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CANCER June 1,1996 I Volume 77 / Number 11
the pooled hazard ratio for death was 0.87 (0.79-0.96; P
< 0.005) for the 11 cisplatin-based trials. For the 3 trials
using vinca-alkaloids or etoposide, the hazard ratio was
0.87 (0.70-1.09), and 0.96 for the 8 other noncisplatin
trials. However, the results of the three trial groups were
not significantly different. For the cisplatin-based trials,
the absolute improvement in survival was 4% (95% CI:
1-7%) at 2 year and 2% (1-4%) at 5 years. Using the same
15% survival rate at 2 years for the control group and the
published OR, it was possible to compute3 the absolute
improvement in survival for the Marino et al. meta-analysis as 5% (1-11%). Based on the results of the two metaanalyses, we don’t share the confidence of Marino et al.
on the reliability of meta-analysis based only on the data
presented in published papers. Although both studies
conclude in favor of cisplatin-based CT, the NSCLCCG
showed a smaller effect than the Marino et al. meta-analysis. This difference could not be explained by the inclusion of the 3 trials giving cisplatin only during RT as the
pooled OR for these 3 trials is 0.75 compared with 0.64
for the other cisplatin-based trials. Thus, if these trials
had been excluded from the Marino et al. study, the results would have shown an even larger effect of CT. To
the best of our knowledge, there are 4 other examples
where both meta-analysis based on data extracted from
publications and meta-analysis based on data from individual patients were p e r f ~ r m e d . ~In- ~three c a ~ e s , the
relative risk of death was overestimated in the literaturebased meta-analysis. In a recent example concerning
breast cancer,6 it was the meta-analysis of updated data
on individual patients with follow-up of 15 years that
showed highly significant results whereas an analysis of
the data extracted from trial publications (before 1990)
would have shown almost no benefit. The mounting evidence of different results obtained by the two approaches
illustrates the need to consider all of the randomized evidence and suggests that meta-analysis based on updated
data from individual patients may be the best method of
obtaining reliable answers to unresolved questions.
Pignon JP, Arriagada R. Role of thoracic radiotherapy in limited-stage small cell lung cancer: quantitative review based
on literature versus meta-analysis based on individual data.
J Clin Oncol 1992;10:1819-20.
5. Marino P, Pampallona S, Preatoni A, Cantoni A, invernizzi
F. Chemotherapy versus supportive care in advanced nonsmall cell lung cancer: results of a meta-analysis of the literature. Chest 1994;106:861-5.
6. Clarke M. Ovarian ablation-Why the Early Breast Cancer
Trialist’ Collaborative Group (EBCTCG) individual patient
data meta-analysis was needed [abstract].Control Clin Trials
Jean-Pierre Pignon, M.D., Ph.D.
Department of Biostatistics
Institut Gustave-Roussy
94805 Villejuif Cedex, France
Lesley A. Stewart, Ph.D.
MRC Cancer Trials Ofice
5 Shaftesbuiy Road
Cambridge, UK
Author Reply
election criteria for our trials was reported in the
“Method” section of our paper. Probably, they were
different from Pignon et al.’s. Although we used a different method of analysis, our results were in agreement
with those of Pignon et al.; in particular both studies
conclude in favor of cisplatin-based chemotherapy.
In a previous paper,’ we discussed the potential
sources of bias affecting our meta-analysis of the literature. However, we believe that the bias was rather small
in this setting. Furthermore, the sensitivity analysis performed on the width of the confidence interval for pooled
odds ratio (OR) seems to suggest statistical significance
of the pooled OR at the 5% level. We believe that our
method, cheaper and faster than meta-analysis of the
individual data, can offer useful results when no conclusions are possible from the data of literature.
Marino P, Preatoni A, Cantoni A. Randomized trials of radiotherapy alone versus combined chemotherapy and radiotherapy in stages IIIa and IIIb nonsmall cell lung cancer: A
meta-analysis. Cancer 1995;76593401.
Non-Small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using
updated individual patients data from 52 randomised clinical trials. EM/ 1995;311:899-909.
Stewart LA, Parmar MKB. Meta-analysis of the literature or
meta-analysis of individual patient data-is there a difference? Lancet 1993;341:418-422.
Marino P, Pampallona S, Preatoni A, Cantoni A, invernizzi
F. Chemotherapy versus supportive care in advanced nonsmall-cell lung cancer. Results of a meta-analysis of the literature. Chest 1994;106:861-5.
Pietro Marino, M.D.
Department of Internal Medicine
University of Milano
S. Paolo Hospital, Milano, Italy
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