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392 Good health: Statistical challengesFIGURE 35.1Genetic tests sold directly to consumers for medical conditions.For example, the Breast Cancer Risk Assessment Tool (BCRAT) assigns awoman a probability of developing breast cancer in the next five years, usingher self-reported risk factors, relative risk estimates obtained from randomizedtrials or observational studies, and national rates for breast cancer incidenceand death from all causes (Costantino et al., 1999; Gail et al., 1989).Personal risk models play important roles in the practice of medicine, asstandards for clinical care become increasingly tailored to patients’ individualcharacteristics and preferences. The need to evaluate risk models is increasingas personalized medicine evolves. A PUBMED search using the key wordsvalidating risk models produced nearly 4000 hits, indicating substantial interestin this topic in current medical practice. Moreover there are now morethan 370 online direct-to-consumer genetic tests with risk assessments for adversehealth outcomes (Figure 35.1). The Food and Drug Administration isconsidering regulating these assessments, so we need reliable methods to validatethem.Determining the probability of a future adverse outcome for a particularperson is not unlike determining the chance of a hurricane or earthquake in aparticular area during a given time period. Not surprisingly therefore, manyof the statistical problems involved in developing and evaluating risk modelshave intrigued meteorologists and seismologists for decades, and their findings