than 90% from 2005.”

Willy Sutton, the depression-era criminal, when asked why he robbed, replied “because that’s where the money is.” If Willy Sutton were alive today, he’s be in the counterfeit drugs business – because that’s where the money is.

Second – and speaking of money – glad to see that the Times is calling on Congress to give the FDA more money to combat prescription medicine counterfeiting. And while they’re at it, the Times editorialists should also call out those members of Congress who want to actually tie FDA’s hands in dealing with this menace.

In 2006, the federal Joint Terrorism Task Force unsealed an indictment charging 19 persons with operating a global crime and terrorism ring spanning Lebanon, Canada, China, Brazil, Paraguay and the United States. The ring sold counterfeit drugs and other contraband materials, largely through direct consumer shipment from Canada, to Americans seeking cheaper drugs. It, in turn, directed its profits to support of the criminal terrorist group Hezbollah.
Less than four months later, as Hezbollah rockets rained down on Israel, the Senate voted for an amendment offered by David Vitter of Louisiana to ban U.S. Customs and Border Protection agents from seizing prescription drugs that Americans import from Canada. For Mr. Vitter, the passage was a defeat of sorts: He wanted to ban Customs agents from seizing medicines imported from anywhere, which suggests that the politicians who voted for the measure knew that dangerous people were trying to sell fake drugs in America.

Canada is already the favorite port of call for fake medicines. According to customs, most of these drugs are not shipped through wholesale distribution channels but are shipped directly to consumers, with Canada being the major transshipment point because of its access to the U.S. market.  Read More & Comment...

The Anti-Pharma Crowd Is Anti-Growth

01/18/2008 03:02 PM |

I have a lot of respect for John McCain but I wonder about what Leon Wieseltier of the New Republic praised and referred to as his "contempt for drug companies."

His contempt is getting in the way of clear thinking and good policy. And at time when we will need all the high paying, green jobs we can get, McCain's stance on pharmaceutical innovation -- where most of those jobs will be created worldwide -- is downright regressive and is at odds with his claim to be a pro growth Republican. If there has been a Republican, nay a member of Congress, with more pronounced and persistent antipathy to the pharmaceutical or biotech industry than John McCain, I can't think of one with the exception of New York’s two senator’s Charles Schumer or Hillary Clinton.

If he took the same position on the auto or housing industry he has on pharmaceuticals and biotech, he would shove the nation into an instant depression.

His contempt has been on display throughout the campaign, most notably in the New Hampshire debate when he call them "the bad guys". Why? From the straight talk express we never seem to get a straight answer. Seems to be related to his belief that drug companies inflate drug costs at government expense and artificial monopolies.

If drug costs reflects value, fine," "But if there are ways to bring greater competition to our drug markets by safe re-importation of drugs, by faster introduction of generic drugs, or by any other means we should do so. If I'm elected President, we will."

McCain has said: Problems with costs are created when market forces are replaced by government regulated prices.."

Yet he has aggressively pushed importation of drugs from foreign countries where "market forces are replaced by government regulated prices." And his legislation would force drug companies to sell as much of their price controlled product that is made to foreign spec -- not US spec -- as distributors would order and then would force the FDA to approve it instantly as safe and effective for the US market. Imagine forcing car, timber, building product, and steel companies to do the same! Meanwhile, Canada is the transhipment point for drugs from Iran, Pakistan, China, Venezuela..all our friends. The ultimate destination. America. McCain has no problem with letting Canada's lax importation policy stand as a surrogate for our drug and homeland security.

What are the “other means?” McCain voted for price controls and government run drug formularies for Medicare, especially when an HMO wanted to save money and pass it on to the government. This approach is used at the VA to restrict access to newer drugs and has actually shortened the lives of veterans. If imposed on Medicare and Medicaid it would mean seniors and the poor would be the last to the get what newer medicines are developed, if any are left.

Meanwhile according to a study by the Milken Institute, the biotechnology industry generated more than 2.7 million jobs and $172 billion in real output in 2003. The average income of each “green: job? $60000 plus benefits. But leave it to McCain to be the sponsor of a bill this coming session of Congress that would give overseas generic drug firms an incentive to sue new biotech firms for their patents before they expire in order to create “competition.”  Read More & Comment...

Don't Ask, Don't Tell? Or All the News that's Fit to Print?

01/18/2008 01:55 PM |

Yesterday we commented on the New York Times neglecting to mention -- in a story about clinical trial transparency and Prozac (along with other drugs) that Eli Lilly & Co. posts its clinical trials on a public website.

Well, sins of omission are seldom fun.

Here's Lilly's response:

INDIANAPOLIS, Jan 18, 2008

"Eli Lilly and Company strongly objects to implications in a New York Times article published Thursday that the company has suppressed results of negative clinical trials.

The story, based on a separate article in The New England Journal of Medicine (NEJM), cited Prozac and Lilly as high-profile examples of how the industry purportedly suppresses negative clinical trial data. Not only was the Times' story inaccurate when it comes to Prozac -- the NEJM article didn't identify a single Prozac study as unpublished -- but it also likely created a strong false impression with readers that Lilly suppresses data.

Lilly is an industry leader in being transparent with our clinical trial data. We are committed to publicly disclosing medical research results -- whether favorable or unfavorable to a Lilly medicine -- in an accurate, objective and balanced manner in order for our customers to make more informed decisions about our products.

In December 2004, Lilly was widely recognized as the first pharmaceutical company to voluntarily launch a clinical trials registry, where we post the results of all Lilly sponsored registration clinical trials for all of our marketed products dating back to 1994, and all clinical trials for marketed products since December 2004.

In addition, the two Cymbalta studies listed in an appendix to the NEJM article as "unpublished" have, in fact, been published in peer-reviewed journals. The results of HMAT-A and HMAQ-B were published twice -- first in the Autumn 2002 issue of Psychopharmacology Bulletin, and again in the Primary Care Companion Journal of Clinical Psychiatry in 2003. In addition, these studies were presented at one or more medical congresses that require peer review of abstract submissions and they also have been available to the general public on LillyTrials.com since 2004.

The authors of the NEJM article decided not to count studies as "published" if the manuscript included data from two or more studies. While this methodology might be suitable for an academic discussion, it's clearly not the appropriate standard for determining whether a company has been transparent in disclosing its data.

We clearly have been transparent. The data is publicly available online; we've presented it to health care professionals at major medical meetings; and we published it -- more than once -- in peer-reviewed medical journals. And we remain committed to transparency. All of which we would have told The New York Times ... if only they had called and asked."

Has the New York Times changed its motto from "All the news that's fit to print" to "Don't ask, don't tell?"  Read More & Comment...

Consumerism vs. Populism

01/18/2008 08:02 AM |

The “authorized generics” debate has made it to the other side of the pond. The Financial Times reports that the EU Commission is concerned that the price of medicines is rising -- while innovation declines—and will investigate whether the pharmaceutical industry abuses patent rights to delay the introduction of low-cost generic alternatives.

The Financial Times writes, “The answer may be that collusion between companies keeps prices high. But the pricing of medicines in much of Europe is more government-controlled than in the US. Companies may profit from national pricing. In the UK, where there is a freer approach, competition is more intense and discounting heavy. Not enough deregulation may be the bigger problem.”

Here is the complete Financial Times editorial:

http://www.ft.com/cms/s/0/75dbce42-c52c-11dc-811a-0000779fd2ac.html?nclick_check=1

For more discussion of the authorized generics issue, along with an economic analysis of the same, please see:

http://drugwonks.com/2007/05/rockys_racoon.html

The conclusion of the Financial Times editorial is spot on – and something we should take to heart on our side of the Atlantic as well – that we must be careful that “a consumer-first approach does not become a populist one.”

And -- when you consider some of the health care rhetoric being bandied about by the Presidential candidates -- that’s a notion worthy of serious consideration.  Read More & Comment...

The Ultimate "Halo" Effect

01/18/2008 07:37 AM |

A US study by the Banner Good Samaritan Medical Center in Phoenix, Arizona has found surgical residents performed better during simulated surgery after playing on the Wii for an hour beforehand.

"The whole point about surgery is to execute small, finely controlled movements with your hands, and that is exactly what you get playing Wii," Kanav Kahol, who conducted the study with colleague Marshall Smith, told New Scientist magazine.

Professor John Quin, executive director of surgical affairs at the Royal Australasian College of Surgeons, said the study was interesting and showed promise, but it was still not clear whether better performance in simulated surgery translated into better performance in surgery on a live patient.

"What it shows at the moment is only that if you repeatedly play video games you get better at playing video games," he said, adding the RACS was conducting a Federal Government-aided study to determine the effectiveness of simulated surgery.

Professor Quin said he hoped high-tech tools like the Wii and simulated surgery proved useful because "it's getting more and more difficult to train the full experience of the surgical operation".

The study found only those games requiring precise movements, like Marble Mania in which a player guides a marble through a 3D obstacle course using the Wii's motion-sensitive remote, are effective.

"You don't gain a lot from swinging an imaginary tennis racket," Kahol said.

Past research by other academics has similarly found video games requiring fine control can help build the skills surgeons need for operations like keyhole surgery.

Kahol and Smith are now reportedly designing Wii software to accurately simulate surgical procedures. For developing countries unable to provide expensive professional training systems, the Wii could be used as a cheap and effective training tool.

In conducting their study, the pair called on eight trainee doctors to play the Wii for an hour before performing virtual surgery using a tool called ProMIS. The training tool provides a 3D simulation of a patient's body and tracks the surgeon's movements while they are "operating".

Movement data was then processed using an algorithm and the surgeons were given scores. Those who played the Wii scored 48 per cent higher on tool control and performance than those who didn't.  Read More & Comment...

The $300 medical prognostication

01/17/2008 12:53 PM |

A combination of common and minor variations in five regions of DNA can help predict a man’s risk of getting prostate cancer, researchers reported Wednesday.

According to today's New York Times:

"A company formed by researchers at Wake Forest University School of Medicine is expected to make the test available in a few months, said Karen Richardson, a Wake Forest spokeswoman. It should cost less than $300.

This is, some medical experts say, a first taste of what is expected to be a revolution in medical prognostication. The results, they agree, are clear. But the question is what happens next."

Here’s a link to the complete story:

http://www.nytimes.com/2008/01/17/health/17cancer.html?scp=1&sq=medical+test  Read More & Comment...

Truth Under Attack At USA Today

01/17/2008 12:26 PM |

Predictably USA Today pushes the panic button on Vytorin

http://www.usatoday.com/news/health/2008-01-16-cholesterol-main_N.htm

But many doctors express frustration. They say they're increasingly asked to prescribe drugs like Vytorin, Zetia and Crestor though the drugs have never have been successfully tested in long-term trials. In the world of billion-dollar medicines, these have a nickname — "me-too" drugs, because they're purportedly like other drugs that have been more extensively tested.

Cholesterol-lowering drugs aren't the only culprits. A number of blood-pressure-lowering ACE-inhibitor drugs are riding on the coattails of the blockbuster Captopril. Zetia and Vytorin are me-too drugs that stretch the limits of the category. Although they were approved on the same basis as statins — for their power to lower bad cholesterol — they aren't statins. They work by an entirely new mechanism that Merck and Schering-Plough promote heavily to doctors and on television, though it's not as well-tested as the statin approach.

Doctors who prescribe them, and patients who use them, take it on faith that the drugs will protect them from heart attacks and prolong their lives, says Yale University cardiologist Harlan Krumholz.

"This is huge," he says. "It's a story of whether or not the profession is going to turn and say, 'We're not going to say me-too drugs are the same unless they prove it.' "


Meanwhile none of the articles picked up on the real reason why most drugs don't work for most people: genetic variations. Nor did they link this story to another important scientific one about cholesterol reported last week.

7 New Cholesterol Genes Found
Genes May Make Good Targets for New Cholesterol Drugs, Experts Say
By Miranda Hitti
WebMD Medical News
Reviewed by Louise Chang, MD

Jan. 14, 2008 -- Scientists have discovered seven genes that affect levels of HDL ("good") cholesterol, LDL ("bad") cholesterol, and triglycerides (another type of blood fat).

Several of those genes "are potentially attractive drug targets" to lower heart disease risk, write the University of Michigan's Cristen Willer, PhD, and colleagues.

Two of the newly identified genes only affect HDL cholesterol, one only affects LDL cholesterol, three only affect triglycerides, and one affects LDL cholesterol and triglycerides.....


....Willer and colleagues also noticed that genes for high LDL cholesterol levels were associated with greater risk of coronary artery disease, which makes heart attacks more likely.

"Nearly all of the gene regions that we found to be involved in higher LDL levels were also involved in coronary artery disease risk," Willer states in a news release. "This is a remarkable result and suggests that new drug therapies that target the genes in these regions will also help prevent coronary artery disease and allow people to live longer and healthier lives."

One day, it may be possible to tailor cholesterol and triglyceride treatments to a patient's gene profile, the researchers note.

Meanwhile, your doctor can check your cholesterol and triglyceride levels and give you advice about how to improve those levels through diet, exercise, and medication, if needed."

Not one article or news account discussed this important factor. It's easier just to make people panic and pick up on the old "me-too" drug issue.
http://www.webmd.com/heart/news/20080114/7-new-cholesterol-genes-found  Read More & Comment...

Google blocked at the NY Times?

01/17/2008 09:37 AM |

912 word story in today's edition of the New York Times under the headline, "Antidepressant Studies Unpublished."

Here's the first paragraph:

"The makers of antidepressants like Prozac and Paxil never published the results of about a third of the drug trials that they conducted to win government approval, misleading doctors and consumers about the drugs’ true effectiveness, a new analysis has found."

And later on:

"The finding is likely to inflame a continuing debate about how drug trial data is reported."

Here's the full story:

http://www.nytimes.com/2008/01/17/health/17depress.html?_r=1&oref=slogin

912 words and not a single one speaking to the fact that Lilly (per Prozac) was the first Pharma company to put all of its clinical trials on a public website.

Is Google blocked at the Grey Lady?  Read More & Comment...

Sanctimony About Vytorin's "Secret" Panel

01/17/2008 09:12 AM |

The increasingly insufferable Roy Poses pontificates again and again and again about how everyone who is a consultant to drug companies cannot be trusted. To point out how zealotry should not be confused with objectivity let us go through the following exercise using the deflation of the self-impressed Dr. Poses as an example, with pharmalot.com giving him the platform: " pretending a panel is independent, when potential or perceived conflicts may exist, is misleading. This only casts more doubt on the willingness of these two drugmakers to let the facts speak for themselves - and not spin or cloak info that should be fully vetted."

So by definition, any financial tie is a conflict or perceived conflict which transmutes into faulty or inaccurate data which cannot be trusted which in turn transforms into a drug that should not be taken. Which is why people should stop taking SSRIs, Avandia, Vytorin,

Now I guess that should also apply to Zocor, the forerunner of simvastatin, the generic version of Zocor, especially if we have a negative risk to benefit result of that drug right? This in keeping with the other Poses or Pharmalot principle that disclosure of all negative trial result are to the public good.

So here is a negative trial reported in JAMA in 2004 on Zocor

he myopathy rate of the 80-mg/d dose of simvastatin observed in the A to Z trial and the previously reported meta-analysis are not particularly surprising. For many years following its introduction, the maximum dose of simvastatin approved by the Food and Drug Administration (FDA) was 40 mg/d. However, in 1997 the manufacturer undertook a development program to study 2 higher doses of simvastatin (80 mg/d and 160 mg/d).8, 19-20 Although a favorable report appeared in the medical literature,20 development of the 160-mg/d dose was abandoned due to high muscle toxicity.8, 19 Although never reported in the scientific literature, the financial community was informed that the rate of muscle-related symptoms was 5.7% for the 160 mg/d dose.19 The dose of 80 mg/d of simvastatin was eventually approved, but in 2002, the FDA product label was modified to include warnings about concomitant medications than inhibit cytochrome P450 3A4, the major metabolic pathway for simvastatin elimination.21 This warning was provoked by cases of rhabdomyolysis when simvastatin was administered with 3A4 inhibitors.21"
It is important to reassure practicing physicians and patients that the unfavorable risk-benefit relationship observed in the A to Z trial does not in any way diminish the value of intensive statin treatment in secondary prevention, including ACS patients. There was a trend toward reduced events in the A to Z trial, a finding that supports the lower is better concept. The increased myopathy rate applies only to a specific dose of a single agent and should not tarnish this remarkable class of drugs.24 It must also be emphasized that simvastatin in doses of up to 40 mg/d has shown excellent safety and efficacy in a series of clinical trials. For now, though, the 80-mg/d dose of simvastatin should be used with caution, particularly because other effective agents are available. Finally, in an era when criticism of selective reporting of positive trial results is common,25 the A to Z investigators are to be commended for their prompt and thorough reporting of a critically important major trial that did not meet its original objectives."

Ok, so we know that high dose simvastatin, the same dose compared in the ENHANCE trial carries risks. But we are reassured that other agents are available and that the 80mg can be used with caution.

Now, the person who wrote that editorial on the A to Z study was a paid consultant to Merck.

Steve Nissen. Who was a consultant to Merck, Astra Zeneca, Pfizer, Sankyo, Sanofi, Eli Lilly, Takeda, Novo Nordisk, Atherogenics, Lipid Sciences, GlaxoSmithKline, Hoffman LaRoche, Kos, and Wyeth. Dr Nissen also has directed clinical trials in collaboration with Astra Zeneca, Pfizer, Sankyo, Eli Lilly, Takeda, Atherogenics, and Lipid Sciences.


The same person now trashing Vytorin.

Sorry to beat the same drug over and over again but the bloggers and MSM keep referring to the same sources as well. Their views are biased and dangerous. I trust the doctors and researchers drug companies pay as advisors ten times more than then the second guessers who would discourage patients from taking drugs because of a built in bias against perceived financial conflicts without even looking at street creds or expertise. That is prejudice, plain and simple. And at a fundamental level it suggests that anyone who consults for drug companies is a prostitute and endangers the public health.

That's not independence or objectivity. That's intellectual thuggery.

http://www.pharmalot.com/2008/01/that-secret-vytorin-panel-truly-independent/



http://forum.lowcarber.org/archive/index.php/t-206955.html









He claims the Vytorin results are doctored  Read More & Comment...

Well If Antidepressants Don't Work There's Always Scientology

01/16/2008 10:10 PM |

Here's Tom Cruise on Scientology's superiority...if this video doesn't make you believe in SSRIs -- or at least Jaegermeister -- nothing will.

http://gawker.com/5002269/the-cruise-indoctrination-video-scientology-tried-to-suppress  Read More & Comment...

Why Trials Are Often Negative

01/16/2008 09:14 PM |

From an editorial in the American Journal of Psychiatry.

Editorial
Demonstrating Drug Action
Carol A. Tamminga, M.D.


The questions that have arisen in the public and scientific literature lately about the use of SSRIs in children and adolescents are addressed for one of the currently available SSRIs by Wagner et al. The issue of whether it is effective to use SSRIs in childhood and adolescent depression has been repeatedly raised over the last years in the context of our field failing to produce clear efficacy answers in children. Depressed children are being treated with SSRIs in greater and greater numbers, without demonstrated efficacy in the age group. The difficulty of demonstrating efficacy with tricyclic antidepressants in children has fueled suspicions that there may exist an age-dependent resistance to treatment. The importance of this well-designed large study for therapeutic strategies in children and adolescents cannot be overstated. It is important that the methodology of this study is solid and the numbers adequate to test the efficacy question asked. The result that citalopram reduced depression more than placebo in this child and adolescent population provides a clear answer for physicians that will (in combination with results from additional studies) guide treatment decisions. It is especially gratifying to see an early onset of action at 1 week of treatment, suggesting an advantage that can be followed up in future studies. This study also set a high methodologic standard for psychiatric diagnosis in pediatric studies. It would be an understatement to say that more such studies are needed.

One would always wish for more in terms of information from drug trials in psychiatric diseases. A common physician complaint about these trials is that they fail to sufficiently inform clinical practice because of restricted entry criteria, fixed-dose design, and limited duration of treatment. It is true that initial registration trials have a goal of demonstrating superiority over placebo to become approved for the market. But this does not rule out additional Phase 4 studies done in large enough patient cohorts to fully inform pressing clinical issues. How do comorbid conditions alter drug response? What treatments are effective in medication nonresponders? What kinds of actions can be expected with long-term treatment? It will be important for industry to address these kinds of Phase 4 questions for clinical use as well as the registration trials.

One particular issue in our field makes informative clinical trials particularly difficult. This is that we do not know what exactly we are treating in terms of its biology. Psychiatric diagnoses are not based on molecular pathology (rather, phenomenology), and new drugs are not directed toward known, disease-related molecules (rather, toward hypotheses). Therefore, we may not be recruiting the correct patient populations for a particular treatment nor have a drug directed toward the disease pathophysiology. Moreover, we may not be measuring anywhere near the optimal outcome measures in our trials (e.g., consider the constraint of only measuring "fatigue" in the treatment of anemia, and not having a RBC count). Nonetheless, even though we do not yet have our molecular targets, we cannot give up on drug development. Indeed, we already have treatments for our diseases, and these may be better treatments than we deserve, based on the state of our knowledge. We need now to hone the treatments that we have and develop the valuable clinical trial methodologies to carry us into the future. Meanwhile, we need to translate the rich basic knowledge accumulating in neuroscience into advances for therapeutics.

http://ajp.psychiatryonline.org/cgi/content/full/161/6/943?etoc  Read More & Comment...

Negative Reporting About Iraqi Vets

01/16/2008 08:45 PM |

Can the NY Times be anymore hypocritical pontificating about drug companies cooking the books on clinical trials when it has transparently done so with respect in it's efforts to depict our soldiers as homicidal maniacs?

And this is not the first time that a so-called objective source has fudged numbers in favor of an agenda. A Soros-funded researcher was behind the oft-stated, inaccurate, but never retracted number of 450,000 deaths due to the Iraq war that ran in Lancet. Read this article from the National Journal about this debacle. In the report the authors also note a study that ran in Lancet by a guy who fakes a story on the heels of the Vioxx scare about the risks of other anti-inflammatory meds. The media bought it hook line and sinker because it wasn't pharma funded. I am sure Health Care ReSewer commented favorably.

Of course the research was not paid for by Pharma so there is no bias.

More on so-called objective no-ax to grind types who criticize us that receive Soros and tort lawyer funding later.  Read More & Comment...

Excuse Me For Being So Negative...

01/16/2008 07:13 PM |

The NEJM of medicine recycles the old story that many of negative studies about antidepressants were not published. That doesn't affect whether the drugs work or not. It does add to the distortion of what a negative study is and why they are negative. Most of the time they are negative because they simply confirm the hypothesis. Other times they are poorly designed or small studies of little statistical power. They don't prove that the drugs fail. There is a difference. Taken together they can often help guide who responds to what medicines or why not...which again is why we need the Critical Path.

To suggest that the failure to publish negative studies is part of a coverup is wrong and leads to fearmongering once again. We have been down this road. And journalists are once again raising unfounded fears about the safety and efficacy of drugs...leading people to die because they stop taking medicines because of the fearmongering the media has engaged in regarding vaccines, SSRIs, Avandia, Vioxx and Vytorin. As for the public relations benefit of publishing negative studies...there is none. Just the opposite. I am afraid the willingness to confuse negative studies with "doesn't work" will lead to further congressional and media assaults on the scientific process. We will all be sicker and more imperiled for it.


To wit:



Lawmakers Have Vytorin Questions
By ANNA WILDE MATHEWS
January 16, 2008 5:08 p.m.


Congress is investigating advertising for the cholesterol-busting drug Vytorin in the wake of a study that suggested the pill may have no advantage over a generic cholesterol-lowering medicine.

In letters dated today and addressed to Schering-Plough Corp. and Merck & Co., which jointly sell Vytorin, and to the U.S. Food and Drug Administration, Reps. John Dingell and Bart Stupak, Michigan Democrats, raised questions about the ads for the medicine. The news was first reported in The Wall Street Journal' Health Blog.


In the letter to the companies, the congressmen wrote that the House of Representatives' Committee on Energy and Commerce and its Subcommittee on Oversight and Investigations are probing the "withholding of clinical trial data that may significantly affect the medical management of hypercholesterolemia, as well as the use of misleading statement in direct-to-consumer advertisements for prescription medicines."

Vytorin is in the news this week after the results of a long-awaited study, called Enhance, indicating that the drug may be no better than a generic statin at slowing the progression of heart disease.

http://online.wsj.com/article/SB120051737443695313.html?mod=googlenews_wsj


Or this...courtesy of Time magazine via fearmonger Steve Nissen:

Tuesday, Jan. 15, 2008
Is Vytorin a Failure?
By Alice Park

After nearly two years of waiting, the results came out on Monday on the long-awaited heart drug Vytorin — and the news wasn't good. Vytorin's manufacturers, Merck and Schering-Plough, announced that while the drug reduced levels of LDL, or bad cholesterol, in a group of 750 patients, the medication, which has been on the market since 2004, had little effect on the buildup of plaque in the arteries, a harbinger of heart attack and stroke.

To many experts, the results were both a surprise and a warning. "The fact that the trial showed a huge LDL" — or bad cholesterol — "reduction, and that things were still going the wrong way [as far as plaque buildup went] is stunning," says Dr. Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic and an outspoken critic of the delay in the release of the study results. "This study shows that it matters how you lower cholesterol, not just how much you lower cholesterol."

Right. It pays to release negative studies. At least the researchers put their name on the study. The same thing can't be said about Nissen.

http://www.time.com/time/health/article/0,8599,1703827,00.html  Read More & Comment...

Beware of All Innovations, Especially New Ones

01/16/2008 02:35 PM |

A non-addictive drug for chronic pain? A breakthrough that sounds too good to be true. And to make matters worse, it's an "just" an "incremental improvement on an existing medication." And horrors of horrors, the brains behind this Clifford Woolf -- one of the world's experts on the molecular pathways of pain -- has been (sorry to say) a consultant to several drug companies.

So obviously nothing he develops can be trusted. Particularly if it relies on techniques developed through partnerships created to promote the Critical Path via the Reagan Udall Foundation.

A poisoned source will only produce poison. Especially if the funding is from Big Pharma at any point in time it's forever tainted and untrustworthy. Everything else said and done and funded from all other sources can be relied on without a doubt.

So the rule of thumb(s) should be. Let us call them the Poses Postulates in honor of Roy Poses MD of the Health Care Renewal bog who believes that anyone who receives any funding from Pharma cannot be trusted.

Don't trust Pharma research or the researchers they pay.

Don't trust the drugs they produce or market since the FDA is nothing but a tool or client of Pharma.

Don't use any drugs, especially those developed since PDUFA was enacted since that institutionalized the incest.

So if and when these new pain drugs come out...those who abide by this ideological approach to prescribing should avoid these treatments out of precaution and principle.
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Right Dr. Poses?  Read More & Comment...

Gray Lady or Grey Matter?

01/16/2008 01:05 PM |

Who do you trust? The New York Times editorial page or the consensus statement of the American College of Cardiology which said with regard to Vytorin:

"The study involved 720 patients with heterozygous familial hypercholesterolemia and showed no significant difference in the primary endpoint between patients treated with ezetimibe and simvastatin versus patients treated with simvastatin alone over a two-year period. The study was designed to prove that Vytorin could slow the growth of plaque in carotid arteries supplying the brain more than simvastatin alone. Media reports indicate that the results of the trial show no benefit from the combination of ezetimibe (Zetia) and simvastatin (sold together as Vytorin) over simvastatin alone.

The American College of Cardiology recommends that major clinical decisions not be made on the basis of the ENHANCE study alone."

According to the American College of Cardiology (ACC), this study deserves serious thought and follow-up. The overall incidence rates of cardiac events were nearly identical between both treatment groups, and both medicines were generally well tolerated. There should no be reason for patients to panic. The difference in IMT changes between the simvastatin group and the Vytorin group was 0.006 mm vs. 0.011 mm.

Health care professionals should speak to their concerned patients using this drug. The ACC is also releasing a public statement explaining that this is not an urgent situation and patients should never stop taking any prescribed medications without first discussing the issue with their health care professional. Further research will be needed in this area to provide conclusive evidence about which lipid lowering strategy is preferred (statin alone vs. statin plus ezetimibe).

Furthermore, the ACC notes that this trial is an imaging study and not a clinical-outcome study. Conclusions should not be made until the three large clinical-outcome trials are presented within the next two to three years. The ACC recommends that Zetia remain a reasonable option for patients who are currently on a high dose statin but have not reached their goal. The ACC also notes that Zetia is a reasonable option for patients who cannot tolerate statins or can only tolerate a low dose statin.

On the subject of endpoints and markers. The Critical Path is not about using surrogate endpoints. Anyone who has listened to Dr. Woodcock more than once knows it is about finding and qualifying biomarkers -- molecular and imaging -- that predict disease progression and outcome as well as response to treatment -- as well as developing novel statistical ways that can be deployed across divisions and technologies to advance understanding of technology impact on disease.

The issue in the ENHANCE study was whether or not imaging studies were accurate measures of disease progression in this small population. Nothing more or less. In this regard, development of better standards and predictive imaging studies will help advance their use in clinical trials. Also let's remember that Dr. Nissen, who has trashed the results might be a bit biased since his own imaging studies demonstrated a regression of atherosclerosis by reducing LDL levels with another drug, something the NY Times failed to point out. And let's remember Dr. Nissen also tossed out imaging studies in another clinical trial looking at plaque regression because they were unreadable, so he just looked at the results of the readable ones.

At the risk of repeating myself again and again -- here's a link to the story we repeated when the MSM was looking for a Vytorin coverup months ago.

http://www.thestreet.com/pf/comment/adamfeuerstein/10195643.html

The problem with the Atherogenic drug that Nissen worked on was the same one -- more or less -- the scientists running the ENHANCE study struggled with. Namely, the statistical correlation was hard to measure because of the unwieldy nature of the biomarker. In each study, patients taking the drug did better than patients taking a placebo on most endpoints, just not on the endpoint most difficult to measure. But unlike the Nissen re-analysis, ENHANCE did not do an interim analysis with fewer patients to produce a benefit. The debate was whether or not to chuck the analysis altogether because of questions about the reliability of the biomarker.

Which is what the Critical Path is all about.

No need to panic or disregard your doctor in favor of the medical advice dispensed by the fearmongers and Pharm-haters on the NY Times editorial page.  Read More & Comment...

Sperm Daddy Author Lectures Artificial Heart Inventor on Ethics

01/16/2008 11:58 AM |

As Mark Twain -- an author of choice here at drugwonks -- once said: "Presume you were an idiot. Then presume you were a member of Congress. But I repeat myself."

Can any be so stupid and petty as to quibble about having the inventor of the artificial heart promoting as important a drug as Lipitor?

Apparently Bart Stupak and John Dingell think it rises to a high enough crime to demand a congressional investigation. And Katie Watson of the Medical Humanities and Bioethics Program at Northwestern University agrees: "To have a celebrity physician associated with cardiac health telling me I need Lipitor and when it costs significantly more than a generic alternative that might be appropriate for me— that's a physician motivated by a paycheck, not by patient health."

Let it be noted that Ms. Watson is famous for her lecture "Playing Doctor: Improvisational Theater & the Medical Encounter" which was presented at the Searle Seminar Room in the Medical Humanites and Bioethics building. That's Searle, as in the drug company, better known as Pharmacia which is now part of...you guessed it...Pfizer.

But I digress. So apparently it is unethical to have a famous doctor who does not practice medicine promoting a brand drug that works. It is ethical to have someone playing doctor promote a generic drug that doesn't? Or how about a Nobel Prize Winner who is no longer licensed promoting a new drug? And how does Ms. Watson know if the Nobel Prize winner is motivated by a paycheck and not patient health? Is it wrong to accept a paycheck in the process of advancing patient care by being a spokesperson.

Back to Ms. Watson. " Katie is also the author of the screenplay Sperm Daddy, and a contributor to the TimeOut Chicago humor back page and the WBEZ news magazine 848." I wonder if she is motivated by a paycheck or patient health?

http://www.sirensimprov.com/katie.html  Read More & Comment...

Scorin' Vytorin

01/16/2008 11:10 AM |

Have a look at today’s New York Times house editorial, “Cholesterol Drug Bombs.”

http://www.nytimes.com/2008/01/16/opinion/16wed2.html?_r=1&ref=opinion&oref=slogin

There are a number of issues going on here, but pay particular attention to these two paragraphs:

“There are reasons to be cautious about interpreting these results. The number of patients was relatively small. And many of them may have used different drug treatments for years before entering the trial, possibly diminishing the effectiveness of adding Zetia …

The findings also raise doubts about the current belief that lowering cholesterol is the key to cardiovascular health. The study showed that Vytorin reduced bad cholesterol significantly more than Zocor alone. The problem was that it failed to reduce the formation of plaque.”

Here’s what well-respected cardiologist (and CMPI board chairman) Dr. Michael Weber has to say:

“The study with Vytorin looked only at surrogate endpoints, not morbidity and mortality. The ongoing clinical outcomes trials will answer the questions definitively. We must hope that the alarmist comments by certain opinion leaders quoted in the lay press will not compromise the integrity of these critical studies by intimidating the patients who have been enrolled. We should not forget that many people simply cannot use statins in full doses due to side effects, so properly studying Zetia and Vytorin is absolutely vital.”

As to whether or not clinical data was withheld (or as the Times writes, “cynically" sat on) is another issue altogether and cannot be allowed to muddy the far more important clinical questions.  Read More & Comment...

Rosa DeLauro's Udder Frustration

01/16/2008 07:04 AM |

Representative Rosa DeLauro has introduced the Cloned Food Labeling Act, which would require the FDA and the Department of Agriculture (USDA) to mandate that all food derived from cloned animals be labeled.

She’s not happy with the FDA’s stance on the safety of food:

“The studies on which the FDA is basing its assessment include very little information on the specific question of whether food from cloned animals is safe."

But, according to the FDA, the agency has "studies that show that the meat and milk from cattle clones and their offspring are as safe as that from conventionally bred animals."

The agency has been studying this issue in great detail for a very long period of time. In fact, many of the world's leading experts on this issue work at the FDA's Center for Veterinary Medicine. During my tenure at the FDA (which ended in 2004), this issue was already being deeply investigated and intensely debated.

Representative DeLauro, rather than shooting from the hip, should call the FDA and ask for a briefing.  Read More & Comment...

Gates Foundation to Invest in Orphan Drug for Global Illness: Yamada Affiliation Questioned

01/15/2008 02:51 PM |

How can we trust that the drugs will be safe or effective? Since Gates Foundation President Yamada is under investigation by Senator Grassley and Cong. DeLauro for his role in talking to Dr. John Buse about Avandia nearly a decade ago, obviously any money he doles out while at Gates must be considered tainted and therefore the results of any studies cannot be trusted. And if the orphan drug for sleeping sickness uses Critical Path steps developed by the Reagan Udall Foundation how do we know they actually are not steps that weaken standards of safety and efficacy to simply line the pockets of the company that the Gates Foundation gave the grant to? We all know that's what the Critical Path is all about: watering down standards so that foundations can give grants to companies who in turn can develop at cost an orphan drug that is neither safe or effective because it uses biomarkers.

http://www.nytimes.com/2008/01/08/health/research/08slee.html?_r=1&ref=health&oref=slogin  Read More & Comment...