Master Protocols in Rare Disease: Practical Approaches to Basket and Umbrella Trial Design for Clinical Study Optimization with Nerissa Kreher

Discover the operational frameworks and real-world considerations for implementing basket and umbrella trials in rare disease, enabling faster, more efficient clinical trial outsourcing and improved CRO selection strategies.

GuestNerissa Kreher, MD, MBAChief Medical Officer, AlltrnaLinkedInExtensive experience in rare disease drug development, clinical operations leadership, and innovative trial design.

Episode OverviewRecorded live at COG New England, this session features Nerissa Kreher, Chief Medical Officer at Alltrna, in conversation with David Jones, Head of Content at The PBC Group. The discussion centers on the application of master protocol designs, basket, umbrella, and platform trials, in optimizing clinical operations for rare disease studies.

The episode addresses the persistent challenges in rare disease R&D: small and heterogeneous patient populations, restricted clinical data, and the inherent barriers to traditional country- and site-level trial models. Nerissa Kreher provides clear definitions of trial types and outlines how operational efficiencies and cross-functional collaboration can be achieved through well-structured master protocols, which have seen broad adoption in oncology but remain underused in rare disease.

Key topics include the use of shared control arms to reduce patient numbers, leveraging biomarker-defined cohorts for more targeted studies, and real-world applications of innovative trial designs which are shaping new models for clinical trial outsourcing and clinical study optimization. Hear practical frameworks and candid examples, with a focus on what needs to change operationally across sponsors, CROs, and regulatory interfaces to unlock these efficiencies.

This session is essential listening for professionals in clinical operations, CRO/vendor management, and clinical development strategy, providing a toolkit for evaluating master protocols and refining CRO selection criteria for rare disease programs.

Key Moments00:01:19 – Essential constraints in rare disease: implications for feasibility, trial design, and clinical trial outsourcing

00:03:19 – The impact of genotypic and phenotypic heterogeneity on CRO selection and study start-up in rare indications

00:05:06 – The case for moving beyond “one trial per disease”: operational inefficiency in traditional models

00:06:34 – Clear definitions and trade-offs between platform, basket, and umbrella trial designs for sponsors and CROs

00:07:01 – How shared control arms redu