Objectives: Although major conceptual paradigms underlying the EEG (i.e., differences between RCT-based efficacy and RWE-based effectiveness estimates) have been well described, few studies have quantitatively evaluated the magnitude of this gap for different cancer therapeutics. The objective of this TLR was to describe the methods and findings of studies that quantified EEG for cancer therapies and to critically synthesize this information to identify paths for future research.

Methods: A targeted literature review was conducted among four databases (PubMed, EMBASE, and two within Ovid) focusing on English-language studies published between 01/2017–12/2021 that sought to quantitatively assess the magnitude of and factors contributing to the EEG for cancer therapeutics. Titles and abstracts of 246 papers were manually reviewed for inclusion per pre-specified criteria.

Results: Ten studies met eligibility criteria for inclusion (most common reason for exclusion was lack of EEG quantification). Cumulatively, these studies formally assessed EEG for over 25 cancers and more than 45 treatments (i.e., systemic, targeted, and immunotherapy drugs). Six of 10 studies focused on one cancer type. Outcomes compared between trials and real-world analyses included progression-free survival, overall survival (OS), and adverse event rates. The most common EEG explanatory factor examined was trial eligibility criteria, but treatment duration/completion, other lines of therapy, and various confounders were also considered. Three studies with overlapping authors calculated a metric called the efficacy-effectiveness factor as a strategy for assessing the magnitude/direction of the EEG. Most studies (n=6) using OS as the outcome found lower effectiveness in RWE studies compared to trial-based efficacy.

Conclusions: A heightened understanding of the scope and drivers of the EEG may pave the way for more inclusive clinical trials and could lead to innovations in study design and methodology for both clinical trials and real-world studies. Research to develop a standardized approach for quantifying EEG is warranted.