総説・解説等

With the progress of molecular biology and other disciplines, biomarkers are becoming increasingly important in both drug discovery and development. Several critical issues, including scientific rationale, study design, marker assessment, cost and feasibility should be carefully considered in the validation of biomarkers through clinical research. Here, we highlight several important aspects related to the design for clinical researches which incorporate biomarkers. First, we define the term "biomarker" and illustrate the difference between prognostic and predictive markers. Second, in exploratory clinical studies, we focus on issues related to study design for screening and evaluating biomarkers. Finally, we review the design of confirmatory clinical trials for new treatments and companion biomarker diagnostic tests.

During the last decade, evidence-based medicine has been described as a paradigm shift in clinical practice, and as "the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients". Appropriate statistical methods for analyzing data are critical for the correct interpretation of the results in proof of the evidence. However, in the medical literature, these statistical methods are often incorrectly interpreted or misinterpreted, leading to serious methodological errors and misinterpretations. This review highlights several important aspects related to the design and statistical analysis for evidence-based reproductive medicine. First, we clarify the distinction between ratios, proportions, and rates, and then provide a definition of pregnancy rate. Second, we focus on a special type of bias called 'confounding bias', which occurs when a factor is associated with both the exposure and the disease but is not part of the causal pathway. Finally, we present concerns regarding misuse of statistical software or application of inappropriate statistical methods, especially in medical research.