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Education And Debate

Users' guide to detecting misleading claims in clinical research reports

BMJ 2004; 329 doi: https://doi.org/10.1136/bmj.329.7474.1093 (Published 04 November 2004) Cite this as: BMJ 2004;329:1093

Rapid Response:

Misleading claims about albumin

Sir,

In their table and narrative text Montori et al make misleading
claims regarding the meta-analyses of the Cochrane group [1] indicating
excess mortality due to albumin administration and of Wilkes and Navickis
[2] detecting no difference in mortality. They argue that the two meta-
analyses generated similar results but differed only in "spin" by the
authors. The premise is factually erroneous. The differences between the
two meta-analyses were both large (51%) and statistically significant, as
we have elsewhere detailed [3]. Contrary to the claim of Montori et al
that the trials included in both meta-analyses were heterogeneous, no
significant heterogeneity could be detected in either meta-analysis by
standard statistical test.

The table misleadingly suggests approximate parity in the scope of
the two meta-analyses (42 vs 31 trials included) and thus equal claim to
validity. The total of 42 included by Wilkes and Navickis was for only
those trials with one or more deaths that contributed to the calculation
of relative risk, whereas the total in the table for the Cochrane meta-
analysis included trials with no deaths. The apples-to-apples comparison
would be 42 trials to 24. It should also be noted that Wilkes and Navickis
included all 24 trials of the Cochrane meta-analysis plus an additional 18
trials. Furthermore, the median size of the trials included by Wilkes and
Navickis was much larger (56 vs 36 patients per trial). Consequently, the
total weight of meta-analytic evidence assembled by Wilkes and Navickis
was approximately three times that of the Cochrane group [4]. Thus, the
disparate results were due to reliance by the Cochrane group on a small,
biased subset of the relevant evidence.

Left uncited was decisive extrinsic evidence that the results reached
by Wilkes and Navickis were correct and those of the Cochrane group
incorrect. The blinded randomized Saline versus Albumin Fluid Evaluation
(SAFE) trial demonstrated no excess mortality due to albumin among nearly
7,000 hypovolemic patients [5].

Albumin is, of course, used only as the primary example for the theme
that bias due to financial interest is everywhere palpable, and that
readers need help sorting it all out. Such help, according to Montori et
al, is to be found in the pages of unbiased publications such as ACP
Journal Club and Evidence-Based Medicine, of which they are editors. Also
recommended is a book edited by one of the co-authors. Most of the
subsections in their paper begin with the word "beware". We would add:
beware those who claim to be unbiased and have journals and books to sell.

Mahlon M. Wilkes and Roberta J. Navickis

1. Cochrane Injuries Group Albumin Reviewers. Human albumin
administration in critically ill patients: systematic review of randomised
controlled trials. BMJ 1998;317:235-40.

2. Wilkes MM, Navickis RJ. Patient survival after human albumin
administration: a meta-analysis of randomized, controlled trials. Ann
Intern Med 2001;135:149-164.

3. Wilkes MM, Navickis RJ. Colloid use in the critically ill. Ann
Intern Med 2002;137:370-1; discussion 370-1.

4. Wilkes MM, Navickis RJ. Does albumin infusion affect survival?
Review of meta-analytic findings. In: Vincent J-L, editor. 2002 Yearbook
of Intensive Care and Emergency Medicine. Berlin: Springer-Verlag,
2002:454-64.

5. SAFE Study Investigators. A comparison of albumin and saline for
fluid resuscitation in the intensive care unit. N Engl J Med 2004;350:2247
-56.

Competing interests:
None declared

Competing interests: No competing interests

10 November 2004
Mahlon M. Wilkes
Consulting Statistician
Roberta J. Navickis
Hygeia Associates, 17988 Brewer Rd., Grass Valley, CA 95949 USA