Marker-of-self becomes marker-of-senescence.

(4/12) of the treatments called useful will be false positives. Of course, the false positive rate rises above 5% as the number of tests of statistical significance performed increases. In this connection, Tannock reported that subgroup analyses were done in 59% of 32 randomized trials published in the New England Journal of Medicine or the Journal of Clinical Oncology, with corrections for multiple testing done in only 13%. 6 Under the circumstances, it is quite plausible that more than 50% of the treatments reported as advances are not. Various biases also need to be considered. Publication bias is well known 7 and has motivated the establishment of trial registries that include unpublished as well as published results. Although not an issue with the current article, funding source influences whether an experimental treatment will be concluded to be " treatment of choice " after a phase 3 trial. Thus, Als-Nielsen et al found that, after accounting for treatment effect, double-blinding, and other covariates, trials funded by for-profit organizations were 5.3-fold more likely to recommend the experimental treatment (95% confidence interval 2.0-14.4). 8 A fundamental purpose of randomization is to achieve balance on unknown covariates. The latter's importance in AML is apparent given that accounting for known covariates (cytogenetics, FLT3, etc) results in an ability to predict long-term outcomes that is closer to a coin flip (area under receiver operating characteristic curve, AUC, ϭ 0.5) than certainty (AUC ϭ 1.0). 9 Yet randomized trials of a given therapy are conducted sequentially and thus perforce differ with respect to these unknown covariates. Hence, the results of ran-domized trials of the same therapy may not be mutually consistent unless the treatment effect is quite large. A recent paper was provocatively entitled " Why most published research findings are false. " 10 Even without necessarily subscribing to this view, physicians' seeming reluctance to be influenced by results of even randomized trials is understandable, even if the reasons for this reluctance are often intuitive. An adage attributed to the late legendary college basketball coach John Wooden is, " Be quick, but do not hurry. " Perhaps, and depending on effect size, we should be quick to organize follow-up trials to confirm " positive " results of well-conducted trials such as that of Pabst et al, but circumspect in altering practice to reflect the results. Conflict-of-interest disclosure: The author declares no competing financial interests. ■ REFERENCES 1. …