We review a recent study, published in Future Oncology, that discussed the benefits and limitations of real-world evidence (RWE), using examples from EGFR mutation-positive non-small-cell lung cancer (NSCLC).
Randomised controlled trials (RCTs) are the gold standard for evidence-based medicine. They are considered to be highly reliable and to have strong internal validity. However, they do not always reflect real-world patient populations. This limits their generalisability and external validity. They are also slow and costly to conduct and analyse.
Real-world evidence (RWE) is an increasingly utilised source of information regarding the efficacy and safety of therapeutic agents obtained from observational data. Recent technological advances and the widespread use of electronic health records (EHRs) have created opportunities for generating RWE.
Benefits and limitations of RWE
Real-world studies reflect clinical experiences across a broader and more diverse distribution of patients than RCTs. They often include larger sample sizes and longer follow-up periods. This can allow assessment of long-term outcomes and provide additional safety information after drug approval. In addition, as these studies use existing data sources, they can be more economical and time efficient than RCTs.
Limitations include inconsistencies in collecting electronic data and also missing data. To maximise validity and applicability, RWD should be accurate, consistently collected and verifiable to a similar level as prospective clinical trials. In addition, recognition of the limitations of each study is also important.
Learnings from EGFR mutation-positive NSCLC
Many EGFR tyrosine kinase inhibitors (TKIs) have become standard-of-care agents for patients with EGFR mutation-positive NSCLC based on data from RCTs. In addition, real-world studies have provided numerous insights into the effectiveness and safety of EGFR TKIs in routine clinical use. The majority of these studies have focussed on the second-generation TKI afatinib. There is less RWE available for the other EGFR TKIs.
RWE expands upon RCT data to support the effectiveness and safety of EGFR TKIs in real-world clinical practice. This includes long-term follow-up data and comparisons of the effectiveness of different EGFR TKIs. It also facilitates analysis of the activity and tolerability of EGFR TKIs in patient subgroups generally underrepresented or excluded from RCTS e.g. elderly. Finally, RWE provides information on real-world management of class-related toxicities and provides valuable information on the sequential use of EGFR TKIs following acquired resistance to first-line therapy.
Although real-world studies are not able to achieve the high internal validity of RCTs, RWD can provide valuable complementary data. Researchers can use this to address the generalisability limitations of RCTs and provide evidence on the external validity. In the example of EGFR mutation-positive NSCLC, real-world studies have confirmed the efficacy and safety profile of TKIs seen in RCTs in real-world populations. While these studies should not be directly compared with clinical trials, it is apparent that quality evidence can provide valuable additional insight into the use of therapies in routine clinical practice.