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With the emergence of basket trials in the early-phase oncology setting, clinical research teams are faced with challenges of enrollment potential across various disease sites. This results in operational considerations that invoke a need for a collaborative “hands on” approach to ensure program success.
Why A Basket Trial?
Used primarily in oncology clinical research, master protocols, which are classified as basket trials, umbrella trials, and platform trials, investigate multiple hypotheses through concurrent sub-studies.
This may entail multiple treatments or populations, or the option to add/remove study arms during the course of a trial. Thus, offering enhanced efficiency and a more ethical approach to trial evaluation.
The figure to the left illustrates a simple graphical representation of basket, umbrella, and platform trials.
Basket trials include enrollment of different tumor types with a common molecular alteration aimed to provide the same investigational agent and regimen.
This is thought to speed up the discovery and approval process of new therapies in oncology research and ultimately provide novel agents to oncology patients.
Early Steps to Success
Scimega is an expert CRO known to foster strong site relationships and in-depth knowledge of the oncology research landscape across Canada. When planning a basket trial, the key to success involves the development of mitigating actions for any anticipated operational challenges.
Firstly, one Principal Investigator, not more, may oversee a clinical trial for each institution selected to participate per regulatory requirements in Canada. Each Principal Investigator’s focus will likely not include all the tumor types “cohorts” selected for a basket trial. Which is why it’s important through effective feasibility analysis to understand clearly what disease sites are of focus for the Sponsor and match an appropriate site/Principal Investigator accordingly.
It is also important to determine the type of site/department selected based on the requirements of the basket trial. For example, a Phase 1 unit at a site may treat multiple tumor types but may not be able to give access to the trial for all tumor types. This holds true mainly for larger institutions that have several departments working in silos, and where cross-functional collaboration is not the norm.
Due to the complexity and workload of these departments, some Principal Investigator’s may agree to oversight of Sub-Investigators from other units within the institution. Other Principal Investigators may not. These important distinctions need to be brought to the Sponsor’s attention early in the feasibility/site selection phase.
Importance of the Study Site Team
When a Principal Investigator agrees to collaborate across departments, the Sponsor relies on Scimega to ensure adequate oversight that translates to frequent communication between the site, CRO and the Sponsor. In turn, the Principal Investigator relies on the study site team to collaborate with the participating departments. The study site team is relied upon not only for the selection of eligible oncology patients, but also for adherence to the study protocol. The study site team also handles logistical aspects such as research coordinator selection, study data access and coordination of the technical aspects within the institution to ensure a successful trial at the center.
It’s a Question of Balance
For a Principal Investigator who agrees to only oversee the study within their department and is recommended by Scimega based on discussions with the Sponsor, the enrollment potential will be limited to the tumor types treated in the department. In such cases, the selection of other Principal Investigators/sites needs to address the balance of the other tumor types to ensure maximum enrollment potential is possible for the trial.
When enrollment targets are reached for some of the cohorts, but not others, Scimega coordinates with the Sponsor to reassess enrollment potential across sites. This may result in closing sites or transferring Principal Investigator responsibilities within the institution as well as, quite frankly, re-initiating site feasibility/selection processes.
Frequent Start-up & Close-out is the Norm
All parties involved in a basket trial must be flexible and adaptable to frequent start-up activities and close-out activities for the duration of these types of trials. More often than not in basket trials, start-up to close-out is not linear. The norm is a more continuous cycle of start-up and close-out activity until enrollment targets and milestones are achieved.
Another key consideration within the context of repeated site selection/feasibility processes is the budgeting for these activities across the key players: The Sponsor, the CRO and the site. Scimega is sensitive to the evolving nature of basket trials that may either lead to opening/closing cohorts or even starting a new protocol for a cohort that shows evidence of response. Scimega’s team of oncology experts strive to be both flexible and proactive to ever changing needs. This nimble player is always ready to adapt to change and collaborate with Sponsors and sites to effectively execute basket trials to ensure Canadian oncology patients have access to novel compounds in the early-phase oncology setting.
The diagram below offers a geographical illustration of accumulating master protocols (basket, umbrella, and platform trials) identifying predominate regions of their occurrence globally; with the majority of master protocols taking place in the US and other high-income countries.
The number of master protocols (basket trials, umbrella trials, and platform trials) has increased dramatically over recent years, and this trend is expected to continue in years to come.
Choosing the Right Region & Partner for Your Basket Trial Expansion
Mobilizing an expert Canadian team significantly enhances study start-up and overall performance. Based on metrics achieved by Canadian oncology CRO, Scimega, biotechs developing cutting edge oncology therapies with this partner are very impressed with where Canada stands in comparison to other regions, including the U.S., when they work together in the region.
With 23 years unparalleled Canadian oncology experience Scimega Research has an optimal operations design critical to its ability to consistently go above-and-beyond for every one of your basket trials.
Contributed by: Sandy Purba, CCRP, Clinical Trial Leader
BioMed Central, Trials Journal, Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols; published 18 Sept, 2019