Association between control group therapy and magnitude of clinical benefit of cancer drugs

Abstract Little is known about the impact of control group therapy on clinical benefit scales such as American Society of Clinical Oncology Value Framework (ASCO-VF), European Society for Medical Oncology Magnitude Clinical Benefit Scale (ESMO-MCBS), National Comprehensive Cancer Network (NCCN) Evidence Blocks and ASCO Cancer Research Committee (ASCO-CRC). We searched Drugs@FDA to identify cancer drugs approved between January 2012 and December 2021 based on randomized trials (RCTs). Definition of substantial clinical benefit was based on recommendations for each scale. Associations between characteristics of control group therapy and clinical benefit were explored using logistic regression. RCTs with a control group of active treatment plus placebo were associated with significantly lower odds of substantial benefit with ESMO-MCBS (OR 0.27, P = 0.003) and ASCO-VF (OR 0.30, P = 0.008) but not with NCCN Evidence Blocks or ASCO-CRC. This effect was attenuated and lost statistical significance without adjustment for quality of life (QoL) and/or toxicity (ESMO-MCBS OR 0.50, P = 0.17; ASCO-VF OR 0.49, P = 0.11). Clinical benefit scales can be sensitive to control group therapy. RCTs with substantial overlap between experimental and control therapy showed lower magnitude of clinical benefit using ESMO-MCBS and ASCO-VF scales; possibly due to differences in the weighting of QoL and toxicity between different frameworks.