The Impact of RWE Data on Regulatory Decision-Making

Real world data can be complementary to clinical trials, but global regulators are still establishing a framework for consistent and compliant use.

In the pharmaceutical and medical device industry — where being first-to-market can make or break a new product or treatment's financial viability — continuous process improvement is essential.

Clinical trial sponsors are always interested in ways to maximize cost-effectiveness and speed the process of commercialization. Real world evidence (RWE), using data that is traditionally outside the realm of clinical trials and academia, could help, providing potential efficiency while maintaining critical subject safety.

In many ways, RWE can be complementary to clinical trials. RWE can be useful for ongoing surveillance and especially in the assessment of long-term clinical outcomes for implants and therapeutic products. What makes this even more interesting is the increasing adoption of technology and widespread use of social media. Many people share their experiences in many types of online platforms, and the potential to collect data, in an ethical way, directly from patients, could provide more insights on the utility and safety of the product.

Defining RWE

Real world evidence, in its broadest form, is evidence that is derived from collecting and analyzing Real world data (RWD). RWD are observational data obtained outside of randomized controlled trials (RCTs) usually generated from routine clinical practice. These data may be collected prospective or retrospectively. RWD sources may include medical charts, electronic patient records, reimbursement figures, billing databases and, more recently, clinical registries and patient reported outcomes.

Current State of RWE Initiatives in U.S., Canada and Europe

U.S.: The Food and Drug Administration (FDA) published a framework for its RWE program in December 2018. In this document, the FDA firmly defines the current use of RWD in evidence generation and the framework for evaluating RWD/RWE for regulatory decision-making. Section 505F(b) of the Federal Food, Drug and Cosmetic Act (FD&C) defines RWE as "data regarding the usage, or the potential benefits or risks, of a drug derived from sources other than traditional clinical trials" (21 U.S.C. 355g(b)).

In developing its RWE program, FDA believes it is helpful to distinguish between the sources of RWD and the evidence derived from that data. Evaluating RWE in the context of regulatory decision-making depends not only on the evaluation of the methodologies used to generate the evidence but also on the reliability and relevance of the underlying RWD. The FDA already piloted this program and it will continue to evaluate and explore ways and methods to optimize the utility of RWE.

Canada: Health Canada (HC) has been actively working to define the role of RWE in regulatory decision-making. In 2018, HC started consulting with multiple stakeholders to identify what role RWE plays in regulated product development lifecycle. Some of this discussion included enhancing regulatory decision making, risk communication, mapping RWE sources, potential new regulations and risk-based framework. HC expects to complete medical device RWE project during fall 2020 and for pharmaceuticals during fall 2022.

Europe: The role of RWE has mainly focused on pricing and reimbursement in the past. Over the last several years there have been multiple discussions on what role, if any, RWE should have in clinical evidence, patient safety and outcomes and ultimately in licensing of products, particularly in pharmaceuticals.

The London School of Economics (LSE) published an Expert Survey from March 2017 in which they collected answers from 35 qualitative and quantitative questions on the use of RWE for licensing and coverage recommendations, RWE ownership and the future of RWE. There were 40 respondents from a variety of countries (mostly Europe) and professions.

In my opinion, what I found most interesting in their conclusion is the acceptance of lower levels of evidence for orphan and oncology, RWE is perceived to have more value in clinical and reimbursement rather than regulatory decision-making, and most respondents see RWE as a complement to RCT rather than a replacement. LSE created a potential RWE roadmap that speaks on Commissioning and Access, Clinical Evidence and Patients and Outcomes. This work was funded by Roche and is publicly accessible through LSE.

Challenges to Consider

The importance of RWE continues to be apparent in many areas of healthcare but in particular, drug reimbursement and health technology assessment. With this in mind, we need to assess where the data is coming from in order to feel assured that the data is representative of the actuals needs of the research methodology. We do not want to run the risk of using data that may lead to flawed conclusions; this will not only be detrimental for the evidence, but it risks public mistrust and patient safety concerns. There are many challenges to consider, I would like to highlight a few that may be impactful on the use of RWE on regulatory decision making:

  • The definition and uses of RWE across the globe continue to be variable; in fact, no consensus has been reached at this time. For RWE to be useful on regulatory decision making, harmonization and standardization will be required.
  • Multiple stakeholders must address data quality and availability for RWD/RWE; this should include transparency of data sources and how this data is communicated to the general public.
  • Databases and registries only become truly useful over a period of time, we must ensure that we do not jump to conclusion when using such resources.


There is no doubt that RWD/RWE has carved out space in the provision of health care, especially in the digital world that we currently live in. RWE may play a greater role, certainly as a complement to RCTs on regulatory decision-making, however, this is contingent upon regulators defining their role and expectations. RWD/RWE is now being used in a small subset of patients, such as in oncology and rare disease. With more robust data (via transparent data sources) and refined methodology and analytics, RWE may garner more support from the regulators and from the general public.