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.
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.
Authors: Michael J Raphael; William Raskin; Steven Habbous; Xiaochen Tai; Jaclyn Beca; Wei F Dai; Jessica Arias; Leta Forbes; Scott Gavura; James J Biagi; Craig C Earle; Kelvin K W Chan Journal: JAMA Netw Open Date: 2021-11-01
Authors: Wei Fang Dai; Jaclyn M Beca; Chenthila Nagamuthu; Ning Liu; Claire de Oliveira; Craig C Earle; Maureen Trudeau; Rebecca E Mercer; Kelvin K W Chan Journal: JAMA Netw Open Date: 2022-02-01
Authors: Vanessa Arciero; Jin Luo; Ambica Parmar; Wei Fang Dai; Jaclyn M Beca; Michael J Raphael; Wanrudee Isaranuwatchai; Steven Habbous; Mina Tadrous; Craig C Earle; Jim J Biagi; Nicole Mittmann; Jessica Arias; Scott Gavura; Kelvin K W Chan Journal: JNCI Cancer Spectr Date: 2022-07-01
Authors: Wei Fang Dai; Claire de Oliveira; Scott Blommaert; Reka E Pataky; David Tran; Zeb Aurangzeb; Cynthia Kendell; Chris Folkins; Chandy Somayaji; Jeff Dowden; Winson Cheung; Erin Strumpf; Jaclyn M Beca; Carol McClure; Robin Urquhart; James Ted McDonald; Riaz Alvi; Donna Turner; Stuart Peacock; Avram Denburg; Rebecca E Mercer; Caroline Muñoz; Ambica Parmar; Mina Tadrous; Pam Takhar; Kelvin K W Chan Journal: Curr Oncol Date: 2022-03-17 Impact factor: 3.677