What is it?

This deliverable, produced for the EU-PEARL, EU Patient-cEntric clinical tRial pLatforms project (2019–2023), funded by the Innovative Medicines Initiative 2, addresses the emerging field of Integrated Research Platforms and Platform Trials, where terminology is still evolving. It provides a selective glossary of terms for complex and platform trials to promote consistent usage.

How can it be useful?

The glossary harmonises terminology for platform trials, improving communication among diverse clinical research stakeholders. By aligning language and concepts, it helps meet regulatory expectations and reduces duplication of effort. This fosters collaboration, streamlines trial implementation, and accelerates adoption of innovative trial designs in Europe and beyond.

What is it?

This document is the EU-PEARL Statistical Analysis Plan (SAP) Template V3 (25 April 2023), developed as part of the EU-PEARL project (IMI2 grant 853966). It provides a standardized framework for drafting statistical analysis plans for platform trials conducted under a Master Protocol. The template builds on the TransCelerate SAP V3.0 model and includes core backbone sections, appendices, and guidance for both master SAPs (mSAP) and intervention-specific appendices (ISA-SAP).

How can it be useful?

This resource is highly practical for researchers designing and conducting adaptive platform trials, as it ensures harmonization, regulatory compliance, and consistency across intervention-specific studies. By following the template, users can structure their SAPs in line with regulatory expectations (EMA,FDA,ICH E9) while accommodating trial-specific needs such as estimands, multiplicity adjustments, sensitivity analyses, and interim analyses. It provides ready-to-use text blocks, suggested formats, and instructions, which can directly save time and ensure quality in trial planning and reporting.

What is it?

This is a commentary that reviews the statistical issues when adding new arms to ongoing platform trials. It discusses methodological challenges such as bias, error rates, multiplicity, and interpretability, as well as practical considerations like changes in control arms, patient eligibility, and operational bias. The paper also examines differences in platform use between phase II and phase III trials and highlights areas for future methodological research.

How can it be useful?

This resource is useful for trialists and statisticians designing or conducting platform trials. It provides clear insights into the statistical implications of protocol amendments, decision-making about error rate control, and strategies for robust inference. Readers can use it to anticipate methodological pitfalls, strengthen trial protocols, and align designs with regulatory expectations.

What is it?

A review article in Annals of Oncology that analyses statistical controversies in basket, umbrella, and platform trials. It highlights misuse of terminology, debates on replacing tumor histology with biomarkers, challenges in small heterogeneous cohorts, Type I error control, and the use of Bayesian adaptive methods. Examples such as NCI-MATCH, FOCUS4, LUNG-MAP, SHIVA, and I-SPY2 are used to illustrate these issues.

How can it be useful?

This article offers a clear explanation of the statistical and methodological pitfalls in master protocols, to guide researchers in selecting the right design, avoiding common misuses of terminology, and anticipating regulatory/statistical concerns such as error control, feasibility in rare populations, and validity of biomarker-driven hypotheses. The practical trial examples help translate these controversies into lessons for designing robust master protocol studies.

What is it?

This is a video presentation by Scott Berry (Berry Consultants), introducing the concept of adaptive platform trials and contrasting them with traditional trials. The educational video explains key ideas such as heterogeneity of disease, umbrella trials (multiple subsets of disease tested with a single drug), platform trials (multiple drugs tested within one disease), and their combination in adaptive platform trials. The presentation also covers statistical efficiencies, shared control designs, perpetual platforms, and response adaptive randomization, using examples from PREPARE (EU, pneumonia/influenza), I-SPY2 (oncology), and IMI Alzheimer’s initiatives.

How can it be useful?

This video provides clear, accessible explanations of trial structures and their efficiencies, showing how adaptive platform trials reduce patient exposure to placebo, accelerate drug testing, and improve statistical power. It also situates platform trials in real-world contexts (pandemic preparedness, oncology, Alzheimer’s disease, stroke models), making it a practical educational tool for understanding why platform trials are considered the future of clinical research.

What is it?

This editorial presents the evolution of oncology trial design from traditional RCTs to innovative methods including Bayesian design, adaptive trials, single-arm trials using historical data, and the threshold-crossing (or counterfactual) model. It emphasizes the role of data-sharing platforms and collaborative initiatives like the Oncology Research Information Exchange Network (ORIEN) in improving patient-trial matching. Case examples include I-SPY2, vemurafenib in BRAF-mutant melanoma, and crizotinib in ALK-positive lung cancer.

How can it be useful?

It offers a framework for designing trials that reduce sample sizes, reuse validated data, and accelerate drug approvals using alternative methods grounded in real-world oncology contexts.

What is it?

This is a systematic literature review published in Clinical Therapeutics (2020; 42:1330–1349). It covers the evolution, definitions, and characteristics of master protocol clinical trial designs, focusing on basket, umbrella, and platform trials. Major themes include design considerations, statistical methods, operational complexities, and regulatory perspectives for these innovative frameworks.

How can it be useful?

This article offers hands-on recommendations for designing and conducting basket, umbrella, and platform trials with examples from oncology and other disease areas. It directly addresses operational and statistical challenges such as control arm choice, adaptive randomization, multiplicity, data management, and regulatory issues. It is valuable for structuring, planning, and implementing complex clinical trials that require flexibility and efficiency, and is relevant for both US and EU settings.
 

What is it?

This article explores ethical challenges in basket trials, umbrella trials, and other master protocols within precision medicine. It examines the role of genetic screening, biopsy, and molecular stratification in allocating patients based on tumor heterogeneity.

How can it be useful?

It discusses the ethical complexity of informed consent, therapeutic expectations, and maintaining scientific validity while balancing risk-benefit considerations. Real-world examples like NCI-MATCH and Lung-MAP illustrate how designs relying on surrogate endpoints raise important questions in clinical oncology trial ethics.

What is it?

This is a systematic review published in Therapeutic Innovation & Regulatory Science (2024; 58:634–644). It analyses 38 pediatric master protocol studies identified through PubMed and ClinicalTrials.gov over the past 10 years. The review covers basket, umbrella, and platform trials, most of them in oncology and early-phase research, with increasing use since 2020 including in COVID-19. The paper highlights challenges such as small patient populations, ethical concerns, use of placebo controls, pediatric dosing strategies (weight-based, BSA-based), incorporation of pediatric arms into adult master protocols, lack of adaptive randomisation, sponsor collaboration, and trial infrastructure needs.

How can it be useful?

The review provides a comprehensive picture of how master protocols are being applied in pediatric drug development. It identifies barriers such as infrastructure setup, trial governance, recruitment, and interpretation of findings, while pointing to opportunities like shared control groups, multi-sponsor collaborations, and integration with adult protocols. It offers insights into the design, conduct, and ethical considerations of pediatric basket, umbrella, and platform trials, supporting efforts to expand their use and reduce delays in pediatric drug approvals.

What is it? 

A systematic review of global trial registries identified 62 eligible trials up to April 2021. Results showed increasing use of the MAMS approach since 2001, with acceleration during the COVID-19 pandemic, mainly in infectious disease and oncology treatment trials.

How can it be useful?

By documenting global uptake, disease focus, and operational characteristics of MAMS platform trials, this review provides an evidence base for teams considering this design in late-phase RCTs. It highlights patterns of use, potential efficiencies, and operational considerations, supporting better planning and delivery. The findings may assist researchers, funders, and policy makers in evaluating whether the MAMS approach could optimise trial efficiency and speed in answering critical clinical questions.

What is it?

A practical introduction to adaptive clinical trial designs, presented by an experienced biostatistician from Cytel—a consultancy group working in statistical software, advanced analytics, and strategic consulting for clinical trial design and execution. The webinar outlines the adaptive design concept, regulatory acceptance, and practical benefits, focusing on widely used approaches such as sample size re-estimation, endpoint switching, seamless phase II/III trials, dose selection, and population enrichment. Real-world case studies show how adaptive designs improve decision-making, manage uncertainty, and enhance trial efficiency while maintaining scientific validity and operational integrity.

How can it be useful?

This resource is designed for clinical development teams, project managers, and non-statistical stakeholders who want to understand when and how to apply adaptive trial designs effectively. It explains how to integrate adaptive approaches into an overall development plan, address regulatory considerations, and safeguard trial integrity. By applying the principles and examples shared, organizations can shorten development timelines, reduce costs, optimize resource use, and improve the likelihood of success in regulatory submissions and patient outcomes.

What is it? 

This is a podcast series developed by NHS, Health Research Authority on Complex Innovative Designs. In this episode, Professor Pam Kearns, Professor of Clinical Paediatric Oncology, Director of the Cancer Research UK Clinical Trials Unit and Institute of Genomic Sciences in Birmingham explains what are Complex Innovative Designs and the difference in different trial methodologies, Basket, Umbrella, Multi Arm Multi Stage (MAMS) Trials. 
 

What is it?

This is a white paper authored by Cytel experts on Data Monitoring Committees (DMCs) for oncology studies. It describes how DMCs safeguard the interests of patients by monitoring safety, efficacy, and study integrity in high-stakes cancer trials. The paper highlights oncology-specific challenges such as open-label studies, co-primary endpoints, interpretation of immature data, censoring, and the role of independent review committees.

How can it be useful?

The white paper provides practical guidance on DMC operations in oncology, including examples of statistical outputs (Kaplan–Meier, waterfall, spider, and volcano plots), handling adverse events, and rapid turnaround of interim analyses. It also discusses regulatory perspectives, firewalling of data, and special considerations in Phase 3 or platform/basket/umbrella oncology trials. This makes it a valuable reference for researchers, sponsors, and regulators planning or managing oncology studies with DMC oversight.