Real-world evidence (RWE) has been growing in relevance and interest among those who are submitting to the FDA and it might become more than an afterthought in regulatory submissions. The FDA has been paying attention to real-world evidence generated by real-world data (RWD) since the Cures Act of 2016, which means that RWE is likely to reach the authoritative level of randomized clinical trials (RCTs) in the near future.
Until now, RCTs have been the standard procedure for creating definitive evidence and are designed to generate results that meet strict criteria in clinical trials, while RWE is more frequently used to support other kinds of results. However, because of the increasing amount of real-world data becoming available every day, the expertise applied to RCTs is now being used to produce RWD that results in real-world evidence.
In this article, we explore some of the differences between RWE and RCTs and show how real-world evidence is becoming increasingly similar to randomized clinical trials both in rigor and methodologies. This includes repurposing data models and methodologies as well as creating new methodologies adapted to post-market surveillance.
Real-world evidence with RCT rigor
Real-world evidence is used by companies to strengthen their submissions to the FDA and other regulatory institutions. RCTs still account for most of the submissions, but RWE is progressively becoming more recognized by the FDA as an important component of the evidence package. Adding RWE to support the submission can help it achieve the “substantial” or “primary” evidence status and prove the product’s safety and efficacy. Real-world evidence can also improve a submission to the FDA by providing “supportive evidence”
Because RCTs have been used as the main evidence in submissions to the FDA, it is logical to draw from the science behind them to help real-world evidence reach the authoritative status of RCTs. The FDA has precise standards that should be met by RCTs in order to qualify a submission, and RWD must be created to meet the same strict criteria to generate fit-for-purpose RWE.
Adopting RCTs standards for real-world evidence
There are several standards that are used by the FDA to validate RCTs and that can be adopted by companies that are making a submission and wish to use RWD. Some of these standards are:
- Relevance: The data must represent the group the product is aimed at. Exposure should be identified, and confounders must be identified and measured.
- Reliability: The data must be accurate, complete and consistent.
- Other factors: Demographics, socioeconomic and insurance status, disease severity, and comorbidities are some confounding factors that are also important and that should be identified and considered when adjusting real-world evidence.
How to deal with systematic bias in real-world evidence
To ensure RWE meets the standards cited above, it is important to consider the question of systematic bias. A systematic bias evaluation may include the following questions:
- Is the dataset composed of patients that represent the population of interest?
- If there is more than one data source, are there data fields that allow proper linking at the patient level?
- Does the dataset include critical fields such as exposures, covariates and outcomes? If not, can they be derived from other data fields that are present?
- Can the expected treatment effect, including possible safety matters, be accurately demonstrated by the persons and follow-up time in the data source?
Why consider using real-world evidence for post-market clinical follow-up (PMCF)
Post-market clinical follow-up (PMCF) is crucial to ensure ongoing safety and monitor efficacy. Also known as post-market surveillance, it allows to prove the real-world safety of a drug or a medical device and demonstrate their effectiveness. Pre-approval studies can never be the single source of knowledge about potential side effects of a drug, for instance.
Real-world evidence is already frequently used in PMCF studies. Alongside with programs such as the FDA Adverse Event Reporting System (FAERS), MedWatch and clinical data registries, RWD is becoming increasingly important to monitor PMCF elements such as reactions to medical products or disease and pathologies progress. Using real-world data in post-market surveillance can enrich the dataset of a clinical trial and strengthen the submission to the FDA.
Including RWE in post-market surveillance could also be a better way to address specific clinical scenarios that are present in real-world medical practices. Using real-world data is ideal to adapt post-market surveillance to the different stages of a real therapy’s life cycle.
Using tokenization for real-world evidence generation
Tokenization is a procedure which uses an anonymized identifier (the “token”) to keep track of a patient’s information without revealing their identity. The tokens containing all information essential to the clinical study replace the sensitive information about the patient (such as name and date of birth). Tokenization allows researchers to link different data sources and examine the results from other vantage points, using different sets of questions. This can improve real-world evidence generation because it broadens the scale of a single post-market surveillance study.
Without revealing the patient’s identity, data from one of their records can be linked with information from another data set of the same patient, creating a more accurate picture of a real-life clinical case. Then, new questions could be asked of the same data set without exposing the patient’s confidential information.
Why does tokenization improve RWE generation?
- It broadens the data sets available in the PMCF study.
- It allows new ways for verifying efficacy.
- It draws from a wide variety of data sources, such as EHR, claims data and social media posts.
- It may result in faster responses to safety matters and foster better risk management strategies.
ECLEVAR experts can help you with your real-world evidence strategies
It is now clear that real-world evidence generation will no longer be a secondary strategy of submissions to the FDA. The agency itself and other regulatory bodies are encouraging the use of RWD in clinical studies and consider it part of the evidence package of submissions seeking authorization to commercialize new drugs, medical products and biologics license applications.
ECLEVAR MEDTECH and its team of experts (Biostatisticians, Data Analysts, Clinical Research Assistants, Clinical Project Managers) rely on best clinical practices, advanced analysis techniques and a strong Quality Management System to ensure high quality real-world evidence clinical studies. We conduct feasibility studies to ensure the quality and the quantity of data and deliver the best evidence reports for your submissions to the FDA.
If you have any questions about how we conduct real-world clinical studies or want to learn more about RWE, you can book a free 30 minute consulting with our experts.
