More from RiskComm II

05/27/2008 05:26 PM |

Only two people offered public comment.  One was a woman talking about advertising for atypical antipsychotics.  The other was me. The buzz among the press corps was "where's pharma?" 

Committee chair Baruch Fischoff seemed somewhat perplexed at the general lack of industry comment (although he did specifically mention the importance of the docket).  He then said a rather disturbing thing -- that industry should attend the meetings of the committee so they could "learn something that can help them make a buck."

I hope that someone at the FDA's Office of Advisory Committee Oversight reminds Dr. Fischoff of his role and the importance of choosing his words more carefully in the future.


  Read More & Comment...

Bridges To Patients

05/27/2008 05:22 PM |

Very pleased to announce the launch of "The Patient," the new benchmark journal for peer-reviewed authoritative and practical articles on the application of pharmacoeconomics and quality-of-life assessment to optimum drug therapy and health outcomes.

According to the publisher (Wolters Kluwer Health), The Patient is "an invaluable source of applied pharmacoeconomic original research and educational material for the healthcare decision maker. The journal is dedicated to the clear communication of complex pharmacoeconomic issues related to patient care and drug utilization."

Here's a link to the magazine's website

John Bridges (Johns Hopkins School of Public Health and Senior Fellow, Center for Medicine in the Public Interest) is the journal's lead editor.

(And, in the interest of full disclosure, I am on the editorial board.)

Here is a link to the magazine's website: http://thepatient.adisonline.com

We welcome this important new voice to the debate.

  Read More & Comment...

HMO Profits Fall..A New Business Model in Order?

05/27/2008 05:12 PM |

Raising premiums and squeezing providers...that will just put HMOs on the political hot seat again.   Ultimately the health care decisions and dollars will have to flow doctors and patients and the real solution will be found in technologies based on underlying mechanisms of disease..

washingtontimes.com/apps/pbcs.dll/article  Read More & Comment...

The devil is in the details – not the detailers

05/16/2008 09:00 PM |

A few members of the New York State Assembly, led by Assemblyman Gottfried, the Chairman of the Assembly’s Health Committee, have introduced a bill that would require pharmaceutical detailers to obtain state licenses and abide by some peculiar rules.

For example: The bill would "establish a code of ethics for the practice of pharmaceutical detailing and collect information from registered pharmaceutical detailers relating to their communication with health care professionals, health care providers, or employees, agents or representatives of health care professionals or health care providers located in the state.”

What about the existing, rather stringent, government and industry regulations? Is the state going to legislate a floor or a ceiling? And as far as “collecting information,” that’s a pretty strong dose of Big Brother if you ask me and begs the question, “Whose next?”

The bill states that, “A pharmaceutical detailer shall not: engage in any deceptive or misleading marketing of a pharmaceutical product … For purposes of this section, it shall be considered an act of deceptive or misleading marketing to provide information regarding a use of a pharmaceutical product not approved by the federal food and drug administration.”

Even though the actual verbiage makes it sound as if pharmaceutical detailers shouldn’t be promoting investigational drugs (no argument there), I’m sure what Mr. Gottfried meant to address is off-label promotion. Perhaps he should have a chat with the folks at the FDA to, um, seek “guidance” on the matter. Or at least he should consult with an attorney familiar with the various and un-subtle legal precedents. (And what about the fact the FDA already regulates all educational efforts between physicians and sales reps? Inconvenient truths.)

Moving from the uninformed to the subjective, the bill states that all pharmaceutical detailers must, “be of good moral character and suitability.” According to whose standards? Elliot Spitzer?Quis custodiet ipsos custodes?

In the “Justification” section, the rational for this legislation states that, “Pharmaceutical companies are increasingly using detailers to go into doctors offices and market their prescription medicines.” But the fact is, for accuracy’s sake, that pharmaceutical detail forces are on the decline. Oops.

But what are facts when you have a research study done by that unbiased arbiter of truth and justice – Public Citizen. In discussing the need for a state-mandated code of ethics, the “Justification” continues, “A 2005 study conducted by Public Citizen and published in The Journal of Public Health Policy found that more than half of the drug makers participating in the 2002 America Psychiatric Association convention violated either the Association's own drug marketing guidelines or FDA rules.”

Further, “Congressman Henry Waxman of the House Committee on Government Reform found that "there has been a marked decline in enforcement actions taken against drug manufacturers by the FDA for illegally promoting their products since December 2001.” Perhaps a conversation with the FDA might enlighten Mr. Gottfried and his co-sponsors to the reality of the situation. (And a primer on federal preemption would also probably be useful.)
If this whole thing sounds familiar – that’s because it is. Remember the District of Columbia “Safe Rx Act of 2007? The devil is in the details – not the detailers.  Read More & Comment...

The Nature of Journal Articles

05/12/2008 05:15 PM |

Very thoughtful and appropriately provocative editorial in the May issue of Nature, "Nothing to see here."  Here's how it begins:

"The Journal of the American Medical Association (JAMA) played a considerable part in manufacturing media outrage last month over an article revealing Merck's use of ghostwriters and rubber stamp experts in the preparation of clinical research articles on Vioxx (rofecoxib).  Although the JAMA article (299, 1800-1812, 2008) revealed nothing new about the ghostwriting practice and so-called guest authorship, the JAMA editors nevertheless felt moved to introduce a new, stricter set of policies on authorship and conflicts of interest."

Here's the complete editorial from Nature:

Click Here to Download

And here's how the editors of Nature conclude their essay:

"But the editors of JAMA and other journals would do well to focus on content, not process.  JAMA's attack casts a cloud over the entire industry.  Stigmatizing any paper that comes from the private sector on the basis of an analysis of one company's poor publishing practices over five years ago is not only unjustified, it is discrimination pure and simple."  Read More & Comment...

Transparency Is Apparently A One Way Street

05/12/2008 10:45 AM |

First, more on the context behind the Brownlee-Lenzer attack on Peter Pitts and Fred Goodwin.  I have written about how the two failed to reveal their bias against SSRIs in their previous selective reporting.  This is relevant since the point of the article Peter and I wrote in the Washington Times "Tabloid Medicine" was precisely about such one-sided coverage about how SSRIs "caused" or were "linked" to suicides.  Turns out that they are, but not in the way people like Brownlee and Lenzer had reported: the decline in SSRI prescribing that fear mongering contributed is associated with an increase in suicides. 

Now comes word from the exec producer of the Infinite Mind that Lenzer pitched a segment about so-called hidden corporate ties in reporting, which was rejected, before running the Slate piece. 

"....In the interest of full disclosure, I also should note for the record that Lenzer, who co-authored the Slate article, called me a few days after the "Prozac Nation: Revisited" program aired to pitch a program that she wanted us to do for The Infinite Mind, called "Journalists on Prozac," which would feature her and her writing partner Shannon Brownlee. Checking into Lenzer's credentials, I found a troubling article in The New York Times taking her to task for a British Medical Journal article that suggested that Eli Lilly and Company, which makes Prozac, had concealed documents about the link between anti-depressants, suicide and violence. The BMJ subsequently retracted the article, with full apologies, and the whole matter was widely covered in the news media.

After we told Jeanne Lenzer that we would not be proceeding with a program featuring her, she and Brownlee wrote the article for Slate."   fray.slate.com/discuss/forums/thread/1237086.aspx

(Lichtenstein also notes that he did not ask Peter about his working for Manning, Selvage and Lee.  Which is true.  But then again, Peter had mentioned it to the producer for the segment in the context of noting that nothing he does for MSL involves CMPI and vice versa.)

One thing Brownlee and Lenzer failed to mention:  all the SSRIs made by the drug companies mentioned in their article have been generic for years. If all drug companies care about is marketing their meds, why would they promote a segment on products they no longer make? 

On another front, and speaking of fronts, the Prescription Project has  released “Toolkits to Guide Hospitals and Medical Schools with Conflicts of Interest”

The guides follow the same flow as the recommendations coming out of the AAMC taskforce. . 

From the titles of the tool kit modules along with the recommendations in the tool kit it appears that they had significant time to digest the AAMC recommendations and take them several steps further to advance their cause (this to be expected).   www.policymed.com/2008/04/aamc-and-prescr.html

The Prescription Project receives funding from trial lawyers and works with Institute for Medicine as Profession, largely funded by George Soros.  IMAP has a project that seeks ultimately to wrest drug development out of the hands of private companies and put it into the hands of government.  

You can see where this is heading ultimately.  Small bites at private sector innovation until nothing is left. 

Lots of people with anti-pharmaceutical innovation bias demand transparency but then hide their own biases, affiliations and funding.  And those that seek to connect the dots and spread their insinuations are equally biased and one-sided.  I think ideas matter and raising the funding link is just a way to divert attention from the debate over substance. 

  Read More & Comment...

Health Care Realities -- What a Concept

05/12/2008 08:34 AM |

Here are some excerpts from Bob Goldberg's excellent piece in today's edition of The Washington Times, "Health Care Realities" ...

Ah, the rites of spring! Baseball, cherry blossoms and the annual report of the Medicare trustees, who duly report that Medicare is going broke. Yet each year we have the routine response of politicians and pundits who wring their hands about the unsustainable rate of growth in health care expenditures.

Here's a typical comment: "Despite a massive increase in health expenditures together with a marked expansion in health workers over the past decade, the nation's health has improved less than expected. The benefits have not appeared to justify the costs. ... We have emphasized high-cost, hospital-based technologies " a situation " made all the more serious by the lack of emphasis on prevention of disease." Those observations were not made yesterday. They were made by Dr. John Knowles in a book titled "Doing Better and Feeling Worse: Health in the United States," published in 1975.

It is useful to look back to see far how we have come even as some things stay the same. In 1974, cardiovascular disease was the cause of 39 percent of all deaths. Today it is about 25 percent. Cerebrovascular diseases were responsible for 11 percent of deaths back then. In 2004 they caused 6.3 percent of deaths. Kidney diseases were linked to 10.4 percent of deaths and now they are associated with 1.8 percent.

Of course, the longer people live the more likely they are to die from cancer or Alzheimer's. The percentages of deaths attributed to influenza and pneumonia have remained almost constant, as have the percentages of people dying from respiratory diseases.

As Harvard University health economist David Cutler has noted: "The average person aged 45 will live three years longer than he used to solely because medical care for cardiovascular disease has improved. Virtually every study of medical innovation suggests that changes in the nature of medical care over time are clearly worth the cost."

As the genetic variations that predict our risk of disease and response to treatment are translated into tests and treatment, the waste from trial and error or unproductive intervention will fall as well. But there is a lot we can do without much effort to save money and improve health. More prevention, shifting care to lower-cost settings and rewarding people for healthier living can move us forward. That's not a crisis; that's an opportunity.

Here's a link to the complete op-ed:

Click Here for Op-Ed

  Read More & Comment...

Where are the dead bodies?

05/12/2008 08:07 AM |

Have you noticed that we're not hearing folks in Washington, DC ask this question any more?

The Lancet 2008; 371:1551
DOI:10.1016/S0140-6736(08)60663-7

Editorial

Combating counterfeit drugs

Last week, the US Food and Drug Administration (FDA) told a Congressional hearing that it believes a contaminant found in batches of heparin, which have killed at least 81 patients, might have been deliberately added. The source of the contaminant—oversulfated chondroitin sulphate—has been traced back to a Chinese supplier of drug manufacturer Baxter International. Why the stocks might have been intentionally contaminated is unclear, but the fact that oversulfated chondroitin sulphate is structurally similar to heparin but about 100 times cheaper, raises the very real possibility that it could have been added by counterfeiters.

If counterfeiting is behind the heparin case, it would not be that surprising; trends indicate that counterfeit medicines, defined by WHO as drugs that have “been deliberately and fraudulently mislabelled with respect to identity and/or source”, are a growing, global problem. The FDA alone has seen an 800% increase in the number of new counterfeit cases between 2000 and 2006. In developing countries, where drug regulatory systems can be weak or non-existent, around 10–30% of medicines might be counterfeit. Antimalarials have been a particular target for counterfeiters, and fakes have flooded the market in many Asian countries.

The substances used to adulterate medicines can vary from chalk, to antibiotics, to highly lethal substances that cause alarming spikes in mortality rates. Subtherapeutic levels of the genuine medicine, such as an antimalarial, can also lead to death or the development of fatal drug resistance. But these deaths, mainly in developing countries, are largely hidden in public-health statistics.

This situation is only likely to worsen as counterfeit drugs are becoming more difficult to combat. Criminals are using more sophisticated techniques to bypass standard laboratory testing such as the addition of cheaper substances that mimic genuine drugs. Holograms on drug packaging, designed to make counterfeiting more difficult, are also being copied with increasing accuracy making boxes of fake products hard to detect by the human eye. These deceptive measures have unfortunately led to a booming, lucrative trade. The Center for Medicine and the Public Interest estimates the sales of counterfeit drugs will reach US$75 billion in 2010. So what is being done to address the problem?

At the international level, the World Health Assembly adopted a resolution against counterfeit and substandard drugs in 1988, and at the end of 2006, the International Medical Products Anti-Counterfeiting Taskforce (IMPACT) was set up by WHO to mobilise action. However, despite these moves, few concrete steps have been taken by countries and political will to adopt anti-counterfeiting measures is lacking.

Most WHO member states are doing a poor job of reporting counterfeiting cases. Incredibly, between 2002 and 2004, WHO received no reports of counterfeit drugs. In many countries, counterfeiting medicines is not even considered a crime and when it is, the penalties for those found guilty often do not tally with the severity of the action. For example, in the UK, the prison sentence and fine for counterfeiting a T-shirt with a trademarked logo can be greater than for counterfeiting a medicine. Tougher prison sentences and heftier fines need to be introduced by governments to deter counterfeiters.

Countries must also strengthen their ability to regulate the drug supply. According to WHO, only 20% of its member states have well-developed drug regulatory systems, and around 30% have no or weak drug regulation. Twinning food and drug authorities in rich countries with ones in resource-poor countries might help nations that are struggling to regulate the market. Drug authorities also need to work effectively with customs, the police, scientists, health workers, WHO, and INTERPOL. This type of collaborative approach has proved successful in tackling counterfeit antimalarials in southeast Asia.

The pharmaceutical industry also has its part to play. It should be legally required to report suspected cases of counterfeiting to the relevant national drug authority—a practice which is currently voluntary. Companies must also be encouraged to lower the prices of their products in developing countries to reduce the economic incentive for counterfeiters.

There is no magic bullet to deal with counterfeit medicines. Countries need to adopt multipronged, multidicisplinary approaches to combat the problem. WHO and donor countries should provide support to developing nations to strengthen their drug regulatory systems. But individual governmental commitment to this goal is essential. Without it, public safety will continue to be compromised.

  Read More & Comment...

Oar Else

05/09/2008 09:00 AM |

Per yesterday’s E&C Subcommittee on Oversight and Investigations "Direct to Consumer Advertising: Marketing, Education or Deception?" hearing (aka:  “MED Ed”), some of the remarks offered by James T. Sage (Pfizer’s Senior Director/Team Leader for Lipitor):

“Pfizer asked Dr. Jarvik to appear in Lipitor advertisements because he is recognized for his work related to the human heart. Dr. Jarvik honestly and sincerely embraced our heart health campaign. He and Pfizer believe the ads were an effective way to deliver an important preventive health message to a large number of people by encouraging them to reduce the risk of heart disease through diet and exercise as well as consultation with their doctors about the importance of managing cholesterol.

Dr. Jarvik received his M.D. degree from the University of Utah College of Medicine in 1976. Although not a practicing physician, he has devoted his entire career to medical science related to the human heart. He has invented medical devices to help patients with advanced heart disease, and has collaborated with other physicians and scientists on these activities. As Dr. Jarvik has said publicly, he has “the training, experience, and medical knowledge to understand the conclusions of the extensive clinical trials that have been conducted to study the safety and effectiveness of Lipitor.”

Both Pfizer and Dr. Jarvik are confident that the statements included in the ads fairly represent the scientific data about Lipitor.

An important objective of the Jarvik advertising campaign for Lipitor was to highlight the importance of diet and exercise in reducing cardiovascular risk. When diet and exercise are not enough, adding medication such as Lipitor may be an important consideration for doctors and patients to discuss.

Some have asked why Pfizer decided to stop using Dr. Jarvik in our advertising. We chose Dr. Jarvik to participate in these ads because he is a nationally prominent expert with the knowledge and experience to speak intelligently and sincerely about the benefits of Lipitor. Unfortunately, the way Dr. Jarvik was presented in these ads has created misimpressions and distractions from our goal of encouraging patient and physician dialogue about the leading cause of death in the world: cardiovascular disease. Going forward, we are committed to ensuring there is greater clarity in our advertising regarding the presentation of spokespeople.

In summary, Pfizer believes that it’s important to educate consumers about the risks associated with elevated cholesterol and the value of Lipitor as a potential treatment option. We believe that DTC ads are an effective way of accomplishing that objective.”

Sage views indeed.

  Read More & Comment...

Tribulations and Trials

05/09/2008 08:42 AM |

According to our buddy David Lepay, the FDA's senior advisor for clinical science, the agency and the HHS Office for Human Research Protections are working on a final rule for registering institutional review boards (IRBs), the first of the FDA’s efforts to issue regulations instead of guidances for clinical trials.

  Read More & Comment...

Kohl Compress

05/08/2008 05:17 PM |

Senator Kohl has assured that $275 million in additional funding for FDA will be included in the Senate version of the FY 2008 emergency supplemental bill.  The Senate Appropriations Committee mark-up is scheduled for next week. The fate of the Kohl amendment is likely to be decided, in part, by House and Senate leadership when they determine the extent to which final Congressional legislation will fund programs other than defense and the war effort.

We'll see.

  Read More & Comment...

Mission Impossible or Risky Business?

05/08/2008 02:09 PM |

Apparently Shannon Brownlee buys into the Tom Cruise notion of mental illness, that it is some mystery or perhaps (my inference with no basis) a Thetan induced stated of disturbance. Here's Ms. Brownlee 'splaining what depression and manic depression is really all about...

"The mind and its illnesses remain as mysterious as the cosmos.."

Meanwhile, all scientists did was support the drug companies in developing medicines that were based on a flimsy excuse to abandon Freud.  Shannon again:

"It's not as if physicians can administer a blood test to determine if a patient is depressed or anxious or obsessive-compulsive. Rather, psychiatry defines -- and diagnoses -- psychiatric disorders on the basis of subjective symptoms that are reported by patients or observed by doctors."

Right, and there are no blood tests for Alzheimer's, Parkinson's, MS, dementia, cerebral palsy or schizophrenia...so I guess there aren't real diseases either...

Brownlee then crosses the Neutral Zone and into Scientology territory...

"The notion that depression is a biological ailment, like Alzheimer's, proved enormously appealing to patients. It relieved much of the stigma of mental illness, which could now be viewed not as a personal or moral failing, but as a glitch of biology. The serotonin theory also appealed to the medical community, for a slightly different reason. It made the mind seem more knowable, less like a black box, and psychiatry seem more like real science, instead of a lot of Freudian talk about repression and sex. Psychiatrists could now say to patients, you are sick because of a deficiency, and these drugs will restore you to normalcy and mental health.

If only psychiatric disease were that simple. In reality, there is little research to show that being a quart low on serotonin leads to depression, and even less to suggest that patients who commit suicide have lower levels of serotonin than normal people. And nobody really knows what SSRIs actually do in the human brain."

This is called ignorance by choice. 

So of course the marketing and prescribing of drugs to people who don't need will lead to horrible events like death, anxiety, etc.  But Brownlee and the Scientology types beg a question:  if mental illness is not biological in nature, and we know so little about serotonin and other neurotransmitters, how would drugs that can't restore people to health then harm so many?

Sorry, I am interrupting her rant:

"What's more likely is that the field of psychiatry, with its shifting, subjective diagnostic categories and its enthusiasm for new drugs, has been acutely vulnerable to "disease mongering." This is the increasingly common practice on the part of the pharmaceutical industry to broaden the perceived market for a drug by persuading doctors and the public that huge numbers of people suffer from this or that disorder. Between disease mongering and some doctors handing out SSRIs like Pez, antidepressant prescriptions for children have surged 27 percent since the mid-1990s. Today, between 1 million and 3 million kids under the age of 19 are on one or more of these drugs for diagnoses ranging from attention deficit disorder to migraines to schizophrenia. Taking SSRIs has become so commonplace that young people talk casually about needing to "adjust their meds" in response to a rough week at school or a bad breakup.

Meanwhile, doctors have been prescribing these medications without knowing until just recently that, according to the FDA, 2 to 3 percent of their young patients could be at risk for drug-induced suicidal thoughts or actions. Maybe that's because academic psychiatry has been too busy performing research with a very different agenda to answer the fundamental questions. In their haste to partake of industry research funds and other perks, academic researchers have focused much of their effort on what Carroll calls "experimercials" -- studies aimed at expanding the drugs' "off-label," or unapproved, markets.

And so doctors still can't tell which patients are most likely to benefit from taking an SSRI. Nor can they predict which ones are most likely to suffer devastating reactions. They still don't have any idea how, biochemically, the drugs might trigger suicide and bipolar disorder. In his book "Let Them Eat Prozac," psychiatrist Healy writes that the story of the SSRIs "reveals a lack of research so complete that academics cannot avoid questions about how well the health science research community serves us."

PS  David Healy is a paid expert witness for trial attorneys.  Something Brownlee never mentions...

Add her bias against using medicines to treat mental illness, indeed her belief that mental illness is just a  marketing gimmick, you might understand why she and Jeanne (I stole the documents) Lenzer who openly collaborated with Peter Breggin (who has his own ties to Scientology) would attack Fred Goodwin and Peter. 

Like I said, context matters.  And there is a lot more of it to come. 

paxilprogress.org/forums/showthread.php  Read More & Comment...

MED Ed

05/08/2008 08:26 AM |

Today's House hearing on pharmaceutical DTC goes forward under the title,"Direct to Consumer Advertising: Marketing, Education or Deception?"  Let's just call it MED Ed.

The prosecution (yes, because it's really a show trial) is led by Representative Bart Stupak (D, MI).  Nuff said.

The real action (meaning where real and meaningful conversations will take place on this issue) takes place later this month when the FDA advisory committee on risk communications meets to discuss DTC and how it can be made better.

That's the right way to do things.

As far as today's hearing being good theater, my advice is to go see Ironman.

(Per full disclosure, neither www.drugwonks.com nor www.cmpi.org receives any funding from Marvel Comics.)

  Read More & Comment...

The Empire -- State -- Strikes Back

05/08/2008 08:10 AM |

Gov. David Paterson inherited a $4.4 billion budget deficit. To close part of it, state Assembly members put public health on the chopping block when they passed the budget last month. Of course, they promised that their legislation would ensure that "quality, affordable health care is available for all New Yorkers." But it will have the opposite effect.

One of the budget's more damaging provisions restricts the medicines doctors can prescribe by applying the "Preferred Drug List" — medications physicians are allowed to prescribe to Medicaid recipients — to the more than 500,000 New Yorkers enrolled in Family Health Plus, a state-run health care program for low-income families. The list consists mainly of older, cheaper alternatives to cutting-edge medicines.

Considering that prescription drugs represent only 4.9 percent of the state's Medicaid budget, it's a penny-wise, pound-foolish proposition.

Drugs not on the list aren't covered unless the patient's doctor gets "prior authorization" from the state. This involves a phone call from the doctor to a government office; a process that severely slows down treatment and deters doctors from prescribing unapproved drugs.

This policy isn't anything new. Some drugs have always required over-the-phone approval by New York's Clinical Drug Review Program before they could be prescribed to Medicaid patients. Prior to the new budget, however, drugs on the Preferred Drug List were exempt from this roundabout procedure.

The results of this reform could be worse than anyone realizes. One survey by Project Patient Care and Harris Interactive found that in 2001 alone, drug restrictions caused 1.1 million Americans to experience negative health outcomes and 1.9 million to experience serious side effects because they couldn't get the meds they needed.

The irony is that this cost-saving plan won't even work. Numerous studies have shown that instituting a rigid list of approved medicines doesn't save any money. This seems obvious — if a patient is denied the appropriate drug, he'll end up visiting the hospital and emergency room more often.

The new budget also hits pharmaceutical companies for the right to treat poor patients. In order to get a drug approved and onto the Preferred Drug List, pharmaceutical companies have to pay a large "rebate" to the state. Drugs that aren't heavily discounted by the manufacturer are often left off the approved list.

Fleecing drug companies in this way isn't only unfair, it threatens public health by siphoning money from research and development on tomorrow's cures. In the long run, this lowers the quality of health care for everybody, not just low-income New Yorkers.

  Read More & Comment...

I Dream of Jeannie ... Retracting

05/07/2008 07:51 PM |

Talk about tight Jeannes!

The New York Times

January 17, 2005

Dispute Puts a Medical Journal Under Fire

By BARRY MEIER

Last year was an especially bad one for the pharmaceutical industry, which experienced controversies over how drug studies are disclosed and the implosion of the painkiller Vioxx. Now, as a result of the recent publication of an article about the antidepressant Prozac, it appears that the staid, usually methodical world of medical journals could suffer its own black eye.

On New Year's Day, the British medical journal BMJ published a news article suggesting that "missing" documents from a decade-old lawsuit indicated that Eli Lilly & Company, the maker of Prozac, had minimized data about the drug's risks of causing suicidal or violent behavior.

Within days, the article was cited in hundreds of television and newspaper reports. An outraged Washington lawmaker demanded to know if Lilly had hidden the information from the Food and Drug Administration. While company officials refuted the article's assertions, it was still repeatedly cited. And last Thursday, Lilly spent about $800,000 to run full-page advertisements in 15 major publications to dispute the article.

The incident may prove to be a messy one for the BMJ, which is based in London and owned by the British Medical Association, a professional group. Much of the journal, formerly known as the British Medical Journal, is devoted to research reports about medical issues that are reviewed by experts. But the BMJ, like some other medical journals, also has a separate news section that prints articles like the recent one about Prozac. As it turns out, some of the Eli Lilly documents, which the BMJ said it received from an anonymous source, have been circulating for years. And, Lilly officials said, the BMJ and its reporter declined to provide the company with copies of the documents at issue prior to the article's publication.

The American freelance reporter who wrote the article, Jeanne Lenzer, declined to be interviewed, referring all questions to the BMJ. Officials there did not respond to written questions, but a spokeswoman, Emma Dickinson, said in an e-mail message on Friday that the publication "takes this issue very seriously" and will address Lilly's concerns after reviewing them.

The BMJ, which is considered a leading medical journal, may have little choice. While Lilly has not taken legal action, its lawyers have notified the publication that the company considers the article to be "inaccurate and defamatory," asserting that the records were not missing and that all their relevant data had been previously submitted to the F.D.A. Also, Lilly issued an analysis last week of the 52 pages of records that the BMJ had received, which the company said supported its claims. Lilly said it got the documents from a congressman who received them from the BMJ.

"You put something out on the newswire with the imprimatur of a medical journal and people think it is fact," said Dr. Alan Brier, the chief medical officer of Eli Lilly, which is based in Indianapolis.

The article's appearance follows the recent controversy over whether drug makers adequately disclosed the risks that antidepressants like Prozac posed to pediatric patients. And its comes as a South Carolina teenager faces trial for murder as an adult on charges that he killed his grandparents when he was 12. The teenager, Christopher Pittman, has acknowledged the crime, but his lawyers have based his defense on the argument that he became violent after taking the drug Zoloft, an antidepressant similar to Prozac.

It was in a little-noticed article written by Ms. Lenzer in the Dec. 11 issue of the BMJ about the Pittman case that she first mentioned that the publication had received "a set of documents that mysteriously went missing from a U.S. mass murder case ten years ago."

That article did not go into specifics. But in her article on Jan. 1, Ms. Lenzer wrote that the documents in question were connected to a Prozac-related lawsuit that grew out of a shooting rampage in 1989 by a Kentucky man, Joseph Wesbecker, that left nine people dead, including Mr. Wesbecker.

Lawyers representing the victims sued Lilly, asserting that Mr. Wesbecker's killing spree was caused by Prozac, a drug he had been prescribed just before the crimes. During the 1994 trial of the case, Lilly pointed to Mr. Wesbecker's long history of severe psychological problems and said that Prozac was safe.

To combat those assertions, plaintiffs' lawyers introduced hundreds of Lilly documents. They argued that the records showed that Lilly had fully disclosed to the F.D.A. in the late 1980's the potential of Prozac to produce suicidal thinking or acts of violence, including all the reviews by drug regulators in Germany of the issue at that time. Lilly disputed that.

The jury found in favor of Lilly. But a legal controversy over the trial later erupted when it was revealed that plaintiff lawyers and Lilly lawyers had reached an undisclosed financial deal just before the case went to the jury to effectively settle by agreeing not to appeal the verdict.

A Lilly spokesman, Phil Belt, said that Ms. Lenzer, who lives in Kingston, N.Y., first contacted the company on Dec. 13, a few days after her article about the Pittman case appeared.

Mr. Belt said Ms. Lenzer asked where a published report about the data in a specific 1988 internal Lilly report had appeared. At that time, she also requested an interview with the company's chief executive, Sidney Taurel, to discuss what she described as "missing" Lilly documents, Mr. Belt said.

Mr. Belt said the company told Ms. Lenzer that Lilly needed to see the records at issue before it proceeded. He added that Ms. Lenzer later told Lilly that she could not do so, saying that the source of the documents was anonymous.

As the Christmas and New Year's season approached, Mr. Belt said that Ms. Lenzer told Lilly officials that they could pick up the issue after the holidays.

At some point in December, however, Ms. Lenzer or her editors apparently sent the documents it had received to Congressman Maurice Hinchey, Democrat of New York, and to the F.D.A. And a few days before New Year's, the BMJ distributed Ms. Lenzer's article to other news organizations with the provision they could not write about it until its publication date on Jan. 1 - a practice known as an "embargo."

That article carried the headline, "FDA to Review 'Missing' Drug Company Documents," which caught the attention of other news organizations. Mr. Belt said that when Lilly became aware of the embargoed news release, it tried to reach editors at BMJ but was unsuccessful. Both Ms. Lenzer and the BMJ did not respond to written questions about the publication's interactions with Lilly, including why the documents were not shown to the drug maker.

The only Lilly document specifically mentioned in the BMJ article was a 1988 report that stated that 38 percent of depressed patients taking Prozac during clinical trials experienced side effects like agitation, insomnia and nervousness, a rate twice that of those taking a placebo.

Such side effects, which are sometimes referred to as "activation," reflect the fact that some depressed patients who take Prozac and drugs like it often experience a surge of physical energy well ahead of psychological recovery. Some experts have long expressed concerns that such reactions can be so severe in a few patients that they may ultimately act on suicidal or violent impulses.

For procedural reasons, the 1988 Lilly memo itself was not introduced as evidence in the Wesbecker case, said Nancy Zettler, one of the two plaintiffs' lawyers involved. But Ms. Zettler said that one of her expert witnesses, Dr. Peter Breggin, testified extensively about its contents at that trial.

Ms. Zettler said that she was so perplexed by the BMJ article that she contacted Ms. Lenzer after it appeared. "Her original article made it seem like we had deep-sixed some of this stuff and I was curious," she said.

Both Ms. Zettler and Paul Smith, the other plaintiffs' lawyer in the Wesbecker case, said that Ms. Lenzer did not contact them prior to the article to talk about the records or ask for others from that case.

Another plaintiffs' lawyer who has used Lilly documents in other lawsuits, Arnold Vickery, also said he did not discuss the records with Ms. Lenzer prior to her report. Mr. Vickery and another lawyer are representing Christopher Pittman.

Dr. Breggin has written articles arguing against the use of Prozac and other drugs and has mentioned the 1988 Lilly memo in his writings; he is scheduled to be an expert witness in the Pittman case.

Several pages sent to the BMJ were not produced by Lilly but are photocopies of slides produced by an F.D.A. official who presented them at a 1991 public hearing that reviewed the possible suicide risks of Prozac. After its review, that agency panel decided not to issue any additional warnings.

Ms. Zettler said she still thinks the issue of what Lilly told the F.D.A. in the mid-1980's about Prozac's potential risks is unsettled. But after more than 15 years of the drug's use, numerous lawsuits and public reviews, it may also be largely moot.

As a result of the recent controversy about the potential suicide risks posed by antidepressants to children and teenagers, the F.D.A. last week sent out final new labeling language about those dangers to all makers of such drugs, including Lilly.

A spokeswoman for the agency, which is still reviewing the records sent to BMJ, said that it had not yet found anything new in them. Ms. Dickinson, the publication's spokeswoman, said that it was reviewing Lilly's rebuttal to its article.

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Slate 'n Slime

05/07/2008 06:53 PM |

Drugwonks rarely expects other bloggers to focus on substance . Rather, we are flogged for the source of our contributions as if others uncovered a corrupt connection instead of the truth, which is that we proactively provided information.  We are aware that our critics don't have the intellectual bandwidth or the maturity to actually engage on the issues or respectfully disagree or debate.  Still we expect accuracy and for others to provide some context even as they take their shots as they are entitled to in a free society.  

But we will do what ever it takes, including legal action, when facts are deliberately omitted, misrepresented and distorted and then willfully repeated to set the record straight. 

Shannon Brownlee and Jeanne Lenzer did a smear job  on Peter and Dr. Fred Goodwin in Slate ...  

www.slate.com/id/2190775/pagenum/all/#page_start

... for a segment on the Infinite Mind, called Prozac Nation Revisited ...

www.lcmedia.com/mind524.htm

The Infinite Mind is an award winning NPR show that has covered a wide variety of topics about the brain and cognition for over a decade with foundation funding, private donation and some corporate contributions directly generated by a production company.   Of course none of that information made it into Slate piece. What's more, the piece never challenged the central thesis of the experts, are SSRIs as dangerous as many in the media have made them out to be, i.e., that they cause suicidality and suicides.  Rather, as is their wont, they shift the line of attack to who has funded them, as if Goodwin (a friend and board member, something that we have made public for years) who has been ranked as one of the world's leading clinical researchers in depression and manic depression is just some industry tool.  

Two can play at that game.  Turns out that Lenzer has been on somewhat of a jihad against SSRIs, "reporting" on their dangers as a free lance journalist with the British Medical Journal  for several years.  What prompted the Slate article was likelly the fact that the Inifinte Mind segment questioned whether people in the media like her and members of Congress hyped up SSRIs dangers to the point that the number of kids taking the drugs declined and in turn suicides went up.  That's a point Peter and I made in a Washington TImes article.  The fact that we were targets for Lenzer, along with Fred, who has been fearless in speaking out for the safety of SSRIs in no surprise.

Neither is Lenzer's attack since she was a close ally of Peter Breggin, a vehement opponent of SSRIs who has it out for Fred Goodwin.  You don't need a financial tie to be biased and Lenzer has lots of reasons to go after Goodwin and Peter.  She also has plenty of bias and a track record of twisting the facts.  BMJ was forced to retract one of her articles and admit she slipped court documents to trial lawyers (perhaps via Breggin) in an unethical fashion.   Here is the BMJ retraction AND apology as it pertains to Lenzer's unethical and sleazy behavior. 

"BMJ  2005;330:211 (29 January), doi:10.1136/bmj.330.7485.211-a

Correction and apology, Lenzer, BMJ 330 (7481) 7

Correction and apology

Eli Lilly: Correction and apology

An article by Jeanne Lenzer in our 1 January issue (BMJ 2005;330:7) reported that the US Food and Drug Administration was to review confidential Eli Lilly documents that had been sent to the BMJ by an anonymous source.

The article stated that these documents had gone "missing" during a 1994 product liability suit filed against Eli Lilly.

That statement has been the subject of a detailed investigation conducted by the BMJ following a complaint by Eli Lilly. That investigation has revealed that all of the documents supplied to the BMJ that were either Eli Lilly documents or were in the hands of Eli Lilly had in fact been disclosed during the suit.

At the end of the trial, all the documents were preserved by Court Order or were disclosed by Eli Lilly to the plaintiffs' lawyers in related Prozac claims.

The BMJ did not intend to suggest that Eli Lilly caused these documents to go missing. As a result of the investigation, it is clear that these documents did not go missing. The BMJ accepts that Eli Lilly acted properly in relation to the disclosure of these documents in these claims. The BMJ is happy to set the record straight and to apologise to Eli Lilly for this statement, which we now retract, but which we published in good faith.

The same article described Dr Peter Breggin as "the medical witness for the Wesbecker case." He was, in fact, the expert witness for the plaintiffs."

Oh, and Jeannie also works for the plaintiff lawyer funded Government Accountability Project. ... no disclosure there.

As for Ms. Brownlee, she is a fellow at the New America Foundation that has funding from the Soros folks and is pushing a VA health system approach on everyone. 

Now that's context for you. 

  Read More & Comment...

Lord of the Flies

05/07/2008 08:13 AM |

Chinese regulators are accusing Baxter of failing to co-operate in an investigation over deaths linked to impurities in blood thinner heparin.

The State Food and Drug Administration, China’s drugs regulator, said on Tuesday that Baxter had not provided all samples and information requested during a visit last month to its New Jersey plant. The SFDA reiterated its position that there was no proven link between the deaths in the US of patients and “a heparin-like substance” found in the drug.

Denial, as my mother used to say, is more than just a river in Egypt.

Baxter replied: “We have been co-operating with all parties in the heparin situation including SFDA and the Chinese government. We plan to continue co-operating with them to help move the investigation forward. We will seek to understand any concerns to the contrary.”

Here’s the rest of the story, courtesy of the Financial Times:

http://www.ft.com/cms/s/0/3587b9b0-1ba7-11dd-9e58-0000779fd2ac.html

Per the larger issue of “tainted” vs. “counterfeit” ingredients, consider the comments of Robert Parkinson, Baxter’s chief executive, who said that the issue in question “appears to be the target of a deliberate adulteration scheme.”

Translation:  Counterfeiting.

There are a lot of issues here that need to be addressed – most notably criminal opportunism.

Consider the Chinese proverb, “Flies never visit an egg that has no crack.”

We must seal the cracks.

  Read More & Comment...

NICE: Don't ask. Don't tell.

05/05/2008 10:53 AM |

In our post-SiCKO, sound-bite-centered politically-charged environment, we’re hearing a lot about the “wonders” of “European-style” healthcare models.

Well, if we’re going to look at Europe – let’s really look. And let’s start with some recent news from London.

Late last week consumer group campaigners won a landmark victory in the fight to overturn a ban on Alzheimer's drugs for tens of thousands of patients.

The Court of Appeal in London said that NICE (the National Institute for Health and Clinical Excellence) the agency that evaluates the cost-effectiveness of drugs -- had acted unfairly by not fully disclosing how it evaluated Alzheimer's drugs.

In 2006, NICE ruled that drugs such as Aricept, Reminyl and Exelon don't benefit some patients enough to be worth their cost and recommended that the state health service pay for the drugs only in patients with moderate rather than mild Alzheimer's disease.

The Court of Appeal decided the process used by the Government's rationing body to ban use of the drugs - which cost only £2.50 a day - was unfair.

The case could pave the way for the drugs to be re-instated for newly diagnosed patients with 'mild' symptoms of the disease.

The three judges yesterday ruled NICE must release a full version of the economic model which it used to produce the guidance restricting access to the drugs.

By refusing to do so, NICE had put those taking part in consultation - including the Alzheimer's Society - at a significant disadvantage in challenging its reliability.

Experts said the ruling could have wider implications because it showed a key part of NICE's work is secretive, undermining confidence in guidance that has led to other drugs being rationed.

Dr Susan Benbow, former chairman of the Faculty of Old Age Psychiatry of the Royal College of Psychiatrists, said: "The next stage should be to overturn the guidance which was not only reached during an unfair process, but is inequitable on grounds of human justice to patients who should have access to these drugs."

The cost of prescribing the drugs to a patient with the early symptoms of Alzheimer's is £2.50 a day, or around £1,000 a year - but the potential savings to taxpayers and families are huge.

Studies show that full-time care for an Alzheimer's patient is £25,000 a year, or around £520 a week.

But the National Institute for Health and Clinical Excellence used a much lower figure of £18,500 - less than £369 a week - for the costs of full-time care when calculating whether the NHS could afford to fund treatment with the drugs.

For some sobering American pharmaco-economic data, have a look at the CMPI report, “Alzheimer’s Disease and Cost-effectiveness Analyses: Ensuring Good Value for Money?

Professor David Wilkinson, a leading old-age psychiatrist, said: "These drugs can stabilise patients for two or three years and it's perfectly possible for those who respond to gain six months or a year living at home.

Professor Wilkinson said that under the ban, some newly diagnosed patients were being told by their doctor to come back in six months' time, by when their symptoms would have got worse and they would be eligible for treatment.

"Doctors have been put in an impossible position - it goes against everything in our medical training,' he added.

If we’re going to look to Europe – then let’s really look. And if we’re going to talk about comparative effectiveness – let’s really talk.

  Read More & Comment...

NICE Stiffs Arthritis Patient Access To Breakthrough Drug

05/05/2008 08:41 AM |

From the Lancet:

Most notable is the following excerpt --  the importance of individual differences --  which the comparative effectiveness crowd in the US blindly and blithely ignores:

"The new treatment approach is to treat early and aggressively to achieve minimum disease progression and ideally remission, a strategy that achieves the best long-term results. However, there is currently no gold standard to define remission. Progression and response to treatment are extremely variable between patients. A substantial proportion of patients (up to 30%) is not adequately controlled with currently available treatment strategies of non-biological disease-modifying antirheumatic drugs and TNF a inhibitors."


UK, 5/5/2008 - The Lancet has been a longstanding supporter of the National Institute for Health and Clinical Excellence (NICE) in the UK. Its procedures are rigorous, scientifically driven, and publicly accountable. NICE is widely admired by many other western European nations. But consternation and disappointment characterised the reaction by patient groups and the British Society for Rheumatology to NICE's latest judgment. On April 23, NICE rejected an appeal on abatacept for patients with severe rheumatoid arthritis brought by the drug's manufacturer Bristol-Myers Squibb, the British Society for Rheumatology, the Royal College of Physicians, the National Rheumatoid Arthritis Society, and the Royal College of Nursing. The appeal committee upheld NICE's decision of October last year, and the only next possible step is an application to the High Court.

Abatacept is, with rituximab and tocilizumab, one of three new drug classes that have shown clinically significant improvement for the treatment of severe refractory rheumatoid arthritis. Abatacept acts as a selective T-cell co-stimulation modulator, designed to block a key co-stimulatory signal required for T-cell activation, a new approach to halt or reverse the inflammatory process. However, with an incremental cost-effectiveness ratio of about £37?000–£43?000, possibly even higher if different estimates are included in the model, abatacept did not provide cost-effective treatment according to NICE's threshold of £30?000 per quality-adjusted life-year (QALY) gained. Many of these estimates are no more than best guesses based on insufficient or incomplete evidence. The committee stated that “while recognising the innovative nature of the drug, the severity of the disease and the limitations around the use of the HAQ [health assessment questionnaire] in the economic modelling, …abatacept would not be a cost-effective use of NHS [National Health Service] resources for patients in whom rituximab failed or in whom rituximab is contraindicated”.

How does abatacept differ from rituximab? Rituximab, a chimeric human-mouse monoclonal antibody directed at the CD20 antigen expressed on mature B cells and pre-B cells, acts on a different pathway. Like abatacept, rituximab was shown to be effective in patients treated with methotrexate who had not responded adequately to an additional TNF a inhibitor. Again like abatacept, there are no good long-term data and no direct head-to-head trials comparing other strategies with rituximab, yet rituximab was approved in August last year. The simple difference is that rituximab is cheaper. Patients only need two infusions every 6 months compared with 14 infusions of abatacept in the first year and 13 thereafter. The incremental cost-effectiveness ratio of rituximab is estimated as somewhere between £12?000 and £30?000 per QALY gained.

Rheumatoid arthritis is common and debilitating. About 1% of the adult population in developed countries is affected, increasing to 5% for women older than 55 years. About 60% of people are unable to work and are severely restricted in daily activities 10 years after diagnosis. Although progress has been made in understanding the underlying pathogenic mechanisms, the cause of rheumatoid arthritis remains unknown. The new treatment approach is to treat early and aggressively to achieve minimum disease progression and ideally remission, a strategy that achieves the best long-term results. However, there is currently no gold standard to define remission. Progression and response to treatment are extremely variable between patients. A substantial proportion of patients (up to 30%) is not adequately controlled with currently available treatment strategies of non-biological disease-modifying antirheumatic drugs and TNF a inhibitors.

Any new and effective treatment for such a debilitating condition as rheumatoid arthritis should be welcomed with enthusiasm. But NICE is at the sharp end of husbanding NHS resources. It has to balance evidence with cost. And here there is a perilous conflict between its dual clinical and political purpose. There will be occasions when exceptions to strict cost-effectiveness guidelines must be made on clinical grounds. Abatacept is a strong candidate to be such an exception. Worse still, NICE's decision may unwittingly act as a disincentive to industry to develop new medicines in this neglected and poorly understood area. Although NICE will rightly say that it has followed the letter of its cost-effectiveness law, patients and the public may, with justification, feel that it has forgotten the spirit of those same laws—namely, that cost-effectiveness evidence needs to be interpreted with compassion as well as impartial science.  Read More & Comment...

Typical Misreporting on Atypical Use in Kids

05/05/2008 08:28 AM |

The AP's Lyndsey Tanner fans the flames of fear by misconstruing  already breathless data dredging operation by Fariz Rani and others in this mont's Pediatirics. about the "soaring" use of atypicals in the treatment of autism and ADHD in the UK:


"American children take anti-psychotic medicines at about six times the rate of children in the United Kingdom, according to a comparison based on a new U.K. study. Does it mean U.S. kids are being over-treated? Or that U.K. children are being under-treated? Experts say that's almost beside the point, because use is rising on both sides of the Atlantic. And with scant long-term safety data, it's likely the drugs are being over-prescribed for both U.S. and U.K. children, research suggests. "

Beside the point? I mean, it sort of matters if there is over or under treatment. But then again, Tanner has already concluded that the drugs are over-prescribed. But what does a six times the rate mean?

"In the U.K. study, anti-psychotics were prescribed for 595 children at a rate of less than four per 10,000 children in 1992. By 2005, 2,917 children were prescribed the drugs at a rate of seven per 10,000 — a near-doubling, said lead author Fariz Rani, a researcher at the University of London's pharmacy school."

Tanner seems to be talking just about kids diagnosed with ADHD and autism. And she conveniently ignores the number of kids who take the drugs for the same diseases in the US. She also ignores the fact that extensive study has gone into use of these drugs for treating of certain aspects of both disorders. In the case of anti-psychotics, risperadone has FDA approval for use in treating irritability in children with autism from ages 5-16 which most certainly explains why the study in Pediatrics found most of the increase in use overall associated with Risperdal scrips. But you don't see that information in the Tanner article...No. What you get is the implicit accusation that drug companies are promoting unsafe and off-label use of the product. Disgusting. Misleading. Damaging to parents and kids alike.

news.yahoo.com/s/ap/20080505/ap_on_he_me/psych_drugs_children  Read More & Comment...