[Bias, biostatistics, and prognostic factors].

Prognostic factors are essential for patient management and counseling. Most cancer patients receive treatment based on the presence or absence of several risk factors. The most prominent example of this is tumor, node, metastasis staging, but many diseases are moving beyond the simple one-sizefits-all stage classification and using stylized prognostic factors. A notable difficulty in the development of prognostic factors in today’s clinical research environment is the lack of implemented guidelines and accepted practices. As a result, it is not clear what constitutes a prognostic factor. This article reviews some of this practice, identifies the various biases that arise from it, and points to solutions, many of which are discussed in detail at other forums but have been somewhat ignored, to this point, in the thymoma literature. The clinical importance of reliable prognostic factors requires little justification. If one can predict the course of disease with reasonable precision, treatment choice, follow-up, and patient counseling are greatly enhanced. As a result, prognostic markers abound in all diseases including thymoma.1–7 There is no question that our ability to accurately prognosticate has improved by leaps and bounds during the past 2 decades. Yet, only a handful of markers have made it into international guidelines for diagnosis, treatment, or follow-up. This article will discuss some of the reasons behind the failure of many prognostic markers to deliver and offer some suggestions to avoid similar disappointments in the future. Several examples I will use, and the arguments that will follow have been made previously elsewhere,8–13 although not necessarily in the context of thymoma. Some of the examples in this study are from diagnostic factor studies; this is because statistical concerns, especially about bias, have much in common between diagnostic and prognostic factor studies. Furthermore, diagnostic factor examples often have the advantage that they are simple and available, and there is more widespread knowledge about the factor or disease or both. For the same reason, some of the general references that discuss methodological issues in biomarker development and early detection of cancer are also relevant in this study.