Study reports: clarification, correction and additional sources
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Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials
Study reports: clarification, correction and additional sources
Study reports: clarification, corrections, and additional sources
Clarification of data sources
The systematic review was prepared from the full company trial reports, as was stated in the paper. As the full company trial reports are not publicly available, we attempted to match them up with journal publications so that interested readers of the review could follow links to the best publicly available trial evidence. Pfizer/Pharmacia have since suggested directly to us that this may have been misleading, and that it would have been more accurate to cite the company trial reports throughout as these were used for the review and not the journal publications cited in the references.
Notably, the criticisms made about CLASS study in the main relate to selective reporting in the journal publication and not problems in the trial itself (Black, Pechlaner, Metcalfe, Jüni, Formoso). It is always important to separate issues of trial quality from those of inadequate reporting. As we stated, our review was prepared from the data presented in the full company trial report, and not the JAMA publication. The criticisms relating to the company’s selective reporting in this publication do not affect our review – all data were available to us. We will respond in detail regarding our presentation of CLASS as the issues deserve detailed discussion and presentation of further data. However, we note that the CLASS trial is only included in 2 of the 17 outcomes summarised in the review. In our opinion Black, Pechlaner and Jüni are not justified in questioning the validity of the whole review based on problems they perceive with this single trial.
Corrections of references
During the matching process we made two minor errors, as pointed out by Jüni and also by Pfizer/Pharmacia, when matching publications with trials [2][4]. While Jüni is correct in suggesting that we have confused duplicate publications of two trials[1-4], all of our analyses are unaffected as we only have made errors with the names of publications attached to trials and not the data from the trials themselves. Each of the trials we included are distinct, and were originally identified by their FDA registered protocol numbers and not their journal publications.
Further published and unpublished sources
When checking these errors, we also came across new publications for two of the trials noted in the review as being unpublished [6][7]. We have also searched the FDA website, it having been brought to our attention by the BMJ editorial by Jüni, Rutjes and Dieppe. Here we have located the original licensing submission, medical, statistical and safety assessments for Celebrex which contain data from trials 20, 21, 22, 23, 41, 54, 62 and 71, as well as data on trials with shorter follow-up and for acute pain [9]. We have also found additional publicly available information about the CLASS trial, not previously cited by Jüni [10]. We would encourage those correspondents (Jenkinson, Wright, Formoso) who wanted more data than we were able to provide in our review to consult these sources.
The table and reference list below should provide clarification as to the company trial numbers, names and references for the trials included in the review, and website addresses where the FDA assessments of these trials can be found.
Company Trial ID
Patients
Comparator
Related publications
FDA website location
20
Bensen 1999
OA
Placebo
Naproxen
(1) (2)
(9)
21
Zhao 1999
OA
Placebo
Naproxen
Abstract only*
(9)
22
Simon 1999
RA
Placebo
Naproxen
(3) (4)
(9)
23
Zhao 2000
RA
Placebo
Naproxen
Abstract only*
(9)
41
Emery 1999
RA
Diclofenac
(5)
(9)
54
Study 054
OA
Placebo
Naproxen
(6)
(9)
62
Study 062
OA/RA
Naproxen
(7)
(9)
71
Study 071
OA/RA
Diclofenac
Ibuprofen
Unpublished
(9)
35/102
Silverstein 2000
OA/RA
Diclofenac
Ibuprofen
(8)
(10)
* the abstracts do not provide adequate data on these trials for meta-analysis
Jonathan J Deeks
Senior Medical Statistician
Centre for Statistics in Medicine
Institute of Health Sciences
Old Road, Headington
Oxford
Bensen WG, Fiechtner JJ, McMillen JI, Zhao WW, Yu SS, Woods EM et al. Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial. Mayo Clin Proc 1999;74:1095-105.
Zhao SZ, McMillen JI, Markenson JA, Dedhiya SD, Zhao WW, Osterhaus JT et al. Evaluation of the functional status aspects of health-related quality of life of patients with osteoarthritis treated with celecoxib. Pharmacotherapy 1999;19:1269-78.
Simon LS, Weaver AL, Graham DY, Kivitz AJ, Lipsky PE, Hubbard RC et al. Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: A randomized controlled trial. Journal of the American Medical Association. 1999; 282:1921-8.
Zhao SZ, Fiechtner JI, Tindall EA, Dedhiya SD, Zhao WW, Osterhaus JT et al. Evaluation of health-related quality of life of rheumatoid arthritis patients treated with celecoxib. Arthritis Care and Research. 2000; 13:112-21.
Emery P, Zeidler H, Kvien TK, Guslandi M, Naudin R, Stead H et al. Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison. Lancet 1999;354:2106-11.
Kivitz AJ, Moskowitz RW, Woods E, Hubbard RC, Verburg KM, Lefkowith JB, Geiss GS. Comparative efficacy and safety of celecoxib and naproxen in the treatment of osteoarthritis of the hip. J Int Med Res 2001; 29: 467-79.
Goldstein JL, Correa P, Zhao WW, Burr AM, Hubbard RC, Verburg KM, Geis GS. Reduced incidence of gastroduodenal ulcers with celecoxib, a novel cyclooxygenase-2 inhibitor, compared to naproxen, in patients with arthritis. Am J Gastroenterol 2001; 96:1018-27.
Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. Journal of the American Medical Association 2000;284:1247-55.
Rapid Response:
Study reports: clarification, correction and additional sources
Study reports: clarification, corrections, and additional sources
Clarification of data sources
The systematic review was prepared from the full company trial reports, as was stated in the paper. As the full company trial reports are not publicly available, we attempted to match them up with journal publications so that interested readers of the review could follow links to the best publicly available trial evidence. Pfizer/Pharmacia have since suggested directly to us that this may have been misleading, and that it would have been more accurate to cite the company trial reports throughout as these were used for the review and not the journal publications cited in the references.
Notably, the criticisms made about CLASS study in the main relate to selective reporting in the journal publication and not problems in the trial itself (Black, Pechlaner, Metcalfe, Jüni, Formoso). It is always important to separate issues of trial quality from those of inadequate reporting. As we stated, our review was prepared from the data presented in the full company trial report, and not the JAMA publication. The criticisms relating to the company’s selective reporting in this publication do not affect our review – all data were available to us. We will respond in detail regarding our presentation of CLASS as the issues deserve detailed discussion and presentation of further data. However, we note that the CLASS trial is only included in 2 of the 17 outcomes summarised in the review. In our opinion Black, Pechlaner and Jüni are not justified in questioning the validity of the whole review based on problems they perceive with this single trial.
Corrections of references
During the matching process we made two minor errors, as pointed out by Jüni and also by Pfizer/Pharmacia, when matching publications with trials [2][4]. While Jüni is correct in suggesting that we have confused duplicate publications of two trials[1-4], all of our analyses are unaffected as we only have made errors with the names of publications attached to trials and not the data from the trials themselves. Each of the trials we included are distinct, and were originally identified by their FDA registered protocol numbers and not their journal publications.
Further published and unpublished sources
When checking these errors, we also came across new publications for two of the trials noted in the review as being unpublished [6][7]. We have also searched the FDA website, it having been brought to our attention by the BMJ editorial by Jüni, Rutjes and Dieppe. Here we have located the original licensing submission, medical, statistical and safety assessments for Celebrex which contain data from trials 20, 21, 22, 23, 41, 54, 62 and 71, as well as data on trials with shorter follow-up and for acute pain [9]. We have also found additional publicly available information about the CLASS trial, not previously cited by Jüni [10]. We would encourage those correspondents (Jenkinson, Wright, Formoso) who wanted more data than we were able to provide in our review to consult these sources.
The table and reference list below should provide clarification as to the company trial numbers, names and references for the trials included in the review, and website addresses where the FDA assessments of these trials can be found.
Company Trial ID
Patients
Comparator
Related publications
FDA website location
20
Bensen 1999
OA
Placebo
Naproxen
(1) (2)
(9)
21
Zhao 1999
OA
Placebo
Naproxen
Abstract only*
(9)
22
Simon 1999
RA
Placebo
Naproxen
(3) (4)
(9)
23
Zhao 2000
RA
Placebo
Naproxen
Abstract only*
(9)
41
Emery 1999
RA
Diclofenac
(5)
(9)
54
Study 054
OA
Placebo
Naproxen
(6)
(9)
62
Study 062
OA/RA
Naproxen
(7)
(9)
71
Study 071
OA/RA
Diclofenac
Ibuprofen
Unpublished
(9)
35/102
Silverstein 2000
OA/RA
Diclofenac
Ibuprofen
(8)
(10)
* the abstracts do not provide adequate data on these trials for meta-analysis
Jonathan J Deeks
Senior Medical Statistician
Centre for Statistics in Medicine
Institute of Health Sciences
Old Road, Headington
Oxford
Competing interests:
see published paper
Competing interests: Name in BMJ review