Oncology and the Evolution of Master Clinical Trials | Lessons from the Beat AML Master Trial

Leveraging experiences from managing the Beat AML Master Trial, our experts share the importance of innovative trial design, data analysis and patient-centricity in managing large-scale platform oncology trials.

In recent years, especially in oncology, the demand for master clinical trials has surged, offering a promising avenue for advancing treatment options. It's essential to understand the distinctions between different trial designs within this landscape. While a platform trial involves evaluating multiple treatments or diseases within the same protocol, an umbrella trial focuses on testing multiple therapies for a single disease with one or more subtypes. These trial design options present a more efficient alternative to traditional clinical trials by allowing researchers to explore various treatment approaches simultaneously.

Master trials, including platform and umbrella trials, leverage predictive biomarkers or patient risk factors to assess different treatments across diverse patient subgroups. By doing so, they aim to expedite the identification of effective therapies and ultimately improve patient outcomes. The increasing demand for platform trials reflects a growing emphasis on personalized and effective care in oncology.

However, the success of master trials hinges on effective collaboration with clinical research organizations (CROs) that possess the necessary expertise. Drawing from their experience managing the Beat Acute Myeloid Leukemia (AML) Master Trial, our experts emphasize the importance of strategic CRO collaboration in realizing the full potential of these trials. The operational approaches, e-technologies and sponsor/CRO’s expertise together allow: the complexity and size of the BAML Master Trial to be better managed; near real-time study data oversight; better collaboration, communication and training; improved data collection, enhanced transmission and accessibility; data integration, review and generation of reports; while maintaining data privacy, and compliance. As the first collaborative precision medicine clinical trial in a blood cancer, the Beat AML Master Trial offers valuable insights and lessons learned that can inform future endeavors in this rapidly evolving field.

• Prior experience and expertise matters. “Successful execution requires not only operational know-how but also the ability to navigate the intricate web of stakeholders involved,” explains Patrick Melvin, Vice President of Therapeutic Strategy and Innovation in Oncology. From his experience with the Beat AML Master Trial, 10 to 12 sponsors and over 1000 patients were enrolled in a single trial. This massive undertaking necessitated the deployment of adaptive trial design techniques to ensure focused collaboration while maintaining the trial's validity and integrity. “The sheer amount of stakeholders involved -- from pharmaceutical companies, clinical sites, patient advocacy groups, regulator bodies and key opinion leaders -- was staggering. Coordinating a master trial with this complexity and size requires the right CRO with an acute understanding of the dynamics within the ecosystem, resulting in better real-time data oversight, collaboration, communication, and training while maintaining data privacy and compliance.”
• Clinical trial design and data analysis can make or break a master trial. Clinical trial design and data analysis play pivotal roles in the success of master trials. “From a statistical perspective, considerations such as handling multiplicity in control, randomization approaches, graduation criteria and data analysis strategies are essential,” noted X.Q Xue, Vice President of Biostatistics. Adaptive trial design offers flexibility and efficiency in adapting to evolving trial needs and insights. “But if not done correctly, adaptive trial designs can introduce biases, increase error rates and diminish the generalizability of results,” Xue added. Careful planning and adherence to rigorous statistical methods are crucial to mitigate these risks and ensure the integrity and validity of trial outcomes.
• Always have the needs and preferences of patients in mind. A patient-centric approach not only improves engagement but also enhances the validity of trial outcomes. “Take, for example, the innovative use of external control arms in trials like the Beat AML Master Trial. Here, a synthetic control arm was devised, drawing upon existing data to provide a reference point for treatment comparison. This approach not only streamlined the trial process but also minimized the burden, risk, and cost for patients involved," notes Melvin. "The strategic integration of patient advocacy groups and patient-centric services further amplifies engagement and ensures that the trial remains responsive to the needs of those it aims to benefit. By continually incorporating patient feedback and insights, master trials can uphold their commitment to improving patient outcomes and advancing the field of oncology.

Master clinical trials, particularly in oncology, offer a more efficient approach to drug development. But while they have the potential to transform clinical research and patient care by expediting therapy development and improving outcomes, the success of these trials hinges on deep therapeutic expertise, operational agility to improve clinical trial outcomes, statistical rigor and a commitment to patient-centricity.?

Is your team looking to enhance their oncology clinical trial strategy? Explore how our experts in clinical trial development can help you meet your goals.

Contributors?

Patrick Melvin | Vice President, Therapeutic Strategy and Innovation, Oncology

X.Q Xue | Vice President, Biostatistics

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