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Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study

BMJ 2010; 341 doi: (Published 16 July 2010) Cite this as: BMJ 2010;341:c3515

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Small Trials Exclusion for Meta-analyses: The effect on heterogeneity

We read with great interest the paper published on BMJ by Nuesch et
al, with regard to the distortion effect provided by small trials upon the
general results of a cumulative meta-analysis[1]. Although in a different
scenario, and with different outcomes, we 'empirically' adopted the very
same approach in the context of a literature-based meta-analysis exploring
the benefit of adjuvant cisplatin-based chemotherapy for non-small-cell
lung cancer[2]. In order to screen for the effect consistency (in this
case the survival benefit provided by chemotherapy), to increase the power
of the analysis, and to decrease the statistical and methodological
heterogeneity between trials, underpowered trials with less than 100
patients per arm were excluded from this population in a sensitivity
analysis fashion. Interestingly, this approach was able to make
heterogeneity disappear; indeed, as the overall population relative risk
(RR) in favour of chemotherapy for overall survival was 0.91 (p=0.011)
with a significant heterogeneity (p=0.048), in the large trial sample (RR
0.91, p=0.001), the heterogeneity test was no more statistically
significant (p=0.45)[2].

When looking at the disease free survival, the
same phenomenon was observed, with a statistically significant
heterogeneity in the overall sample (p=0.001), and without any
significance in the large trials population (p=0.53). Although no
interaction in the outcome effect between the overall sample and the large
trials population was detected (regardless of the explored outcome), the
sensitivity analysis empirically performed according to trials sample size
was able to significantly decrease heterogeneity across the trials,
allowing the interpretation of the overall meta-analysis results more
useful for clinical practice. The paper published by Nuesch et al
represents a first-in-literature demonstration of this effect and should
be quoted as a reference paper for all upcoming meta-analyses.


1. Nuesch E, Trelle S, Reichenbach S, et al: Small study effects in
meta-analyses of osteoarthritis trials: meta-epidemiological study. BMJ

2. Bria E, Gralla RJ, Raftopoulos H, et al: Magnitude of benefit of
adjuvant chemotherapy for non-small cell lung cancer: meta-analysis of
randomized clinical trials. Lung Cancer 63:50-7, 2009

Competing interests: No competing interests

07 September 2010
Emilio Bria
Vanja Vaccaro, M.D., Federica Cuppone, M.D., Francesco Cognetti, M.D. (Director of Department), Diana Giannarelli, Ph.D.
Regina Elena National Cancer Institute, Rome, ITALY