70S Abstracts

65A CHAOS THEORY AND PROGNOSIS: SELECTION OF PATIENTS

WITH ARRHYTHMIAS AND AN INCREASED RISK OF SUDDEN CARDIAC DEATH

K. Ulm 1, G. Schmidt z, G. Morrill 3 b~stitut fiir Medizinische Statistik

Munich, Germany

In recent years research has focused on the increase of the prediction of cardiac mortality among patients with arrhythmias. Beside the left ventricular ejection fraction (LVEF) the analysis of the heart rate variability has been the target of the investigations. However, with the results obtained so far, the prediction is not sufficient enough. The prognosis is used to assess the appropriate treatment, e.g., implantation of an defibrillator.

We will present a new method to describe the complexity of the heart beats within 24 hours based on methods derived from, chaos theory. For each patient intervals between three consecutive heart beats were analyzed in the following steps: 1) representation of all intervals in a three dimensional phase space, 2) analysis of the complexity by computing a scaling index (= a) for each point in the phase space and 3) calculation of the complexity measure (= A~) in analyzing the frequency distribution of all scaling indices a.

In our sample of 54 patients with coronary heart disease and frequent arrhythmias 22 died, 16 out of them suddenly. In the Cox-regression analysis and the CART method beside LVEF the Aa-value turned out to be the variable with most prognostic impact, t4 our of the 54 patients had a LVEF < 42 % and Ac~ > 1.5 and all of them died suddenly.

Chaos theory seems to be a very sensitive method to analyze the complexity of a biological system like heart rate variability.

66A RANDOMIZED AND NON-RANDOMIZED PATIENTS IN C L I N I C A L TRIALS:

EXPERIENCES WITH C O M P R E H E N S I V E C O H O R T STUDIES

W. Sauerbrei, C. Schmoor, M. OIschewski, and M. Schumacher

Institute for Medical Biometry and lnformatics University of Freiburg

Freiburg, Germany

In clinical research, randomized trials are widely accepted as the definitive method of evaluating the efficacy of therapies. The random assignment of patients to their treatment ensures the internal validity of the comparison of new treatments with controls. An assessment of the external validity of the result of a randomized trial can best be achieved by comparing the randomized study population to the population of patients who met the eligibility criteria but did not consent to randomization. The Comprehensive Cohort Study (CCS) is designed to recruit all patients fulfilling the clinical eligibility criteria regardless of their consent to randomization. The CCS concept was adopted in three clinical trials of the German Breast Cancer Study Group (GBSG) conducted between 1993 and 1989, where 124 centres recruited 2084 patients. 734 (35 %) of these patients accepted being randomized, while 1350 (65%) chose one of the treatments under study by themselves with remarkably differences between trials. We first examine the representatives of the population of randomized patients and then present results with regard to the external validity of the treatment effects estimated in the randomized patients by means of Cox's proportional hazards