Merck making waves, again

August 21, 2008 – 12:51 pm

Merck made headlines not just once, but twice this week, and not in a nice way. First, Merck has been accused of conducting a trial for Vioxx not based on science, but strictly for marketing purposes, without informing the doctors what the trial was all about. Pharma bloggers hopped all over that one. The second story, in the New York Times, chronicled the rise of the HPV vaccine Gardasil. The writer, Elisabeth Rosenthal, has raised some questions about whether the cost of getting every girl vaccinated is worth the benefits or the possible, not-yet-understood risks, but a lot of the news she talks about is old stuff. There’s been some reaction from bloggers, but not as much as I thought. Maybe it will take a few days for folks to gather their thoughts. Meanwhile, you can see some of my thoughts, and what I’ve managed to dredge up from the blogosphere about Gardasil, below.

Seeds of suspicion

Ed Silverman at Pharmalot, back from vacation, picks up the AP story about the 1999 Vioxx study, as well as provides a link to the original report in the Annals of Internal Medicine. Mr. Silverman notes that Merck has denied the accusations. “Merck spokesman Ron Rogers tells the AP that Hill and his colleagues have been critics of Merck and just cherrypicked ’some documents to support their thesis,’” Mr. Silverman says.

Mr. Silverman talks with Dr. Kevin Hill, one of the writers of the paper, who explains that seeding trials are not new, but the paper is the first to show how a pharmaceutical company designed and conducted a seeding trial. “…what’s troubling is that physicians and patients weren’t told of the objective of the trial,” Dr. Hill tells Pharmalot. “And that’s problematic, because patients risk their health when they are signed up for such a trial, instead of advancing the cause of science.”

Jacob Goldstein at the Wall Street Journal Health Blog also picks up the AP story, and gets a quote from Jonathan Edelman, a senior official at Merck Research Laboratories. Mr. Edelman says the study was done to answer important medical questions, and, “This is a trial that had good, scientific merit and was judged by the editors of the Annals when they accepted it for publication.”

John Mack at the Pharma Marketing Blog meanwhile shares some jokes about Merck gleaned from the message board at Cafe Pharma. I like that he picked up this internal document from Merck, which has a discussion by Merck’s PR department about how to pitch the results of the Advantage study to the media. He finds some of the statements amusing, as do I. Here’s a direct quote, in the original caps: “PLEASE EXCISE THE WORD PITCH LETTER FROM YOUR WRITTEN VOCABULARY. WE MAY USE THE TERM IN TALKING, I DO NOT LIKE IT IN DOCUMENTS. THESE ARE MEDIA DISCUSSION LETTERS, NOT PITCH LETTERS. PITCHING IS WHAT USED CAR SALESMEN DO. I’D LIKE TO THINK WE ARE DIFFERENT. THINK ABOUT DEFENDING THE TERM PITCH LETTER TO A CONGRESSIONAL COMMITTEE OR DDMAC.”

Oh, for crying out loud, pharma PR people … stop deluding yourselves. Whether you call it a “media discussion letter” or a “pitch letter,” the aim is the same: to get a reporter or assigning editor to take notice of what you are announcing and either write a story or (even better for you) just run the release, no questions asked. The term “media discussion letter’ is perhaps even more inaccurate, because that implies that there will be a discussion at some point. The plain truth is, most of the time, there is not. The sheer volume of releases the average reporter receives each day, and news considerations, preclude this. And the replacement term “media discussion letter” is just plain weasel-worded.

But I digress. Dr. Daniel Carlat at the Carlat Psychiatry blog also takes a look at the seeding study issue, and also talks with Dr. Hill. Dr. Carlat gets Dr. Hill to describe the purpose of a seeding trial (”A seeding trial is a study that is designed to appear as though it is answering a scientific question but whose true purpose is to market a medication.”) and how it differentiates from a regular clinical trial.

“…So the ’seeds’ are the physician/researchers, and the hope is that these seeds grow into a positive buzz for Vioxx among colleagues,” Dr. Carlat says. “Exactly,” Dr. Hill responds.

The anonymous blogger at Clinical Psychology and Psychiatry: A Closer Look expresses contempt for Merck’s methods. “… using the guise of science to recruit naive (or greedy) physicians to serve as Vioxx pushers is contemptible,” this blogger says.

Dr. Roy Poses at Healthcare Renewal tells us the importance of the Annals report. “The article demonstrates how clinical research may be twisted into marketing,” he says. “The article demonstrates how an ostensibly scientific endeavor may be based on deception, when science is supposed to be about the pursuit of truth. The article demonstrates how the ethos of the huckster has replaced that of the physician in large organizations once regarded as ethical. Once again, this is a reminder that patients, physicians and policy makers must be extremely skeptical of clinical research sponsored by organizations which have something to gain if the research turns out a certain way. Furthermore, it is a reminder to physicians that generous offers from organizations selling products, services or ideologies do not arise from altruism.”

Dr. Poses’ fellow blogger at Healthcare Renewal, Dr. Scot M. Silverstein, asks, “Who actually was in charge of R&D?” He raises some interesting questions, for example, pointing out that even though the president of Merck Research Labs, Dr. Edward Scolnick, questioned the value of the Advantage trial, he apparently could not stop it. “If the President of the Research Labs, ostensibly the head of R&D at the company, could not stop such a ’seed trial’ study of a drug not yet released and/or its publication, then who was actually in charge of R&D?” Dr. Silverstein asks. “Why did Roger Perlmutter, M.D., Ph.D., former Merck Executive Vice President of Worldwide Basic and Preclinical Research — who was believed to be Merck Research Labs (MRL) leadership heir apparent — suddenly leave Merck in 2001? Could it have something to do with perceived lack of control of the MRL President’s office over pre-release drug studies?”

Lots of questions have been raised by this paper, and Merck has to do a better job of explaining what went on. And if anyone at Merck is reading this, feel free to send me a pitch letter. Or even better, call me!

More frenzy over Gardasil

Jim Edwards at Jim Edwards’ NRx was quite puzzled over Ms. Rosenthal’s article. “The Times is finally bringing down the hammer on one of the most controversial drug launches ever, just like I predicted … right?” he says. “Er, no. The piece has a number of problems that will leave drug industry folk scratching their heads as to why it was published. Doubtless the folks at Drug Wonks are already banging furiously at their keyboards in outrage at the Times’ anti-pharma bias.”

Ed Silverman at Pharmalot, meanwhile, picked up the study from the New England Journal of Medicine that concludes Gardasil is not worth the cost for women over the age of 18. “The study … comes as the drugmaker is already struggling to convince college-age and older women to get the vaccine, which costs about $360 for a three-dose regimen,” he says. Mr. Silverman is referring to Merck’s Tuesday announcement that the company is offering a free replacement dosage of Gardasil to doctors if an insurer refuses coverage.

Jacob Goldstein also picked up the NEJM study at the Wall Street Journal Health Blog. “A Merck official told Dow Jones that the editorial raised “theoretical concerns that have been considered and largely dismissed by the scientific community,” Mr. Goldstein says.

Dr. Robert Goldberg at DrugWonks leaps into the fray, asking, “Is it worth letting women get cervical cancer?” “I guess if you take a ’societal’ (read government or HMO) perspective it does, especially if you believe that an additional year of disease-free life for a women 21-26 is only worth $100K, which is an arbitrary number developed in 1985 that reflects a ’societal perspective’ on the cut off or rationing point.” he says.

Merrill Goozner at GoozNews has his own perspective on the New York Times story and the NEJM study. He says the money that states spend on Gardasil vaccinations could be better spent on smoking cessation programs, diabetes prevention programs, and screening programs for alcohol abuse, but “It’s a lot easier for the pols to take Merck’s corporate campaign contributions, pass a vaccine mandate, and ask the health care system to pick up the tab. The still unfolding Gardasil story provides a textbook example of why we spend more than any country on earth on health care, yet still rank in the second tier in terms of life expectancy. We’re throwing big bucks at small problems while ignoring the obesity, smoking, and substance abuse epidemics that are the major drivers of poor health in our society.”

Poking around at BlogHer, I’ve found that the main complaint is that Merck is using fear to drive parents to get their children vaccinated, and these moms do not like that at all, not one little bit, and they don’t like being mandated to vaccinate their children.

Here’s my opinion on this (and you can go ahead and take it with a whole salt mine). I think both Merck’s campaign and all of the accompanying stories that criticize the value of Gardasil overlook something that could be more significant. Merck’s campaign drives people to think that they’re protecting their daughters from cervical cancer, but really, when you get down to it, Gardasil protects against getting severe cervical dysplasia, or precancerous lesions, from HPV. Although Gardasil has not been shown at this point to reduce cervical cancer, it has been shown to be effective in reducing the risk of these lesions.

Now here’s what I think has been overlooked in this discussion. Most often what’s done to treat severe cervical dysplasia is a cone biopsy, to make sure every single abnormal cell is eliminated. For the men reading this: That means the doctor is taking a chunk out of the cervix either using a laser or a scalpel (for milder cases of dysplasia, cryosurgery or electrocauterization are used, but if the doctor suspects carcinoma and wants a good sample of cells, he or she will opt for cone biopsy and the knife). Although all of these procedures are performed on an outpatient basis, a cone biopsy involves general anesthesia; the patient needs to be observed for a few hours in a recovery room and is told not to drive herself home from the procedure because she can be in pain and still fuddled from the anesthesia. Everyone I have known who has had it done has needed at least a day off to recover (and sometimes two or three, in addition to the day they had to take off to get the procedure done). For some women (not a lot, but some), cone biopsies can scar and weaken their cervixes so that they have a harder time getting pregnant or can’t bear children to term.

A rundown of the various procedures done to remove abnormal cells, plus the side effects from each procedure, can be found here. (Side effects of the cryosurgery procedure, for example, are, “Fainting, hot flushes, severe abdominal pain that lasts a short period of time, and small chance of infection.” Oh, that sounds like SO much FUN! Sign me up for some of THAT!)

So, ultimately, how many days of productivity are lost from having to get a cone biopsy or other procedure to remove abnormal cells? Does anyone know this? I am sure it’s not a small number, and if Gardasil can cut down the number of these types of procedures and their accompanying lost hours of productivity (perhaps reducing employers’ healthcare costs and maybe reducing cases of infertility), that in itself may be a more compelling reason than the shadowy fear of cancer.

I do agree that parents should have the choice of getting their kids vaccinated with Gardasil, and not be mandated by the law to do so. I feel differently about contagious and potentially deadly diseases such as smallpox, mumps, polio, and measles — the parents who believe that all vaccines are bad would maybe change their tune fast if smallpox made a comeback, as whooping cough has in Colorado or measles in seven states.

Ultimately, my suppositions will vanish in a puff of hot air if it’s proved that Gardasil vaccinations do not decrease the number of cone biopsies or other cervical dysplasia treatment procedures done. If anyone has been able to figure this out, please let me know. A pitch letter is fine …

Around and about …

Jim Edwards at Jim EdwardsNRx points out an interesting little battle at Genentech’s CafePharma board. A religious “discussion,” of all things, between atheists and Christians. One gets the feeling that it’s not all Genentech employees in on this one.

Here’s a partial rundown of what Ed Silverman at Pharmalot has found interesting since he has gotten back from vacation: GlaxoSmithKline is going to disclose educational and charitable grants; FDA wants more information on J&J’s pneumonia drug Doribax; Schering-Plough CEO Fred Hassan will have to testify on videotape in a Celebrex trial this fall; a drug company must provide an experimental drug to a 16-year-old boy suffering from a rare form of muscular dystrophy; cancer grabs the largest share of clinical trials (FYI, our repeat feature in R&D Directions about the top 10 therapeutic areas has named cancer as the top drug development area for drugs for years; the sheer number of compounds in development remains high and keeps increasing); the deaths of 49 infants involved in clinical trials at an Indian hospital are being investigated; Roche is trying to bar an expert witness in an Accutane trial; and he continues to wonder whether Vytorin scrips can go any lower (and links to some juicy gossip on Cafe Pharma).

Picking up some non-repeating stuff from the Wall Street Journal Health Blog, Scott Hensley says the coverage of the Vytorin cancer data has faded quickly. “Our colleagues at Dow Jones Insight, who track press coverage, took a look at Vytorin mentions over the last year,” he says. “There was a huge spike in coverage of Vytorin to 512 stories during the week starting July 21. But … the attention was short-lived, and even at its peak the coverage was less intense than the jump at the end of March when disappointing data from the Enhance trial were presented at a meeting of the American College of Cardiology.” (You can see a chart by clicking the link.) Jacob Goldstein picks up the London Observer story in which the chairman of U.K.’s NICE proclaims that high drug prices fatten pharm execs’ paychecks. Mr. Goldstein also looks at how FDA is trying to figure out how to reduce deaths from prescription narcotics.

John Mack at the Pharma Marketing Blog finds some interesting information at Cafe Pharma about what could be a new trend: doctors’ offices banning free drug samples. And check out the lyrics to “The Hotel Calipharma.” If the original anonymous poster can’t continue as a pharma rep, that person’s future may be in comedy writing.

Dr. Howard Brody at Hooked: Medicine, Ethics, and Pharma, asks what really happened in the debate that led to SSRI warnings.

Peter Pitts at DrugWonks wonders whether it seems counterintuitive that universal healthcare results in restricted access and poor outcomes. He looks at some studies of survival outcomes and healthcare costs and concludes, “Pharma is not the enemy – disease is the enemy.”

JNJBTW has more employee blogging from Beijing. Diego Lombera MartÍnez, junior sales representative, Johnson & Johnson Medical Mexico, shares his impressions of the city and the Chinese. “The Chinese are very nice and everybody is ready to help you,” he says. “The first impressions from our trip so far are very spectacular!”

The blogger at Pharm-Aid speaks out against rationing care. “Tara Parker-Pope’s recent article on prostate cancer in the New York Times just about sent me over the edge,” this blogger complains. “Of course, what Tara Parker-Pope doesn’t tell readers is the motivation behind the article. The rationing of care, particularly for men’s prostate cancer, has been an agenda item for America’s Health Insurance Plans (AHIP). AHIP, in an effort to boost profits for its members corporations, has been selecting disease categories to target for restricting care. If the standard of care becomes to not test or treat for prostate cancer, these corporations could save loads of money. Who cares if an extra 30,000 to 50,000 men die?”

Fard Johnmar at Healthcare Vox looks at research that says most online communities tank, and he tries to figure out why that is the case. In fact, he wants you to talk about it at his Facebook page (caveat: you have to have a Facebook account to see it). BTW, yes, I have a Facebook account, but I hardly spend any time there, because of all the stupid time-sucking, potentially identity-thieving apps people keep “inviting” me into. No, I don’t want to join your vampire, zombie, slayer, or other armies, find out how hot I am, play Scrabble, “hug” you (or throw a donut or a beer or a flower, etc.), or find out if we have shared movie interests, or post stuff on your FunWall. K, thx, bye.

Thomas Sullivan at Policy and Medicine says doctors appreciate commercial support of CME. Well, of course they do! Who doesn’t like free stuff, especially free stuff that you’d otherwise have to spend your own hard-earned cash for?

Well, that’s it for me for this entry. As Mr. Silverman, a fellow “caffiend,” would say, it’s time to seek out a hot beverage. …