Real and Virtual Clinical Trials: A Formal Analysis

Systems biology is an interdisciplinary approach to complex biological problems through modelling, simulation, and systems-level analysis, which is increasingly establishing itself as an alternative and complementary source of knowledge to standards laboratory, clinical and epidemiologic studies in medicine. It has been proposed that such computer simulation and computer-aided modelling techniques could be employed in the setting of clinical testing, in order to support the planning of clinical trials, refine their conduct and reduce the possibility of their failure. According to this view, patient-specific computer models should be used to generate simulated populations, on which new biomedical products can be safely tested. The Avicenna Alliance refers to this methodology as In Silico Clinical Trial (ISCT). In their recently published Roadmap (Viceconti et al., 2016), the Avicenna alliance produced an in-depth examination of the scientific, technological, and societal obstacles that have to be overcome in order to establish a role for the ISCT in medical research. With the present paper we provide an analysis of ISCTs epistemological status, in particular with respect to the gold standard instrument of clinical investigation: Randomized Controlled Trials. We draw on Cartwright's analysis (2011) of RCTs as a basis for a formal analysis of their epistemic value and as a benchmark for investigating ISCTs. Britton et al.'s study (Britton et al., 2013) on the impact of ion current variability on cardiac electrophysiology is used for illustrative purposes.