Violation of the intent-to-treat principle and rate of missing data in superiority trials assessing structural outcomes in rheumatic diseases.
OBJECTIVE
To evaluate the methodologic quality of and identify methodologic issues in superiority trials assessing structural outcomes in rheumatic diseases.


METHODS
We searched Medline and the Cochrane Central Register of Controlled Trials for reports of randomized controlled trials assessing structural outcomes in osteoarthritis (OA), rheumatoid arthritis (RA), and osteoporosis (OP) published between January 1994 and December 2003 in high-impact factor general medical and specialty journals. One reader extracted data (quality assessment, intent-to-treat analysis [ITT analysis], rate of missing data, and methods of handling missing data), using a standardized form.


RESULTS
A total of 81 reports were included in the analysis (37 on OP, 34 on RA, and 10 on OA). The mean +/- SD methodologic quality scores on the Jadad scale (possible range 0-5) and the Delphi list (possible range 0-9) were 2.9 +/- 1.2 and 6.4 +/- 1.3, respectively. Although it was reported in 54 articles (66.7%) that the analysis was done on an ITT basis, full ITT analysis was performed in only 6 of the studies (7.4%), modified ITT analysis in 11 (13.6%), and case-complete analysis in 48 (59.3%); the analysis was unclear in 16 articles (19.8%). The rate of missing data on structural outcomes could be determined in only 63 articles (77.8%) and was >20% in approximately one-third of these reports. Methods for handling missing data on structural outcomes were described in 19 articles (23.5%) and were, in general, inappropriate.


CONCLUSIONS
Lack of ITT analysis and a high rate of missing data in superiority trials assessing structural outcomes may bias results from such trials. Our recommendations for improving these shortcomings may help researchers plan, analyze, and report the results of such trials.
Baron
Gabriel
G
INSERM U 738, Groupe Hospitalier Bichat-Claude Bernard, Assistance Publique Hôpitaux de Paris, Paris, France. gabriel.baron@bch.ap-hop-paris.fr
Boutron
Isabelle
I
Giraudeau
Bruno
B
Ravaud
Philippe
P
D001172:Arthritis, Rheumatoid / Q000453:epidemiology; D015982:Bias; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards*; D006801:Humans; D010003:Osteoarthritis / Q000453:epidemiology; D010024:Osteoporosis / Q000453:epidemiology; D017063:Outcome Assessment, Health Care; D012107:Research Design; D012216:Rheumatic Diseases / Q000453:epidemiology*