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News flash! Doctors aren’t all compliant pharma drones!

There’s an oft-quoted saying that’s become a bit of a cliché among skeptics that goes something like this: There are two kinds of medicine: medicine that’s been proven scientifically to work, and medicine that hasn’t. This is then often followed up with a rhetorical question and its answer: What do call “alternative medicine” that’s been proven to work? Medicine. Of course, being the kind of guy that I am, I have to make it a bit more complicated than that while driving home in essence the same message. In my hands, the way this argument goes is that the whole concept of “alternative” medicine is a false dichotomy. There is no such thing. In reality, there are three kinds of medicine: Medicine that has been shown to efficacious and safe (i.e., shown to work); medicine that has not yet been shown to work (i.e., that is unproven); and medicine that has been shown not to work (i.e., that is disproven). So-called “complementary and alternative medicine” (CAM or, its newer, shinier name, “integrative medicine”) consists almost completely of the latter two categories.

Part of the reason why this saying and its variants have become so commonplace among those of us who support science-based medicine is that they strike at a common truth about medicine, both science-based and “alternative.” That common truth is what we here at SBM have been arguing since the very inception of this blog, namely that there must be one science-based standard of evidence for all treatments, be they “alternative” or the latest creation of big pharma. That point informs everything I write here and everything my blogging parters in crime write about too. What that means is a single, clear set of standards for evaluating medical evidence, in which clinical evidence is coupled to basic science and scientific plausibility. Indeed, one of our main complaints against CAM and its supporters has been how they invoke a double standard, in which they expect their therapies to be accepted as “working” on the basis of a much lower standard of evidence. Indeed, when they see high quality clinical trials demonstrating that, for example, acupuncture doesn’t work, they will frequently advocate the use of “pragmatic” trials, lower quality trials of “real world effectiveness” that do not adequately control for placebo effects. It’s putting the cart before the horse.
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Posted in: Clinical Trials, Pharmaceuticals, Politics and Regulation

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Don’t Believe The Hype: Cholinesterase Inhibitors As A Treatment For Dementia

Don’t Believe The Hype: Cholinesterase Inhibitors As A Treatment For Dementia
I distinctly remember the day I attended a “drug lunch” (as a PM&R resident in New York City) to learn about the value of donepezil (aricept) for the treatment of dementia. I was astonished by the drug’s lack of efficacy – the graph displayed in the PowerPoint show demonstrated a 2-point improvement on the Mini Mental State Exam (MMSE), an effect that began after 6 months of donepezil use, and persisted for only 6 months after that. A 2-point difference on the MMSE has no clinical relevance of which I’m aware. The drug’s common side effects include: nausea, vomiting, diarrhea, loss of appetite, tiredness, drowsiness, trouble sleeping, or muscle cramps. That day I vowed never to prescribe the drug to my elderly patients.
Nonetheless, I was dumbfounded by the number of patients who came to the hospital already on the medication. Over and over again I heard the same story: “mom is becoming forgetful so our doctor started her on this medication to help her memory.”
When I asked if the family if they thought the medicine helped, the response was equally predictable: a shrug and then “what else can we do?”
Here we have a classic example of a medical problem with no satisfactory treatment or cure – and a desperate desire on the part of patients and family members to do something – anything – about it. Many times people in these predicaments turn to alternative medicines, herbal supplements and faith –based remedies. And sometimes they turn to FDA-approved drugs.
The Cochrane Collaborative has reviewed the scientific literature on the use of cholinesterase inhibitors (like donepezil) in mild dementia, and has found:
There is no evidence to support the use of donepezil for patients with mild cognitive impairment (MCI). The putative benefits are minor, short lived and associated with significant side effects. http://www.cochrane.org/reviews/en/ab006104.html
So how did this drug get approved? Well, there do seem to be some small improvements (of dubious clinical significance in my opinion) in measures of cognitive impairment in patients with Alzheimer’s dementia in particular. http://www.cochrane.org/reviews/en/ab005593.html
AHRQ states:
The evidence is mixed, however, about the effects of cholinesterase inhibitors on functional measures such as instrumental activities of daily living (i.e., ability to use the telephone, mode of transportation, responsibility for medication, and ability to handle finances). In general, the studies show little or no effect on functional decline after 6 months of treatment and a small but statistically significant difference from placebo after 12 months of treatment.
Research has found no clinically important differences between people taking cholinesterase inhibitors and those taking placebo in the development of behavioral and psychological symptoms… Studies rarely addressed other important health outcomes such as utilization of health care services, injuries, and caregiver burden.
http://www.ahrq.gov/clinic/3rduspstf/dementia/dementsum.htm
Pfizer’s press release (when they received FDA approval to market Aricept in 1996) noted:
Alzheimer’s disease is a family tragedy. ARICEPT will benefit patients and families alike by improving or maintaining patient function, which in turn may help ease the burden for caregivers and help maintain personal dignity… “ARICEPT represents a significant step forward in addressing the therapeutic needs of the Alzheimer’s disease community…This therapy will help to change the approach to the management of Alzheimer’s disease.
http://www.pslgroup.com/dg/e2aa.htm
Global sales of Aricept were approximately $1.1 billion for 2008 alone.
Me-too cholinesterase inhibitors have seen similar global profits, with sales of namenda at about $1 billion as well in 2008. http://www.businessweek.com/magazine/content/04_14/b3877629_mz073.htm All this while the AHRQ can find no clinically relevant difference between the drugs in this class, and the effects they have are small and short lived.
There are pharmaceutical innovations that have changed the course of history (imagine where we’d be without the polio or smallpox vaccines), while others leverage the tiniest statistically-significant effects to drive global drug empires driven by public feelings of helplessness in the face of currently incurable diseases.
It’s no wonder that the public has a mistrust of pharma – their marketing engines drive sales of drugs that have vastly different clinical value. That means it’s up to physicians and scientists to tease out the legitimate enthusiasm from the marketing hype. And judging from all the patients with mild dementia that I see on cholinesterase inhibitors, I give us a failing grade.

I distinctly remember the day I attended a “drug lunch” (as a PM&R resident in New York City) to learn about the value of donepezil (Aricept) for the treatment of dementia. I was surprised by the drug’s lack of efficacy – the graph displayed in the PowerPoint show demonstrated a 2-point improvement on the Mini Mental State Exam (MMSE), an effect that began after 6 months of donepezil use, and persisted for only 6 months after that. A 2-point difference on the MMSE has no clinical relevance of which I’m aware. The drug’s common side effects include: nausea, vomiting, diarrhea, loss of appetite, tiredness, drowsiness, trouble sleeping, or muscle cramps. That day I realized that the risk-benefit profile did not support its use.

Nonetheless, I was perplexed by the number of patients who came to the hospital already on the medication. Over and over again I heard the same story: “Mom is becoming forgetful so our doctor started her on this medication to help her memory.” (more…)

Posted in: Pharmaceuticals

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