Real world evidence (RWE) can contribute valuable information to new medicine registrations, in particular for diseases that are difficult to assess in randomized clinical trials (RCTs) and for emerging technologies such as gene and cell therapies to help enhance our understanding of such products.

Regulatory agencies worldwide are considering how they may incorporate RWE into their decision- making processes for new medicine applications. The US FDA has highlighted that the use of RWE is one of its key priorities. In light of the advancements made in the use of RWE, the FDA released a framework to define real world data (RWD) and how RWE may be used to support regulatory decision-making for new drugs and biologics (FDA 2021).

To-date RWE has been successfully used to support the approval of new drug registrations by the FDA with an estimated 85% of approvals between January 2019 to June 2021 incorporating RWE to support the benefit-risk analysis (Purpura 2021).

Whilst the TGA is currently using RWE to support their decision-making for registrations of rare diseases there is no transparency of how this information is assessed and included in submissions.

As a result, the TGA has made a commitment to communicate when RWE is used in their decision- making through the AusPAR publications starting in 2022/2023.

Although RWE studies submitted as supportive clinical evidence will be considered by the health authorities, it is highly recommended that sponsors discuss the study design and obtain agreement on the inclusion of the data in the registration dossier before proceeding. The FDA recommends that sponsors request a Type C meeting to discuss the proposed study protocol and statistical analysis plan incorporating RWE prior to trial initiation. It is important for sponsors to design RWE studies with the same degree of quality as RCTs. The most common issues relating to rejections of RWE submissions are methodological issues such as inadequate data collection, sample size concerns, differences in follow-up and response assessments and biases in endpoint assessments. It is recommended that sponsors use transparent RWD sources that are current and to undertake systematic forms of data collection to support registration. The use of RWE to support new medicine registrations is evolving with the FDA in particular leading the way. The FDA have published a number of guidelines over the past 5 years on RWE and RWD, and the TGA is planning to issue consultations later this year before adopting formal definitions and guidance. It is expected that the TGA will align with the major regulators particularly in the context of how RWE can be used to support new medicine approvals.


References: FDA Guidance for Industry: Considerations for the Use of Real-World Data and Real World Evidence to Support Regulatory Decision-Making for Drug and Biological Products, December 2021

Purpura CA, Garry EM, Honig N, Case A, Rassen JA. The Role of Real-World Evidence in FDA-Approved New Drug and Biologics License Applications. Clin Pharmacol Ther. 2022;111(1):135-144