A regulatory perspective on real-world data and real-world evidence
Discover insights from Sanyam Gandhi, Regulatory Strategy Lead at Takeda, as he analyzes the regulatory framework of using real world data and real world evidence in clinical trials
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Even if a drug is successful in a clinical trial and approved by regulators, it is very difficult to guarantee that it is safe and effective on each individual patient. Biochemical and physiologic effects of a drug on patients can be very different because clinical trials are often conducted on a mass patient scale.
Real-world data (RWD) and real-world evidence (RWE) can be used to navigate the safety and efficacy profiles of a drug prior to patients receiving the medicine. Pharma regulators, however, are still in the early stages of developing a clear strategy for using these data solutions in practice.
What is the regulatory position of the FDA and EMA on RWD and RWE?
As per the definition by the US Food and Drug Administration (FDA), RWD is: “data relating to patient health status and/or the delivery of healthcare that comes from a number of sources”. These sources include:
- Electronic health records,
- Claims and billing activities,
- Product and disease registries,
- Patient-generated data including in home-use settings,
- Data gathered from other sources that can inform on health status, such as mobile devices.
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Figure one: Further examples of different RWD sources (Source: FDA)
Additionally, the FDA defines RWE as: “The clinical evidence regarding the usage and potential benefits or risks of a medical product derived from analysis of RWD. RWE can be generated by different study designs or analyses, including but not limited to, randomized trials, including large simple trials, pragmatic trials and observational studies.”
While these definitions are helpful for determining the use of these types of data in the pharma industry, there are still some unanswered questions around how to meet the FDA’s regulatory requirements when it comes to RWE. Will the requirements differ if companies are using a database versus another data collection approach, for example, and what are the requirements for a retrospective study in comparison to a prospective study? It will be interesting to see how the FDA develops its guidance documents around RWE to answer these questions in the future.
Despite the obscurity around how to approach the FDA’s guidelines, the pharma industry is still showing to be positively adopting RWE into its drug development process. Few companies are using RWE to assess product safety of drug development programs and rather using it in a range of areas such as disease, treatment patterns, and improving standards of care available in many different geographies.
Amgen’s cancer therapies gained their first regulatory approval based on a single-armed Phase 2 study supported by RWE from medical records. The company did not include a traditional standard-of-care comparator arm in the study because the patients that had enrolled already failed to respond to standard therapies.
The European Medicine Agency (EMA) defines RWE as: “the evidence derived from the analysis and/or synthesis of RWD.”
EMA guidelines are focused on data quality and validity, so companies should focus on utilizing the EMA scientific advice pathway. This pathway will allow manufacturers to consult the agency on study design and methodological considerations. In addition, the industry is also learning how to adopt new guidelines to facilitate a harmonized approach regarding the use and validation of RWD.
What is the role of technologies in RWE based drug development?
The FDA has developed an app called MyStudies to collect consent data from users, which can be analyzed by both patients and researchers. All regulatory-related guidance around the app has been published on the FDA’s website. MyStudies was remarkably helpful in conducting clinical trials for the Covid-19 vaccine as it helped pharma companies inform consent and collect data remotely.
The 21st Century Cures Act, signed into law on December 13, 2016, by the FDA aims to encourage the pharma industry to adopt new technologies into drug development and approval. The Cures Act helped to provide faster approval for regenerative medicine advanced therapy such as cell therapy, gene therapy and therapeutic tissue. The Cures Act, recently supported by The National Coordinator for Health Information Technology (ONC) and Centers for Medicare Medicaid Services (CMS), also helps physicians, hospitals, insurers and information networks exchange data faster.
Like MyStudies, many other mobile technologies, biosensors and health tools can provide the industry with a lot of continuous data at a very low cost. This area is likely to grow rapidly in the future because it gives healthcare professionals direct and complete access to patient data compared to clinical trials where data is collected only in clinical facilities. The accuracy of this data may be higher also as immunosensors can depict higher sensitivity and faster analysis for cardiac symptoms and few cancer markers.
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Recently Verantos partnered with Amgen to provide real-world insight through advanced data and technologies focused on high-validity observational studies. The firms have together implemented studies in hyperlipidemia, non-alcoholic steato-hepatitis, and heart failure to enable insight into unmet patient needs.
What are the processes and outcomes of RWE in the pharma industry?
RWD can be collected from public or private records. Data scientists and subject matter experts can set the criteria for data collection based on the target outcome. Once the data is collected it is stored for abstraction and analysis and can also be used for future reference (see figure two).
Many technologies and tools can be used to analyze the data and results can be presented visually in a table, dashboard or graphic format. These visual outcomes serve the basis for RWE. Pharma companies can utilize RWE as a way to showcase drug approval, trial optimization, and product safety and efficacy to health authorities.
Figure two: Process timeline of RWD and RWE in the pharma industry
What is the expected future guidance from regulators?
At present, RWE is helpful for pharma regulators to determine the safety and efficiency of rare disease products and overcome unmet patient needs where patient enrolment for clinical trials can be difficult.
Many products have been registered in the last few years based on the RWE best practices, but regulators do prefer to be more vigilant with an RWE-based approach.
It is expected that the FDA will issue more guidance about the RWE based drug approval process because at this stage it is too early to replace traditional clinical trials with an RWE solution. Similarly, the EMA is working on new guidance’s about RWE and other health agencies and pharma companies are also evolving to adopt and implement RWD-based approaches for drug registration for faster traction to the commercial market.
