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

More Opaque than Transparent: Drug Industry Just Does Not Get It

Boston Globe lays into the pharmaceutical industry on its failure to deliver openness on data from its own clinical trials. -- Art Caplan

AIDS Fatigue: Celia Farber on "the AIDS Spin Machine"

From New York Press, a lengthy and thorough argument, right or wrong, from Celia Farber, with particular attention to Uganda and to Jonathan Fishbein:

After 20 years of hysteria, alarmism, misplaced recrimination and guilt, AIDS fatigue has beaten the newspaper-reading mind into a kind of blank. Citizens can't be faulted for not knowing how exactly to respond to last week's eruption of scandal from an NIH whistle-blower named Jonathan Fishbein, an AIDS researcher charged with overseeing clinical trials here and abroad. A reverberating language of bureaucracy and euphemism surrounds AIDS stories, making it impossible to know what has actually transpired. When people die from AIDS drugs, for instance, the word "death" is studiously avoided. I have seen medical articles documenting the fact that more people now die of toxicities from AIDS drugs than from the vanishingly opaque syndrome we once called AIDS. Death was referred to as a "grade four event," thus placing it eerily within the acceptable parameters of predictable phenomena in AIDS research—not as a failure, a crisis or even something to lament.

All Sorts of NY Times Stuff: Autism, Clinical Trials, Tsunami

The NY Times reported this week that many with autism have essentially adopted the argument of those with Downs who make the claim that theirs is a different form of human life and experience, rather than a disability, syndrome or disease. Now they cover the absence of real evidence on what cures autism, if anything, and the meaning of that absence for patients and the health professions. Getting treatment for autism is increasingly difficult, because insurers do not want to pay, and the burden on siblings is more profound that has been realized. Each of these articles will be helpful for anyone dealing either with autism or with the more general issues in the ethics of just distribution of health care.

One piece on the Celebrex, Vioxx, Aleve problems and their implications for public perception of the FDA.

Are physicians boring? Like this needed an article.

NY Times covers medical relief efforts in the aftermath of the incredible tsunami devastation. This piece itemizes the hurdles that physicians and other health relief forces will face. Among the most significant distribution issues is one that involves the general inability of international and national groups in healthcare to work together or to do their own logistics:

The aim is to avoid much of the competition and lack of coordination that have hampered the response of governments and private organizations to earlier catastrophes, Robert Holden, a member of the command center team, said in a telephone interview. In responding to the tsunami in South and Southeast Asia, he said: "The biggest problem is ensuring that those who survived continue to survive and provide the materials they need. We must avoid creating a secondary disaster because we can't get the necessary materials through."

Denise Grady writes about the lives of five people enrolled in different clinical trials. This piece should be used by anyone teaching research ethics to clinicians.

An AIDS Vaccine that Works??

Nature Medicine reports that a French research trial fuels hope for prevention and mollification of the effects of HIV infection. Even as preliminary data, this is promises to be the biggest news in the history of HIV & AIDS research and will be cause for much discussion about next steps. The sample size is very very small and it is very important that the results not be blown out of proportion, which no doubt they will - although at the time of this posting lots of American papers are clueless about this finding. But let's just say that the research pans out ... what happens then? Let your mind wander back to the early science and policy wars over the way in which AIDS research is prioritized, and then consider a political world in which gay marriage might have been the defining issue in an election that brought to power a president who "owes" fundamentalist protestants and despises the UN...

Women and Infants in HIV Trials

A WHO and UNAIDS meeting discussed the issues of gender and age, as well as race, in HIV trials. Macklin is quoted: "We have identified measures aimed at rectifying the injustice stemming from the frequent exclusion or low participation of women and adolescents in HIV vaccine clinical trials. Clinical trial enrolment needs to be more inclusive, so the benefits of research are more fairly distributed."

FT.com: ReNeuron hES Stroke Therapy "Ready for Trial"

Financial Times' David Firn reports that an honest-to-goodness hES clinical trial is ready to start for the improvement of sensory motor abilities lost in stroke.