Statistical issues in tumor marker studies

Context. - Inferences from tumor marker studies are complicated by a variety of statistical concerns, which can make proper interpretation of results difficult. This article focuses on important issues that should be addressed when designing, conducting, and analyzing tumor marker studies. Objective. - To highlight the importance of considering statistical significance, risk ratios, statistical power, reproducibility, multiple testing, confirmatory studies, and missing data in the design of marker studies used for prognosis. Results. - Suggestions are provided for more effectively conducting marker studies. These include more careful attention to adequacy of the number of subjects for a marker study and improved documentation and standardization of assay methods. The importance of complete reporting of study results and description of the statistical analysis methods used is also emphasized. Conclusion. - Cooperation among clinicians, laboratory scientists, and statisticians will be required to conduct statistically sound tumor marker studies and to facilitate prioritizing markers for new and confirmatory studies in an environment of limited patient and specimen resources.