Is there an efficacy-effectiveness gap between randomized controlled trials and real-world studies in colorectal cancer: a systematic review and meta-analysis

BACKGROUND: To investigate whether patients with colorectal cancer (CRC) enrolled in randomized controlled trials (RCTs) and real-world studies (RWS) differ in terms of baseline characteristics, leading to an efficacy-effectiveness gap. METHODS: A systematic literature reviews was conducted to identify RCTs and RWS with CRC, treated with bevacizumab (BEV), cetuximab (CET) or oxaliplatin combined with capecitabine (XELOX). Using random-effects meta-analyses compared the baseline characteristics and treatment effects of RCTs and RWS, overall and by drug. Correlation between treatment effects and baseline characteristics and study types were estimated using meta-regression analyses. RESULTS: Two hundred and fifty-three studies were included. Compared with patients enrolled in RWS, the proportion of male patients in RCTs was 0.032 higher (P=0.004), the proportion of patients with Eastern Cooperative Oncology Group (ECOG) performance ≥2 was 0.085 less (P<0.001). No significant differences in treatment effects [progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR)] were found by overall analysis. But the OS of patients in RCTs was 4.184 higher (P=0.023) in the CET group. Meta-regression results showed that OS difference in the CET group was related to the difference in treatment lines, not related to other baseline characteristics and study types. CONCLUSIONS: No efficacy-effectiveness gap was found in CRC between RCTs and RWS. CRC treatment effects Between RCTs and RWS had high consistency.