Heather Davis

	Managing a successful Phase III global oncology trial presents one of the most complex challenges drug companies face within the development cycle. Phase III clinical trials require a global scope to access larger patient pools, obtain exposure to a more demographically diverse patient population, and deploy regulatory strategies that can ultimately support commercialization.

	For smaller biopharma companies, where resources and pipelines are frequently limited, navigating the development and successful execution of a global Phase III trial is critical, not only to the ultimate success of the compound, but sometimes even to the survival of the company.

	Given the challenges of late phase global trials, strategic and detailed planning is critical to success-especially in the first six to 12 months. The following are four study design activities every drug developer must undertake to clear cross-border barriers and deliver a successful global oncology trial.

Establish a firm scientific foundation for the trial

	Prioritize study plan completion in alignment with clinical trial process. Plans that affect study start-up, such as regulatory plans, should be completed first-before tackling those which impact a trial's readout phase, such as the statistical analysis plan. All plans should address staffing, training, documentation, and compliance requirements. For example, does the plan consider global variations in imaging methods and account for differences in radiologist training? This is certainly crucial to any global oncology trial that looks at target lesions, responses, and progression as part of its major endpoints, especially in light of recent trends to leverage surrogate endpoints in lieu of overall survival for registration.

	Performing clinical trial feasibility is one of the initial and most important steps in conducting a global clinical trial. Feasibility can help determine the best mix of countries and sites, each of which has challenges that could influence the completion of a study. Conducting extensive and early feasibility allows a better understanding of the global climate and the competition for the patient population. It can help determine where your compound fits in terms of both clinical interest and regional considerations. This includes determining provision and reimbursement requirements as well as access to marketed and available comparator or supportive drugs required by the protocol design.

Ensure comprehensive operational and regulatory plans are in place

	Developing a model for trial start-up and enrollment timelines provides a comprehensive view from start-up to last patient that begins on day one. This enables sponsors to allow for the "real-world" planning of a trial. Because of the variance in timelines for approvals, an understanding of the country, region, and site-specific requirements can help a sponsor navigate the concurrent processes necessary to obtain authorization for international trials. While no timeline is perfect, ones that account for delays, questions, changes, and even holidays permit realistic planning.

Engage required vendors in successful partnerships

	Working with an experienced contract research organization (CRO) to develop a comprehensive set of study plans and step-by-step processes assures regional issues are proactively addressed before the first patient is even enrolled. On-the-ground knowledge, acquired via an oncology CRO's daily experience working with local regulatory agencies, local labs, logistic experts, study sites, and investigators is critical to a global oncology trial's success. Making sure your outsourcing partner has comprehensive study plans on a trial will ensure all team members, globally, understand their function and how to address unforeseen issues that may arise.

- Heather Davis, Director of Project Management, Late Phase Oncology Programs, Novella Clinical 

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Following four key study-design steps is crucial to the delivery of a successful cross-border cancer study

Planning for Success in Late Phase Global Oncology Trials

	Managing a successful Phase III global oncology trial presents one of the most complex challenges drug companies face within the development cycle. Phase III trials require a global scope to access larger patient pools, obtain exposure to a more demographically diverse patient population and deploy regulatory strategies that can ultimately support commercialization.  

	Given the challenges of late phase global trials, strategic and detailed planning is critical to success - especially in the first six to 12 months. Novella Clinical has identified four study design activities every drug developer must undertake to clear cross-border barriers and deliver a successful global oncology trial.

Establish a firm scientific foundation for the trial. 

Prioritize study plan completion in alignment with clinical trial process. Plans that affect study start-up, such as regulatory plans, should be completed first –before tackling those which impact a trial’s readout phase, such as the statistical analysis plan. All plans should address staffing, training, documentation and compliance requirements. For example, does the plan consider global variations in imaging methods and account for differences in radiologist training? This is certainly crucial to any global oncology trial that looks at target lesions, responses and progression as part of its major endpoints, especially in light of recent trends to leverage surrogate endpoints in lieu of overall survival for registration.

. Performing clinical trial feasibility is one of the initial and most important steps in conducting a global clinical trial. Feasibility can help determine the best mix of countries and sites, each of which has challenges that could influence the completion of a study. Conducting extensive and early feasibility allows a better understanding of the global climate and the competition for the patient population. It can help determine where your compound fits in terms of both clinical interest and regional considerations. This includes determining provision and reimbursement requirements as well as access to marketed and available comparator or supportive drugs required by the protocol design.

Ensure comprehensive operational and regulatory plans are in place. 

Developing a model for trial start-up and enrollment timelines provides a comprehensive view from start-up to last patient that begins on day one. This enables sponsors to allow for the “real world” planning of a trial. Because of the variance in timelines for approvals, an understanding of the country, region and site-specific requirements can help a sponsor navigate the concurrent processes necessary to obtain authorization for international trials. While no timeline is perfect, ones that account for delays, questions, changes and even holidays permit realistic planning.

Engage required vendors in successful partnerships. 

Working with an experienced CRO to develop a comprehensive set of study plans and step-by-step processes assures regional issues are proactively addressed before the first patient is even enrolled. On-the-ground knowledge, acquired via an oncology CRO’s daily experience working with local regulatory agencies, local labs, logistic experts, study sites and investigators, is critical to a global oncology trial’s success. Making sure your outsourcing partner has comprehensive study plans on a trial will ensure all team members, globally, understand their function and how to address unforeseen issues that may arise.

, Director of Project Management, Late Phase Oncology Programs at Novella Clinical 

Managing a successful Phase III global oncology trial presents one of the most complex challenges drug companies face within the development cycle.