New drugs are launched based on data from randomized controlled trials (RCTs), the gold standard for determining the efficacy of a molecule. Yet, even when efficacy is known, we cannot know the effectiveness of the same drug in routine clinical practice. 

This blind spot is called the efficacy-effectiveness gap

Real-world evidence (RWE) provides visibility into this gap. The evaluation of a drug’s performance in the real world — where health technology assessment (HTA) agencies operate and make decisions — is a priority for RWE researchers. Yet, in 2018, when Makady, et al. tracked the use of RWE in melanoma HTAs from five EU agencies, they found that from 2011 to 2016, these agencies did not increase their use of RWE and comparative effectiveness RWE was rarely used. 

Charged with understanding how a drug will perform in their own country’s treatment pathways and clinical settings, HTA agencies remain hesitant to rely on RWE. Why? 

With a wide range of use cases for RWE in HTA decision-making, both from a clinical and economic perspective, the value of evidence derived from clinical care and transactions is clear. Clear clinical uses for RWE include:

  • Estimating burden (e.g., prevalence and incidence) and natural history of disease;
  • Understanding local treatment pathways;
  • Determining comparative effectiveness and safety in the real world vs. relevant comparators and in relevant patient populations; and
  • Demonstrating long-term effectiveness.

Economic uses of RWE include:

  • Evaluating costs and resource utilization; and
  • Collecting data on, and measuring, patient quality of life.

In light of this broad range of uses for RWE in clinical care — particularly in the effectiveness estimates that are the backbone of HTAs — consider these recently published and presented findings:  


Broadening the hierarchical perspective on evidence 

A key reason why HTAs remain hesitant to maximize the use of RWE is because they tend to subscribe to a hierarchical structure of evidence. Randomized controlled studies remain the preferred source of evidence in the eyes of HTA agencies. When HTAs frame evidence in this way, however, the utility of RWE may be downgraded and the strengths of well-developed RWE (generalizability to clinical practice) overlooked. The reliance on RCTs in reimbursement decisions leaves the efficacy-effectiveness gap wide open, increasing the risk and uncertainty of HTA decisions. 

With regulatory agencies like the FDA, EMA, and Health Canada leading the way in setting standards for RWE use, HTA agencies are exploring and are committed to leveraging RWE, as well as innovative and methodologically sound analytical techniques, in their assessments. Determining how to leverage RWE is a step in the right direction and will likely move HTA agencies past their historical hierarchical mindset to considering not which evidence is best, but which is fit for purpose.  

Implications for biopharma in this move toward greater use of RWE from both regulatory and HTA agencies include the need for RWE development plans across the drug lifecycle to support submissions. Development plans will need to include identifying fit-for-purpose data sets and ensuring transparency and replicability of findings. HTAs plan to rely on RWE for a wide range of use cases, so biopharma will need to develop the infrastructure needed to identify, collect, and analyze RWE across their drug’s lifecycle in order to meet the needs of the agencies and to demonstrate the real-world value of their products.