ABSTRACT
Randomized clinical trials (RCTs) are the gold standard for clinical trials comparing treatment groups. When randomization is not feasible because of ethical concerns, patient preference, or regulatory acceptability, historical control trials (HCTs) are an alternative. A strong argument for using HCTs is that all patients can receive the new treatment. The major benefits of HCTs include their contribution to medical knowledge and the potential cost savings with respect to sample size and length of study. However, HCTs may suffer from patient selection bias because patients with more favorable prognoses may be more likely to be selected to receive the new treatment. HCTs may also suffer from outcome evaluation bias due to changes in the experimental environment, as well as in technology, and have been criticized accordingly (Pocock, 1976; Gehan, 1982; Gehan and Freireich, Farewell 1981).
