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American Journal of Respiratory and Critical Care Medicine Vol 173. pp. 1414a-1415, (2006)
© 2006 American Thoracic Society


Correspondence

Negative Studies Deserve More Attention

To the Editor:

With regard to their recent article, Kacmarek and colleagues (1) are to be congratulated not only for their trial on partial liquid ventilation (PLV) but also for their persistence in reporting the results of an important "negative" clinical study with liquid perfluorocarbons for the therapy of acute lung injury. The fact that this study failed in demonstrating beneficial effects of PLV has important implications for both study design and the peer-review process itself.

Most of the previous experimental studies that led to acceptance of PLV as a possible alternative in the therapy of acute lung injury were conducted with mechanical ventilation strategies suggested to be hazardous, namely, relatively high tidal volumes and low positive end-expiratory pressure levels (2). When evidence accumulated that such strategies were associated with further lung injury (ventilator-associated lung injury), phase II trials with PLV were conducted, and control groups received the best possible mechanical ventilation (3), which aimed at minimizing the mechanical stress on lung tissues through overdistension and/or cycling collapse/reopening of lung units. Two important questions arise: Should the experimental evidence on the benefits of PLV not have been put in question at that time, when the approach to mechanical ventilation changed considerably? Were there any "negative" experimental studies on PLV that used alternate ventilatory modes in their control groups and were rejected, using the argument: "You cannot affirm PLV does not work if so many other studies show it does"? Clearly, the latter is a highly speculative and provocative question.

As pointed out by Kacmarek and colleagues (1), it is difficult to convince reviewers and editors to publish "negative" results. Moreover, authors often are not motivated to publish their work when a given therapy is not successful. I consider this an "antiscientific" view that should be banned from publication politics and suggest that much more attention should be paid to so-called negative experimental studies. In addition, editors and reviewers should be more careful when considering the publication of "positive" studies that do not use state-of-the-art approaches in their control groups. We cannot change the past, and also we probably cannot save PLV from death, but we can learn from this experience and avoid similar mistakes in the future.

Marcelo Gama de Abreu

University Clinic Carl Gustav Carus, Technical University Dresden, Dresden, Germany

FOOTNOTES

Conflict of Interest Statement: M.G.d.A. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

  1. Kacmarek RM, Wiedemann HP, Lavin PT, Wedel MK, Tütüncü AS, Slutsky AS. Partial liquid lentilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2006;173:882–889.[Abstract/Free Full Text]
  2. Mead J, Takishima T, Leith D. Stress distribution in lungs: a model of pulmonary elasticity. J Appl Physiol 1970;28:596–608.[Free Full Text]
  3. Hirschl RB, Croce M, Gore D, Wiedemann H, Davis K, Bartlett RH. Prospective, randomized, controlled pilot study of partial liquid ventilation in adult acute respiratory distress syndrome. Am J Respir Crit Care Med 2002;165:781–787.[Abstract/Free Full Text]




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Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2006 American Thoracic Society