By Ray Tobey, Chief Medical Officer on Jan 24, 2018 9:00:00 AM
New methods of clinical trial design are thought to allow more patients to participate and test new treatments at a faster rate. Two relatively new types of studies for cancer care are umbrella and basket studies.
Umbrella trial design take patients with the same type of cancer and assign them to different arms of a study based on their mutations. Basket trial design groups patients by mutation, regardless of which organs are involved. So, which study is best for your needs? Here we outline the characteristics for each study type to help you decide.
Characteristics of Umbrella Studies:
The defining characteristic of an umbrella trial is that it is performed within a national network of clinical sites with molecularly targeted clinical trials using a common genomic screening platform. Patients are screened for a specific set of biomarkers and assigned to a biomarker-driven sub-study. Such a structure is essential for conducting targeted clinical trials in an increasingly stratified set of tumors.
- The focus is on a single tumor type or histology.
- There are multiple sub-trials within the umbrella framework.
- Each sub-trial tests a targeted therapy within a molecularly defined subset.
- There is the flexibility to add, modify or drop sub-trials with molecularly targeted drugs. and companion diagnostics based on accumulating evidence of the ongoing trial and nearly emerging data.
Characteristics of Basket Studies:
Basket trials offer the possibility to include multiple molecularly defined subpopulations, but across histologic subtypes or tumor types. This is thought to be an efficient way for screening experimental therapeutics across multiple patient populations in an early-phase of development.
- There is one cohesive design to evaluate the targeted therapy in question.
- Assignment of treatments to patients is based on the molecular alterations the tumors. contain, regardless of the histologic type of the tumor.
- They have a common genetic screening platform, especially if the cohort defined in the study is histology agnostic, and defined only by the presence of a single molecular aberration.
- The cohort eligibility is either histology or mutation specific.
Challenges in Clinical Trial Design
With the ever-increasing complexity of molecular signatures of tumor and tumor types, new statistical approaches or novel applications of existing design framework, are needed for any successful trial. For example, how do we handle assignment of patients with multiple targets? Do we randomize equally, or use a weighted randomization? In addition, there are logistical challenges to implementing these umbrella and basket screening protocols since there are not always centralized assay testing. For these studies to be implemented effectively, there needs to be a multidisciplinary approach to establish the appropriate infrastructure requirements with bioinformatics platforms depending on the complexity of the study.
Have you ever used one of these clinical trial design methods? What were your experiences? Please comment below.