Healthy Skepticism Library item: 6378

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Publication type: news

Duffy A.
Studies challenge drugmakers' claims
The Ottawa Citizen 2006 Oct 26

Full text:

Studies challenge drugmakers’ claims
Canadians are spending tens of millions of dollars on drugs that offer only
‘modest,’ short-term benefits, according to a federal-provincial research
review

Andrew Duffy, The Ottawa Citizen
Published: Thursday, October 26, 2006

Canadians spent $143 million last year on three major drugs to treat
Alzheimer’s disease, but a national study suggests that investment produces
few meaningful results for patients or their caregivers.

The Canadian Agency for Drugs and Technologies in Health last year completed
a thorough review of drug trials related to the Alzheimer’s drugs Aricept,
Exelon and Reminyl.

The products belong to a class of drugs known as cholinesterase inhibitors,
designed to hinder the breakdown of a brain chemical essential to memory and
concentration.

They came onto the Canadian market in the late 1990s with great fanfare.
Some studies suggested the drugs could slow the advance of Alzheimer’s,
delay nursing-home placements and significantly reduce the cost of care.

Drug manufacturer Pfizer Canada claimed that Aricept, the first Alzheimer’s
medication approved in Canada, could improve the quality of life for
patients and caregivers for up to three years.

But a series of recent studies, including the review by Canada’s drug
agency, have concluded that the compounds offer only marginal, short-lived
benefits.

In its 118-page report, issued in September 2005, the Agency for Drugs and
Technologies in Health found a “statistically significant, yet modest”
improvement in the cognitive function of Alzheimer’s patients who used the
drugs. There is no evidence, it said, that Aricept improved the quality of
life of patients or delayed their institutionalization.

Researchers considered evidence from 25 drug trials that followed patients
for at least 12 weeks.

“Although statistical improvements were noted in the analyses, they do not
necessarily translate into clinically relevant benefits for the patients
receiving these drugs or for their caregivers,” the research panel found.

The report invited provincial politicians to make the final determination as
to whether the drugs’ modest, short-term clinical benefits are worth their
escalating annual cost. The drugs — any of which can cost more than $1,800
for a year’s supply — continue to be widely prescribed.

“As a result, policy and decision makers are faced with the difficult
decision of whether to make these drugs available because of pressure from
families and caregivers,” the drug agency report concludes.

The little-known agency reviews the effectiveness of prescription drugs for
provincial officials who then must decide what products to make available
under their publicly funded drug plans.

Two provinces, British Columbia and Newfoundland and Labrador, refuse to
cover the Alzheimer’s drugs.

Last year, a B.C. drug research group also examined clinical-trial evidence
for the four Alzheimer’s drugs now approved in Canada. (The fourth, Ebixa, a
neuro-receptor antagonist, was approved in 2004 to treat moderate to severe
Alzheimer’s disease.) The B.C. Therapeutics Initiative concluded that all
four products have not been shown to improve outcomes of importance to
patients and caregivers.

The researchers said there’s no evidence that the drugs delay important
milestones, such as the loss of the ability to read, write or hold
conversations; to enjoy television or music; or to stay at home.

Most Alzheimer’s patients eventually require institutional care and the
purported ability of Aricept and other inhibitors to delay that outcome has
been a powerful selling point.

But a key British study, published by the medical journal The Lancet in June
2004, found that Aricept does not reduce the risk that an Alzheimer’s
patient will enter institutional care.

Known as the AD2000 Study, it was led by researchers at the University of
Birmingham who followed 565 patients with mild to moderate symptoms for up
to 26 months, measuring the time it took them to enter nursing homes or
suffer disabilities. The researchers found no significant difference between
the experiences of those who took Aricept and those who took a placebo.

Taken together, the studies have dissipated the optimism that greeted the
arrival of Aricept on the Canadian market almost a decade ago.

Indeed, there is growing controversy about the merit of prescribing the
existing drugs to Alzheimer’s patients in light of their cost and their side
effects, which can include severe stomach upset and nausea.

Alan Cassels, a pharmaceutical policy researcher at the University of
Victoria who has studied the Alzheimer’s medications, said the sales of the
drugs have been driven by desperation, not science.

“With these drugs … the marketing and hype around them far, far eclipses
the evidence,” Mr. Cassels said.

Patients need to be fully informed, he said, about the marginal benefits and
potentially significant side-effects of the drugs. What’s more, he said,
taxpayers need to understand that by funding these drugs their governments
eliminate the possibility of paying for other, more valuable health care
services.

“People have to ask themselves, ‘What are we not going to fund because we
pay for these drugs?’” Mr. Cassels said.

“For the marginal benefit you are getting from these drugs, how much better
could you make the lives of elderly people? Could you provide caregiver
support, home support, better long-term care?”

But many clinicians contend that the modest benefits conferred by the drugs
are vital.

Dr. Inge Loy-English, medical director of the SCO Health Service Memory
Disorder Clinic in Ottawa, said she has found the drugs to be effective. It
remains the standard of care in Canada, she said, for patients with mild to
moderate Alzheimer’s disease to be on one of the three cholinesterase
inhibitors.

“I tell patients that the drugs are not a cure for the disease, but they
help people function a little better for a little longer,” said Dr.
Loy-English, a neurologist.

It has been her clinical experience, she added, that patients who have
suddenly stopped the medication often “crash” and deteriorate.

Dr. Loy-English said some of the studies that have questioned the efficacy
of the drugs were themselves flawed, while others failed to capture
important outcomes. For instance, she said, some clinicians have noted that
patients on the medications often display less apathy, something that comes
as a relief to their families but is not well-measured in clinical trials.

“One of the things we notice, especially in early disease stages,” Dr.
Loy-English said, “is that people tend to be a little more activated, be a
little more like their old self, have a bit more initiative.

“I would agree: it’s a modest effect, it’s not a great effect. But it does
keep people a little better for a little longer.”

The controversy has done nothing to slow sales of Alzheimer’s drugs.

Led by Aricept, Alzheimer’s drugs generated $2.16 billion U.S. in worldwide
sales last year.

In Canada, according to market watcher IMS Health, the four Alzheimer’s
drugs recorded sales of $147.3 million last year — a 14-per-cent increase
over 2004.

The number of prescriptions for Alzheimer’s drugs has more than tripled, to
1.2 million, during the last five years.

The market for Alzheimer’s drugs is projected to grow substantially as more
people live longer, increasing the population most at risk for the disease.

Drug companies are rushing to serve that market: more than 30 drugs are now
in pre-marketing clinical trials worldwide.

And while there’s no consensus about the relative value of existing drugs,
experts all agree that better treatments are badly needed.

“None of the drugs we have do anything about the underlying condition, so
people will continue to deteriorate,” said Dr. Loy-English.

Some promising work centres on developing drugs that control the buildup of
proteins in the brain that lead to plaque deposits, a defining feature of
Alzheimer’s disease. At least three drug companies are working on products
to clean out the plaque deposits from the brain, while others are trying to
develop a vaccine that would trigger an immune-system response to eliminate
the deposits.

It could be years, however, before any new drugs complete clinical trials
and receive approval to enter the marketplace.
Cheers,
Alan Cassels
423 Stannard Avenue
Victoria, BC Canada V8S 3M6
(250) 361-3120
cassels@uvic.ca