© 2009 American Thoracic Society
The INSPIRE Trial Results: Are They Truly Breathtaking?From the Authors:Ms. Chui and Dr. Tejani raise important questions regarding the reporting of serious adverse events and the analysis of responses to the St. George's Respiratory Questionnaire (SGRQ) in the INSPIRE study as discussed in our article (1). We can confirm that all deaths were included as serious adverse events (SAEs). The incidence of SAEs was 30% for salmeterol/fluticasone (SFC) compared with 24% for tiotropium. We observed an increase in pneumonia reports in the SFC arm, and this was discussed in detail in the article (1). In addition, the exposure to SFC in the trial was also greater because of the differential withdrawal between the two treatment arms. We disagree, however, with Chui's and Tejani's assertion that a reduction in death with SFC should be reflected in a reduction in SAEs with SFC. This would assume that all SAEs are equally likely to result in death, and would also imply the existence of a causal relationship between the occurrence of an SAE and risk of death, which is clearly not true. For example, cardiac failure is more likely to lead to death than a lower respiratory tract infection. We also disagree with the implication that SAEs and mortality are equally important. Regarding the SGRQ, we can clarify some details on the analysis. If the SGRQ score was missing, the patient was classified as a "nonresponder" when any of the following applied: death, withdrawal due to respiratory AE, healthcare utilization exacerbation that started in the previous 28 days, withdrawal due to lack of efficacy, or the patient having started oxygen therapy. Despite this, for 87 patients, we had no post-treatment SGRQ data and no information available on which to decide whether there was improvement. These patients were therefore excluded from the analysis. As previously discussed in our response to Prof. Suissa's letter (2), intent-to-treat analysis allows for exclusion for patients due to missing data. We conclude that all relevant data were included in the analysis and the results presented in our paper are from a valid intent-to-treat analysis.
Royal Free and University College Medical School
University Hospital Aintree
The University of the West Indies
GlaxoSmithKline
University Hospital Birmingham NHS Foundation Trust FOOTNOTES Conflict of Interest Statement: In the past 3 years, J.A.W. has received research funding from GlaxoSmithKline (GSK), Boehringer Ingelheim (BI), and AstraZeneca (AZ); she has also received honoraria for lectures and/or attendance at advisory boards from GSK, BI, AZ, and Novartis. P.M.A.C. has received funding from GSK, Altana/Nycomed, BI, Roche, and Chiesi to conduct clinical research trials in COPD; he has led several large studies sponsored by GSK, Roche, Chiesi, and Altana; and he has spoken at meetings supported by these companies and by AZ, Pfizer/BI, and BOC/Linde. T.A.S. has no conflict of interest to declare other than the sponsorship of this work by GSK. G.H. retired as an employee from GSK in August 2008; he was employed by GSK from 1996. Z.A. was employed by GSK between October 2002 and November 2006 as a full-time employee; her salary started at £24,250, and when she left the company her salary was £33,850. R.A.S. has received funding to attend international conferences from BI and Talecris, and for speaking at conferences organized by GSK and AZ; he served on advisory panels from Roche, GSK, and Merck, Sharpe & Dohme ($5,000 in 2006); he is in receipt of an unrestricted noncommercial grant from AZ (£100,000 in 2006–2007) and Talecris (£634,000 in 2006–2007). REFERENCES
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