To The Editor:
The conclusions reached in the study, "Therapeutic Effects of
Hyaluronic Acid on Osteoarthritis of the Knee. A Meta-Analysis of Randomized
Controlled Trials"
(2004;86:538-45), by Wang et
al.—namely, that "the therapeutic efficacy and safety of
intra-articular injection of hyaluronic acid for the treatment of
osteoarthritis of the knee" was confirmed—seems to be in conflict
with a paper that appeared in JAMA just a few months ago1.
In that meta-analysis, the authors concluded: "Intra-articular
hyaluronic acid has a small effect when compared with an intra-articular
placebo. The presence of publication bias suggests even this effect may be
overestimated."
Can the authors please comment on this apparent discrepancy? Also, can the
authors give us some pointers on how we, the readers, can approach these
studies critically? It is not hard to imagine that patients (or pharmaceutical
representatives) will visit our offices with these studies in hand.
We appreciate Dr. Bernstein's interest in our article, and we have read the
meta-analysis by Lo et
al.1 reported in
JAMA. Here are some of our opinions.
Conducting a systematic review consists of several steps: formulating the
review question, defining inclusion and exclusion criteria, locating studies,
selecting studies, assessing study quality, extracting data, analyzing and
presenting results, and, finally, interpreting results. In each step, the
reviewers should do their best to answer the review question. Any
extrapolation should be avoided.
Lo et al.1 and we
formulated the same question in our meta-analyses: "Is hyaluronic acid
effective in the treatment of osteoarthritis of the knee?" However, the
steps following the formulation of this question were somewhat different. For
example, Lo et al. used effect size to summarize the therapeutic efficacy,
whereas we designed our own measure scales in the meta-analysis. The searching
date and searching source were also different. Despite the differences, the
answer to the review question is still the same: intra-articular hyaluronic
acid has therapeutic efficacy compared with an intra-articular placebo.
Lo et al. claimed that the effect might be overestimated because of the
skewed funnel plot. The therapeutic efficacy, however, is still confirmed in
their article because the 95% confidence interval of the pooled effect size
does not include zero, which is the same as in our analysis. Lo et al. even
obtained a homogeneous effect size in the final pooling, which means that the
result is highly convincing. Both Lo et al. and we concluded that there is
still a need for high-quality trials to reevaluate the therapeutic efficacy of
hyaluronic acid. The only difference between their and our meta-analyses are
the funnel plots, which were distorted in the work by Lo et al. but not in
ours.
There are many complex reasons for the distortion of funnel plots,
including publication bias, citation bias, language bias, and biased inclusion
criteria. Therefore, we disagree with Lo et al. that the therapeutic efficacy
is overestimated, as their comment is based only on a distorted funnel plot.
We would also direct Dr. Bernstein to other comments regarding those authors'
meta-analysis in
JAMA2,3.
Dr. Bernstein asked another important question: how to critically appraise
the hyaluronic acid trials. We don't think that we can answer this big
question clearly in this short reply. Instead, we suggest that readers find a
textbook on evidence-based medicine or search with the keyword
"evidence-based medicine" (EBM) with an Internet searching engine
for appraisal guidelines of therapy. Only after the appropriate appraisal can
we exactly know whether the results are valid, what the results are, and how
the results can help us in patient care.
Lo GH, LaValley M, McAlindon T,
Felson DT. Intra-articular hyaluronic acid in treatment of knee
osteoarthritis: a meta-analysis. JAMA.
2003;290:
3115-21.2903115
2003
[PubMed][CrossRef]
Band PA. Intra-articular
hyaluronic acid for treatment of osteoarthritis of the knee.
JAMA. 2004; 291:
1440-2.2911440
2004
[PubMed][CrossRef]
Moskowitz R, Altman R.
Intra-articular hyaluronic acid for treatment of osteoarthritis of the knee.
JAMA. 2004;291:
1440-2.2911440
2004
[PubMed][CrossRef]