How to obtain High-Quality Real-World Data and Evidence for Regulatory Submissions

Interest Area/Track:
Regulatory Strategy

Objective: 
Identification of key characteristics essential for the successful usage of real-world data (RWD) and real-world evidence (RWE) to support regulatory submissions of medicinal products.
Method (max 300 characters): 
Reasons for success or rejection of regulatory submissions present within different data packages were analyzed. Positive factors were directly included into the formulation of RWD/RWE criteria whereas improvement measures were defined for the factors that caused the rejection of the submissions.

Results: 
Data Collection and Quality Control
The collection process should include a certain degree of standardization in order to generate uniform data. Continuous quality control of the data should also be implemented in order to detect any emerging or present data gaps.

Prospective studies, in combination with the initiation of a registry, are a viable approach in order to meet the above-mentioned criteria. Additionally, registries can undergo a qualification process through collaboration with agencies such as EMA. Retrospective data analyses can also be used to acquire RWD. However, the before-mentioned criteria will likely not be fulfilled, since the initial studies did not have real-world data analysis in mind. Finally, collected RWD should always be compared with data present in the scientific literature. 

Addressing selection bias

Randomized clinical trials (RCTs) are considered the gold standard to prove the efficacy of a medicinal product. A randomization step can rarely be included into the RWE study design. Therefore, RWE studies are often confronted with the problem of selection bias and this aspect must be addressed and, if present, justified.

Landscape Assessment

The context in which RWD is used has a substantial impact on its regulatory acceptance. For instance, advance therapies mostly are associated with rare diseases. These indications are difficult to study only within RCTs due to small size of the patient population. Therefore, other approaches such as long-term follow-ups and the collection of RWD are needed to prove the effectiveness of the treatment. Broader evidence generation strategies such as the use of RWE is also critical to support the introduction of new innovative treatments and extension of existing treatments to new indications. Other factors that impact the acceptability of RWD are the availability of other treatment options for the targeted indication as well as the experience of the authority evaluating the application containing RWE. 

Conclusion: 
Real-world data has been identified as a potential source to support regulatory decision making. However, EU regulators have so far not published specific guidance on key aspects that enable the efficient utilization of real-world data to support regulatory applications. 

Even though the usage and acceptance of RWD/RWE within the regulatory community is currently variable, we could identify key aspects that can enhance the chance of regulatory success.

Beside standardization of both the collection process and analysis of RWD, considerable effort should also be made to carefully plan the studies generating RWD. These key quality characteristics in return are essential to address other aspects such as the potential presence of a selection bias and enable the cross-validation with the literature present within the scientific community and efficient statistical analysis. The context of the data has also been linked with the regulatory acceptance of RWD and should be factored into the overall submission strategy.

These identified RWD characteristics should be understood as a thread on how to systematically approach the usage of this type of data. More experience is being gathered both within the industry and regulatory bodies as the regulatory submissions using RWD/RWE have considerably increased in the recent years, This in return enhances the confidence and reliability towards this novel approach and will likely catalyze the development of new methods to obtain higher quality RWD.

New technologies, such as various gene therapies, already show that RWD/RWE are a viable option to assess the benefit/risk of a medicinal product. Recently, a number of programs and collaborations launched by EU authorities aim to use RWD to help evaluate potential treatments for COVID-19.
RWD has the potential to be routinely used in the near future for classical medicines in order to complement data from clinical trials with the aim to generally improve patient health.

How to obtain High-Quality Real-World Data and Evidence for Regulatory Submissions

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