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Single-arm clinical trials are gaining attention as potential registrational studies in oncology research. This webinar provides an overview of single-arm trials, their foundations for registration, and regulatory strategies associated with the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
A single-arm trial involves enrolling participants who receive a single treatment at a specific dose level. Unlike randomized multiple-arm trials, single-arm studies rely on observations from a single treatment group. These trials are considered when a randomized control trial is unfeasible or unethical due to factors like acute medical needs or the absence of suitable treatments.
Benefits and limitations:
Single-arm trials offer advantages such as shorter study duration, smaller sample sizes, and early detection of efficacy signals. However, they present limitations regarding interpretability due to the absence of a control group, smaller safety databases, potential biases, and challenges in assessing safety events and treatment effects.
Single-arm trials are commonly used in oncology, particularly in early stages or indications with limited treatment options. They can be suitable for subpopulations with severe disease states or shorter expected survival times. Genetic markers, biomarker indicators, or later lines of therapy may also warrant using single-arm studies.
Regulatory Considerations:
To justify a single-arm trial as a registrational study, an unmet medical need must exist, where no appropriate comparator treatment is available. Demonstrating rapid, durable, and clinically meaningful activity becomes crucial.
Foundations of Single Arm Trials:
Defining the target population and assessing the current treatment landscape are essential steps. Identifying an appropriate control arm for a randomized trial, if feasible, is crucial. Surrogate endpoints like objective response rate with supportive evidence of duration of response are commonly used. However, the association between surrogate endpoints and overall survival varies, making class of drugs a critical factor.
Bias Mitigation and Study Design:
Reducing bias is challenging in single arm trials due to the absence of a control arm and blinding. Strategies include pre-specified planning, independent central review of response assessments, rigorous execution, and bias mitigation in protocols and analysis plans. Sample size determination relies on a predefined threshold, typically set based on clinical significance and prior studies.
Single-arm clinical trials have a role in oncology research, especially when randomized control trials are impractical. While they offer benefits in specific scenarios, careful consideration of limitations, regulatory expectations, and bias mitigation is essential. Collaborating with regulatory authorities can help establish appropriate study designs and determine thresholds for clinically meaningful responses. Ultimately, the use of single arm trials should be justified, aiming to provide safe and effective treatment options for patients in need.
Learning points:
Veristat experts discuss single-arm oncology registrational studies, success stories, and lessons learned. The following considerations will be discussed during the webinar:
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How to know if there is an unmet medical need that may allow for a single-arm registrational study
- How to develop a single-arm study design for registration, including:
- Defining the population
- Selecting study endpoints and defining a clinically meaningful benefit
- How to determine a regulatory strategy, including:
- Accelerated approval vs. full approval
- Planning for agency interaction – when and how to approach the US FDA and what key questions to ask
Meet the speakers and authors:
Robin Bliss, PhD
Vice President, Strategic Consulting, Veristat
Robin Bliss, PhD joined Veristat in 2011, and is currently Vice President, Strategic Consulting. In her role, Robin oversees and executes Strategic Clinical Development Consulting, collaborating with Regulatory Consulting, Clinical and Medical Consulting and Statistical Consulting. A statistician with 15+ years’ experience, Robin is skilled in planning and implementing complex study protocols, planning and executing study analysis, marketing applications, and providing statistical and strategy representation at regulatory agency meetings. Robin earned her PhD and MA in Biostatistics from Boston University, US.
Debora Manning, MPH
Strategic Consulting Fellow, Biostatistician, Veristat
Debora Manning, Strategic Consulting Fellow and Biostatistician at Veristat, is a strategic contributor, providing consulting services on study-specific and global programs, including input towards clinical development plans, protocols, study design, biostatistical plans and analysis, and regulatory submissions. Debora has played pivotal roles in leading interactions with regulators and developing successful marketing applications (NDA, BLA, MAA). Debora received her BA in mathematics from Wheaton College (MA), her MPH in biostatistics from Boston University School of Public Health, and her graduate certificate in regulatory affairs and health policy from the Massachusetts College of Pharmacy and Health Sciences.