How does real-world evidence complement RCTs, and why is it important for small patient populations?

Real-world evidence (RWE) and randomized controlled trial (RCT) data each have both advantages and disadvantages, and they can be complementary.¹ In general, outcomes of real-world studies are given lower credibility compared with RCT research, which is characterized as having the highest reliability.¹ However, real-world studies can be particularly advantageous in specific patient populations, for instance in chronic graft-versus-host disease (cGvHD), which may have a lack of RCT data.

The GvHD Hub spoke to Steven Pavletic, National Cancer Institute, Bethesda, US, about his perspectives on how RWE can complement RCTs, and why it may be important for small patient populations. 

RCT vs RWE 

• Data from RCTs are considered the ‘gold-standard’ for investigating the efficacy and safety of treatments, owing to the well-controlled, observational environment, with strict inclusion and exclusion criteria. 

• A major challenge with RCT data is that they generally apply to a specific population of patients but may not be relevant for all individuals with the disease.  

• Ideally, RCTs and real-world studies should be developed to be complementary. For example, if an RCT investigates the efficacy of a drug, the real-world studies can focus on the epidemiology, effectiveness, safety, or costs of treatment related to that drug (Table 1).¹ 

Real-world data in cGvHD 

• cGvHD is heterogeneous in presentation, with variability in severity, organ involvement, and manifestations. 

• It is important to identify less common adverse effects that may result from treatment in patients with varied clinical manifestations of cGvHD, which is not always possible in clinical trials. 

• Therefore, further RWE and observational studies are needed to provide additional data on the safety and efficacy of treatments, particularly in cGvHD which can have distinct patient populations. However, these studies lack the consistency of RCTs, and caution should be used when interpreting results. 

• Several recent prospective phase II/III studies have led to the approval of new agents for cGvHD, including ibrutinib, ruxolitinib, and belumosudil. In the case of belumosudil, real-world studies have consistently shown safety and effectiveness similar to the RCTs, which is encouraging for the broader cGvHD patient population. 

• Both RWE and RCTs can be helpful tools for advancing clinical research and informing patient care, especially when considered together.

This educational resource is independently supported by Sanofi. All content was developed by SES in collaboration with an expert steering committee; funders were allowed no influence on the content of this resource.