Although we have used this objective end point to eval- uate changes in haemoglobin, as suggested by the US Food and Drug Administration (FDA) and used by others, we did not directly evaluate medical outcomes associated with the development of this meaningful drop in haemo- globin. These end points, such as recurrent falls, hospitali- sations and mortality, would not be expected to occur to a signiﬁcant degree over the limited time frame of this study and given the limited number of patients. Based on our 6-month data as shown above, and in Fig- ure 3a,b, there is a discrepancy between the trials in the rel- ative number of patients achieving the laboratory-deﬁned (£11.5 g ⁄ dL) anaemia end point. In CONDOR a signiﬁ- cantly greater number of patients in the diclofenac group had a ‡2 g ⁄ dL decrease in haemoglobin and a haemoglobin value £11.5 g ⁄ dL during 6 months. However, in CLASS this difference was not apparent. Interestingly the differ- ence between the two trials is not readily explained by a dif- ference in the mean haemoglobin values for the two populations at baseline. In the CLASS trial, the mean hae- moglobin values at the onset of the study were 13.6 (s.d. 1.3) in the celecoxib and diclofenac treatment arms, respec- tively. In the CONDOR trial the mean haemoglobin values at baseline were 13.6 (s.d. 1.1) for both treatment arms (Table 2). Given the small number of patients achieving haemoglobin values £11.5 g ⁄ dL in the CLASS trial it would be imprudent to draw any immediate conclusions regard- ing the development of anaemia in this trial. Despite its limitations we believe this study provides important clinical ﬁndings. Decreases in haemoglobin are clinically meaningful in that they drive medical evalua- tions and increased cost of care – the use of the absolute cut-off of ‡2 g ⁄ dL has been advocated by the FDA18 and supported by the European Medicines Agency (EMA), among other researchers. In these two large-scale, randomised and independent outcome trials clinically meaningful decreases in haemo- globin ‡2 g ⁄ dL occurred in a similar fashion over time despite differences in trial design. Among non-aspirin using populations, a signiﬁcantly greater number of patients treated with diclofenac had reductions in haemoglobin as compared with patients treated with celecoxib over 6 months. Interestingly, the difference between these two arms in CLASS, in both the aspirin and non-aspirin using population, is consistent with numerically similar odds ratios. We believe that the reproducibility of these ﬁndings over 6 months conﬁrms their clinical importance in this age-relevant population with arthritis and that these data will provide the foundation for future research regarding Aliment Pharmacol Ther 2011; 34: 808–816 ª 2011 Blackwell Publishing Ltd Haemoglobin decreases in NSAID users the effects of anti-inﬂammatory agents throughout the entire GI tract. ACKNOWLEDGEMENTS Declaration of personal interests: Jay Goldstein has served as a speaker, a consultant and ⁄ or advisory board member for Amgen, AstraZeneca, Astrellas Pharma US, Horizon, Logical Therapeutics, Merck, Novartis, Pﬁzer, PLX, Pozen, Proctor Gamble, Tap Pharmaceuticals, Takeda ⁄ Sucampo and Wyeth, and has received research funding from Am- gen, AstraZeneca, Glaxo Smith Kline, Given, Logical Thera- peutics, Novartis, Pﬁzer, Pozen, Tap Pharmaceuticals and Takeda ⁄ Sucampo. Francis Chan has served as a speaker, consultant and ⁄ advisory board member for AstraZeneca, Eisai, Pﬁzer and Takeda. Angel Lanas has served as an advi- sor for AstraZeneca, Pﬁzer and Nicox, and has received research funding from AstraZeneca and Pﬁzer. Charles Wilcox has served as a speaker, a consultant and ⁄ or advi- sory board member for Tap Pharmaceuticals and Salix Pharmaceuticals, and has received research funding from Tap Pharmaceuticals. David Peura has served as a speaker and consultant for Takeda Pharmaceuticals NA, and a con- sultant for AstraZeneca, Glaxo Smith Kline, Novartis Con- sumer Health and Pﬁzer. Jim Scheiman has served as a speaker, a consultant and ⁄ or advisory board member for AstraZeneca, Nicox, Novartis, Pﬁzer, Pozen, Tap Pharma- ceuticals and Xlumena, and has received research funding from AstraZeneca. Manuela Berger, George Sands and Ha Nguyen are full-time employees of Pﬁzer Inc. and all own stocks and shares in Pﬁzer Inc. Jim Scheiman owns a patent for optical spectroscopy devices through the University of Michigan. Declaration of funding interests: These studies were funded in full by Pﬁzer Inc. Writing support was provided by L. Prevost, BSc, of PAREXEL, and funded by Pﬁzer Inc. SUPPORTING INFORMATION Additional Supporting Information may be found in the online version of this article: Table S1. Reasons for withdrawing from the CLASS trial in non-aspirin users. Table S2. Reasons for withdrawing from the CON- DOR trial in non-aspirin users. Table S3. Incidence of clinically signiﬁcant haemoglo- bin decreases (‡2 g ⁄ dL) up to month 6 in non-aspirin users in the CLASS trial by sex. Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. 815