Background to the project: Basket designs are an innovative trial design used increasingly often in cancer trials to evaluate targeted therapies on related cancers in multiple locations. A basket trial is designed to study multiple patient subgroups (baskets): a single treatment is delivered to subgroups of patients with the same disease, aiming to draw conclusions about effectiveness within rather than across subgroups. Borrowing evidence across baskets can be beneficial in enabling conclusions to be drawn about effective treatments in rare diseases or small patient populations which could not be studied in a standalone clinical trial. The aim of this project is to explore methods for borrowing evidence across baskets or subgroups in a clinical trial, in order to provide guidance and recommendations for practice.
The project will address the following research questions:
When should we borrow evidence?
This decision is influenced by sizes and numbers of baskets, expected similarity of treatment effects across baskets, importance of drawing separate conclusions for each basket, acceptability of borrowing methods to investigators and stakeholders. Simulations will be carried out to explore how much information would be gained by borrowing evidence under varying scenarios. Acceptability of borrowing methods will be explored through a survey of clinical investigators. The simulations and survey design will be informed by three Clinical Trials Unit-run trials that are borrowing evidence: ODYSSEY, TB-CHAMP, IMPART.
Where should we borrow evidence from?
Evidence could potentially be borrowed from one other basket, multiple baskets or external data. Models for borrowing and methods for informing degree of borrowing are more complicated when borrowing from multiple baskets rather than one basket; the student will review and discuss which models could be used and how the degree of borrowing could be informed. Methods for borrowing from relevant external data will be reviewed.
How should we choose the degree of borrowing?
The degree of borrowing can be informed by external evidence, opinion, a combination of evidence and opinion, additional evidence within the trial such as biomarkers, or learned from the trial data (if enough baskets have well estimated treatment effects). The student will review what has been done in practice and discuss the advantages and disadvantages of each approach in general and for particular example case studies.
How should we assess our approach to borrowing evidence?
The student will explore whether existing methods for exploring prior/data conflict are directly applicable for use in basket trial settings and whether additional work is required to make the methods more accessible for use in practice (e.g. implementation in Stata). Sensitivity analyses will be carried out in example data sets, to explore how robust the conclusions are. Practical recommendations will be made about performing sensitivity analyses in basket trials.
How should basket trials be designed when we intend to borrow evidence?
Work will be carried out to investigate how basket trials should be designed when investigators intend to borrow evidence across baskets. This work will draw on the findings obtained when addressing each of the above research questions and will investigate how to take into account the planned analysis in the trial design. Simulations will be carried out to explore the potential gains from increasing basket sizes under example scenarios.
The student will meet with Becky Turner once per week and additionally with Ian White once per month, and will also keep in touch by e-mail as required. The student will investigate the acceptability of borrowing evidence across disease areas with the MRC Clinical Trials Unit’s Methodology PPI panel.
Candidates should hold, or expect to achieve, an undergraduate degree in mathematics/statistics (upper second-class or first-class) or a Masters degree in statistics.
HOW TO APPLY
You are applying for a PhD studentship from the MRC TMRP DTP. A list of potential projects and the application form is available online at:
Please complete the form fully. Incomplete forms will not be considered. CVs will not be accepted for this scheme.
Please apply giving details for your first choice project. You can provide details of up to two other TMRP DTP projects you may be interested in at section B of the application form.
Before making an application, applicants should contact the project primary supervisor to find out more about the project and to discuss their interests in the research.
The deadline for applications is 4pm (GMT) 18 February 2022. Late applications will not be considered.
Completed application forms must be returned to: [Email Address Removed]
Informal enquiries may be made to [Email Address Removed]