Strategies for Success
The clinical trial landscape is constantly evolving, particularly in oncology early development, influenced by shifts in regulatory guidance such as the US Food and Drug Administration’s Project Optimus initiative or its draft guidance on Multiregional Clinical Trials in Oncology. This new era requires a solid understanding of the requirements and potential challenges, along with a strong command of the solutions needed to mitigate risks and optimize trial outcomes.
Below are suggested strategies to ensure success in operationalizing global early-phase oncology trials.
Managing dose optimization and complex study designs
Project Optimus emphasizes dose optimization in early-phase oncology trials should not be based solely on maximum tolerated dose (MTD) but should include pharmacokinetic (PK) and pharmacodynamic (PD) data, resulting in complex study designs that necessitate larger sample sizes and a broader global footprint. Sponsors and contract research organizations (CROs) must balance robust data collection with the practicalities of patient recruitment and retention across diverse regions and regulatory environments.
Tackling operational execution on a global scale
Operational execution in early-phase trials involves coordinating numerous factors during study startup and trial planning. A strong understanding of regulatory requirements and compliance with local laws is crucial for smooth trial initiation and progression. Knowledge of regional data privacy regulations safeguards patient information and maintains trust.
Enrollment and cohort management can be challenging in global trials with multiple sites located across various regions and time zones. Global study teams must be proficient in protocol knowledge, including managing multiple treatment arms, varying doses, and adaptive trial designs.
Sites must be adequately staffed and equipped to handle cohort-specific needs, requiring coordination of specialized personnel, medical equipment, and materials. Adding to the complexity of early-phase trials is risk-based monitoring, safety review, vendor management, investigational product (IP), and sample management. Effective communication and coordination among the various stakeholders are essential to trial success.
Planning for trial success, adapting to changes
Mapping out the clinical study plan from the beginning is vital, especially for small biotechs. Capitalizing on a CRO’s knowledge and experiences can be beneficial. Risk mitigation methods, including planning for unexpected events such as natural disasters and geopolitical climates, are essential in early planning.
Leveraging automated document management tools can reduce administrative burdens and speed study startup. Likewise, master service agreements can fast-track site contract negotiations and have a positive impact on global startup timelines.
Changes are inevitable in early-phase oncology trials, so remaining adaptable is key. Amendments to study protocols are frequent, so having a flexible setup process that allows for adjustments is crucial. For example, a trial may start as a first-in-human trial in one country and expand globally over time. Careful advanced planning helps anticipate amendments and effectively manage transitions and predict trial milestones.
Planning strategic country- and site-level decisions
Early-phase trials require a strong command of country- and site-level feasibility, ethics, and informed consent processes, along with the ability to navigate cultural differences and local regulatory climates. Global startup durations have been impacted due to the adaptation of European Clinical Trial Regulation (EU CTR) 536 and the transition to the Clinical Trial Information System (CTIS). Increased collaboration with investigators and sites has improved feasibility efforts. Critical outreach efforts, focusing on protocol-specific nuances, aid in selecting the right sites for study participation.
Understanding disease prevalence, analyzing the competition, and leveraging local relationships with country-level experts and key opinion leaders (KOLs) help ensure a strong study design and smooth startup process. For example, in Asia-Pacific, knowing the country landscape and having strong experts on the ground is essential. Understanding demographics and diversity of patient populations help determine how well protocols will be adopted. Finding the right sites with the necessary equipment and knowledgeable investigators is crucial for quick activation and patient enrollment.
Predictive data analytics can help expedite informed decisions about country selection; and incidence rates and prescribing history facilitate the identification of suitable sites. Next-generation, novel oncology treatments sometimes face greater scrutiny and longer regulatory reviews, so risk mitigation and strategic planning are necessary.
Selecting sites and engaging KOLs
Recruiting the right sites and patients in early-phase oncology trials is critical. Site selection involves assessing experience and expertise, prior knowledge of the site, and identifying KOLs. Qualification assessments ensure sites have the right capabilities, facilities, and staff to support the trial. Geographic considerations, patient demographics, and healthcare access are also important.
Strong, collaborative site relationships are fundamental for successful trial delivery, so feasibility questionnaires should be streamlined through conversations during qualification visits or calls with site coordinators. This helps reduce the site burden, support site engagement, shorten the startup time, and reduce costs.
Early involvement with KOLs is invaluable for identifying suitable sites and countries for trials. Knowledge gained from KOL and patient engagement can help avoid prolonged back-and-forth with regulatory agencies. Patient advocacy groups support CROs and sponsors in understanding patient perspectives about current treatments and how they differ. Patient outlooks, often found in online groups and message boards, are valuable for helping make more informed decisions.
While rapid site activation is critical to trial success, it’s important to remain flexible. It is imperative to recruit the most appropriate sites and patients to optimize trial outcomes.
Coordinating clinical trial logistics
Managing clinical trial logistics on early-phase trials has become increasingly multifaceted. Flexibility and planning from the outset are crucial for operational success. While using a central supply is recommended, it is important to assess trial needs and plan accordingly.
Using a central supply for comparator drugs is considered optimal as it de-risks the supply chain. Flexibility is necessary, however, to handle potential shortages. Expanding to additional countries may require local supplies, which can vary from region to region or even within hospitals. Each approach has associated costs, and it’s essential to ensure the system can withstand audits and track every pill to avoid recalls and patient issues. Reimbursement cards can simplify the process and may add a layer of complexity for drug reconciliation. Using real-world data arms can potentially replace the need for purchasing comparators.
Each country and region have specific approvals and packaging requirements, which can be challenging to navigate, so being prepared for these complexities and any potential shortages is essential.
Innovating oncology trials with AI
Innovation in early-phase oncology trials often focuses on AI-powered platforms that automate tasks and workflows, reducing site burden and administrative challenges. Document workflow automation and forecasting tools are becoming more prominent, aligning multiple data points for better efficiency.
AI can also assist with streamlining processes, improving data acquisition and analysis, and optimizing trial performance. Early indicators and trends can help plan downstream activities. Real-world data arms and AI tools may reduce the number of patients required for trials by leveraging historical data sets. Overall, these innovations aim to enhance clinical trial efficiency, reduce costs, and improve outcomes by leveraging advanced technologies and data-driven approaches.
Successfully operationalizing early-phase oncology trials involves a multifaceted and well-planned approach. Familiarity with disease prevalence, knowledge of local regulations and customs, leveraging local relationships, and engaging with KOLs and patients are critical to ensuring operational successes. Proficiency with global enrollment, cohort management, and clinical trial logistic coordination is critical. Effective planning and preparation, including the use of innovative tools like AI, are essential for making informed decisions and ensuring smooth trial execution. Flexibility in drug supply management and implementing cost-saving measures are crucial for operational success. Innovations such as AI-powered platforms and real-world data arms are transforming trial processes, aiming to reduce site burden, and enhancing efficiency.
By embracing change, leveraging expertise, and utilizing cutting-edge technologies, early-phase oncology study teams can produce reliable data that supports regulatory submissions and advances drug development for sponsors and patients.
