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Biotech / Medical : Elan Corporation, plc (ELN) -- Ignore unavailable to you. Want to Upgrade?

To: Qualified Opinion who wrote (4408)	5/25/2003 9:51:44 AM
From: Icebrg	Read Replies (1) \| Respond to of 10345

Rob >>The placebo group response rate seems to be unusually high for Antegren phase II results for crohn's.>> Yes, that is the correct answer. You might be aware of the following which offers a potential explanation. But it doesn't explain why statistical significance was achieved at 4 and 8 weeks. to the editor: In the study by Ghosh et al. (Jan. 2 issue), a regimen of two infusions of natalizumab at a dose of 6 mg per kilogram of body weight was associated with higher remission rates than was placebo at several intervals, except at week 6 (the primary end point). The failure to demonstrate a difference may be due in part to chance and to the use of a small study sample. Randomization is supposed to ensure equal distribution of base-line characteristics that may confound a clinical trial. However, in this study, the randomization process assigned 63 patients to placebo and only 51 patients to two infusions of 6 mg of natalizumab per kilogram (a 19 percent difference). The authors attribute their failure to detect significant differences at week 6 to the unusually high remission rate in the placebo group. However, concomitant therapy with azathioprine or mercaptopurine was being given to a larger percentage of patients in the placebo group (35 percent) than in the group assigned to two infusions of 6 mg of natalizumab per kilogram (18 percent) (P=0.04). It appears that the shortcomings of randomization may have contributed to the reported null findings with regard to the primary study end point in this trial. Edward A. Lew, M.D., M.P.H. Elena Martinez Stoffel, M.D. Brigham and Women’s Hospital Boston, MA 02115 edward_lew@hms.harvard.edu 1. Ghosh S, Goldin E, Gordon FH, et al. Natalizumab for active Crohn’s disease. N Engl J Med 2003;348:24-32. To which Ghosh answered: We thank Drs. Lew and Stoffel for their discussion of base-line imbalances between the placebo group and the group receiving two infusions of 6 mg of natalizumab per kilogram and for their discussion of the potential effect of such imbalances on the analysis of the primary end point. Subrata Ghosh, M.D. Imperial College of Medicine London W1Z 0NN, United Kingdom s.ghosh@ic.ac.uk Now, I don't know if Ghosh felt a little bit embarrassed about having been caught with a messed-up randomization or if he just felt that the letter didn't deserve any further comments, I cannot judge. The "episode" serves as a reminder though, that there are many ways in which a trial may go wrong. Far too many. >>I will search for the Remicade phase II results.>> No, you shouldn't. That would be senseless. You should pick up the phase III results - that led to the approval - from the label. That way you will gain an idea about what Antegren is up against. There is no reason to suppose that the two drugs were playing at a level playing field when their resp. phase II trials were concluded. Erik