Table 4.

Delivering Multi-Drug Portfolio Studies

1. Participant screening and recruitment in to trials
Requires a viable means to identify low prevalence subpopulations and direct individuals to an appropriate clinical trial, through a patient-centric approach whereby each individual can have access to many options via a single screening process	Region-wide and collaborative screening programs Links to umbrella and basket studies Drug portfolios available – via collaboration – and safeguards for proprietary information when using many partner portfolios Harmonized and/or cross-validated multiplexed diagnostic platforms and systems – to allow recruitment irrespective of technology Regulators open to change in how clinical trials need to be run Networks, collaborations and good partners
2. Deep phenotyping
Requires a system (platform, screening/selection algorithm) that enables broad but robust patient profiling and provides viable development routes for larger studies and regulatory interactions	Platform Screening/selection algorithm Broad patient profiling Sample efficient Robust data generation Cost-effective Transferable, widely deployable Works to agreed standards Viable development route Support regulatory interactions
3. Protocol flexibility
Requires an early development protocol that is flexible allowing change to emerging science and understanding of patient markers and novel sub-phenotypes, and/or a confirmatory development protocol permitting regulatory interactions using different types of datasets	Single or aligned protocol Aligned and efficient review – using a centralized regulatory/ethics process Flexible Modular Rolling – open ended Adaptable to emerging science Allows different datasets to accumulate Allows regulatory interactions
4. Availability and delivery of therapies
Requires an operational machinery that allows studies to be conducted over diverse groups and geographical areas with aligned and efficient regulatory and ethics processes, patient screening/recruitment and ability to distribute multiple candidate drugs to multiple sites in a cost-effective and efficient manner	Hub-and-spoke models Must accommodate diverse groups and geographical areas Centralized pharmacy – to enable cost effective delivery of multiple drugs to multiple sites Highly collaborative working – across many different groups Good partners

^*Successful delivery of multidrug portfolio studies requires innovation across clinical design and implementation; key aspects to consider for diagnostics, clinical protocol operational delivery. Reproduced with permission from Ref. #21 (Biankin AV, et al. Patient-centric trials for therapeutic development in precision oncology. Nature 2015; 526:361–370).