Medical registers as historical controls: analysis of an open clinical trial of inosiplex in subacute sclerosing panencephalitis

Abstract

Clinical trials of treatments for rare or fatal diseases must often use historical rather than randomized concurrent controls. Randomized trials may not be possible if (1) the number of patients available is quite small, (2) ethical considerations discourage the assignment of patients to control treatments known to be ineffective or (3) some evidence suggests that the proposed new treatment is substantially more effective than the control. We suggest that, when randomization is not feasible, adequately maintained medical registers can serve as a source of control patients. Investigators must pay careful attention to prognostic factors that might bias the results. However, statistical techniques for controlling such bias exist and, if these are properly employed, registry-derived historical controls can be used to evaluate the effectiveness of treatment.