Analysis of clinical follow-up databases: risk stratification studies and prospective trial design

Design of new prospective studies should utilize detailed retrospective evaluations of clinical data. For this purpose, clinical data are needed containing both prospectively recorded values of risk factors and follow-up events. A concept of a new trial can then be modeled within the existing data-set. The development of such a model consists of the following steps: (a) the distribution of values of risk factors has to be investigated in the whole recorded population and the statistical association of the risk factors with follow-up events has to be established; (b) the stratification characteristics (sensitivity, specificity, and predictive accuracies) have to be evaluated for individual risk factors and for their multivariate combinations; (c) the stratification characteristics have to be converted into estimates of mortality reduction expected within the high risk group and used for the optimum trial design in terms of screened and randomized patient numbers. In this review, the strategy of designing a new trial is demonstrated using data of 644 survivors of acute myocardial infarction with available 3-year follow-up during which 74 patients died. A model of a new trial is considered involving reduced left ventricular ejection fraction, increased 24-hour mean heart rate, and depressed 24-hour heart rate variability as risk stratifiers.