Predicting the future: a critical appraisal of cancer prognosis studies

Many studies have attempted to define useful prognostic and predictive fact ors in cancer but few have achieved acceptance in clinical practice because of methodological weaknesses. These include failure to test clearly formul ated hypotheses, inadequate sample size, inappropriate multiple significanc e testing, arbitrary definition of patient groups, inadequately reproducibl e assays, and failure to verify prognostic factors with data independent of the data which suggested the original hypothesis. This unsatisfactory situ ation will persist until critical attention is routinely paid to study desi gn and prospective validation of supposed prognostic and predictive factors , without which classical approaches will be suboptimally exploited and the flood of data from new molecular technologies will not be used effectively . We propose that prognostic factors should be evaluated in three phases: I , assay definition; II, retrospective testing; III, prospective testing, id eally as a designed part of clinical trials.