The biopharmaceutical industry has witnessed a paradigm shift towards integrating Real World Evidence (RWE) and Real World Data (RWD) in recent years. These data sources, derived from real-world clinical settings, offer invaluable insights that traditional clinical trials might not capture, especially when considering diverse patient populations and real-world scenarios1. The increasing relevance of RWE and RWD in decision-making, particularly in drug regulation and safety monitoring, has been underscored by various regulatory bodies globally2. Recognizing the potential of RWE and RWD in enhancing drug development and post-market surveillance, the U.S. Food and Drug Administration (FDA) took a pivotal step by releasing a draft guidance document to provide clarity on the use of RWE and RWD in non-interventional studies3. This move signifies the FDA’s commitment to harnessing the power of real-world data while ensuring its rigorous and appropriate use in regulatory decision-making.
FDA Definition: Interventional vs. Non-Interventional Trials
- Interventional Studies: Participants are assigned to one or more interventions according to a specific study protocol to evaluate the effects of those interventions. For example, in a traditional randomized controlled trial, some participants receive a new drug while others receive a placebo.
- Non-interventional (Observational) Studies: Patients receive the marketed drug as part of their routine medical practice without any intervention according to a protocol. An example could be studying the outcomes of patients via a post-marketing RWE/RWD study.
FDA’s guidance focuses on monitoring non-interventional RWE/RWD studies.
Brief Overview of FDA Guidance on Monitoring RWD/RWE Studies
The FDA’s guidance on RWD and RWE stresses the importance of these data sources, especially in understanding the real-world applications and implications of medical products. This understanding is crucial as it can influence regulatory decisions about these products. Therefore, rigorous monitoring of non-interventional studies becomes imperative to ensure the reliability of the data and its subsequent evidence.
Why It’s Important to Monitor RWE/RWD Non-Interventional Studies
Monitoring ensures that the study aligns with the predefined protocol, ensuring the data’s reliability. In the context of RWD and RWE, monitoring is even more critical because these data sources are diverse, coming from electronic health records, medical claims, and patient registries. For instance, if a study pulls data from a patient registry and electronic health records, discrepancies can arise due to different data recording practices. Monitoring can identify and rectify inconsistencies, ensuring the derived RWE is accurate.
FDA Requirements for Monitoring Non-Interventional Trials
The FDA provides clear guidelines for monitoring non-interventional trials using real-world data (RWD) and real-world evidence (RWE). Here’s a breakdown of the pivotal requirements:
- Data Integrity and Protection: The process of monitoring should be initiated right from the phase of data extraction from RWD sources. The primary emphasis should be on assuring data integrity and safeguarding the rights and well-being of human subjects, especially in cases where the non-interventional study integrates additional protocol-specified activities or procedures, and vigilance in data protection becomes even more crucial. Consider a study leveraging electronic health records (EHR) to assess the real-world efficacy of a new diabetes medication. Any discrepancies or errors in EHR data extraction could lead to incorrect conclusions about the drug’s effectiveness or safety. Additionally, if the study adds patient surveys to gather further insights, ensuring the confidentiality and correct recording of this data becomes paramount.
- Adherence to Protocol and Procedures: It’s imperative for sponsors to ascertain that the study progresses in strict alignment with the approved protocol. Should there be any deviations from this protocol, they must be meticulously documented. More importantly, deviations that could potentially impact study outcomes or patient safety need immediate attention and resolution. For instance, in a non-interventional study observing the long-term impacts of an arthritis medication, if certain patient groups are inadvertently excluded, or specific data points are overlooked, it might skew the results. Such deviations from the study protocol can lead to misleading conclusions and potentially compromise patient safety.
- Audit Trails: Maintaining a comprehensive and transparent audit trail is non-negotiable. This entails tracking the journey of the data right from its extraction through its retention phase. Crucially, this includes keeping tabs on who accesses the data, any modifications made to it, and all analyses that are conducted using this data. For example, imagine a scenario where a particular data set on patient outcomes after using a certain medication gets modified. Without a clear audit trail, it would be nearly impossible to trace back the changes, understand the rationale behind them, or even identify potential data tampering.
Discovering Safety Events
Even though non-interventional studies observe routine medical practices, they can uncover adverse events or safety concerns related to the drug or medical product. If such events are identified, they must be reported in line with postmarketing reporting requirements. For instance, if a non-interventional study finds an unexpected spike in adverse reactions to a recently introduced hypertension drug, it is crucial to report this immediately. Such insights can lead to recalls, additional warnings, or further studies.
As the biopharmaceutical industry increasingly relies on RWD and RWE to inform regulatory decisions, the significance of diligent monitoring cannot be overstated. It ensures that data reflects real-world scenarios accurately, leading to safer and more effective medical products. Sponsors, researchers, and regulatory authorities must work in tandem, ensuring that the treasure trove of RWD is translated into actionable and reliable RWE.
- Maintaining patient registries, on the basis of which regulatory authorities can make decisions regarding medicines
- Real-World Evidence in EU Medicines Regulation: Enabling Use and Establishing Value
- Guest Editors’ Note on the Special Issue Real-World Evidence
- U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), & Oncology Center of Excellence (OCE). (2023). Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products: Guidance for Industry. Retrieved from https://www.fda.gov/media/171667/download?utm_content=bufferf1cd4&utm_medium=social&utm_source=linkedin.com&utm_campaign=buffer
Moe Alsumidaie is Chief Editor of The Clinical Trial Vanguard. Moe holds decades of experience in the clinical trials industry. Moe also serves as Head of Research at CliniBiz and Chief Data Scientist at Annex Clinical Corporation.