The US Food and Drug Administration (FDA) has released guidance about innovative trial designs for cell and gene therapy (CGT) studies.
In the eight-page draft guidance, titled ‘Innovative Designs for Clinical Trials of Cellular and Gene Therapy Products in Small Populations’, the agency said the framework is a response to the Prescription Drug User Fee Act (PDUFA) VII commitment to increase efficiency in the development of CGT products. The draft guidance was released on 24 September 2025.
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The draft guidance reads: “Given the urgent need for safe and effective products to treat serious and severely debilitating diseases in small populations, FDA recognises the importance of innovative and efficient trial designs, including selection of appropriate endpoints that are feasible and capable of generating the necessary evidence for approval.”
The agency has included six trial designs in the docket: single-arm trials utilising participants as their own control, disease progression modelling, externally controlled studies, adaptive clinical trial designs, Bayesian trial designs and master protocol designs.
The FDA guidance adds that this is not an exhaustive list of the possible trial designs and that sponsors should speak to the agency.
The guidance also discusses considerations for patient selection in CGT trials, with the FDA stating that sponsors should carefully consider what previous treatments patients have received before they are enrolled onto a study to ensure the study would facilitate generalisable results if the product were approved.
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By GlobalDataThe FDA requests sponsors to consider endpoints within the study design, as patients’ symptoms may be mild or absent in certain cases. This could provide those conducting the trials with uncertainty as to whether all affected patients will develop symptoms, at what time point, and how those may progress or change over time.
This may mean sponsors consider trial designs that “incorporate surrogate endpoints, biomarkers, or intermediate clinical endpoints prior to symptom onset”, potentially utilising digital health technologies (DHTs) to best capture meaningful changes in clinical function.
Finally, the FDA discusses the importance of study population representation, especially in paediatric studies. The agency states that the sponsor must “address requirements for permission by parents/guardians and, where appropriate, assent by children, the level of risk posed to children as subjects, and additional safeguards”.
The guidance states: “When planning a CGT clinical development programme, sponsors should consider whether the disease affects the paediatric population differently than adults with the same disease; whether the data generated in adults would be relevant to the paediatric population with the condition; and what available data and information from their clinical development program and from other sources can support an assessment of the prospect of clinical benefit in paediatric patients.”
For years, sponsors have been utilising innovative trial designs in CGT. Analysis by Clinical Trials Arena in May 2024, using GlobalData’s Pharmaceutical Intelligence Center, found that the single-group assignment trial design was by far the most used approach for cell and gene therapies. The type of trial has, however, been determined by the patient population and the indication, as is suggested by the FDA in the new guidance.
Cell & Gene therapy coverage on Clinical Trials Arena is supported by Cytiva.
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