Statistical methods to assess the prognostic value of risk prediction rules in clinical research.

Prognosis aims at estimating the future course of a given disease in probabilistic terms. As in diagnosis, where clinicians are interested in knowing the accuracy of a new test to identify patients affected by a given disease, in prognosis they wish to accurately identify patients at risk of a future event conditional to one or more prognostic factors. Thus, accurate risk predictions play a primary role in all fields of clinical medicine and in geriatrics as well because they can help clinicians to tailor the intensity of a treatment and to schedule clinical surveillance according to the risk of the concerned patient. Statistical methods able to evaluate the prognostic accuracy of a risk score demand the assessment of discrimination (the Harrell's C-index), calibration (Hosmer-May test) and risk reclassification abilities (IDI, an index of risk reclassification) of the same risk prediction rule whereas, in spite of the popular belief that traditional statistical techniques providing relative measures of effect (such as the hazard ratio derived by Cox regression analysis or the odds ratio obtained by logistic regression analysis) could be per se enough to assess the prognostic value of a biomarker or of a risk score. In this paper we provide a brief theoretical background of each statistical test and a practical approach to the issue. For didactic purposes, in the paper we also provide a dataset (n = 40) to allow the reader to train in the application of the proposed statistical methods.