OptimalHealthResearch.com

The recent study by Clegg et al[1] published in the February 2006 issue of the New England Journal of Medicine is worthy of analysis as it exemplifies how conflicts of interest and subtle alterations in the use of language may create confusion and the appearance of therapeutic inefficacy. The authors introduce their study with the statement “Glucosamine and chondroitin sulfate are used to treat osteoarthritis”, and this could lead the reader to believe that their study utilized glucosamine sulfate and and chondroitin sulfate. In fact, however, reading the materials and methods of the study reveals that glucosamine hydrochloride rather than glucosamine sulfate was used; this is an important discrepancy because many clinicians observe that while glucosamine hydrochloride is better tolerated by sulfur-sensitive patients, glucosamine sulfate is therapeutically superior. Why then would such a large and well-publicized trial in a major medical journal utilize an inferior formulation under the guise of “glucosamine sulfate”?

Why was the celecoxib dose of 200 mg/day chosen in contrast to other available doses of 50 or 100 mg? 

Why was the duration of the study only 6 months when all other studies using glucosamine/chondroitin have had a duration of about 3 years, most appropriate for a slow-acting treatment?

Further, why is the conclusion of the study “Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee” when the data results (Table 2) clearly favor glucosamine and/or chondroitin over placebo on many outcomes and when “patient’s global assessment of response to therapy” clearly favored glucosamine and/or chondroitin over celexcoxib and favored placebo over celexcoxib?

“Patient’s global assessment of disease status” and “physician’s global assessment of disease status” both favored glucosamine+chondroitin over celexcoxib.

Among patients with moderate-to-severe pain, glucosamine+chondroitin outperformed celexcoxib on 9 of 13 measures showing difference, yet the second conclusion of the study reads “Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain.” [Italics added.] 

Statements omitted from the publicized conclusions include “Treatment with chondroitin sulfate was associated with a significant decrease in the incidence of joint swelling, effusion, or both” and “…celecoxib therapy was associated with a clinically meaningful difference in the primary outcome measure of 15 percentage points, but the difference did not reach statistical significance.” 

Many of the article’s authors had received payment from various pharmaceutical companies, and five of the authors (Brandt, Moskowitz, Schnitzer, Schumacher, Weisman) had been paid by Pfizer or have equity interests in Pfizer, the drug company that makes celexcoxib.

Of the 25 main authors of this study, 11 of them have been paid by Pfizer, the maker of the competing drug celecoxib:

1)       Clegg DO,

2)       Reda DJ,

3)       Harris CL,

4)       Klein MA,

5)       O'Dell JR,

6)       Hooper MM,

7)       Bradley JD,

8)       Bingham CO 3rd,

9)       Weisman MH,

10)    Jackson CG,

11)    Lane NE,

12)    Cush JJ,

13)    Moreland LW,

14)    Schumacher HR Jr,

15)    Oddis CV,

16)    Wolfe F,

17)    Molitor JA,

18)    Yocum DE,

19)    Schnitzer TJ,

20)    Furst DE,

21)    Sawitzke AD,

22)    Shi H,

23)    Brandt KD,

24)    Moskowitz RW,

25)  Williams HJ