Using RWE research to extend clinical trials in diabetes: An example with implications for the future

Abstract

Background Although randomized, controlled trials (RCTs) are seen as the gold standard for evidence in clinical medicine, a number of considerations are increasing the use of real‐world data (RWD) to generate evidence. A series of methodological challenges must be overcome in order for such real‐world evidence (RWE) to gain acceptance. In diabetes, RWE faces some particular issues that have limited its development. As the natural history of diabetes progresses, patients' disease changes over time and treatments will be modified as a result. This evolving disease and treatment pattern requires application of methods that account for such changes over time. Research developing RWE in diabetes and other conditions has sometimes been subject to important biases, and researchers should be aware of, and take steps to mitigate potential for bias in order to enhance the evidence produced. Results We review a RWE study that replicated and extended evidence provided by a RCT regarding the effects of weekly exenatide relative to basal insulin (glargine or detemir) to illustrate a potential application of RWE. This study observed a 0.7% decrease in HbA1C for weekly exenatide relative to a 0.5% decrease in HbA1C for the comparator along with a 2 kg weight loss for weekly exenatide relative to a 0.25 kg weight gain, effects that were close to those from the RCT. Further, the RWE study was able to extend results to patient populations that were not well represented in the RCT. Conclusion Despite numerous challenges, RWE can be used to complement evidence from RCTs.

Exposure to dipeptidyl‐peptidase 4 inhibitors and the risk of pneumonia among people with type 2 diabetes: Retrospective cohort study and meta‐analysis

“…It should be noted that generalizing RCT findings to clinical practice can be challenging because of the many differences between the RCT setting and routine care. 30,31 Therefore, we believe it is reasonable to take into account all the available evidence, including observational studies, before drawing any conclusions.…”

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“…Real-world evidence obtained from comparative effectiveness research can be used to complement evidence from trials through translating the efficacy of interventions in trials to the effectiveness of them in clinical practice among a broader spectrum of patient populations [8]. Evidence regarding the head-to-head comparative effectiveness of GLP-1RAs is critical for supporting clinical decisions and formulating healthcare reimbursement policies in real-world practice.…”

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“…From the perspective of the clinical care of T2D patients who require intensified injection therapy, our findings are consistent with existing treatment guidelines [ 1 , 3 ] and a real-world study [ 47 ], showing that using a GLP-1RA versus insulin therapy has therapeutic benefits in terms of reduced risks of hypoglycemia and all-cause death. Our real-world evidence of the comparative effectiveness of GLP-1RAs versus insulin complements existing trial evidence by translating the efficacy of GLP-1RAs in clinical trials to its effectiveness in clinical practice among a broader spectrum of real-world patient populations for supporting the rational selection of GLAs in clinical practice [ 48 ].…”