A gap in our understanding
Randomized clinical trials are the trusted standard and a crucial step in securing a medicine’s regulatory approval. However, they do not tell us everything about the safety and efficacy of a treatment in daily clinical practice. Scientists have spent years refining trial methodology, using the controlled conditions permitted by selecting a study population and environment to determine whether a medicine can yield a desired effect in patients. Once approved, it is launched into a world full of variables, and we cannot predict what influence these will have. So, how can we gain knowledge about the impact of usage of a medication outside a controlled environment, in the real-world?
Beyond the clinical setting
A solution may lie in the supplementation of clinical trial data with ongoing data collection, using sources such as non interventional studies, patient registries and databases including electronic health records to follow the journey of medical treatments after regulatory approval in daily clinical practice. This is what is termed real-world evidence (RWE). RWE can allow us to determine the benefits and risks associated with treatments in patients who may have been underutilized in the clinical trial, and under conditions that would not be observed in a ‘controlled’ environment1.
Painting a more detailed picture with RWE
This is not to say that RWE should replace randomized clinical trials – rather RWE can complement randomized clinical trial data to help us better understand the impact of the prescription of a medication on safety and effectiveness of such medication in daily clinical practice. In a sense, if clinical trial evidence forms the outline picture of a medicine, RWE is the color and shading that is added to show the nuances that we cannot see in black and white. With the potential to show the realities of treatment in a wider population, RWE can better inform healthcare decision making by confirming results from randomized controlled trials. RWE can demonstrate the safety and effectiveness of a treatment in populations, such as those with specific comorbidities which were not well represented in a randomized controlled trial (RCT). Findings from real world studies can be used to support the approval process and improve access to treatments for patients.
RWE in healthcare decision-making
The valuable contribution made by RWE towards the development of new treatments, outcomes research, and safety surveillance, has contributed to its growing role in healthcare decision-making2. This potential is evidenced by a surge in the popularity of wearable technology, enabling us to continually monitor and record our heart rates by wearing smart watches, presenting exciting new possibilities for collecting RWE.
In late 2018, the FDA published its RWE framework which aimed to evaluate the potential use of RWE for assessing a medical product’s effectiveness, and also improve usage of RWE for public health purposes. By providing guidance around the design of studies that take RWE into account, the updated framework is further proof that RWE is being increasingly recognized as a valuable source of data that is worth considering in healthcare decision-making.
Refining RWE methodology
However, there are limitations associated with RWE that we must remain aware of. The quality of RWE varies and is uneven across the sources used to generate RWE. A lot of RWE is generated with the help of large and diversified datasets, which are relatively easily accessible but might be prone to biases and confounding, which could possibly hinder the ability of RWE to accurately answer research questions3. There might also be privacy concerns around the sharing of medical data. However, protecting patient privacy and making it clear who owns data is of high interest to everyone conducting studies using RWE4.
As we have continually refined clinical trial methodology, we can do the same for RWE. To help overcome limitations around data quality, the FDA framework recommends conducting assessments to ensure data is fit for purpose.
RWE can help bridge the gap between the controlled environment of a clinical trial and the realities of everyday clinical practice, providing healthcare decision-makers with the data they need to provide the right treatments to the right patients.