© 2009 American Thoracic Society
The INSPIRE Trial Results: Are They Truly Breathtaking?To the Editor:We are skeptical of the conclusions drawn by Dr. Wedzicha and colleagues in their article on the results from the INSPIRE trial; the authors suggest that salmeterol/fluticasone (SFC) provides a "small beneficial effect" compared with tiotropium in patients with chronic obstructive pulmonary disease (COPD) (1). Our concerns are as follows. First, the authors fail to emphasize the significance of and correctly interpret an increased rate of serious adverse events (SAE) in patients treated with SFC compared with patients treated with tiotropium. The reduction in death (2.5%) with SFC should be reflected by a similar reduction in SAE if you assume, as Wezdicha and coworkers do, that SFC provides a net benefit in patients with COPD. It is unclear whether death was included in the serious adverse event totals. If death was included, patients on SFC were more likely to experience an SAE (absolute risk increase 5.9%; 95% confidence interval [CI], 1.1–10.7%). This implies that some other SAEs are offsetting the mortality benefit. However, we recalculated (by adding deaths to the totals) the SAE analysis assuming that death was not included in the reported SAE comparison. In this case, there was no statistically significant difference between the two groups (risk difference 95% CI, –1.65 to 8.37%). Again, as SAE rates are the same (based on our recalculation), this implies that something serious is happening more frequently in patients treated with SFC to drive the SAE total in this group to be equal to that of the patients treated with tiotropium. Either way, if SAE are the same or worse with SFC, the implied net benefit is questionable. Second, the authors state that "all efficacy and safety analyses used the intent-to-treat population." In Table 3, under the St. George's Respiratory Questionnaire (SGRQ) score for Week 32, they stated that 35% of patients with SFC had a change of 4 units or more from the baseline compared with 30% of patients with tiotropium. Recalculating the percentage using the denominator with the total number of participants, one finds 32% (211/658) for the SFC group versus 29% (190/665) for the tiotropium group. This will show a smaller difference between the two groups compared with the percentage provided by the authors (3% versus 5%). The calculation uses 603 patients treated with SFC and 633 patients treated with tiotropium. In other words, the calculation is missing data from 55 and 32 patients, respectively, with no explanation. Therefore the "health status benefit" is questionable. Inconsistencies noted in the intention-to-treat analysis, coupled with the lack of emphasis placed on the SAE analysis, make the authors' conclusions questionable.
Fraser Health Pharmacy Services FOOTNOTES Conflict of Interest Statement: Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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