12/14/2021
Photo by Joshua Sortino on Unsplash
The US Food and Drug Administration (FDA) released a draft guidance “Considerations for the Use of Real-World Data and Real-World Evidence To Support Regulatory Decision-Making for Drug and Biological Products” for public comment in December 2021. This draft guidance is published as part of a series of real-world evidence (RWE) guidance in line with the 21st Century Cures Act (Cures Act). Part of the Cures Act is related to the use of real-world evidence (RWE) to help support regulatory decision making, including the approval of a new indication for an approved drug or to support post approval study requirements. This draft guidance discusses its applicability in using RWE in clinical trials and observational studies.
Summary of Draft Guidance
For clinical trials, RWE may best be used:
for the identification of potential study participants
to identify endpoints or outcomes, or
as a comparator arm in an externally controlled trial
Some considerations when using RWE in observational studies are:
It is recommended for the sponsor to contact the FDA early in the study design if there are plans to use RWE in an observational study to support a marketing application.
They should provide draft versions of the proposed protocol and statistical analysis plan (SAP) and can request a Type C meeting.
Consider data privacy and security issues when designing the study and consult data privacy experts when applicable to ensure protection.
Even though the observation is not a clinical trial, if the study includes protocol-specified activities or procedures that collect additional data, human subject protection and IRB regulations apply (21 CFR 50 and 56).
To demonstrate there was not a data selection bias, the sponsor needs to finalize the protocol and SAP before reviewing outcome data and analyzing it.
Protocol revisions should be date stamped and the rationale documented.
The protocol should include a description of all the data sources accessed when designing the study and a justification for selecting or excluding certain sources.
The draft guidance outlines further steps to demonstrating transparency in data collection and analysis, such as:
describing the characteristics of the source and study populations and indicate any differences that may impact data analysis
posting in a publicly available site (e.g., clinicaltrials.gov)
conducting and documenting feasibility evaluations and exploratory analyses
including audit trails in the datasets that track access to analyses and what analyses were conducted
Monitoring and oversight should follow a risk based quality management approach,
with a focus on preventing or mitigating important or likely risks to study quality, or
on processes that protect participant safety when protocol specified activities or procedures are utilized.
Safety reporting is required in observational studies if data on adverse events are discovered in database searches that would meet the postmarketing reporting requirements.
The FDA does not require an extensive search to try to uncover safety data when using RWE to support a labeling change.
The draft guidance includes a good reminder that any data submitted to the FDA in a marketing application that supports safety and/or effectiveness must meet the regulatory standards and there is not a lowered threshold for RWE. Sponsors are responsible for the design, conduct, and oversight of observational studies, including selection of qualified individuals, monitoring, oversight, ensuring the study follows the protocol and SAP, and maintaining records. Using RWE to support applications for drug or biologics may expedite the data collection process to back labeling changes for additional uses of products. Additional guidance on the use of RWE can be expected.
Comment now through March 08, 2022 HERE.
For more information on the FDA’s framework for RWE, visit our blog “FDA Framework for Use of Real-World Evidence.”
In September, the FDA published a draft guidance “Real-World Data: Assessing Electronic Health Records and Medical Claims Data to Support Regulatory Decision Making for Drug and Biological Products.” Read our blog HERE for more information.
In October, the FDA published a draft guidance “Data Standards for Drug and Biological Product Submissions Containing Real-World Data.” Read our blog HERE for more information.
In November, the FDA published a draft guidance “Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products.” Read our blog HERE for more information.
If you are preparing a regulatory submission and need assistance with utilizing RWE, Clinical Pathways can provide training as it is important to know how to apply these methods. Contact us at info@clinicalpathwaysresearch.com.
- The Clinical Pathways Team
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