Streamlining Drug Safety: A Look at FDA's New Framework for Smarter Clinical Trial Data Collection
The CDER just published a new white paper on Selective Safety Data Collection. We dissect it.
The CDER’s Center for Clinical Trial Innovation is out with a new white paper that provides an overview of the agency’s regulatory framework for collecting safety data throughout the clinical development process of a drug depending on what is already known about it.
The “Selective Safety Data Collection” approach “refers to a planned reduction in the collection of certain types of data in a clinical investigation for drugs with a well-characterized safety profile and for which the continued collection of common, non-serious adverse events or routine laboratory assessments is unlikely to provide additional knowledge of clinical importance,” the FDA explained.
The agency adopted this approach several years ago, and the white paper gives us examples of how companies can use a more streamlined approach to collecting safety data.
Here’s the concept, in a nutshell: for drugs with well-established safety profiles, why continue collecting mountains of routine safety data that are unlikely to yield new clinically meaningful insights? SSDC is a targeted approach to data collection, which promises to reduce participant burden, slash study costs, and accelerate the development of life-saving medications—all while maintaining the standard of patient safety that regulators demand.
But despite international regulatory harmonization and compelling real-world success stories spanning oncology to cardiovascular medicine, adoption of SSDC remains surprisingly limited. This latest white paper documents this untapped potential and lays down a roadmap for how pharma can embrace it.
Here’s our breakdown of the paper.
Core definition and purpose
Selective Safety Data Collection is a planned reduction in collecting certain types of safety data for drugs with well-characterized safety profiles, where continued collection of common, non-serious adverse events or routine laboratory assessments is unlikely to provide additional clinically important knowledge.
The history of this framework
The approach has evolved significantly over the past decade or so. Here are the five major milestones at a glance:
2001: The FDA issued guidance for cancer drugs discussing data reduction possibilities.
February 2016: FDA published guidance "Determining the Extent of Safety Data Collection Needed in Late-Stage Premarket and Postapproval Clinical Investigations."
2017: The International Council for Harmonisation (ICH) formed the E19 Expert Work Group.
September 2022: ICH E19 guidance finalized: "A Selective Approach to Safety Data Collection in Specific Late-Stage Pre-Approval or Post-Approval Clinical Trials."
December 2022: The FDA implemented ICH E19.
Eligibility criteria for SSDC
The white paper outlines specific requirements for trials to qualify for SSDC. First, there are drug profile requirements: Late-stage pre- or post-marketing trials for drugs where the safety profile regarding commonly occurring adverse events is well understood and documented.
The trial type matters, too:
Trials for approved drugs seeking new indications in similar populations.
Label expansion trials for additional endpoints in the same patient population.
Safety trials investigating specific safety concerns (e.g., postmarketing requirements).
Trials providing additional efficacy evidence when safety is well-characterized.
What SSDC does NOT include
The paper explicitly emphasizes critical limitations:
Does not eliminate data necessary for participant safety.
Does not reduce comprehensive baseline assessments.
Must continue collecting serious adverse events (SAEs).
Must continue collecting AEs resulting in study drug discontinuation.
Does not alter local/regional safety reporting requirements.
Real-World examples and case studies
The examples are instructive here for oncology, cardiovascular, and a few other applications.
Pragmatica-Lung Study (NCT05633602):
Primary objective: Compare overall survival in previously treated non-small cell lung cancer patients.
SSDC Implementation: Limited safety collection to grade 3+ severity AEs and fatalities only.
Rationale: Well-established safety profiles of pembrolizumab and ramucirumab.
Additional streamlining: Broad eligibility, community recruitment optimization, and omission of protocol-required disease assessments.
VICTORION-2-PREVENT (NCT05030428):
Dramatic reduction in visit frequency: Every 6 months vs. monthly-quarterly standard.
Streamlined assessments:
Vital signs only at screening vs. all visits.
.No scheduled ECGs vs. all visits
Laboratory assessments at screening only vs. all visits.
Liver function tests in the subset (20%) were performed annually vs. all patients at all visits.
EMPA-KIDNEY and EMPACT-MI Studies: The paper provides detailed comparison tables showing how empagliflozin studies implemented SSDC.
EMPACT-MI: The most streamlined approach, with only one visit at 2 weeks post-randomization, followed by remote follow-ups every 6 months.
Limited AE collection: Only SAEs, adverse events of special interest (AESIs), and those leading to treatment discontinuation.
Stated benefits across stakeholders
For study participants, the paper claims that the approach will reduce participation burden (fewer blood draws, lab tests, and visits) and lead to higher enrollment and retention rates.
For investigators, simpler protocols, a better focus on relevant study objectives, and easier implementation. For sponsors, lower costs and a clearer incentive for running adequate and well-controlled studies. And for regulators, a better focus on relevant data for evaluating benefit-risk.