Alan Milstein on Pfizer and Torcetrapib

The media coverage of the recent termination of the Pfizer torcetrapib clinical trial has been nothing short of startling in this age of aggressive investigative journalism. In short, the stories have been about Money, Money, Money. In announcing the halt of this experiment after a finding that human subjects had died because of their participation, the New York Times announced, “End of Drug Trial is a Big Loss for Pfizer.” Bloomberg broke the story by observing: “Pfizer Shares Drop After Company Abandons Cholesterol Drug.” The Toronto Star had a different take: ‘Drug Failure Cost Pfizer 23 Billion.”

In its front page story, the New York Times further added this remarkable conclusion: “Pfizer will not face the product liability lawsuits that have dogged Merck over its painkiller, Vioxx . . . Patients in clinical trials must sign waivers confirming that they understand the risks they face when they take unapproved medicines in clinical trials.” Do they?.

Why am I skeptical? Money. Money. Money. Pfizer had long touted this drug in meetings with shareholders, actual and potential, as the Mother of all Blockbusters. Could this potential have delayed the end of this experiment, even though some researchers had long warned that such drugs might actually pose more risks than benefits.

Two aspects of this trial, what surprisingly little we know about it, trouble me. First, the experiment took place largely in the offices of thousands of cardiologists across the country. What this means is that the subjects may have been induced to participate by their long trusted physician and signed on not to better mankind (or “Pfizer”) but because they believed their physician thought it was in their best therapeutic interest to do so. This might make the informed consent document neither voluntary nor informed.

Second, Pfizer says the delay in halting the trial was because this was a double blinded experiment with one arm taking Lipitor only and the other adding torcetrpib. Only when the data managing subcontractor removed the blinds were the devastating results revealed.

Call me naïve (I’ve been called worse), but why double blind a study where the data is comprised of good and bad cholesterol numbers? Does anyone believe there could be a placebo response that would raise good cholesterol? I have long advocated that the industry’s reliance on this “gold standard” is not always to eliminate researcher bias or that dreaded placebo response. Sometimes it is to keep subjects and physicians in the game. And if this had not been a double blinded study, could the ongoing results have been known to the physicians and disclosed to their patients earlier?
Alan Milstein

Pharma Discusses How to be Ethical

Pharmaceutical Executive prints a transcript of the proceedings of a high-power discussion of how to be ethical in the pharmaceutical business. "The conversation was moderated by Joseph Cohen, a partner at the law firm. The participants were Raul Perea-Henze, MD, senior director/team leader, science and medical advocacy, for Pfizer; Roger Louis, chief compliance officer for Genzyme; Nicholas Capaldi, PhD, Legendre-Soule chair in business ethics at Loyola University New Orleans; Kevin Soden, MD, worldwide medical director for Texas Instruments and Celanese, and medical reporter for NBC and MSNBC; and Patrick Clinton, editor-in-chief of Pharm Exec." Trust me, you want to read this. But go get a good strong drink first, then re-open your laptop.

Pfizer and Merck: Different Strokes

Business Week discusses the difference between the two drugmakers reactions to safety issues surrounding Celebrex and Vioxx.

Well, NIH Doesn't Pay a Lot

So P. Trey Sunderland III, leading NIH psychiatric researcher, earned $508,050 from Pfizer while working for NIH.

But did the Celebrex Guys Train There?

The Yale Herald reports on the completion of the Pfizer building in New Haven, where it is setting up shop to do an incredible amount of clinical research. Bob Levine and Samuel Gorovitz are quoted. The relationship with Yale promises to be, um, interesting:

THE CONSTRUCTION SITE OVERLOOKS the Yale Medical School, a neighbor which Pfizer is glad to have. In fact, the Medical School proved a tipping point in Pfizer's decision to build its new unit in New Haven.

Dr. Robert Alpern, Dean of the Medical School, expressed enthusiasm over collaborations between the institutions. "We're extremely excited about the opening of the unit in New Haven," he said. "Pfizer has a lot of talent, skills, and resources that Yale doesn't have, and vice versa, so we think we're actually in a position to help each other a lot" ...

And also, well, there are lots of really poor people in New Haven with not much to do, which prompts all sorts of interesting criticism

When Pfizer announced its plans in 2003, the initial reaction from the people of New Haven was mixed. The New Haven Advocate featured an article on its front cover, headlined, "Guinea Pig City." Written by Paul Bass, the article accused Pfizer of exploiting the inner city population of New Haven by offering volunteers high prices to take experimental drugs. Bass proposes that Pfizer allow community input on its ethical review boards.

Levine is point-blank about the risks of this cozy relationship: "'What if Pfizer says we want certain sorts of research done here? Are the review committees at Yale going to be intimidated? These people have already given us a $35 million building plus the funding, so we better do what they want,' said Levine. 'Even to a university with Yale's endowment, that's a pretty attractive thing.'"

What's Up Roundup

Ten myths about assisted suicide from Spiked Liberties.

Ethics of compulsory drug screening.

Amusing "please call our expert" release on Pfizer Celebrex heart risks, from Saint Louis University

Knight Ridder piece by April Lynch on hiding genetic testing results from insurance companies

Another PR piece fed to the media on an ethicist, this time Penn's Martha Farah and neuroethics.

Depo-Provera Safety

Majikthise blogs a London Globe and Mail news release that is getting almost no media attention in the U.S.: Pfizer's injectible contraceptive can cause irreversible bone loss, putting users at significantly increased risk for osteoporosis. FDA has just required Pfizer to put a black box warning on Depo indicating that it should be used only if no other birth control mechanism is adequate. Where are the discussions of the evolution of this warning?