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

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. GUEST * Nerissa Kreher, MD, MBA * Chief Medical Officer, Alltrna * LinkedIn [https://www.linkedin.com/in/nerissa-kreher-md-mba-1387465/] * Extensive experience in rare disease drug development, clinical operations leadership, and innovative trial design. EPISODE OVERVIEW Recorded 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 MOMENTS 00:01:19 – 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 reduce patient burden and streamline clinical study optimization 00:09:05 – Underuse of basket trials in rare disease: key barriers and opportunities for innovative clinical outsourcing 00:12:18 – Real-world example: efficiently enrolling multiple rare immune-mediated diseases under a single protocol 00:14:04 – Framework for umbrella INDs: template-based approaches for rapid therapy development in ultra-rare settings 00:18:09 – Statistical and regulatory efficiencies: leveraging concurrent evidence generation and shared INDs 00:21:12 – Platform technology designation: implications for vendor partnerships, manufacturing, and regulatory submission efficiency 00:26:41 – The need for biomarker validation, cross-functional collaboration, and adaptive design in rare disease clinical operations TOP 3 TAKEAWAYS 1. Master protocols offer concrete operational efficiency 2. Converging studies through basket and umbrella designs allows for single INDs, shared sites and data, and streamlined CRO selection, resulting in faster start-up and reduced patient burden across rare diseases. 3. Shared control arms and biomarker-defined groups improve both patient experience and clinical study optimization 4. Pooling patients and endpoints through robust master protocols delivers more statistical power in diseases where sample sizes are inherently limited, driving better outcomes for both sponsors and clinical outsourcing partners. 5. Successful rare disease trials require proactive stakeholder engagement 6. Cross-functional collaboration, including patient advocacy, academia, and vendor alignment, is fundamental for effective trial execution, regulatory navigation, and future-facing clinical operations best practices. LINKS & RESOURCES * The PBC Group: Events and Resources [https://thepbcgroup.com/] Clinical Outsourcing Group meetings, agendas, and content library. * NORD: Master Protocols in Rare Disease [https://rarediseases.org/] Systematic reviews and scientific resources on platform and basket trial design. * FDA – Platform Technologies for Drug Development [https://www.fda.gov/] Guidance and updates on regulatory innovation relevant to master protocols. * Alltrna Biotech [https://alltrna.com/] Details on emerging tRNA therapies and clinical strategy. QUOTES “Aggregating patient populations across shared molecular backgrounds allows for efficiency across every step of drug development.” “If you have a shared control arm instead of multiple for each therapy, you can see how that reduces sample size, and speeds decision making.” “We’re still not utilizing basket trials in rare disease as broadly as we could. The operational and regulatory barriers are significant, but the need for change is clear.” “Instead of a disease-by-disease approach, a master protocol enables a single IND across multiple conditions, with concurrent evidence generation and tangible benefits for patients and sponsors.” “Continued advancements will require collaboration: patient advocacy groups, CROs, sponsors, academia, regulatory bodies, all working to validate biomarkers and optimize adaptive trial designs.” ----------- Further content and agendas: h [https://thepbcgroup.com/blog]https://thepbcgroup.com [https://thepbcgroup.com/blog] ----------- Further content and agendas: h [https://thepbcgroup.com/blog]https://thepbcgroup.com [https://thepbcgroup.com/blog] Copyright 2026 The PBC Group

Flexibility by Design: Rethinking hybrid models for today’s trials with Bianca Fajardo

Discover how to move beyond inherited outsourcing templates and intentionally design operational models that fit your trial’s priorities, improving speed, oversight, and cost control in clinical operations. GUEST * Bianca Fajardo * Director of Clinical Operations, Functional Services Group, Premier Research * LinkedIn [https://www.linkedin.com/in/bianca-fajardo-09483499/] EPISODE OVERVIEW Recorded live at COG New England, this session features Bianca Fajardo, Director of Clinical Operations at Premier Research, sharing high-value insights into clinical trial outsourcing decisions and the shift toward more tailored operational models. Drawing on over two decades in the field, Fajardo addresses a key operational challenge: most sponsor organizations inherit legacy outsourcing models instead of designing them to fit evolving trial needs. The discussion walks through practical frameworks for clinical outsourcing - from leveraging the RFP process as a design dialogue rather than a simple price exercise, to using a “soundboard” approach to weigh competing priorities like speed, cost, oversight, and geography. Bianca presents real-world examples of hybrid delivery in action, highlighting trade-offs and how to architect models that flex with program needs. Designed for professionals managing clinical trial outsourcing, vendor management, and CRO selection, this session offers concrete best practices that can be implemented across sponsor, CRO, and clinical service teams. Whether you work on study startup, country/site activation, or portfolio-level oversight, you'll find operational strategies for clinical study optimization that are focused, actionable, and relevant amid growing complexity and new technology adoption. KEY MOMENTS 00:02:21 – Why most clinical teams default to legacy outsourcing models instead of intentional design 00:04:00 – The role of organizational habit and RFP constraints in narrowing outsourcing options 00:05:29 – Soundboard analogy: how to tune operational models for speed, cost, oversight, capacity, and geography 00:06:44 – When and why to prioritize speed, cost control, or scientific oversight during clinical trial vendor selection 00:09:39 – Moving from selecting predefined models to assembling customized hybrid solutions 00:10:40 – The importance of sponsor self-reflection before entering the RFP process for clinical outsourcing 00:13:01 – Reframing the RFP as a design conversation to co-create an operating model with your CRO 00:14:24 – Concrete examples: modular and region-specific hybrid models for global clinical studies 00:18:42 – Mitigating added complexity in hybrid outsourcing models through proactive coordination and clear oversight 00:24:35 – Why strong partnership, transparency, and upfront collaboration set clinical trials up for success TOP 3 TAKEAWAYS 1. Intentional Design Drives Value 2. The most effective clinical trial outsourcing models are engineered—not inherited. Start by clarifying study priorities, then design the operational mix accordingly rather than defaulting to templates. 3. Transform the RFP Process 4. Use the RFP as the foundation for a design conversation, not just a price comparison. Early, candid dialogue about sponsor needs and capabilities leads to better CRO selection and clinical operations best practices. 5. Hybrid Doesn’t Mean Complicated—If Well-Structured 6. A hybrid approach requires careful up-front planning and partnership but can replace downstream inefficiencies. Matching model components to program realities enables true clinical study optimization. LINKS & RESOURCES * COG Event Series and Agenda [https://thepbcgroup.com/] * Explore upcoming meetings, curated session line-ups, and global events for clinical operations and outsourcing leaders. * Premier Research [https://premier-research.com/] * Information on clinical operations, functional service provision, and partnership models. * COG Blog: CRO Selection and Clinical Outsourcing Playbooks [https://thepbcgroup.com/blog] * Articles and frameworks on clinical trial vendor management, RFP design, and best practices in outsourcing. QUOTES “Most often, we think we’re selecting our outsourcing models, but in reality, we’re inheriting them—defaulting to legacy processes and partnerships.” “Instead of asking ‘Which model should we use?’ the better question is ‘What are we optimizing for in this trial?’” “The RFP process shouldn’t just be transactional. It’s the perfect moment to co-create the right operating model with your CRO.” “No single fixed model ever fits every study. Hybrid approaches, when thoughtfully designed, enable us to match operational strategy to our trial’s real needs.” “Strong partnerships and intentional design up front do more to prevent inefficiency and delay than any ready-made template.” ----------- Further content and agendas: h [https://thepbcgroup.com/blog]https://thepbcgroup.com [https://thepbcgroup.com/blog] ----------- Further content and agendas: h [https://thepbcgroup.com/blog]https://thepbcgroup.com [https://thepbcgroup.com/blog] Copyright 2026 The PBC Group

How To Build Trust and Engage Patients in African Clinical Trials with Dr Sam Mbunya

Discover how global sponsors and CROs can optimize clinical trial outsourcing and patient engagement in Africa by addressing cultural, operational, and regulatory complexities from day one. GUEST * Dr. Sam Mbunya [https://www.linkedin.com/in/dr-mbunya-s-misiani-dba-b3a69799/] * Global Patient Advocate; Consultant in Patient Education, Advocacy & Program Management * Focus: Sickle cell disease, hemophilia, rare blood disorders, and cancer in African regions * Based in Malmö, Sweden; Active in global project collaborations (US, Kenya, African universities) EPISODE OVERVIEW This session, recorded live at COG Nordics, features a practical fireside chat with Dr. Sam Mbunya—an experienced patient advocate and program consultant—exploring the real-world nuances of launching and sustaining clinical trial operations in Africa. The discussion moves beyond broad generalizations, highlighting how local context, community trust, and operational diligence are critical in clinical trial outsourcing and CRO selection for African sites. Key topics include the operational and cultural barriers sponsors often overlook, such as health literacy, transport, family decision dynamics, and the legacy of previous studies. Dr. Mbunya outlines best practices for early and ongoing engagement with patient groups, community leaders, and local health systems, emphasizing why these steps are essential for both participant protection and long-term study viability. Listeners working in clinical operations, clinical trial outsourcing, and CRO/vendor management will find actionable strategies for designing studies that respect local realities. The conversation also explores how partnerships, clear communication, and data stewardship can help sponsors and CROs avoid common pitfalls and deliver on inclusion goals—turning compliance into true community impact and clinical study optimization. KEY MOMENTS 00:00:20 – Why Africa is not a single trial environment and the operational impact of country and community diversity 00:02:53 – The health literacy gap: How poor understanding of diseases and research affects trial recruitment and retention 00:04:21 – Patient “hope” vs. informed participation: Why transparent communication matters in clinical trial outsourcing settings 00:06:03 – Addressing practical barriers such as transport, family dynamics, and cultural decision-making during CRO selection and protocol development 00:08:02 – The pitfalls of a “one size fits all” approach: Communicating and customizing study materials for multilingual, multicultural settings 00:10:09 – The importance of engagement after negative outcomes: Building trust and credibility post-trial, not just during recruitment 00:12:44 – Distinguishing participants from implementers: How involving patients from the outset improves both feasibility and ethical compliance 00:16:25 – Regulatory maturity and bottlenecks: Strategies to work with local and national ethics boards for timeline and approval optimization 00:18:09 – Leveraging technology and patient advocates for scalable education and improved health literacy 00:20:02 – The role of roundtables, advisory councils, and WhatsApp groups in ongoing community dialogue and study support 00:26:04 – Top three challenges for sponsors: Open-minded protocol design, governmental engagement, and robust data stewardship TOP 3 TAKEAWAYS * Prioritize Early Engagement with Local Stakeholders - Integrate patient groups, community leaders, and local systems into study design and CRO selection processes well before recruitment begins to ensure buy-in, accurate feasibility, and operational alignment. * Invest in Health Literacy and Culturally Relevant Communication - Optimize study materials and participant discussions for language, tradition, and educational context—driving true understanding, reducing risk, and strengthening clinical operations best practices. * Treat Regulatory and Data Strategies as Core Pillars, Not Afterthoughts - Engage proactively with national authorities and invest in transparent, locally tailored data management to streamline approvals, foster trust, and enable long-term clinical study optimization at new sites. LINKS & RESOURCES * The PBC Group – COG Series Events & Resources [https://thepbcgroup.com/] * ClinicalTrials.gov – African Trial Registry Snapshot [https://clinicaltrials.gov/] * Project ECHO – All Teach, All Learn Platform [https://hsc.unm.edu/echo/] * WHO – Guidance for Good Clinical Practice in Africa [https://www.who.int/publications/i/item/9789240026176] QUOTES “Have an open-minded approach where you look at how people live, listen to their challenges, and engage government and patient advocacy groups from the protocol stage, not after.” – Dr. Sam Mbunya “It’s not just about recruiting fast—it’s about protecting participants, building trust, and ensuring the process starts with patients and families, not just ends with them.” – Dr. Sam Mbunya “Data protection and ownership are critical—robust registries and transparent practices help optimize clinical trial outsourcing and build credibility.” “There’s always this backdrop that the global north puts Africa as a one size fits all project; but the dynamics, language, and context require a fundamentally different operational approach.” ----------- Further content and agendas: h [https://thepbcgroup.com/blog]https://thepbcgroup.com [https://thepbcgroup.com/blog] Copyright 2026 The PBC Group

Direct Clinical Trial Management: Practical Approaches to CRO Selection and Clinical Outsourcing for Lean Biotech Teams with Antonio Bermejo Gomez

Unlock best practices for sponsor-led decision-making in clinical trial outsourcing, with real-world insight into optimizing CRO selection, partnership models, and operational efficiency, straight from a lean biotech team navigating these choices under budget and time constraints. GUEST * Antonio Bermejo Gomez, Chief Development Officer, Synartro * Operational leader at a Swedish clinical-stage biotech, hands-on with direct sponsor oversight, CRO/vendor selection, and clinical trial delivery * LinkedIn: Antonio Bermejo Gomez [https://www.linkedin.com/in/antonio-bermejo-g%C3%B3mez-05203445/] * Moderator: Sverre Bengtsson, Clinical Trials Advisor EPISODE OVERVIEW Recorded live at COG Nordics, this focused session features Antonio Bermejo Gomez, Chief Development Officer at Synartro, sharing a sponsor’s perspective on direct clinical trial management. The discussion, guided by David Jones and Sverre Bengtsson, centers on how very small biotech organizations can retain control, make more agile decisions, and achieve clinical study optimization even with limited team size and resources. This episode addresses the core of clinical trial outsourcing: how to maximize operational efficiency, preserve sponsor accountability, and adapt CRO selection frameworks for niche or highly constrained environments. Antonio Bermejo Gomez breaks down real-world strategies for working with specialized consultants, defining sponsor versus CRO responsibilities, and ensuring transparent decision ownership throughout a trial’s lifecycle. Listeners will hear practical insights on: * Structuring lean teams to optimize clinical operations without traditional full-service CRO partnerships * Balancing the roles of independent consultants, vendor partners, and in-house expertise * Critical considerations in CRO and CDMO selection when project fit and operational transparency are business-critical Professionals involved in CRO selection, clinical outsourcing strategy, or day-to-day study delivery will find actionable perspectives and frameworks to apply in their own clinical operations best practices. KEY MOMENTS 00:02:39 – The realities of running clinical operations with only two core sponsor staff, emphasizing strict budget control and constrained capital 00:04:47 – Key principle: Sponsor dependence on external partners demands robust clinical outsourcing strategies and clear delegation 00:10:03 – Communication and transparency: Why honest dialogue between sponsor leadership and consultants is essential for small, resource-limited biotechs 00:11:16 – Decision ownership: The sponsor, not external consultants, must make and stand by major study decisions for full accountability 00:13:41 – Clinical trial delivery model: Weekly operational meetings with CRO; continuous sponsor oversight even when lacking direct experience 00:15:02 – Accelerating timelines: How a transparent, focused approach enabled rapid recruitment and completion, delivering the full trial in just seven months 00:16:49 – “Focus on what not to do”: Prioritization as the driver of clinical study optimization under budget and time pressures 00:17:12 – CRO selection lessons: Honest assessment and fit over promises, why first conversations should clarify expectations and capabilities from both sides 00:18:49 – Adaptability: Navigating late-stage process changes (e.g., syringe manufacturing) through cross-functional collaboration among sponsor, CRO, and regulators 00:22:24 – Next steps: Preparing for partnership, licensing, or fundraising as a small team based on strong clinical proof points TOP 3 TAKEAWAYS 1. Sponsor ownership of key decisions is fundamental, successful clinical outsourcing models are built on clear accountability, not delegation of strategic calls to CROs or consultants. 2. CRO selection should prioritize honesty, project fit, and early mutual understanding, rather than optimistic capability claims; one wrong outsourcing decision can jeopardize a lean biotech’s entire clinical program. 3. Clinical operations best practices for lean teams include ruthless prioritization, knowing what not to do is as valuable as knowing what to execute, ensuring every action ties directly to data value and milestone delivery. LINKS & RESOURCES * The PBC Group – COG Event Series and Blog [https://thepbcgroup.com/] * Synartro – Company Overview [https://synartro.com/] * COG Nordics – Conference Information [https://thepbcgroup.com/cog-nordics/] QUOTES “The sponsor always needs to be accountable and responsible for all the decisions.” , Antonio Bermejo Gomez “A small team can be very efficient if everyone is comfortable with uncertainty and focused on what really matters for clinical study optimization.” “It’s easy to say the consultant or CRO advised it, but as sponsor you must own the outcome, good or bad.” “In CRO selection, be polite but never pretend during first discussions. You only have one shot, and a mismatch can close down the whole clinical program.” “When you can’t do everything, knowing what not to do, and saying no to the ‘easy path’, is critical for operational efficiency in clinical trial outsourcing.” ----------- Further content and agendas: h [https://thepbcgroup.com/blog]https://thepbcgroup.com [https://thepbcgroup.com/blog] Copyright 2026 The PBC Group

Strategic CRO Selection & Vendor Partnerships: Real-World Approaches for Emerging Biopharma

Learn practical strategies and insights from experts on how to outsource clinical trials and choose CROs, aimed at helping clinical operations leaders improve study execution and strengthen relationships with vendors. SPEAKERS * Nara Daubany – CEO & Co-Founder, Phaim Pharma [https://uk.linkedin.com/in/nara-daubeney] * Graeme Duncan – Head of Clinical Development, Neurocentrix [https://uk.linkedin.com/in/graeme-duncan-584b75b] * Claire Herholdt – VP Clinical Operations, Levicept [https://uk.linkedin.com/in/claire-herholdt-7356b316] * Bradley Norton – VP Clinical Operations, Gylden Pharma [https://uk.linkedin.com/in/bradley-norton-017819a] * Sarah Whalley – Director Clinical Operations, Uploid Biotechnologies [https://www.linkedin.com/posts/u-ploid-biotechnologies_coguk-clinicaloperations-biotech-activity-7429174965834448896-1ODY] * Deirdre Flaherty – VP Product Strategy & Clinical Operations, Alchemab Therapeutics [https://uk.linkedin.com/in/deirdreflaherty] * Julia Vassiliadou – VP Clinical Operations, F2G [https://uk.linkedin.com/in/julia-vassiliadou] EPISODE OVERVIEW Recorded live at COG UK, this panel brings together senior clinical operations leaders from emerging biopharma and specialty biotech companies to share their operational realities, decision frameworks, and lessons learned in clinical trial outsourcing and CRO selection. Panelists reveal how small, lean teams evaluate CRO fit beyond price, integrating clinical operations best practices to ensure continuity, ownership, and transparency throughout the study lifecycle. The discussion examines differences in working with small- and mid-sized CROs versus the Big Five providers, including non-negotiables in vendor selection and the impact of global studies on CRO partnership decisions. Key questions addressed include: * How do sponsors prioritize CRO selection criteria beyond cost? * What practical signals indicate a CRO’s operational capacity, therapeutic expertise, and partnership mindset? * How do sponsors manage global clinical outsourcing, regional complexity, and adapt outsourcing models for rare disease, vaccines, or novel therapeutic areas? The session offers a real-world look at study startup, site activation, patient recruitment, and the evolving landscape of sponsor, vendor collaboration, all with a focus on clinical study optimization and actionable takeaways for operations, outsourcing, and stakeholder teams. KEY MOMENTS 00:01:49 – Defining the scope: clinical trial outsourcing, vendor fit, and operational efficiency 00:09:18 – Key decision levers for study location and CRO selection, balancing funding, patient access, and regulatory challenges 00:12:18 – Sponsor “killer questions” for CROs: assessing experience, partnership, and project de-risking 00:13:29 – Site selection frameworks: the role of specialty CROs in pain and OA studies, evidence-based site/country choice 00:14:43 – Global partnerships for vaccine trials: aligning CRO selection with endemic regions and collaborative partners 00:17:29 – Rare disease clinical outsourcing: CRO global presence, therapeutic expertise, and sponsor oversight 00:21:10 – Fitting the CRO model to novel, non-traditional clinical trial designs (e.g., IVF, women’s health) 00:24:31 – Weighing small/mid-sized versus large CROs: sponsor risk, project fit, and operational agility 00:27:28 – Sponsor oversight with large CROs: importance of clear communication, consistency, and global reach 00:29:12 – Transparency and adaptive CRO selection across study phases and pivotal trials 00:31:33 – Risk-sharing and creative contracting: milestone payments, outsourcing models, and sponsor independence 00:34:34 – Panel’s “non-negotiables”: continuity, ownership, proactive risk management, and transparent relationships TOP 3 TAKEAWAYS * Deep partnership matters more than price in CRO selection. Sponsors should prioritize operational fit, core team continuity, and shared ownership for clinical study optimization. * Clinical trial outsourcing models are not one-size-fits-all. Consider therapeutic complexity, geographical spread, internal capabilities, and need for oversight when choosing between small, mid-sized, or global CROs. * Early, collaborative protocol engagement with CROs reduces downstream amendments and fosters sponsor–vendor alignment, empowering teams to manage risk and accelerate delivery. LINKS & RESOURCES * The PBC Group – Clinical Outsourcing Group events [https://thepbcgroup.com/clinical-outsourcing-group] * Phaim Pharma [https://www.phaim.co.uk/] * Neurocentrix [https://www.neurocentrx.com/] * Levicept [https://levicept.com/] * Gylden Pharma [https://www.gyldenpharma.com/] * Uploid Biotechnologies [https://www.u-ploid.com/] * Alchemab Therapeutics [https://www.alchemab.com/] * F2G [https://f2g.com/] QUOTES “Fit when they come into the room in that bid defense means a lot. Your ability as a small team to know that you can work with this other group of people collaboratively—that partnership is built through paper as well as formal interactions.” – Deirdre Flaherty “The traditional setup of the biggest CROs… the worse your project is doing, the more money they make. If you have to add sites or amend, it translates into more cost. That’s untenable for small biotechs.” – Claire Herholdt “The non-negotiable is the core team assigned to the project. My expectation is during award, that person remains on the study throughout.” – Graeme Duncan “For rare disease, every patient counts. We needed a CRO with global presence and proven therapeutic expertise, plus strong sponsor oversight.” – Julia Vassiliadou “It’s rarely cost. What matters to our investors is how fast you can get to a value inflection—how quickly you can get data. All those factors roll into what we want in a CRO partner.” – Deirdre Flaherty ----------- Further content and agendas: h [https://thepbcgroup.com/blog]https://thepbcgroup.com [https://thepbcgroup.com/blog] ----------- Further content and agendas: h [https://thepbcgroup.com/blog]https://thepbcgroup.com [https://thepbcgroup.com/blog] Copyright 2026 The PBC Group