Schwitzer health news blog

Why didn't FDA act on Procrit ads?

The Cancer Letter reports:

Internal FDA documents show that the agency made a series of unsuccessful attempts to stop a direct-to-consumer advertising campaign that claimed that Johnson & Johnson’s erythropoiesis-stimulating agent Procrit (epoetin alfa) improved “fatigue” associated with chemotherapy-induced anemia.

The advertising campaign, which is widely credited with making ESAs into the biggest-selling class of oncology drugs, was allowed to proceed with relatively minor changes after the FDA Office of Chief Counsel became involved in the controversy.

Getting "informed consent" for drug trials in poor countries

Merrill Goozner reports that the FDA decided that it will no longer require that clinical trials submitted to the agency to get regulatory approval for a new drug adhere to the Helsinki Declaration.

Why should you care? Gooz says this "increases the likelihood that more trials will go abroad and that more of them will not even be registered with the FDA, which makes them all but impossible to monitor."

Huge issue. And, as Gooz points out, one not reported by many news organizations.

Did you want butter on your cigarette butt?

The Wall Street Journal reports on a World Health Organization announcement about problems with the new generation of sleeping pills - a market that grew by 10% last year.

Among the oddities reported by the Journal:

• people eat, walk, make phone calls or get behind the wheel while still asleep after taking the drugs;
• some people have cut themselves with knives, consumed inedibles like buttered cigarettes and woken up gasping for air with their mouths full of peanut butter, a particular sleep-eating favorite.

Shearlings plowed - or Plough shares in blogosphere

In the hyper-specialization of the blogosphere, now we even have a blog tracking an individual drug company.

Shearlings Got Plowed is the name of a blog covering recent problems at drugmaker Schering-Plough

Drug companies' 1,044 broken promises

Bloomberg News reports:

Drugmakers haven't made progress in starting studies that they promised to conduct after their products were approved by U.S. regulators, according to data released today.

The Food and Drug Administration determined that 1,044, or 62 percent, of incomplete studies for conventional drugs and biotechnology medications had yet to be started as of Sept. 30. At the same time in 2006, 1,026, or 63 percent, of the unfinished studies hadn't begun, according to the FDA.

To receive FDA approval, drugmakers often agree to perform additional studies of safety, dosing and other matters after medications come to market. The research is usually voluntary, and lawmakers have repeatedly complained it isn't completed. President George W. Bush signed legislation in September that allows the FDA to require certain post-approval studies.

``Drugs often come on the market with an expectation that studies will be conducted,'' said Peter Lurie, deputy director of the Health Research Group at Washington-based Public Citizen, an advocacy organization, in an interview. ``In fact, many of these studies begin late or do not begin at all.''

Doctors say post-approval studies may be needed to fully assess the risks of medications because some dangers don't emerge until products are in widespread use.

Some research has been pending for years. Of the 1,044 studies that hadn't begun, drugmakers committed before Oct. 1, 2004, to undertake 444 of them, according to the FDA.

So don't be surprised when you hear the next news about a "blockbuster" drug that is found to have "surprise" side effects months or years after it's been on the market.

Off-label promotion equals 19th Century medicine

Drs. Adriane Fugh-Berman and Douglas Melnick have written to the FDA:

"Loosening restrictions on the distribution of materials on off-label uses is an abdication of the FDA’s responsibility to protect the public. Off-label uses of pharmaceuticals have not been subject to the testing and review required for marketing approval. The scientific review of evidence of effectiveness and safety that drugs undergo prior to an approved, labeled indication for a drug protects patients. With off-label use, this protection does not exist.

While off-label use is sometimes necessary, it should be undertaken with the care and caution due the uncontrolled experiment to which a patient is being subjected. While some off-label uses are supported by randomized controlled trials, 73% of 150 million off-label prescriptions written in 2001 were for conditions that had little to no scientific support for efficacy.

Belief is an unreliable gauge of efficacy. In the 19th century, physicians believed that mercury, arsenic, and bloodletting were effective for common ailments. More recently, physicians believed that oxygen therapy benefited premature babies when instead it caused blindness , and that menopausal hormone therapy benefited women’s health when the opposite was true . In these and many other cases, randomized controlled trials trumped prevailing medical opinion with truth. While “medically-recognized standards of care” may exist outside of a product’s approved product labeling, it is inappropriate for the manufacturers to create or promote these off-label uses without conducting the studies and applying for the new indication with the agency.

Industry has much to gain, and the public health much to lose, by the implementation of this guidance. Restrictions on off-label promotion of drugs should be strengthened, not gutted. The FDA should not jettison its responsibilities to protect consumers."

Drug-and-device-reps-free zone

Psychiatrist Daniel Carlat, whose blog is one of the smartest publications on the Web, recently
wrote:

I've had it. As of today, I am no longer allowing drug reps into my office.

Yes, until today, I was seeing reps a few times a month for 5 minute visits in order to keep up on trends in drug company marketing techniques. But today, an Astra Zeneca rep and his district manager came in to push Seroquel for bipolar depression. They came armed with the two studies that won Seroquel its FDA approval. The studies have their limitations, but somehow these reps didn't bring these up.

Instead, what I got was a ridiculous hard sell: "Dr. Carlat, given this data, would you choose Seroquel over the other atypical antipsychotics for bipolar depression?" I asked them if Astra Zeneca had done any head-to-head studies comparing Seroquel with the others. The rep adopted a pseudo-confused look, and said, "I'm not even sure that kind of study would be ethical--would the FDA even allow you to compare an approved drug with an unapproved drug?" I pointed out that the FDA, in fact, requires that drugs be compared with placebo, the ultimate in "unapproved" drugs, and that they deem this ethical enough.

He tried another tack. "What are the symptoms of bipolar depression that you have the hardest time treating?" I said that all the symptoms are hard to treat--that, in fact, bipolar depression is a very difficult illness to treat. Out came his computer, with a slide showing that Seroquel successfully treated every one of the depressive symptoms in one study. "Now doctor, if you had a patient come into your office with suicidal ideation, and you had an agent that would help those symptoms in a week, wouldn't you want to use that agent?"

Of course I would, and there are many other agents that will work better than placebo in a week. But my rep wasn't interested in talking about the alternatives. The focus, as always, was on his product, and on his bonus.

I've printed out the National Physicians Alliance's brochure, "Why Doesn't My Doctor See Drug Reps?" and will put it in my waiting room. I'll let you know how my patients respond. For now, I'm still accepting samples (making me the most despised of doctors among drug reps, a "sample-grabber") but that will be the next to go.

Meantime, my local Star Tribune newspaper today published a story cheerleading for a local device manufacturer.

With the story came the photo above, showing a device rep making his pitch to health care professionals. The story and the photo seem to come from a different planet - far away from any controversy or concerns about the coziness of such a reps-in-the-clinical-setting repertoire. Not a word about the kind of concerns that Dr. Carlat and so many others have raised. But as I've noted before, there appears to be an "anything goes" attitude with a different code of ethics for local business news on the business page.

Protesting off-label drug promotion

In his blog yesterday, Merrill Goozner wrote how "Patients Protest Promiscuous Promotion of Off-Label Prescribing."
Excerpt:

A coalition of consumer groups later today will send a scathing letter to the Food and Drug Administration protesting a proposal to give manufacturers a blank check to promote the off-label use of drugs and devices. The letter, signed by Consumers Union, the Center for Science in the Public Interest, the Government Accountability Project and a half dozen other patient and consumer groups, charges the lenient guidelines will undermine the FDA's authority to regulate off-label marketing and lower incentives for firms to conduct rigorous clinical trials or seek agency approval for the uses to which the drugs are being put.

The guidelines mark a "180-degree reversal of prior practice (by) eliminating Food and Drug Administration review of articles that manufacturers plan to distribute to physicians. As a weak and dangerous alternative, the draft guidance proposes a de minimus self-regulating standard," the letter asserts.

Drug ads should tell you the cost

A South Carolina physician states in a letter to the editor in this week's BMJ:

"Practising in the United States, I am well acquainted with direct to consumer advertising of prescription drugs. I suggest (and have suggested in the past to the Food and Drug Administration) that if such advertising is allowed, it should be mandatory for the manufacturer to state the typical cost of a course of treatment with the drug. My own experience of the $600 (£300; {euro}385) treatment for onychomycosis was that this information could save a great deal of time in explaining to the patient why the drug is not covered by their insurance. It could also prevent a whole unnecessary discussion in the first place as patients quite readily recognise that the cost is out of proportion to their problem."

Onychomycosis is toenail fungus. You know the ads.

WSJ Health Blog Flogs Vytorin Again

Scott Hensley of the Wall Street Journal Health Blog just posted this:

Merck and Schering-Plough attempted to recreate information from a crucial meeting about a major study on cholesterol blockbuster Vytorin after a Congressional panel began an investigation, according to documents obtained by a Congressional subcommittee, the WSJ reports.

In a letter Friday, Rep. John Dingell (D-Mich.) and Rep. Bart Stupak (D-Mich.) asked why minutes of the companies’ ad hoc expert panel, which had met in mid-November, had been “created after the fact” in December. Spokesmen for Merck and Schering-Plough couldn’t be reached immediately by the WSJ for comment.

The minutes, circulated Dec. 19, a week after Dingell’s investigation began, suggest that the companies’ experts had agreed to move the goal post for the study, which would have made Vytorin and its sister drug Zetia look better. Internal company documents released by the House Commerce Committee, which Dingell chairs, include strong complaints from one of the study panel members. Click on image at right to see the documents.

“It was my understanding that there were no minutes or transcript of this meeting,” James Stein, a cardiac imaging expert at the University of Wisconsin, wrote in an email to Schering-Plough. (See his comment to the same effect in the margin of draft minutes that appears in the image above.) Some of the new minutes of the Nov. 16 meeting didn’t accurately represent his recollections or details of the debate during the meeting said Stein in an email to Schering-Plough.

“It was the decision of the company to change the endpoint,” Stein wrote in comments back to company about the minutes.

The companies had issued a press release on Nov. 19, shortly after the consultants’ meeting saying the outside experts recommended such a change, which is contrary to generally accepted scientific practice.

Earlier this month the Merck/Schering-Plough joint venture that sells Vytorin made public an email exchange with John Kastelein, the cardiologist who ran the study called Enhance, and who had objected to the proposed change in the endpoint for the study.

In March, Forbes’ Matt Herper laid out the challenge for Dingell’s panel posed by the creation of minutes from the meeting after the fact. The retrospective memo writing, he wrote, “could also make it more difficult for the companies to defend their own decision making with regard to the study.”

Two views about drugs from other countries

Amidst all the stink over the drug Vytorin in this country - including the barrage of two-sided full-page ads in US newspapers - Canadians are chucklingbecause they never got hooked on Vytorin like Americans did. And the story suggests that direct-to-consumer drug ads in the US (not allowed in Canada) may have a lot to do with the higher use here.

Then, from the UK comes a story that claims that cancer drug trials are being stopped too soon. An Italian research team says that the usefulness of some cancer drugs is being exaggerated because manufacturers are stopping trials the moment they find a benefit - but before all the evidence is in hand.

How drug companies wine & dine doctors

An Australian newspaper gives a glimpse of how much drug companies spend to wine and dine doctors at "educational events." Excerpt:

"A drug giant spent more than $514,000 on a weekend seminar that included just six hours of "education content".

The symposium by Australian-based AstraZeneca included gourmet meals, alcohol and two nights free accommodation.

A new report shows "Big Pharma" is prepared to spend millions showering doctors with hospitality in the hope they will prescribe their drugs.

It reveals drug companies spent $31 million on educational events in the second half of last year, including $16 million on meals, airfares and accommodation.

Drug companies funded 14,643 functions during the period, 52 of which are under investigation for possible breaches of new industry rules.

Critics attacked the spending as an "orgy of wining and dining designed to schmooze doctors and boost the sales of new medicines".

But doctors claimed the hospitality amounted to little more than "a glass of orange juice and a sandwich".

Industry body Medicines Australia said drug companies had to keep doctors informed about new medicines.

"No one knows more about pharmaceuticals than the people who make them," chief executive Ian Chalmers said.

Medicines Australia refused to disclose which companies hosted the suspect events until the cases are reviewed.

Companies that breach the rules face $200,000 fines.

More than 220 gastroenterologists attended the AstraZeneca event, which was one of the most expensive disclosed.

Another company, Roche Products, spent $511,791 on a weekend hepatitis symposium for 337 specialists at Melbourne's Grand Hyatt, including $415,000 on hospitality.

Pfizer spent $340,000 on a cardiovascular forum for 220 specialists in Sydney, and Wyeth spent $333,000 sending 178 psychiatrists to an $1800-a-head event on Sydney.

Australian Medical Association president Rosanna Capolingua said the events were necessary and spending was reasonable."

More suggestions of drug company deceit on Vytorin

The New York Times adds more questions to the Vytorin drug data delay story. Excerpt:

"The lead outside investigator on a crucial trial of two widely used heart drugs said in an e-mail message last July that Merck and Schering-Plough, the companies that make the drugs, were deliberately delaying the release of the trial results “to hide something.”

The companies did not release the preliminary results of the trial, called Enhance, until January, almost two years after the trial was finished. When they were finally released, the trial’s results showed that the drugs, Vytorin and Zetia, did not work to reduce plaque in arteries. The results led a panel of cardiologists to recommend on Sunday that the drugs be used only as a last resort. ... The drugs are used to lower cholesterol and are among the most widely prescribed medicines in the United States, with sales of $5 billion last year. Shares of Merck and Schering plunged on Monday."

WSJ Health Blog's March Madness drug company CEO brackets

At a conference yesterday, Scott Hensley of the Wall Street Journal Health blog showed off a story I had missed. Since it's the last day of March and basketball's Final Four is now set, the time is just right to look at it. See the Journal's “Our March Madness: The Drug Company CEO Bracket”.

They explain:

Restless shareholders, listless labs and a tidal wave of generic competition confront the top executives at drug makers around the globe. Big Biotech has plenty of problems of its own. Did we mention pushback on prices?

So we wonder who among the leaders of the current executive pack will win the test of endurance to remain the last CEO standing? Take a look at our second annual bracket by clicking on the image at the right. Feel free to start your own office pool.

The posting is fun. It's interactive. You can vote on the poll. And the user comments are worth reading. One wrote: "A more relevant question is - which CEO has the most integrity?"

Top 5 reasons to question a new antidepressant

I just heard psychiatrist Dan Carlat give a talk that touched on Wyeth's new antidepressant Pristiq. Much of what he said is captured in a post on his terrific blog.

In short, here are his top 5 reasons to forget about Pristiq. You can read the details on his blog.

1. It’s a blatant patent extender.
2. It's not very effective.
3. It is not more easily dosed than Effexor XR (as the company claims).
4. It has no meaningful metabolic advantages.
5. Wyeth’s own lead investigator is unimpressed.

25 Shocking Facts About Pharma

The Nursing Online Education Database has posted an article entitled, "25 Shocking Facts About the Pharmaceutical Industry."

Here's a part of their list. You can read the full entries by going to their site.

• The price of drugs is increasing faster than anything else a patient pays for.
• Your doctor may have an ulterior motive behind your prescription.
• Pharmaceutical companies spend more on marketing than research.
• Brand name meds often have a 1,000% mark-up price.
• Drug reps often have no medical or science education.
• Pharmaceutical companies are helping, hurting the AIDS epidemics.
• Doctors can choose to reveal or keep private their prescription records.
• Good PR trumps patient care.
• Abbott Laboratories charged Medi-Cal nearly $10 for saline solution.
• Guilty of Medicare fraud: Pharmaceutical companies are also being tried in federal courts as an answer to their exploitation of Medicare.
• Combined wealth of top 5 pharmaceutical companies outweighs GNP of sub-Saharan Africa.
• Pfizer is fifth-best wealth creator.
• Americans pay more for prescription meds than anyone else in the world.
• "New" Drugs aren't really new:
• Some drug companies are taking advantage of underdeveloped countries to perform clinical trials.

Pfizer Enlists a Labor Union (SEIU) to Promote Lipitor

On her terrific Health Beat blog, Maggie Mahar reports:

A couple of weeks ago Dr. Alicia Fernandez, an associate professor of clinical medicine at UC San Francisco, received a very unusual letter from The International Association of EMTS and Paramedics, an affiliate of The National Association of Government Employees (IAEP/SEIU).

The letter began by noting that Fernandez is part of the union’s approved physician network, and then launched into what can only be described as a shameless sales pitch for Lipitor, Pfizer’s blockbuster cholesterol-lowering drug.

First, the alarming statistics presented in the letter:

* 1 in 3 adults has some form of CVD (cardio-vascular disease)
* About every 26 seconds, an American will suffer a coronary event
* Stroke is a leading cause of serious, long-term disability in the United States
* Every 45 seconds, someone will suffer a stroke.

Then, the endorsement: “Lipitor is available to our members through their prescription plan. IAEP leadership stands behind LIPITOR as the lipid-lowering agent of choice when it is prescribed by a physician. This confidence in LIPITOR is based on its proven efficacy and is supported by its vast clinical experience of more than 15 years…"

The letter went on, at length, to praise Lipitor’s benefits and to downplay the drug’s risks. In clinical trials, the letter states, “the most common adverse events were constipation, flatulence, dyspepsia and abdominal pain.” But while other risks may not be as “common” they are certainly worth mentioning. They include memory loss which can look like Alzheimer’s and severe muscle pain.

A few days ago, Fernandez received a second, identical letter. Never before in her professional experience had she received a drug ad from a union.

“I’ve never seen anything like this. I’ve never seen Labor endorse a drug product,” she told me. “This is incredible.” Unfortunately, Fernandez adds, this is not the first time that she has seen a drug company use a progressive organization to promote its product. ...

Why would Pfizer need the union’s help in peddling its drug? Lipitor, after all, is the best-selling drug in the world, with sales of almost $13 billion in 2006.

But recently, Lipitor has been attracting some decidedly negative publicity.

Read her blog for the rest of the entry. Drug promotion becomes curiouser and curiouser.

Laws to overcome Pharma's influence

Two items in the news recently highlighted proposed legislation to limit the influence of drug companies on physicians - and therefore, on consumers as well.

The Boston Globe reports on a proposed state law that would ban all gifts to doctors from drug companies.

"Other states have passed laws attempting to limit the pharmaceutical industry's influence. In Minnesota, legislators enacted a ban on gifts in excess of $50 from pharmaceutical companies. In Vermont, legislators have passed laws requiring pharmaceutical company representatives to disclose the dollar value of gifts over $25 to doctors. Peggy Kerns, director of the ethics center at the National Conference of State Legislatures in Denver, said Murray's legislation is the first attempt at an outright ban on gifts to doctors that she had heard of."

Then, the Integrity in Science Watch project reports that:

Legislation that would send government-funded educators into doctors’ offices with independent information about prescription drugs received a boost last week at a Senate Committee on Aging hearing. “Pharmaceutical sales reps (known as detailers) are currently one of the only ways doctors can learn about the latest drugs on the market,” said Sen. Herb Kohl (D-WI). “These sales reps often confuse educating with selling, and evidence shows that doctors’ prescribing patterns can be heavily influenced by the biased information often put forth by these sales representatives.” Experimental programs that send scientific professionals with clinical training into physicians’ office to provide them with objective, unbiased information – sometimes known as academic detailing – are now underway in five states and the District of Columbia. Kohl and Sen. Dick Durbin (D-IL) will introduce legislation that would create a federal academic detailing program later this spring.

The program is a potential moneysaver for the federal government, which added a senior citizen drug benefit to Medicare in 2003 and spent an estimated $47 billion on the program last year. Pennsylvania’s academic detailing program reduced the total cost of patient prescription by $60 per physician in the six months after an academic detailer’s visit, according to Nora Dowd Eisenhower, head of the state’s Department of Aging. Jerry Avorn of Harvard Medical School told the committee that an experimental academic detailing program that reached 400 doctors in four states saved $2 for every $1 in costs. “Research has shown that when doctors have full access to comprehensive and unbiased data on all the drugs available, they prescribe the best drug--not just the newest one--and healthcare spending is lowered,” said Kohl. The pharmaceutical industry spends an estimated $7 billion a year on direct-to-physician marketing, employing over 80,000 detailers to reach the nation’s 700,000 practicing physicians.

Sleep may be not be the big problem special interests claim it is

I've blogged about the cloud of doubt that should hang over the annual proclamations made by the National Sleep Foundation during the highly-promoted National Sleep Awareness Week. The reason: special interests like sleeping pill makers fund the effort.

Now the Washington Post reports:

Americans are not as sleep-deprived as they think they are and, in fact, appear to be getting more Z's these days than they got a few years ago, according to an independent analysis of government statistics.

The new findings run counter to the widespread public perception that Americans are getting less and less sleep because of increasing workplace demands and the plethora of distractions available around the clock on the Internet and cable television.

"Many Americans work too much, but most do not seem to be cutting corners on their sleep to do so," said John P. Robinson, a sociologist at the University of Maryland, who led the analysis with faculty colleague Steven Martin.

Their report, "Not So Deprived: Sleep in America, 1965-2005," scheduled for release by the university today, finds that Americans on average got 59 hours of sleep per week in 2005, the latest year for which precise statistics are available. That is three hours more than in 2000.

The new numbers contrast significantly with the 2008 "Sleep in America" poll, the oft-quoted survey conducted annually by the Washington-based National Sleep Foundation, which advocates for better diagnosis and treatment of sleep problems.

Released last week, that survey concluded that Americans get an average of 48 hours of sleep per week.

The difference, experts said, reflects the two groups' methodologies. The Sleep Foundation survey asks Americans to estimate how much sleep they typically get. By contrast, the Maryland analysis draws upon detailed "time-use" data collected by the U.S. Census Bureau for the Department of Labor Statistics. In that approach, individuals must account for every minute of the previous day.

"This gives us a much better picture of where the time goes than when people just make an estimate," Robinson said.

The butterfly in your bedroom

Just as the nation awakes from another National Sleep Awareness Week, funded in part by sleeping pill manufacturers (a fact often not reported by journalists who dutifully report from the news release), we are reminded of rising sleeping pill usage patterns.

The Wall Street Journal reported last week:

"The increased use of sleeping pills has “been particularly sharp for young adults,” William Marder, SVP and general manager of Thomson Healthcare, told the Health Blog. A lot of the uptick, he said, is driven by the availability of newer sleep aids, such as Sanofi-Aventis’ Ambien and Sepracor’s Lunesta."

That would be the same Ambien and Lunesta that have been so heavily advertised on TV and in print, perhaps making sleep pill use appear to young people like it's a harmless trip to butterfly land.

How much will we spend for so modest a benefit?

A great letter to the editor appeared in the Wall Street Journal yesterday:

I am still trying to recover from the Food and Drug Administration's recent decision to go against its advisory panel's recommendation and approve Avastin to treat advanced breast cancer ("Genentech Clears Hurdle on Cancer Drug Avastin," Leading the News, Feb. 23).

Although Avastin is ushering in a new wave of "targeted" cancer therapies, which minimize the gut-wrenching side-effects that many of us previously endured with our cancer treatment, the cost to our health-care system is astronomical. What is the true cost of this drug? While the average charge a provider may pay for Avastin may be $7,700 a month, it certainly isn't what a patient is billed. My experience in reviewing hundreds of medical claims involving Avastin shows that the average monthly patient charge when given in an oncologist's office is closer to $18,000 a month, while many hospitals charge more than $35,000 a month. With 38,000 American women eligible for this drug and an average treatment of six months, we suddenly have several billion dollars added to our annual health-care tab.

If the FDA has been given the power to make decisions that have such huge ramifications, it must be accountable for the cost-benefit ratio of these decisions. In this case, a study showed there was no survival benefit yet the cost will be billions of dollars per year. Is there any wonder why our health-care expenditures are expected to double to over $4 trillion within 10 years?

Peter S. Dumich, M.D.
Augusta, Ga.

We don't know jack

Journalists Jeanne Lenzer and Shannon Brownlee have a column in this week’s BMJ, “Do we really know the truth about antidepressants?” But the question could be applied to any drug on the market.

They explain that not all drug trials have to be registered and access to full data is constrained by trade secrecy laws that permit companies to withhold all information about drugs that do not win approval for a new indication, even when the drug is already on the market for other indications.

Trade secrecy protection?

Where does consumer protection enter in?

Why aren’t these failed trials made public?

It’s a very thoughtful piece by two of this country’s best health journalists.

Four related stories in one day – impact of the drug ad assault

In an interesting piece of work, MIT’s Dan Ariely reports on research that suggests that people given identical pills receive greater pain relief from the one they think costs more. He says this might explain why people lack confidence in generic pills and believe that more expensive brand name equivalents work better.

Meantime, Reuters reports that generic drug use may have slowed the growth of U.S. prescription drug costs last year to its lowest level in more than a decade.

However, USA Today reports that drug ads are pushing more Americans to ask their doctors about drugs that are advertised. And, as a result, more docs are then recommending prescriptions.

And the Associated Press reports:

“In a David vs. Goliath battle, Pennsylvania is among a handful of states trying _ with modest results at best - to counter the pharmaceutical industry's multibillion-dollar marketing and cut costs for prescription-aid programs for senior citizens, who are bombarded with "ask your doctor" advertising.”

Drug Trials Should Not Be Done for Marketing Purposes Only

I've blogged earlier about something being smelly about the ENHANCE trial, comparing the cholesterol drug Zetia plus Zocor versus Zocor alone.

This week, a commentary in the Journal of the American Medical Association addresses some of the stink. Excerpts:

The unusual release on January 14, 2008, in the news media and on a drug company Web site, of a portion of the Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE) trial data resulted in numerous articles and commentaries in the lay media. The availability of only fragmentary information created massive confusion and raised many more questions than answers for patients, physicians, pharmaceutical companies, and regulators. A full report of the ENHANCE trial in a peer-reviewed medical journal is not expected for months, and the first public presentation of the study's findings in a medical setting will not occur before late March 2008.

Lesson 1: Drug Trials Should Not Be Done for Marketing Purposes Only

Lesson 2: The News Media Must Be Sure to Get the Facts Straight. Errors in Reporting Can Cause Serious Damage, and Patients May Be Harmed or Become Distressed From the Resulting Confusion

Lesson 3: Leading Scientific, Patient-Oriented, and Disease-Oriented Organizations Must Scrupulously Avoid Conflict of Interest

Pfizer pulls plug on Dr. J ads

This just in.

Pfizer's President of Worldwide Pharmaceutical Operations Ian Read said:

"...the way in which we presented Dr. Jarvik in these ads has, unfortunately, led to misimpressions and distractions from our primary goal of encouraging patient and physician dialogue on the leading cause of death in the world -- cardiovascular disease. We regret this. Going forward, we commit to ensuring there is greater clarity in our advertising regarding the presentation of spokespeople."

Hail the power of public opinion.

Probably the best example yet of a direct-to-consumer drug ad blowing up in the drug company's face.

FDA considers opening the door to more "off-label" promotion

In a move that leaves you wondering about health policy in this country, the Food and Drug Administration is considering loosening regulations on "off-label" promotion of drugs. The Wall Street Journal reports:

The FDA's move already is raising objections from industry critics. Democratic Rep. Henry Waxman of California wrote to the agency urging it to hold off on issuing the guidelines, which he argued would create a "large loophole" in the laws against off-label promotion. "It's a conflict of interest for the company to be promoting sales when they haven't been able to establish that a drug is safe and effective through the rigorous FDA process," Mr. Waxman said.

On his blog, Merrill Goozner writes:

As the nation grapples with how to pay for skyrocketing health care costs and policy wonks grapple with how to get more physicians to follow evidence-based medical practices, the Bush administration's FDA... has proposed opening the floodgates to wider promotion and use of unproven drugs.

There's a name for that kind of policy: Lack-of-Evidence-Based Medicine.

This is a head-scratcher. It raises anew the old questions about whom the FDA is protecting: citizens or industry.

Do statins like Lipitor "make women stupid"?

The Wall Street Journal published anecdotal reports that statins like Lipitor "make women stupid" - that the drug "dulls the minds of some patients."

The Journal reminds us that anecdotes don't equal data, but that:

Researchers at the University of California at San Diego are nearing completion of a randomized controlled trial examining the effects of statins on thinking, mood, behavior, and quality of life. Separately, the UCSD researchers are collecting anecdotal experiences of patients, good and bad, on statins; memory problems are the second most common side effect, after muscle aches, in about 5,000 reports to date.

"We have some compelling cases," says Beatrice Golomb, the study's lead researcher. In one of them, a San Diego woman, Jane Brunzie, was so forgetful that her daughter was investigating Alzheimer's care for her and refused to let her babysit for her 9-year-old granddaughter. Then the mother stopped taking a statin. "Literally, within eight days, I was back to normal -- it was that dramatic," says Mrs. Brunzie, 69 years old.

Dr. J's drug ad stunt double; fighting the fog

The New York Times provides even more questions and answers about the Lipitor ads starring artificial heart inventor Dr. Robert Jarvik.

The Times reports:

"...it has helped rekindle a smoldering debate over whether it is appropriate to aim ads for prescription drugs directly at consumers.

A Congressional committee, concerned that the Lipitor ads could be misleading, has said it wants to interview Dr. Jarvik about his role as the drug’s pitchman.

Some of the questions may involve his credentials. Even though Dr. Jarvik holds a medical degree, for example, he is not a cardiologist and is not licensed to practice medicine. So what, critics ask, qualifies him to recommend Lipitor on television — even if, as he says in some of the ads, he takes the drug himself?

And, for that matter, what qualifies him to pose as a rowing enthusiast? As it turns out, Dr. Jarvik, 61, does not actually practice the sport. The ad agency hired a stunt double for the sculling scenes."

Meantime, the Los Angeles Times has a column on a new ad campaign for a sleep disorder pill:

You'd probably be interested in a drug that'll keep you peppy even when you're running on fumes.

How about a drug that can cause depression, anxiety, hallucinations, psychosis, mania and suicidal thoughts? How about chest pain, sores or serious rashes?

You had to sift through the fine print of full-page newspaper ads that ran coast to coast last week to learn that these drugs are one and the same. The ads were for Provigil, which its maker, Cephalon Inc., is pitching to consumers as the solution for something many people might not even realize is a disorder: excessive sleepiness.

Provigil, the ads said, can help "fight the fog."

Next time I find the urge to go rowing through the fog on an early morning after a sleepless night, I hope I can find a stunt double.

Drug companies use ads to overcome what the data showed

An Advertising Age story appearing on PRWatch.org:

The pharmaceutical companies Merck and Schering-Plough, which co-market the cholesterol drug Vytorin, "have gone into damage-control mode, taking out newspaper ads." The PR campaign follows the companies' reluctant publication of a study showing that neither of the drugs present in Vytorin "reduced the buildup of fatty plaque in arteries." The study "was completed in 2006, but Merck and Schering said they didn't release it for nearly 21 months due to the complexity of the data and their own scientific concerns." The drug companies' ads, which ran in the New York Times and USA Today, refer to the damning study as "a single study that has generated a lot of confusion." The ads stress that the drugs "have been proven to lower LDL (bad) cholesterol," but what the study showed was that Vytorin is not "any better than generic Zocor in reducing the buildup of fatty plaque." Members of Congress have called for an investigation into why the "massive advertisement campaign for Vytorin was allowed to continue," after the study was belatedly made public. (The drug makers pulled their Vytorin TV -- but not print -- ads on January 22, reports Associated Press.) Class-action lawsuits are also being filed, alleging that the drug companies "misrepresented and withheld significant information" from the Food and Drug Administration and the public.

When Drug Trials Go Wrong

Don't miss an important story from the Wall Street Journal last week about things going wrong in clinical trials, questions about informed consent forms, and about liability - especially as companies speed up the pace of trials.

Possible Billion Dollar Fine For Off-Label Drug Promotion

The New York Times reports on what would be the largest fine ever paid by a drug company for violating laws on how drug makers can promote their medicines. It involves Eli Lilly's marketing of the antipsychotic drug Zyprexa.

Excerpts:

"Zyprexa has serious side effects and is approved only to treat people with schizophrenia and severe bipolar disorder. But documents from Eli Lilly show that from 2000 to 2003 the company encouraged doctors to prescribe Zyprexa to people with age-related dementia, as well as people with mild bipolar disorder who had previously had a diagnosis of depression.

Although doctors can prescribe drugs for any use once they are on the market, it is illegal for drug makers to promote their medicines for any uses not formally approved by the Food and Drug Administration. ...

Zyprexa is Lilly’s most profitable product and among the world’s best-selling medicines, with 2007 sales of $4.8 billion, about half in the United States."

More Pharma Tricks With Off-Label Claims About Their Drugs

I've been meaning to blog about this for some time.

Paul Goldberg of The Cancer Letter allowed the PRWatch.org website to post one of his columns about how the Amgen drug company seemed to try to circumvent regulations on off-label claims about drugs by inviting patient testimonials on a website called ProtectCancerPatients.org.

Goldberg wrote:

Though the Internet designation ".org" suggests that the site is operated by an advocacy group, the "privacy policy" section notes that "this site is owned and operated by Amgen Inc." and can be used for communications with the company.

On the home page, the site is described as "online headquarters of a national campaign to protect cancer patients on Medicare from a decision denying them ... coverage for needed medicines."

"Amgen's mission is to serve patients, which is why we openly support the Protect Cancer Patients website," Kelley Davenport, an Amgen spokesman, said in an email. "The site educates cancer patients on Medicare and their caregivers about a Medicare policy that impacts cancer patients, so that their voices and concerns are heard by government policymakers.

"As evidenced by the personal testimonials on the site, the current Medicare policy will have a significant, direct impact to cancer patients on chemotherapy, and will limit the ability of physicians to make well-informed treatment decisions for their patients," Davenport said.

In testimonials, patients and their family members wrote that ESAs alleviated symptoms of anemia, improved quality of life, and were essential for survival. (Excerpts from the testimonials appear below.)

Considering that ESAs are approved only as a substitute for blood transfusions in solid tumors, many of these letters were discussing off-label uses, thereby potentially exposing the company to an FDA enforcement action, said several attorneys familiar with regulation of drug promotion.

"The question is Amgen's control over what went on there," said a former FDA attorney, who spoke on condition that his name wouldn't be used. "Unless Amgen gave a blind grant to somebody and had no idea that this was going to happen, they have potential liability."

When pharmaceutical companies are caught making claims beyond the label, punishment is usually limited to warning letters and the public embarrassment they create, lawyers say. "On a lobbying campaign like this, a company like Amgen views this as just one battle in the campaign," said Sheldon Rampton, research director of the Center for Media and Democracy and author of books on the public relations industry. "It's conceivable that they may end up suffering some minor consequence, but if the rest of the effort succeeds in overturning the CMS decision, they will have lost this battle but won the war."

Drug company suppression of bad news

Journalist Jeanne Lenzer was interviewed on NPR's On The Media program last weekend, talking about drug compression suppression of negative data.

Her main points:

1.) Some patient deaths are considered "trade secrets" and are not reported

2.) New England Journal of Medicine reported last week that 97% of positive studies of antidepressants were published but only 8% of negative studies were reported as negative (the rest were either spun as positive or not reported at all).

3.) Data suppression is pervasive and affects far more than just antidepressant trials.

Pharma profits

On his blog, Merrill Goozner (author of The $800 Million Pill) writes about drug company profits at 20% of sales.

Excerpt:

"The industry may be dogged by expiring patents, a collapsing new drug pipeline, and a steady drumbeat of bad news on its best-selling drugs like Vytorin, but none of it appears to have affected the bottom line. Only beverage and tobacco companies came close to the drug industry's profit margins. Even with $3-a-gallon gasoline, the oil and gas industry lagged far behind with profits at 8.7 percent of sales.

Perhaps the pummeling the drug companies are taking on the campaign trail from the leading Democrats signals the salad days are behind the industry. Each of the leading candidates is promising to give Medicare the right to negotiate drug pricing, which, given the larger role the government is playing in overall drug sales because of the senior drug benefit, should put a dent in those profit margins."

Dr. J - all-star drug promoter

Pfizer, battling for its Lipitor drug which is now facing generic competition from simvastatin, has trotted out one-time artificial heart inventor Dr. Robert Jarvik for what have become ubiquitous TV ads. But the Wall Street Journal's health blog reports a new twist to the Dr. J story. Excerpt:

Now Congress has seen enough of Jarvik to ask Pfizer some questions about his qualifications to be recommending the cholesterol buster.

The House Committee on Energy and Commerce said today that it is investigating the use of celebrity endorsements in marketing prescription drugs directly to consumers. And Jarvik is Celebrity No. 1 on the list.

“In the ads, Dr. Jarvik appears to be giving medical advice, but apparently, he has never obtained a license to practice or prescribe medicine,” John Dingell (D-Mich.), chairman of the committee, said in a press release.

The Cost of Pushing Pills

A new article in PLoS Medicine, "The Cost of Pushing Pills: A New Estimate of Pharmaceutical Promotion Expenditures in the United States," concludes that:

"...it appears that pharmaceutical companies spend almost twice as much on promotion as they do on R&D. These numbers clearly show how promotion predominates over R&D in the pharmaceutical industry, contrary to the industry's claim. ...(This) confirms the public image of a marketing-driven industry and provides an important argument to petition in favor of transforming the workings of the industry in the direction of more research and less promotion."

Pharma free samples - who gets 'em?

The drug industry often claims that the free samples of prescription drugs they give to doctors help the uninsured or those with low incomes. But - no big surprise - a study published in the American Journal of Public Health shows those people are the least likely to get the freebies.

A Reuters story quotes co-author Dr. Sara Cutrona: "Our findings suggest the free samples serve as a marketing tool, not a safety net." Other excerpts from that story:

"About $16.4 billion in drug samples were given out in the United States in 2004, up from $4.9 billion in 1996, the study said. Distributed by sales representatives, samples are nearly always the newest, most expensive drugs, the report said.

Critics have said that in addition to steering doctors and patients to pricey drugs, samples can lead to medications being used for conditions they were not intended to treat.

Drugmakers are forbidden from recommending drugs for uses for which they have not been approved by the U.S. Food and Drug Administration, but doctors can prescribe drugs for any use.

The now-recalled painkiller Vioxx, made by Merck & Co, was the most frequently distributed free drug sample in 2002, the study found.

Vioxx was often prescribed beyond its approved uses before it was withdrawn from the marketplace because of a link to an increased rate of heart attacks and death."

Stocking Stuffers From Big Pharma

If you're hurting for last-minute stocking-stuffer ideas, you may want to ask a friendly physician for some of his/her leftover pharma fun trinkets. For inspiration, visit the website Drug Rep Toys: The toys and trinkets with which drug companies make themselves known to physicians.

More than a year ago, the publisher of the site started posting pictures of all the Pharma handouts he or his site visitors had received.

On a brief visit, I found:

• a pill counter (helpful reminder to take each and every "me too" drug)
• a calculator (helpful when tabulating one's health premium debt)
• a laser pointer (drives your dog crazy enough that he may need an anti-psychotic)
• a reflex hammer (always wanted one of those in the home toolkit)
• a six-pack tote (for self-medication)
• calipers (for wallet biopsies)
• stress balls (not a new DSM disease entity)

No one posted any pictures of airline tickets to resort settings for a "scientific meeting." I'm shopping for a different such website - perhaps one from a "key opinion leader" who has better stuff in his/her stocking this Christmas.

Something smelly about statin trial: Congress investigates

The Integrity in Science Watch project of the Center for Science in the Public Interest reports:

The investigations subcommittee of the House Energy and Commerce Committee last week gave Schering-Plough and Merck until Christmas to turn over documents from a clinical trial involving the cholesterol-lowering drug Zetia. The New York Times reported last month that the companies had failed to meet last spring's release date for a trial that compared the efficacy of a combination of Zetia and Zocor to Zocor alone. The companies then missed a fall deadline and said they wouldn’t release the data from the 720-person Enhance trial until next spring. They also wanted to change the trial's clinical endpoint, which drew heavy criticism from cardiologists who prescribe the drug. The companies backed off that decision last week and reinstated the original protocols of the trial, according to the Wall Street Journal.

The letter, signed by chairman John Dingell (D-MI) and investigations subcommittee chairman Bart Stupak (D-MI), wanted to know why the clinical trial wasn’t registered in the government’s database until 18 months after its completion. Until the recently enacted Food and Drug Administration reform law required registration of most clinical trials prior to their start-up, registration was voluntary. Zetia, whose generic name is ezetimibe, was approved by the Food and Drug Administration in 2002 because it lowered bad (LDL) cholesterol. But, unlike statin drugs, it has never been tested in a clinical trial to show that it actually decreases mortality from heart attacks and strokes. Even the Enhance trial will only measure the drug’s impact on arterial plaque, not if it reduces deaths from heart disease. The drug is sold primarily as part of Vytorin, a pill combining Zetia and Zocor (simvastatin) that has captured 20 percent of the cholesterol-lowering drug market.

Drug company ghostwriting

The Wall Street Journal's Health Blog recently had an item that suggests that drug companies' use of ghostwriters to promote positive findings and to not ask tough questions is alive and well.

Off-label drug promotion guidelines off-target

Many health policy observers are concerned about the impact of drug company promotion of "off-label uses" - unapproved or new uses of drugs that were approved for another primary use.

The FDA is now drafting guidelines on promotion of off-label uses, but the draft concerns Senator Henry Waxman, as Ed Silverman explains on his Pharmalot blog. Excerpt:

Waxman is concerned the agency is opening what he calls an “ill-advised guidance” and a big loophole for drug and device makers. The plan would allow companies to “short-circuit FDA review and approval by sponsoring drug trials that are carefully constructed to deliver positive results and then using the results to influence prescribing patterns,” he writes in a letter to FDA commish Andy von Eschenbach. “This undercuts the prohibition on marketing of unapproved uses of drugs and devices, and puts the public at risk for ineffective and dangerous uses of drugs.”

Dr. Drug Rep

The New York Times magazine on Sunday offered a fascinating insider view from a physician who agreed to work for a drug company as a speaker.

"Troubling pattern of behavior by pharmaceutical executives"

The Wall Street Journal reports:

"Over a period of several years, drug maker GlaxoSmithKline PLC was so concerned about a prominent physician's negative views of its diabetes drug that it engaged in a concerted effort to intimidate him and stifle his opinion, a report by the U.S. Senate Finance Committee found.

The report offers a window into the rarely acknowledged practice among drug companies of monitoring and seeking to influence the opinions of leading physicians, who can make or break a drug's sales.

The Senate Finance Committee released the report Thursday, after researching Glaxo's relationship with John Buse, a diabetes expert and professor of medicine at the University of North Carolina in Chapel Hill. In 1999, Dr. Buse began expressing concerns about the cardiovascular risks of Avandia, one of Glaxo's top selling drugs.

The Senate Finance Committee investigated the matter because it has jurisdiction over Medicare and Medicaid and wants to ensure that they are paying for safe and effective medicines, the report says. The committee, led by Montana Democrat Max Baucus and Iowa Republican Chuck Grassley, didn't recommend any particular action. It said it feared the Avandia case was part of a "troubling pattern of behavior by pharmaceutical executives."

"The effect of silencing [Dr. Buse's] criticism is, in our opinion, extremely serious," the report concludes, noting that patients may have needlessly suffered heart attacks during the period. "Had GSK considered Avandia's increased cardiovascular risk more seriously when the issue was first raised in 1999 by Dr. Buse, instead of trying to smother an independent medical opinion, some of these heart attacks may have been avoided," the report says.

This week, the Food and Drug Administration forced Glaxo to add a strong new warning to Avandia's prescribing label about potential heart-attack risks for patients taking the drug.

A Glaxo spokeswoman, Nancy Pekarek, said the company strongly disputes the committee's conclusions. She said Glaxo had tried to correct Dr. Buse's "inaccuracies" about Avandia but had never tried to intimidate or silence him."

Consumer Reports' terrific new drug ad watch

You must see Consumer Reports' terrific new "antidote to TV drug ads" - its new AdWatch feature.

In it, they dismantle the claims made in the ads for the drug Requip for restless leg syndrome.

I've spoken with some folks at CR and they're very pleased with the initial response to the new feature and plan many more like it.