To the editor:

Stasi et al report a valuable systematic review and meta-analysis to conclude that treating Helicobacter pylori is worthwhile in immune thrombocytopenic purpura (ITP).1  However, we have several reservations about the methodology of this review, which may have led to misleading conclusions.

First, the search strategy was incomplete. Including textwords as well as MeSH headings into the search strategy reveals 38 extra possible studies for inclusion.2  The Cochrane Handbook3  also recommends searching conference abstracts as these may provide studies in prepublication and unpublished studies, which can have significant positive and negative affects on conclusions.4 

Second, the exclusion criteria of this review may have led to bias. No reason is given why studies with fewer than 15 subjects were excluded. Much relevant research has been undertaken in Japan; the exclusion of foreign language studies may have excluded relevant papers, which tend to be negative.5  Excluding studies that only diagnosed H pylori infection serologically may also have excluded useful higher quality studies. The quoted reference6  describes enzyme-linked immunosorbent assay (ELISA) tests with good sensitivity and specificity. If the authors were concerned about these they could have been examined in a subgroup analysis. The authors thereby excluded a randomized trial,7  which may be less biased than observational studies. More information could have been provided on quality assessment and its impact on the review's conclusions.

The authors' measures of publication bias do not demonstrate the absence of bias, as the Egger test should not be used when heterogeneity (I2 = 86%), is present.8  Visual inspection of the funnel plot does not show the normal inverted V that would be consistent with no publication bias.

Third, we consider that combining studies in a meta-analysis was inappropriate in this area, like combining apples and pears. It would have been more helpful to detail the individual studies especially the control groups, previous treatments and severity of ITP. Egger et al state that there is a danger that meta-analysis of observational data produce very precise but spurious results and the statistical combination of data should therefore not be a prominent component of systematic reviews of observational studies.9  The large variation in the study results implies heterogeneity, suggesting either confounding factors, bias, or biologic factors (eg, ethnicity, strain of bacterium), all of which suggest meta-analysis is not appropriate. There seems to have been little attempt to investigate this heterogeneity. Combining observational data by the DerSimonian-Laird method may introduce bias because it increases the weight given to larger studies; in controlled trials larger studies are more precise, but in observational studies they may be more biased.

In summary, we believe the incomplete search strategy and inclusion of several sources of bias compromise the systematic review. The heterogeneity of results obtained implies that meta-analysis should not have been performed. We agree with the authors that further randomized controlled trials are required in this important area.

Authorship

Contribution: M.C. and A.A. critically appraised the paper, and all 3 authors wrote the letter.

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Mark Crowther, Department of Haematology, Ward 16, Aberdeen Royal Infirmary, Aberdeen, AB25 2ZD, United Kingdom; e-mail: mark.crowther@nhs.net.

References

References
1
Stasi
 
R
Sarpatwari
 
A
Segal
 
JB
, et al. 
Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenia purpura: a systematic review.
Blood
2009
, vol. 
113
 (pg. 
1231
-
1240
)
2
Jenuwine
 
ES
Floyd
 
JA
Comparison of Medical Subject Headings and text-word searches in MEDLINE to retrieve studies on sleep in healthy individuals.
J Med Libr Assoc
2004
, vol. 
92
 (pg. 
349
-
353
)
3
Higgins
 
JPT
Green
 
S
Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 [updated September 2008].
The Cochrane Collaboration
2008
Accessed March 6, 2009 
4
Egger
 
M
Juni
 
P
Bartlett
 
C
Holenstein
 
F
Sterne
 
J
How important are comprehensive literature searches and the assessment of trial quality in systematic review? Empirical study.
Health Technol Assess
2003
, vol. 
7
 (pg. 
1
-
76
)
5
Moher
 
D
Fortin
 
P
Jadad
 
AR
, et al. 
Completeness of reporting of trials published in languages other than English: implications for the conduct and reporting of systematic reviews.
Lancet
1996
, vol. 
347
 (pg. 
363
-
366
)
6
Logan
 
RP
Walker
 
MM
ABC of the upper gastrointestinal tract: epidemiology and diagnosis of Helicobacter pylori infection.
BMJ
2001
, vol. 
323
 (pg. 
920
-
922
)
7
Tsutsumi
 
Y
Kanamori
 
H
Yamoto
 
H
, et al. 
Randomized study of Helicobacter pylori eradication therapy and proton pump inhibitor monotherapy for idiopathic thrombocytopenic purpura.
Ann Hematol
2005
, vol. 
84
 (pg. 
807
-
811
)
8
Ioannidis
 
JPA
Trikalinos
 
TA
The appropriateness of asymmetry tests for publication bias in meta-analyses: a large survey.
CMAJ
2007
, vol. 
176
 (pg. 
1091
-
1096
)
9
Egger
 
M
Davey-Smith
 
G
Schneider
 
M
Egger
 
M
Davey-Smith
 
G
Altman
 
DG
Systematic reviews of observational studies.
Systematic Reviews in Health Care. Meta-Analysis in Context
2001
2nd Ed
London, United Kingdom
BMJ Books
(pg. 
211
-
227
)