Validity of Nicotine Replacement Therapy Studies in Serious Question
Does NRT really double a smoker’s chances? While real-world quitting surveys find no advantage, their simplicity has been attacked as unscientific by double-blind clinical trial NRT researchers. Now the clinical trial's integrity is in serious question as a new study reports blinding failures in 71% of NRT studies assessing blindness.
Charleston, SC (PRWEB) May 20, 2004 -- Imagine deeply believing the “double
your chances” NRT marketing slogan and hearing about a study offering a 50/50
chance of receiving three months of free nicotine patches. Once in the study,
imagine being able to sense that the flow of nicotine to your brain had ended,
as you grew confident that the patch on your arm was empty when placed there.
Would frustrated expectations have destroyed your resolve to
continue?
NRT'S BLIND SPOT
A study in the June 2004 edition of
Addictive Behaviors identified 73 double-blind placebo controlled NRT trials and
found that only 17 had conducted blinding assessments. During assessments
participants were asked to surmise whether they had been using a real nicotine
delivery device or an empty placebo.
According to the authors, 12 of the
17 studies (71%) reported blinding failures as "subjects accurately judged
treatment assignment at a rate significantly above chance."
Entitled
"The blind spot in the nicotine replacement therapy literature: Assessment of
the double-blind in clinical trials," the study was led by Marc Mooney at the
University of Minnesota's Tobacco Use Research Center. It found that almost
two-thirds of placebo patch quitters were "confident" that they had not received
the real nicotine patch.
The study lists a number of prior studies
foreshadowing that attempts to use placebo controls in clinical NRT trials might
not produce accurate assessments of NRT's true merits.
The authors
assert that nicotine is a psychoactive drug providing cues making it easier to
discriminate and cite a 1996 study in which smokers were “trained to reliably
distinguish various doses of nicotine from placebo."
It cites a series of
studies indicating that using nicotine will "reliably reduce withdrawal
symptoms," that "most have quit several times before entering clinical trials,
and many are only too familiar with the syndrome," and that "the use of a
double-blind design provides no guarantee that ... participants remain blind to
their treatment assignment."
BLIND TO MISSING TURKEYS
Although
current NRT marketing asserts that NRT "doubles a smoker's chances of quitting
versus cold turkey," smokers might be surprised to learn that "real" cold turkey
quitters were not invited to formal NRT studies to compete against NRT quitters.
Instead, the industry's "double your chances" assertion is based
entirely upon clinical odds ratio victories generated by performance of quitters
receiving months of free nicotine products, over those who wanted to receive
months of free nicotine products but were instead randomly assigned to receive
placebo products.
Does cutting back on nicotine intake prior to ending
its use alter any quitter's underlying dream of freedom? Instead, could
frustrated expectations and rewarded expectations have handed NRT an unearned
victory? Could a billion dollar nicotine replacement industry have been built
almost entirely upon known blinding failures?
CLUES THE BLIND COULD
FOLLOW
Aside from "real-world" quitting surveys in California, London and
Quebec in which those choosing to quit cold turkey performed just as well as
those using a growing array of expensive NRT products, a March 2003
meta-analysis that combined and averaged all seven over-the-counter (OTC) patch
and gum studies provides highly visible evidence that the merits of NRT may have
been vastly overstated.
The study found that only 7% of OTC patch and
gum users and 3% of placebo group quitters were still not smoking at six months.
Although it again provided NRT with its much heralded "double your chances"
victory margin, according to June 2000 U.S. Clinical Practice Guideline evidence
tables, the 3% placebo rate is at least three times lower than historic
six-month "on-your-own" quitting rates.
The authors of the March 2003
study speculate that the extremely low rate could be due to less dependent
smokers having already successfully quit, with remaining smokers comprising a
"hardened" heavily dependent population. But the hardening argument is in
obvious conflict with real-world findings.
The Journal of the American
Medical Association published the results of the California smoker survey on
September 11, 2002. It contains graphs indicating absolutely no long-term NRT
advantage for light smokers (less than 15 cigarettes per day) or heavy smokers
(more than 15 per day).
The California survey review boldly concludes
that, "NRT appears no longer effective in increasing long-term successful
cessation in California smokers."
GRASPING FOR BLINDNESS
How long
were the pharmaceutical industry and researchers aware of serious blinding
concerns? According to the "Blind Spot" study they began toying with trying to
fool placebo group quitters by putting small amounts of nicotine (.5 or 1 mg.)
into pieces of placebo gum as early as 1982.
The study indicates that the
practice was also used in a number of nicotine patch studies where patches worn
by placebo group members released up to 3 mg. of nicotine, the nicotine
equivalent of smoking three cigarettes a day. No formal clinical study can be
found testing the effects upon placebo group cessation rates of using nicotine
as a masking agent.
Although the new study asserts that a dozen failures
are not sufficient in number, depth of analysis or uniformity to allow
definitive conclusions about their "consequences," it warns researches that "the
validity of NRT clinical trial results could be questioned" if future studies
fail to make proper blinding assessments.
In that the pharmaceutical
industry funded a large percentage of NRT studies, what the "Blind Spot" study
leaves unaddressed is why the 71% failure rate would be any lower in the 56
studies that chose not to conduct blinding assessments or, at least, to not
publish their results.
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Source : http://www.prweb.com/releases/2004/5/prweb127213.htm