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Communications to the Editor |

A Difficult Step in Meta-analysis : Refining the Search FREE TO VIEW

Mihai-Sergiu Jalba, MD, PhD
Author and Funding Information

Affiliations: Brooklyn Hospital Brooklyn, NY,  Division of Emergency Medicine, University of Alberta Edmonton, AB, Canada

Correspondence to: Mihai S. Jalba, MD, PhD, 17-15 Woodbine St, Ridgewood, NY 11385; e-mail: msj@about.com



Chest. 2003;123(3):960-961. doi:10.1378/chest.123.3.960
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Published online

To the Editor:

I found the meta-analysis performed by Edmonds et al (June 2002)1 to be very instructive, but in some areas it needs to be refined.

The inclusion in the meta-analysis of patients who had been treated with a combination of corticosteroids (CS) and long-acting β2-agonists clearly should have been avoided in a meta-analysis in which the primary outcome was the relapse rate. It has been demonstrated2 that this rate is lower when using a combination of long-acting β2-agonists and CS, compared with studies using short-acting β2-agonists and CS.

Some of the outcomes described are too heterogeneous. In my view, to give the same significance and to pool together the “treatment failures” during the first 3 days and to pool together the relapses at 7 days and after is a mistake. While the first pooling might be due to specific triggers, the latter could have a more complex causality, including noncompliance.

In the face of significant heterogeneity, reviewers need to be mindful; they should refrain from the statistical pooling of data and should refine their search, focusing more on the exploration and description of the sources of heterogeneity.

This research has been supported by the Division of Emergency Medicine, University of Alberta. Dr. Rowe was supported by a salary award from the Canada Research Council as the Chair of Emergency Airway Diseases (Ottawa, ON).

References

Edmonds, ML, Camargo, CA, Jr, Brenner, BE, et al (2002) Replacement of oral corticosteroids with inhaled corticosteroids in the treatment of acute asthma following emergency department discharge: a meta-analysis.Chest121,1798-1805. [PubMed] [CrossRef]
 
Markham, A, Jarvis, B Inhaled salmeterol/fluticasone propionate combination: a review of its use in persistent asthma.Drugs2000;60,1207-1233. [PubMed]
 

To the Editor:

We are pleased to respond to the points raised by Dr. Jalba about our article in CHEST (June 2002).1First, we feel the concern about long-acting β-agonists (LABAs) is misleading, for a number of reasons. It is unlikely that any of the trials included in the review would employ therapy with the combination of LABAs and corticosteroids (CS). However, even if they had, one would imagine the distribution would be similar across the groups in a randomized controlled trial, and their effect would be of limited concern. The trials in the review are older, and these drugs are infrequently used, even today. Furthermore, Dr. Jalba's claim of benefit from LABAs only relates to the treatment of patients with chronic asthma,2 since there is no evidence that adding LABAs to therapy for patients with acute asthma is beneficial.

When trials using similar designs (ie, randomized controlled trials), comparisons (ie, inhaled CS vs CS), populations (ie, acute asthma), and outcomes (ie, relapse) exist, pooling is justified. In our review,1 where there was no significant clinical or statistical heterogeneity, pooling was clearly appropriate. If the results of pooling demonstrate heterogeneity, then limited exploration is warranted, and pooling may not be appropriate. Conversely, searching for subgroup differences has been shown to generate erroneous results and should be considered far more carefully than Dr. Jalba would suggest.3 We further believe that the timing of relapse needs to be more fully evaluated before assigning the blame to patients for “late relapses.” We clearly appreciate the fact that the timing of relapse is important. That is precisely why we separated the outcomes based on time in the review.1

Finally, we challenge Dr. Jalba on the need for a better search and more exploration of heterogeneity. Cochrane reviews pride themselves on comprehensive, exhaustive (even exhausting!) searches to identify all available evidence on a focused question.4 Precisely how would Dr. Jalba suggest that the current search (which included searching for published, unpublished, English, and foreign language literature using a variety of well-accepted resources) could be more comprehensive? The recommendation to focus more on the sources of heterogeneity is a dangerous one, and we would strongly warn against it unless there is the strict application of accepted guidelines.3 Such fishing expeditions are to be strongly discouraged.

References
Edmonds, ML, Camargo, CA, Jr, Brenner, BE, et al Replacement of oral corticosteroids with inhaled corticosteroids in the treatment of acute asthma following emergency department discharge: a meta-analysis.Chest2002;121,1798-1805. [PubMed] [CrossRef]
 
Wilson, AJ, Gibson, PG, Coughlan, J Long acting beta-agonists vs theophylline for maintenance treatment of asthma (Cochrane Review). The Cochrane Library, Issue 3. 2002; Update Software. Oxford, UK:.
 
Oxman, AD, Guyatt, GH Guidelines for reading literature reviews.Can Med Assoc J1988;138,697-703
 
Clarke, M, Oxman, AD. Cochrane reviewers handbook. 2000; The Cochrane Collaboration. Oxford, UK:.
 

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References

Edmonds, ML, Camargo, CA, Jr, Brenner, BE, et al (2002) Replacement of oral corticosteroids with inhaled corticosteroids in the treatment of acute asthma following emergency department discharge: a meta-analysis.Chest121,1798-1805. [PubMed] [CrossRef]
 
Markham, A, Jarvis, B Inhaled salmeterol/fluticasone propionate combination: a review of its use in persistent asthma.Drugs2000;60,1207-1233. [PubMed]
 
Edmonds, ML, Camargo, CA, Jr, Brenner, BE, et al Replacement of oral corticosteroids with inhaled corticosteroids in the treatment of acute asthma following emergency department discharge: a meta-analysis.Chest2002;121,1798-1805. [PubMed] [CrossRef]
 
Wilson, AJ, Gibson, PG, Coughlan, J Long acting beta-agonists vs theophylline for maintenance treatment of asthma (Cochrane Review). The Cochrane Library, Issue 3. 2002; Update Software. Oxford, UK:.
 
Oxman, AD, Guyatt, GH Guidelines for reading literature reviews.Can Med Assoc J1988;138,697-703
 
Clarke, M, Oxman, AD. Cochrane reviewers handbook. 2000; The Cochrane Collaboration. Oxford, UK:.
 
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