In a significant development for pharmaceutical research and development, the FDA released new guidance in August 2023 on the use of real-world data (RWD) in regulatory decision-making. The guidelines, which fulfill requirements under the 2016 21st Century Cures Act, aim to accelerate medical product development by clarifying when and how RWD can be incorporated into clinical trial designs and regulatory submissions.
FDA Commissioner Robert Califf signaled the importance of this shift at the Medical Device Innovation Consortium, stating, "I believe we're moving very rapidly now to a place where more and more of the data we use for evidence is going to come from the so-called real-world clinical environment."
Key Provisions of the FDA Guidance
The new guidance makes a critical distinction between non-interventional studies (such as cohort and case-control designs) and interventional studies (clinical trials). According to the guidelines, non-interventional studies do not require an investigational new drug (IND) application, potentially streamlining the regulatory process for marketed medical products seeking new indications.
The FDA has expanded the definition of acceptable RWD sources to include electronic health records, medical claims, registries, and data generated under emergency use authorizations (EUAs). This broader acceptance of diverse data sources opens new avenues for evidence generation outside traditional clinical trial settings.
Addressing Three Major Pain Points in Drug Development
Long-Term Patient Follow-Up
One significant challenge in clinical trials is the inability to monitor participants over extended periods after the trial concludes. This limitation often means that delayed adverse events or long-term efficacy outcomes remain undocumented.
The new guidance acknowledges RWD's potential to bridge this gap by enabling continuous monitoring of patient outcomes beyond the formal trial period. Technologies like HealthVerity FLOW offer solutions by assigning universal identifiers to trial participants, allowing their de-identified data to be tracked across various healthcare databases while maintaining privacy compliance.
Participants Lost to Follow-Up
The financial impact of participants who drop out of clinical trials is substantial. With phase 3 trials costing approximately $52,000 per patient and dropout rates ranging from 5% to 20%, even a 5% loss in a 1,500-patient trial represents nearly $2 million in potentially wasted investment.
Under the new guidance, pharmaceutical companies can potentially recover valuable insights from these "lost" participants by accessing their RWD (with appropriate consent), providing a more complete picture of treatment outcomes despite formal trial discontinuation.
Demonstrating Value for Reimbursement
For approved therapies, especially those for rare diseases or gene therapies, securing insurance coverage remains challenging due to high costs. The guidance supports using RWD to demonstrate comparative value by tracking long-term healthcare utilization and costs among treated versus untreated patients.
This approach could help manufacturers show that while a therapy may have a high upfront cost, it potentially reduces overall healthcare expenditures by preventing complications or reducing the need for other interventions.
Implementation Considerations
The FDA emphasizes early collaboration with both the agency and data privacy experts when incorporating RWD into marketing applications. These discussions can help ensure appropriate study design, data source selection, and address potential implementation challenges before they arise.
Transparency remains a critical requirement for RWD supporting marketing applications. The guidance acknowledges that sponsors may not always have direct access to patient-level data and outlines regulatory pathways such as Type V drug master files and pre-investigational new drug applications that can be used for data submission.
Industry Implications
For pharmaceutical companies, the guidance suggests that RWD planning can begin as early as phase 2 clinical trials, running parallel to randomized controlled trials (RCTs). This approach allows for an optimal regulatory submission package that combines gold-standard RCT data with complementary RWD providing additional context on real-world endpoints, underrepresented populations, and long-term or rare events.
The FDA's clarification that only 25-30% of phase 3 clinical trials currently reach a new drug application underscores the potential impact of these guidelines. By incorporating RWD appropriately, companies may improve this success rate while accelerating the development timeline for therapies that address unmet medical needs.
Governance and Compliance Requirements
While offering new flexibility, the guidance maintains strict requirements for data integrity and patient privacy. Solutions must be HIPAA-compliant and, where applicable, 21 CFR Part 11-certified to ensure proper electronic records management.
The guidance emphasizes that while RWD offers valuable insights, it must be collected, analyzed, and presented with the same scientific rigor as traditional clinical trial data. This includes appropriate consent management, data usage rights documentation, and clear separation between identifiable and de-identified information.
Future Outlook
The FDA's new guidance represents a significant step toward a more integrated approach to clinical evidence generation, where traditional trial data and real-world evidence complement each other throughout the drug development and approval process.
As pharmaceutical companies adapt to these guidelines, we can expect to see more innovative trial designs that incorporate RWD from the outset, potentially reducing development costs while providing more comprehensive evidence of safety and efficacy across diverse patient populations and extended timeframes.
For patients, particularly those with rare diseases or conditions lacking effective treatments, these changes could mean faster access to innovative therapies supported by more robust and relevant evidence of real-world effectiveness.
