To the Editor:
In the Letter of Response from Watkins and Rukazenkov (J Cell Mol Med 2010), the paragraph
starting with ‘It is important to note…’ summarizes potential sources of error in
our pooled analysis. We were aware of the points correctly raised by Watkins and Rukazenkov
when conducting our analysis and we agree that it is important to see the limitations
of the performed study; these have been carefully detailed in the discussion part
of the paper. The pooled analysis strived for a concise summary of the published data
and we acknowledge that simplifying assumptions like the exponential distribution
were indispensible to accomplish this. We would like to point out that the simplifications
were applied to all treatments in an identical way and that a weighted pooled analysis
was performed to adjust for different sample sizes. That this process would favour
only one treatment and/or be detrimental to another treatment can therefore be ruled
In many places within the paper we point to the need to exercise caution when interpreting
the presented data, for example, it is repeatedly noted that the conclusions from
the pooled analysis only apply to the considered patient pool and may not be readily
extrapolated to an unseen patient population. Similarly, the reported P values gained
from permutation runs are statistically valid, but apply as any conditional test to
the considered patient pool only.
Watkins and Rukazenkov refer correctly to randomized clinical trials (RCTs) as the
gold standard to evaluate treatments; however, the pooled analysis of published studies
provides a relevant view of the accumulated treatment experience in its own right.
We consider this summary as a worthwhile contribution to the scientific/medical discussion
in the area.
Finally, we note that new RCT data have recently become available. The OPTIMAL study,
a randomized phase III trial conducted only in patients with epidermal growth factor
receptor (EGFR) activating mutation-positive non small cell lung cancer (NSCLC), evaluated
first-line platinum doublet chemotherapy versus erlotinib. This study (n = 165) was
reported at the ESMO congress in October 2010 and showed a hazard ratio for progression-free
survival of 0.16 in favour of the erlotinib-treated patients. The median progression
free survival (PFS) of 13.1 months in the erlotinib-treated group and 4.6 in the chemotherapy-treated
group further support the results of our pooled analyses.