To the Editor: We are concerned about possible data discrepancies in the systematic review and meta-analysis of inhaled corticosteroids in patients with stable chronic obstructive pulmonary disease (COPD) by Dr Drummond and colleagues.1 In the analysis of pneumonia events from the study by Burge et al,2 Drummond et al reported 87 of 372 events in the inhaled corticosteroid group vs 101 of 370 events in the control group, reflecting a control event rate that is considerably higher than any other trial in the meta-analysis. However, the trial publication2 actually reports on “lower respiratory serious adverse events” rather than pneumonia events. The company trial report from the GlaxoSmithKline Clinical Trial Register (FLTB3054, the identification number for the study by Burge et al) shows that there were only 18 and 8 pneumonia events in the fluticasone and control groups, respectively.3 We believe that a substantial proportion of the lower respiratory serious adverse events data in the trial publication were actually COPD exacerbations.
We question the inclusion of the trial by Wedzicha et al4 in this meta-analysis. For an unconfounded comparison to be possible, Drummond et al should have selected trials in which the sole difference between the intervention arms was the use of an inhaled corticosteroid. In the context of a meta-analysis focusing on inhaled corticosteroids, the study by Wedzicha et al represents a confounded comparison of fluticasone/salmeterol combination vs tiotropium.4 The corticosteroid-treated group differed in 2 important respects from the control tiotropium arm: patients received an inhaled corticosteroid, and patients received salmeterol. Any differences in relative treatment effect could have arisen from the administration of salmeterol rather than from the inhaled corticosteroid.
Finally, for the Calverley et al 2007 trial (reference 12 in the study by Drummond et al), we refer to the updated pneumonia data in the UK Medicines and Healthcare Regulatory Authority safety newsletter.5 Drummond et al appear to have estimated the number of pneumonia events using the percentage probability of pneumonia (based on Kaplan-Meier analysis) for this trial. However, the percentage probability of pneumonia does not provide an exact estimate of the absolute event rate for pneumonia, as is apparent from the different figures presented within the regulatory agency document.5
These issues argue for meta-analysis on adverse effects to include data from clinical trial registries as well as those submitted to regulatory agencies to obtain accurate estimates of risk. Moreover, consistent and clear reporting of adverse events is essential. Resolving these discrepancies in the data are likely to remove the substantial heterogeneity that exists in this meta-analysis of pneumonia.
Financial Disclosures: None reported.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
Instructions
Comments are moderated and will appear on the site at the discretion of the Journal of American Medical Association editors. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest* Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more
Subscribe for full-text access to content from 1998 forward and a host of useful features
Activate your current subscription (AMA members and current subscribers)
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Customize your page view by dragging & repositioning the boxes below.
and access these and other features:
Register Now
Enter your username and email address. We'll send you a reminder to the email address on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.