© 2003 American Thoracic Society
Ensuring Quality in Pharmaceutical StudiesTo the Editor:
We feel compelled to raise scientific concerns over the article by O'Sullivan and colleagues (1) that compared inflammation in 28 patients with asthma after low-dose fluticasone and after fluticasone plus montelukast. O'Sullivan and colleagues report that 5 T-cells were present at baseline in a tissue section 104 µm2 in area. Similar log ranges of numbers were seen for other cells. This is an unusual way of reporting endobronchial biopsy data. The more usual manner is cells/mm2 of tissue (see article by Chetta and colleagues [2] in the same issue). To convert the numbers from cells/104 µm2 to cells/mm2, one must multiply by 100. The converted counts equate to 500 T-cells/mm2 of tissue, with the other cells falling into similar, slightly lower mean values. These are unbelievably high values. The authors also purport to measure percentage of area stained for IL-4 or IFN- Of most concern are the almost unperceivable standard error bars (see Figures 1 and 2 in Reference 1). Anyone with experience in these studies can attest to the high degree of variability in biopsy specimens, which is more so for percentage measures than cell counts. These tiny standard error bars suggest that nearly every subject had the same or extremely similar degree of inflammation. Standard error bars that small are never seen. Finally, the study was corporate-sponsored and many of the studies were done by or at the pharmaceutical company. However, the authors associated with the company were not listed. This article, by its nature and the nature of the results, should have been put through a higher review standard than that for an independently funded study. These are the studies that influence clinicians and their prescribing practices and they must be beyond reproach. As avid readers, editorial board members, and advocates of the Blue Journal, we are chagrined that a paper of this quality passed through the peer review process and was published. We hope that a more thorough review of studies such as these will occur in the future, especially in light of potential sponsor "conflict of interest."
National Jewish Medical and Research Center University of Colorado Health Sciences Center Denver, Colorado FOOTNOTES Conflict of Interest Statement: S.E.W. and P.S. have both served as investigators and consulting board members for both Merck and GSK. REFERENCES
From the Authors:Dr. Wenzel and colleagues express methodological concerns with respect to our article (1), and more seriously they question the integrity of the data and hence the authors. We refute in the strongest possible terms that the data presented are anything but a true and accurate representation of the results obtained. The data can be made available to an independent third party for verification. The study was performed, interpreted, and written by the authors with complete scientific independence and was peer reviewed.The number of T cells reported in this study is comparatively high (likely because of the cocktail of antibodies used to detect T cells as clearly stated in the methodology section) but hardly unprecedented. Karjalainen and colleagues (2) and Sont and coworkers (3) report T cell numbers in similar patients receiving similar medication that are up to 50% higher than those reported in our article (1). Moreover, an investigator blinded to the study treatment code performed T cell counts and results are similar to those recorded in previous studies from this laboratory (4, 5).
The method by which IL-4 and IFN- With regard to the allegation of Dr. Wenzel and colleagues that "standard error bars that small are never seen," we can only report what we find. However, in an examination of biopsy studies published in AJRCCM within the last year, we identified six studies with similarly small errors of the mean (8–13). Finally, contrary to the suggestions of Dr. Wenzel and colleagues, none of the experimental work was done in the laboratories of GlaxoSmithKline. Furthermore, Martijn Akveld, the scientist at GlaxoSmithKline with responsibility for the study, is clearly listed as second author. We agree with Dr. Wenzel and colleagues that corporate-sponsored trials should achieve high standards. However, we are perplexed by the implication that standards should be lower for investigator-driven trials. We are of the opinion that the same high standards should be applied to all studies, regardless of the source of funding. While we applaud Dr. Wenzel and colleagues in their crusade for independent, unbiased research, may we respectfully suggest that their aim would be better served by refraining from unwarranted, fallacious allegations against other researchers working in the field of respiratory medicine.
a Royal Free University School of Medicine London, United Kingdom REFERENCES
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. Why would the authors wish to identify either of these markers by area of tissue staining? These are cellular, not tissue markers. Percentage measurements are also very imprecise, even more imprecise than cell count measures. Representative samples should have been included. 
