The U.S. trial enrolled patients aged 40 and older with knee pain due to osteoarthritis.
They were randomly assigned to one of five treatments:
- Inactive
placebo pills
- Glucosamine
hydrochloride at a dose of 500 milligrams three times a day
- Sodium
chondroitin at a dose of 400 milligrams three times a day
- Combination
glucosamine and chondroitin
- Celebrex
at a dose of 200 milligrams per day
It is common for a pain study to show that many patients report relief from
inactive placebo pills. And that happened here. Nearly 60% of patients given only placebo pills said they had less pain. So
did about 67% of patients treated with combination glucosamine and chondroitin. But that isn't what scientists call a significant
difference -- that is, there's more than a 7% chance the findings are just coincidence. {The point is that for one in 20 feeling a bit more relief from pain isn’t worth 6 pills a day and
a hundred dollars a month. If codiene worked in just 7% of the cases and only
somewhat, would it be taken for chronic pain?}
"I really feel the study is a negative study," Clegg says. "I would say to
patients that the safety data are really reassuring, the efficacy data are not."
When Clegg's team looked only at patients with moderate to severe pain. Only
54% of these patients got relief from placebo. But 79% reported relief from combination glucosamine and chondroitin. That
is a significant difference. But there's a problem, Clegg says. The study wasn't designed to look at just this group. The
effect here is based on only a small number of patients.
"About 20% of the study patients have moderate to severe pain," Clegg says.
"Interestingly, in that subgroup, the combination of glucosamine and chondroitin appeared to be effective in relieving pain.
I think this outcome is really interesting but just from a research standpoint. It is an exploratory, hypothesis-generating
finding -- not a finding on which to base treatment."
{While there is other studies supporting their effectiveness, none are that postive as to eliminate the placebo effect. When an innert placebo is given, the very taste of the pill is enough to inform its
taker which arm of the test they are in. A percentage of those tested will perform a
taste test to satisfy their curiosity. Thus every test when the control group receives an innert tasting placebo, it will demonstrate effectiveness, when the measure of effectiveness is self-reporting.}
SECOND
STUDY
What the pharmaceutical industry does for drug
research, those that promote alternative treatments do the same—and they have less scrutiny. Below is a meta-study done to evaluate glucosamine and chondrotin (very popular, alternative arthritis
treatment). Quantifiable results were not possible because of experimenter bias.
Glucosamine and Chondroitin for Treatment of Osteoarthritis
A Systematic
Quality Assessment and Meta-analysis
Timothy E. McAlindon,
DM; Michael P. LaValley, PhD; Juan P. Gulin, MD; David T. Felson, MD
JAMA. 2000;283:1469-1475.
Context Glucosamine and
chondroitin preparations are widely touted in the lay press as remedies for osteoarthritis (OA), but
uncertainty about their efficacy exists among the medical community.
Objective To evaluate benefit
of glucosamine and chondroitin preparations for OA symptoms using meta-analysis combined with systematic
quality assessment of clinical trials of these preparations in knee and/or hip OA.
Data Sources We searched for
human clinical trials in MEDLINE (1966 to June 1999) and the Cochrane Controlled Trials Register using
the terms osteoarthritis, osteoarthrosis, degenerative arthritis, glucosamine, chondroitin,
and glycosaminoglycans. We also manually searched review articles, manuscripts, and supplements
from rheumatology and OA journals and sought unpublished data by contacting content experts, study authors, and
manufacturers of glucosamine or chondroitin.
Study Selection Studies were included
if they were published or unpublished double-blind, randomized, placebo-controlled trials of 4 or more
weeks' duration that tested glucosamine or chondroitin for knee or hip OA and reported extractable data on
the effect of treatment on symptoms. Fifteen of 37 studies were included in the analysis.
Data Extraction Reviewers performed
data extraction and scored each trial using a quality assessment instrument. We computed an effect size
from the intergroup difference in mean outcome values at trial end, divided by the SD of the outcome value
in the placebo group (0.2, small effect; 0.5, moderate; 0.8, large), and applied a correction factor to reduce
bias. We tested for trial heterogeneity and publication bias and stratified for trial quality and size.
We pooled effect sizes using a random effects model.
Data Synthesis Quality scores
ranged from 12.3% to 55.4% of the maximum, with a mean (SD) of 35.5% (12%).
Only 1 study described adequate allocation concealment and 2 reported an intent-to-treat analysis. Most
were supported or performed by a manufacturer. Funnel plots showed significant asymmetry (P .01)
compatible with publication bias. Tests for heterogeneity were nonsignificant after removing 1 outlier
trial. The aggregated effect sizes were 0.44 (95% confidence interval [CI], 0.24-0.64) for glucosamine
and 0.78 (95% CI, 0.60-0.95) for chondroitin, but they were diminished when only high-quality or large trials
were considered. The effect sizes were relatively consistent for pain and functional outcomes.
Conclusions Trials of glucosamine
and chondroitin preparations for OA symptoms demonstrate moderate to large effects, but quality issues and likely publication bias suggest that these effects are exaggerated. Nevertheless,
some degree of efficacy appears probable for these preparations.
Author Affiliation: The Arthritis Center, Boston University School of Medicine, Boston, Mass.
