What are the implications of the FDA’s draft guidance on “Real-World Data: Assessing Electronic Health Records and Medical Claims Data to Support Regulatory Decision-Making for Drug and Biological Products” for current and planned studies? Our Jeff Trotter, senior vice president, Worldwide Evidence, explores.
Many forward-thinking biopharmaceutical companies have been exploring the use of real-world data to help guide development decisions for years. Now with advancements in technology and analytics, and greater availability of data sources, RWE is going mainstream – and the FDA is joining the conversation.
Here are the takeaways that deserve a closer look:
- RWD is not replacing clinical trials. The FDA isn’t suggesting RWD is going to replace traditional clinical trials for drug approval. Rather, the guidance refers to the potential use of real-world evidence (RWE) “to help support the approval of a new indication for a drug already approved” or “to help support or satisfy post-approval study requirements…” The focus here is on RWD in the post-appoval setting (i.e., label expansions and post-approval safety surveillance). And the guidance emphasizes a point that I often make, that RWD is used to “derive” RWE: absent a purpose, RWD is just…data.
- RWD can powerfully augment clinical trials. While RWD won’t – and shouldn’t – magically expedite drug development, it can provide opportunities to understand the real-world landscape of a particular disease. For example, in a natural history study for rare diseases. Or for use as an external control when a placebo arm isn’t feasible. And also with care, it can be an opportunity to understand the post-approval safety and effectiveness of a particular product under actual medical practice conditions (with patients who may, for all the right reasons, have been excluded from pre-approval clinical trials).
- RWD should be considered long before study start. While the FDA is increasingly comfortable with and open to RWE, it also strongly encourages a dialogue and collaboration before moving forward, stating, “For all studies using EHRs or medical claims data that will be submitted to FDA to support a regulatory decision, sponsors should submit protocols and statistical analysis plans before conducting the study. Sponsors seeking FDA input before conducting the study should request comments or a meeting to discuss the study with the relevant FDA review division. All essential elements of study design, analysis, conduct, and reporting should be predefined, and, for each study element, the protocol and final study report should describe how that element was ascertained from the selected RWD source…” The field is still evolving, and an open and conscientious dialogue will avoid unnecessary risk and potential waste of time and money.
- RWD should be part of the entire picture. The guidance is intended to present “considerations when proposing to use electronic health records (EHRs) or medical claims data…to support a regulatory decision on effectiveness or safety.” So, the focus is on these sources of RWD, to the exclusion of datasets, partial or otherwise, that may be derived from other real-world sources, such as wearables, and employing evolving methodologies such as social listening and artificial intelligence. Be aware that these other sources and methods may play an important role in characterizing certain aspects – the patient’s perspective, for example – of a drug’s real-world experience. And that the prospective generation of RWD remains a very important (with its own pros and cons).
- There are parameters for considering the veracity RWD. The guidance does frame up some important factors in assessing RWD source and study design, including:
Relevance. What factors influence case inclusion, data integrity, and generalizability?
Data capture. How is a study protocol addressed by or accommodated within the routine data collection in an EHR or medical claims system? How are linkages with other study components (e.g., PRO questionnaire processes) addressed? How are unstructured data (e.g., physician notes) acquired and used?
Missing data. How are missing (e.g., intended but not collected) or absent (not intended to be collected) data addressed (and what are the reasons why the data are missing in the first place)?
Validation. How are data elements (study variables) defined, obtained, classified, and verified?
Study design elements. The data source shouldn’t define the study design, rather just the elements.
With precedent for the FDA accepting RWD in expanding a product label, the future for RWD in clinical research is, indeed, quite promising. Although there are also viable initiatives for accommodating RWD within pre-approval drug development processes, the FDA’s guidance at this time is focused primarily on RWE derived from RWD for use in the post-approval timeframe. The bottom line is that the RWD sources – having been designed for purposes other than clinical research – are imperfect and their use will require a considerable amount of conscientious documentation and explanation – but promises very exciting potential for improving the efficiency of prospective research in the future.
Read the following information to learn more: