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A. Ferrari et al.
may also be a byproduct of using aggregate data as predic- tors, with subsequent loss of information on individual patients.36
A third strength is that by extracting data on follow-up duration and integrating them in the analysis, we were able to model the time-dependent evolution of outcome risk, thus overcoming a common bias in meta-analysis of binary outcomes, i.e. lack of temporal information. A potential source of bias in this respect is our decision to use median follow-up time when the mean was not avail- able, which can lead to biased risk estimates when the actual distribution of follow-up times in the study is very skewed. However, using the median as an estimator of mean has been shown to be reliable in most cases.39
In conclusion, this meta-analysis provides reliable risk estimates for thrombosis, hemorrhage, evolution to MF and AML, and mortality in PV patients under standard treat-
ment with HU. This can be a valid point of reference for the clinician. It can support the information given to the patient and counseling, and can also help calculate sample size in future comparative clinical trials by providing a reference value. We also prove the feasibility of clinical trials adopting critical efficacy end points such as frequency of cardiovas- cular events in selected populations. Lastly, we underline the value of a cheap, old and safe molecule as a reliable and accessible resource for those settings where there is a need to reconcile economic sustainability with the right to a qualitative-quantitative life advantage.
Acknowledgments
We wish to thank Franca Boschini (Ospedale Papa Giovanni XIII, Bergamo, Italy), for help with database searches and Gianni Tognoni (FROM research foundation, Ospedale Papa Giovanni XIII, Bergamo, Italy), for useful discussion of the results.
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