Assessing the efficacy‐effectiveness gap for cancer therapies: A comparison of overall survival and toxicity between clinical trial and population‐based, real‐world data for contemporary parenteral cancer therapeutics

Background Although increasing evidence has suggested that an efficacy‐effectiveness gap exists between clinical trial (CT) and real‐world evidence (RWE), to the authors' knowledge, the magnitude of this difference remains undercharacterized. The objective of the current study was to quantify the magnitude of survival and toxicity differences between CT and RWE for contemporary cancer systemic therapies. Methods Patients receiving cancer therapies funded under Cancer Care Ontario's New Drug Funding Program (NDFP) were identified. Landmark CTs with data regarding survival and adverse events (AEs) for each drug indication were identified. RWE for survival and hospitalization rates during treatment were ascertained through Canadian population‐based databases. The efficacy‐effectiveness gap for each drug indication was calculated as the difference between RWE and CT data for median overall survival (OS), 1‐year OS, and generated hazard ratios (HRs) with 95% CIs from Kaplan‐Meier OS curves. Toxicity differences were calculated as the difference between RWE of hospitalization rates and CT serious AE rates. Results Twenty‐nine indications from 20 systemic therapies were included. Twenty‐eight of 29 indications (97%) demonstrated worse survival in RWE, with a median OS difference of 5.2 months (interquartile range, 3.0‐12.1 months). Lower effectiveness in RWE also was demonstrated through a meta‐analysis of an OS hazard ratio of 1.58 (95% CI, 1.39‐1.80). The median difference between RWE for hospitalization rates and CT serious AEs was 14% (95% CI, 9%‐22%). Conclusions An efficacy‐effectiveness gap exists for contemporary cancer systemic therapies, with a 5.2‐month lower median OS observed in RWE compared with CT data. These data supports the use of RWE to better inform real‐world decision making regarding the use of cancer systemic therapies. Through a review of clinical trial and real‐world evidence for contemporary cancer systemic therapies, an efficacy‐effectiveness gap has been demonstrated. Thus, supportive evidence is provided in the current study for the further investigation of real‐world outcomes of patients to inform real‐world decision making.