What is it?

This article presents a case study of the FLAIR trial’s transformation from a standard randomised controlled trial to a multi-arm platform trial for chronic lymphocytic leukaemia. It details the complex innovative design used to facilitate adding treatment arms—notably ibrutinib plus venetoclax—without disrupting recruitment or compromising statistical methodology. The platform’s flexible design supported the evaluation of confirmatory hypotheses.

How can it be useful?

It offers practical insights into trial management, regulatory and ethical processes, and maintaining Type I error control. It is valuable for teams implementing multi-arm clinical trials using platform approaches in oncology.

What is it? 

PANDA (Practical Adaptive & Novel Designs and Analysis toolkit) is an open-access, online educational platform developed by the University of Sheffield in collaboration with multiple partner institutions (including Cardiff, Lancaster, UCL, and University of Western Australia). It provides practical guidance, tools, and resources to support the design, conduct, analysis, and reporting of adaptive clinical trials—delivered through accessible, self‑paced learning modules. 

How can it be useful?

PANDA offers practical statistical resources and guidance to help researchers design, plan, and implement adaptive trials. It includes worked examples, software recommendations, and operational considerations, supporting statisticians, trial managers, and investigators in preparing robust protocols and funding applications. This makes it a valuable resource for both complex innovative design planning and for accessing hands-on statistical tools to support adaptive methodology.

What is it?

This is a multi-stakeholder workshop report titled “Accelerating Complex Clinical Trials (CCTs)”, published in October 2021 by European Federation of Pharmaceutical Industries and Associations (EFPIA). The report summarises discussions from a two-day online workshop with over 400 participants, including regulators (EU, FDA), patients, Health Technology Assessment (HTA) bodies, ethics committees, academia, and industry. The workshop explored opportunities and challenges of CCTs, with focus on master protocols, regulatory processes, patient involvement, adaptive features, operational aspects, historical controls, and education and training.

How can it be useful?

The report provides a practical overview of stakeholder expectations and regulatory perspectives on implementing complex trials in Europe and globally. It highlights lessons learned, barriers, and opportunities for collaboration, patient engagement, and regulatory convergence. As part of the toolbox, it can be used as a reference for best practices, stakeholder priorities, and regulatory-scientific context when designing or managing CCTs.

What is it?

This is a research article published in Trials (2014; 15:383). It reports on a survey of 59 scientific advice letters issued by the European Medicines Agency (EMA) between 2007 and 2012, focusing on adaptive clinical trial designs in phases II and III. The article analyses proposed adaptations such as sample size reassessment, dropping of treatment arms, and population enrichment, and presents case studies to illustrate regulatory feedback and methodological challenges.

How can it be useful?

This article provides practical insights into the EMA’s regulatory perspective on adaptive designs, including common concerns about type I error rate control, bias, justification of adaptations, and the use of adaptive trials as single pivotal studies. It helps researchers understand which adaptive design proposals were accepted, conditionally accepted, or rejected, and why. It is useful for planning adaptive trials in Europe, offering concrete examples of regulatory expectations and scientific advice outcomes.

What is it?

This is a research article that analyses how adaptive designs in confirmatory clinical trials have been implemented in practice and their role in supporting marketing authorisation within the EMA centralised procedure. The study followed up on 59 medicines for which adaptive trials had been submitted to EMA Scientific Advice, examining whether these trials started, their outcomes, the adaptive elements used, and their influence on regulatory approval. It also discusses current regulatory perspectives on adaptive designs.

How can it be useful?

This article provides concrete data on how such designs have been applied in real-world regulatory settings. It highlights the most commonly used adaptive elements (dose selection, sample size reassessment, stopping for futility), outlines regulatory expectations (type I error control, trial integrity, consistency of results), and offers insights on successful pathways to marketing authorisation

What is it?

A comprehensive review of innovative clinical trial designs in precision oncology, focusing on methodologies such as precision dose-finding, master protocols (basket, umbrella, and platform trials), subgroup analyses, and emerging approaches using real-world data, patient-reported outcomes, and N-of-1 trials. It summarizes Bayesian and model-based statistical methods and provides real-world examples from major cancer trials like NCI-MATCH, TAPUR, and I-SPY-2.

How can it be useful?

This resource can guide researchers, clinicians, and trial designers in developing more efficient, adaptive, and patient-specific oncology trials. It helps identify suitable trial designs for targeted therapies, optimize dosing strategies, and match patients to treatments based on biomarkers or molecular profiles. It is also valuable for understanding regulatory perspectives, leveraging real-world evidence, and applying advanced statistical methods to improve trial efficiency and patient outcomes in precision oncology.
 

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 article updates the 2020 consensus recommendations for conducting oncology trials during and after COVID-19, with an emphasis on reducing environmental impact and applying lessons from the RECOVERY trial. It adds new guidance on focused data collection, paperless systems, direct-to-patient approaches, remote monitoring, and enhanced Patient and Public Involvement (PPI). These additions complement the original 10 recommendations, which addressed protocol design, regulatory engagement, training, and public health evaluation in Complex Innovative Design (CID) trials.

How can it be useful?

It outlines 13 actionable recommendations that support more efficient, sustainable, and inclusive CID trial design based on pandemic-driven innovations.

What is it?

This article provides a comprehensive review of precision oncology and precision medicine trial frameworks. It focuses on biomarker-guided trials that use molecular profiling and genomic profiling to match patients to targeted therapies. The paper explains how tumor-agnostic and histology-agnostic strategies guide inclusion across cancer types.

How can it be useful?

It outlines core design features such as randomization and biospecimen collection, and presents clinical examples to illustrate the operational and scientific considerations that shape biomarker-driven trial implementation in oncology.

What is it?

This peer-reviewed article reviews the role of precision medicine in oncology through innovative clinical trial designs, such as basket trials and umbrella trials. It highlights key studies—IMPACT, IMPACT2, WINTHER, NCI-MATCH, NCI-MPACT, and TAPUR—that use molecular profiling, including genomic profiling and proteomic analysis, to guide targeted therapy selection. These trials compare outcomes between matched and non-matched therapy groups.

How can it be useful?

The article shows how molecular profiling supports personalized treatment strategies and demonstrates clinical benefit from using matched targeted therapies in precision oncology.

What is it?

This webcast is available on eCancer featuring Dr. Elia Biganzoli (University of Milan), discussing basket and umbrella trials in the context of oncology and big data during the Milan Summit on Precision Medicine (February, 2018). The video explains how these master protocol designs work: basket trials test a single therapy across different cancers with shared biomarkers, while umbrella trials test multiple therapies within a single cancer type. It highlights the growing role of biomarkers, precision medicine, and data integration in making such trials feasible and effective.

How can it be useful?

The video provides a practical overview of basket and umbrella trials for researchers and clinicians exploring innovative designs in oncology. It shows how these frameworks can improve efficiency, patient stratification, and drug development by leveraging biomarker-driven approaches. For toolbox users, it serves as an accessible learning resource on the opportunities and challenges of implementing complex trial designs in the era of precision oncology and big data.

What is it?

This is a technical and methodological paper focused on the design, analysis, and operational challenges of implementing basket, umbrella, and master protocol trials in precision oncology. It presents key biostatistical principles and logistical strategies needed to match patients to targeted therapies based on tumor biomarkers, with examples from major trials like NCI-MATCH, ALCHEMIST, and Pediatric MATCH.

Why is it useful? 

The article provides practical guidance on how to structure complex biomarker-driven trials and manage challenges such as assay validation, centralized vs. local testing, pooling data across subgroups, interim monitoring, and administrative protocol models. It is especially valuable for clinical trial designers, statisticians, and operational leads seeking to implement or refine master protocols or multi-arm precision medicine trials.

What is it?

This article outlines practical considerations for implementing master protocol trials in precision medicine. Using examples like TAPUR, NCI-MATCH, Lung-MAP, and Beat AML, it describes how molecular profiling and genomic studies inform design decisions, including the use of surrogate endpoints and patient matching.

How can it be useful?

It discusses challenges such as feasibility, informed consent, and operational complexity, and emphasizes the importance of building scalable platform infrastructure. The article highlights the role of stakeholder collaboration in coordinating trials across institutions and shares best practices for structuring real-time, adaptive studies in oncology.

What is it?

A peer-reviewed, conceptual review of clinical trials design shifts in immunotherapy cancer. This article explores the evolving needs in oncology trials driven by immunotherapy and targeted therapies. It discusses the value of biomarker-based designs, including master protocols like basket and umbrella trials, for more precise patient selection. The review highlights limitations of traditional survival analysis models in this context, such as the breakdown of the proportional hazard assumption, and proposes alternatives like milestone survival to better reflect long-term outcomes.

How can it be useful?

It helps readers understand statistical and structural innovations necessary to evaluate modern immunotherapy treatments, offering strong foundational knowledge.

What is it?

This article summarizes discussions from the 2018 Annual Accelerating Anticancer Agent Development and Validation (AAADV) Workshop, which focused on challenges in implementing master protocols in oncology. Topics include adaptive design, biomarker-driven enrollment, real-time amendments, and coordinating phase I and II trials. It also addresses tissue-agnostic strategies and large expansion cohorts.

How can it be useful?

It outlines informed consent, operational complexity, and the role of external controls, with examples from I-SPY2, BATTLE, Lung-MAP, NCI-MATCH, Keynote-158, 164 and 001 and offers practical strategies for biomarker stratification, adaptive protocols, regulatory compliance, and patient consent.

What is it?

This is a methodological review focused on advanced clinical trial design for precision oncology. It explores innovations in basket trials, umbrella trials, adaptive design, dose-finding design, and enrichment design, comparing Bayesian hierarchical models and Frequentist design strategies. Examples include BATTLE, GBM AGILE, and RAMPART, with a focus on biomarker-guided stratification and subgroup heterogeneity.

How can it be useful?

It provides guidance for structuring adaptive designs in molecularly defined populations and discusses statistical and operational barriers such as complexity, modeling transparency, and clinical usability in the context of implementing innovative precision oncology trials.

What is it?

A practical and detailed methodology paper that explores data management challenges in adaptive trials using a platform protocol structure. Drawing on the STAMPEDE and FOCUS4 multi-arm multi-stage (MAMS) trials, it focuses on case report forms, database design, and randomisation systems in trials where arms are added or closed over time.

How can it be useful?

It offers hands-on, step-by-step recommendations for managing the evolving data needs in the lifecycle of adaptive trials—from CRF planning to concurrent analysis preparation. It offers real-world strategies for flexible data systems, handling amendments, and ensuring robust performance across CRFs, databases, and randomisation during complex adaptive designs. The article also identifies risks to data integrity and patient safety, providing tested solutions for common pain points in long-term, multi-arm oncology trials.

There is limited research and literature on the data management challenges encountered in multi-arm, multi-stage platform and umbrella protocols. These trial designs allow both (1) seamless addition of new research comparisons and (2) early stopping of accrual to individual comparisons that do not show sufficient activity. We share our experiences from the operational aspects of running these adaptive trials, focusing on data management.

What is it?

This article reviews evolving clinical trial frameworks in precision medicine, including tumor-agnostic and N-of-1 trial models guided by biomarkers, genomic profiling, molecular stratification, and liquid biopsy. It explains how these methods personalize therapy selection for patients with rare or heterogeneous cancers.

How can it be useful?

The article explores how machine learning, artificial intelligence (AI), and real-world data support trial design, analysis, and patient stratification. It also discusses emerging innovations in trial delivery, such as decentralised and home-based trials, aimed at improving accessibility and flexibility in personalized therapy development.

What is it?

This is a technical statistical study evaluating Bayesian information borrowing methods in oncology trials, with a focus on improving efficiency in platform trials and adaptive designs. It compares concurrent and nonconcurrent borrowing using simulation data. Methods assessed include the Bayesian Hierarchical Model (BHM), Multisource Exchangeability Models (MEMs), Power Prior, and Robust Meta-Analytic Predictive Prior (RMAP), in trials with historical controls and varying heterogeneity. Performance is measured by bias, type I error, and power.

How can it be useful?

It provides a decision framework for selecting Bayesian borrowing methods based on trial characteristics. The study guides oncology trialists in choosing the right model—such as Bayesian Hierarchical Model (BHM), Multisource Exchangeability Models (MEMs), or Robust Meta-Analytic Predictive Prior (RMAP)—by balancing type I error, power, and bias. This helps optimize adaptive, platform, or historically controlled trials, particularly where sample sizes or control arms are constrained.

What is it?

This 2022 guidance document from the European Medicines Agency presents a structured Q&A on the regulatory expectations for complex clinical trials under the EU Clinical Trials Regulation (EU CTR). It addresses seven major areas: general principles for the planning and conduct of complex clinical trials; design and conduct considerations for studies using master protocols; the use of Bayesian approaches in complex clinical trials; planning and use of control data to support regulatory decisions; considerations related to biomarkers and associated assays; oversight and safety for trial participants; and approaches to transparency and communication with stakeholders.

How can it be useful?

It provides regulatory clarity for preparing Clinical Trial Authorisation (CTA) and marketing authorisation applications (MAA) involving complex or adaptive designs. It also outlines expectations for trial design, trial analysis, modifications, and cross-stakeholder engagement, promoting transparent and robust implementation of innovative trials across Europe.

What is it?

This 2022 European Medicines Agency (EMA) concept paper on platform trials announces plans to draft a new Reflection Paper on Platform trials—complex Trial designs often conducted under Master Protocols to evaluate multiple interventions in one ongoing framework. Platform trials are likely to play an increasingly important role in marketing authorisation applications
in the future. It is anticipated that this document will improve planning of confirmatory platform trials by sponsors and lead to improved consistency in scientific advice and regulatory assessment. It will address the unique challenges presented by platform trials in planning, conduct and reporting of a clinical trial. This resource is added as an information, and will be updated as soon as the EMA Concept Paper becomes available. 

What is it?

The CONSORT (Consolidated Standards of Reporting Trials) statement has been updated (CONSORT 2025). The statement consists of a 30-item checklist of essential items for reporting the results of randomised trials.   it aims to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996 and was updated in 2001 and 2010. CONSORT comprises a checklist of essential items that should be included in reports of randomised trials and a diagram for documenting the flow of participants through a trial.

How can it be useful? 

This updated explanation and elaboration article describes the rationale and scientific background for each checklist item and provide published examples of good reporting. It provides detailed guidance to authors to enhance the use, understanding, and dissemination of CONSORT 2025, and how to improve the reporting of their trials so that trial reports are complete, and transparent.

What is it?

This is a research article reporting the results of the Costing Adaptive Trials (CAT) project in the UK. It combined a mock costing exercise across seven Clinical Trials Units and qualitative interviews to assess the additional financial and staffing resources required for adaptive trials compared to non-adaptive designs. The study quantified cost differences across scenarios and identified drivers of variability, particularly in statistical and data management needs.

How can it be useful?

This article provides practical evidence and guidance for investigators and funders on the resource implications of adaptive trial designs. It can be directly used when preparing grant applications or planning trial budgets, offering realistic expectations on staffing (statistical, data management, trial management) and operational costs. The insights support more accurate resourcing and reduce risks of underfunding adaptive clinical trials.

What is it?

This document is the EU-PEARL Data Monitoring Committee (DMC) Charter Template (Version 1, April 2023). It provides a structured framework for defining the roles, responsibilities, and procedures of Data Monitoring Committees in platform trials. It includes guidance on confidentiality, conflict of interest, interim analyses, statistical support, communication flows, and meeting procedures.

How can it be useful?

This tool is in the form of a template that can be directly applied by trial sponsors and investigators to create DMC charters for adaptive platform trials. It ensures consistency, transparency, and regulatory compliance, while helping safeguard patient safety and study integrity. By offering pre-defined structures, responsibilities, and flowcharts, it saves time in trial preparation and supports harmonisation across multi-stakeholder studies.

What is it?

This article published in Pharmaceutical Statistics presents decision rules for identifying combination therapies in open entry randomized platform trials. It describes statistical methods that evaluate multiple treatment regimens and explains how to design and implement rules that determine which combinations should continue or be dropped during the course of a trial. The work provides methodological guidance for improving the efficiency and robustness of complex innovative designs.

How can it be useful?

The article is useful for researchers designing adaptive platform trials that include combination therapies. It offers practical statistical guidance that can be directly applied to trial planning by informing decision making frameworks optimising efficiency and reducing risks of false positives or negatives. The resource serves as a reference point for investigators and statisticians seeking to strengthen the design and analysis of combination therapy trials in a master protocol context.

What is it? 

This is a podcast series developed by NHS, Health Research Authority on Complex Innovative Designs. In this episode, David Sebag-Montefiore, Clinical oncologist at the University of Leeds and Clinical Director Leeds Cancer Research Centre shares how adaptive platform trials allow researchers to evaluate several novel interventions at the same time within the trial framework, comparing them against a common control arm. Hence researchers can evaluate multipe new treatments, much more efficiently, under the framework of the platform trial. This podcast mentions the advantages and design and funding challenges of platform trials. Examples of Platform Trials like STAMPEDE and PLATO (Personalising anal cancer radiotherapy dose)have been discussed. 

How can it be useful? 

What is it?

This is a podcast series developed by NHS, Health Research Authority on Complex Innovative Designs. Dr. Catey Bunce, Reader in Medical Statistics, School of Population Health & Environmental Sciences, Faculty of Life Sciences and Medicine, King’s College London talks on the statistical challenges and opportunities of defining, designing and analysing CID Trials. This podcast discusses how complex trails are defined and analysed and the challenges and opportunities from the point of view of a medical statistician. 

How can it be useful? 

A statistician explains how she understands complex clinical trials, and how statisticians need to think critically how to navigate the study, they are looking at type 1 and type 2 errors. Statistics of these trials are more complicated. 

What is it?

This is a National Institute for Health and Care Research (NIHR) webpage that highlights the UK’s  approach to Complex Innovative Trials (CITs). It introduces different innovative trial designs, including adaptive (platform, basket, umbrella, dose-ranging), targeted or stratified, Real-world, Bayesian, seamless phase II/III trials, and stopping rules for futility or efficacy, as well as master protocol approaches. The webpage also showcases examples of such trials supported by NIHR, the role of the NIHR Clinical Research Network in delivering them, and opportunities for industry collaboration.

How can it be useful?

This resource can serve as a practical guidance for EU researchers, sponsors, and industry partners seeking to plan and implement complex and adaptive trial methodologies in collaboration with the UK. It provides practical entry points into NIHR support structures, outlines methodologies with real-world examples, and shows how NIHR facilitates collaboration to run such studies across multiple diseases and populations.

What is it?

This is a systematic review published in Frontiers in Medicine (2022; 9:1037439), it examines 38 umbrella trials and the statistical methods used in their design and analysis, focusing on both oncology and non-oncology settings. The paper highlights challenges such as adaptive vs. non-adaptive designs, patient eligibility for multiple biomarker subgroups, error rate control, sample size calculation, borrowing of information, Bayesian vs. frequentist approaches, and reporting quality. It also discusses links with related designs (platform and basket trials) and outlines open questions for further methodological development.

How can it be useful?

The review provides a consolidated overview of the design, conduct, and statistical challenges of umbrella trials, with practical lessons from early-phase oncology studies and emerging non-oncology applications. It offers insights into adaptive features, biomarker-driven designs, control arm strategies, and error rate considerations, making it a useful reference for planning or evaluating umbrella trials. It can also help to identify current gaps in methodology, reporting, and sample size calculation, and highlights future directions for improving the efficiency and robustness of complex clinical trial designs.

What is it?

This is a consensus paper developed by the Experimental Cancer Medicine Centres (ECMC) CID trials working group in the UK. It provides detailed guidance on the design, conduct, and evaluation of Complex Innovative Design (CID) cancer trials, which aim to answer multiple clinical questions within a single, adaptable study protocol.

Why is it useful?

It serves as a practical, stakeholder-driven guide to help researchers and sponsors manage the complexities of CID trials, thereby accelerating the delivery of new cancer treatments. It provides ten consensus recommendations addressing regulatory engagement, protocol development, patient involvement, statistical methods, training needs, and public health impact of complex oncology trials. The guidance emphasizes early stakeholder engagement, scalability, and strategies for efficient implementation in academic and commercial settings. While it has been prepared for oncology within the United Kingdom setting, the recommendations could be of general use for adaptive platform trials.

What is it?

This deliverable (EU-PEARL D2.9) report describes the methodological framework and tools developed within EU-PEARL to guide the selection of interventions for Integrated Research Platforms (IRPs). The report includes criteria, statistical approaches, and practical considerations for evaluating and prioritising candidate interventions across different disease areas, ensuring transparency and consistency in decision-making .

How can it be useful?

This resource can be helpful in planning multi-arm or platform trials. It provides practical methodological guidance on how to decide which interventions to include, supported by statistical tools and evaluation frameworks. Using this report can help to adopt a structured, transparent, and evidence-based approach to intervention selection, reducing bias and strengthening the design of master protocol studies.

What is it?

This EU-PEARL deliverable (D2.11) provides an overview of the regulatory framework and issues relevant to Integrated Research Platforms (IRPs) and platform trials. It reviews European and international regulatory requirements, explores challenges such as data protection, patient safety, and protocol approval, and suggests pathways for regulatory alignment. The document also summarizes stakeholder perspectives and outlines potential solutions for smoother implementation of IRPs.

How can it be useful?

The report is useful for researchers, sponsors, and regulators seeking guidance on how to navigate regulatory barriers when setting up and conducting platform trials and IRPs. It provides practical insights into European regulatory processes, highlights common challenges, and points to possible solutions. This can support better trial planning, compliance with data and ethical requirements, and improved collaboration between stakeholders across borders .

What is it?

This EU-PEARL deliverable (D3.7) describes tools and methodologies to improve trial feasibility assessments using federated hospital networks and Electronic Health Records (EHRs). It outlines surveys for assessing hospital eSource readiness, guidance on transforming EHR data into the OMOP Common Data Model, and use of the OHDSI Atlas tool to generate patient counts. The report includes three disease-specific use cases (Neurofibromatosis-Type-1, Major Depressive Disorder, and Non-Alcoholic Steatohepatitis) and provides general disease-agnostic guidance for estimating patient availability across sites.

How can it be useful?

This resource provides practical tools to assess hospital readiness, standardize EHR data, and run feasibility queries across federated networks. It helps identify potential trial participants, improve recruitment planning, and streamline site selection. The deliverable also gives best-practice recommendations for handling data variability, ensuring privacy, and leveraging federated EHR systems for platform trial infrastructure

What is it?

This is a final report and excel based tool produced by the EU-PEARL consortium provides best practice recommendations for the operational planning and conduct of platform trials. The report describes the development of the Platform Trial Best Practices Tool, that identifies operational tasks across trial functions (e.g., clinical operations, data management, safety, governance, patient engagement, electronic health records, safety, clinical supplies, regulatory, etc.). It highlights what differs between platform trials and conventional trials, and includes guidance to support oversight, planning, and cross-functional team collaboration.

How can it be useful?

The accompanying excel tool serves as a practical checklist to guide operational planning, ensuring roles and responsibilities are clearly defined and regulatory/GCP requirements are integrated. It helps identify unique operational challenges in master protocols, supports efficient trial set-up, and facilitates collaboration between stakeholders in multi-company and academic-led platform trials.

What is it?

This report, EU-PEARL’s Patients and Communities Engagement: Towards Improving Platform Trials is a set of recommendations from EU-Pearl project (2019–2023), funded through the Innovative Medicines Initiative 2. It describes the creation of the Patient and Community Engagement Platform (PaCEPT), an online repository explaining platform trials and providing practical tools, videos, and guidance. Developed with input from a Patient Advisory Group, Expert Advisory Group, and multi-stakeholder Task Force, it supports patient involvement in all stages of platform trial design, conduct, and dissemination

How can it be useful?

PaCEPT offers a one-stop repository for researchers, sponsors, and patient/community representatives to access training materials, templates, operational tools, and best practice guidance for patient-centred platform trials. It supports co-creation of Master Protocols, informed consent forms, and decision algorithms, and shows how patients can be involved in early, mid-trial, and governance activities. The platform also facilitates multi-stakeholder collaboration via the PFMD Synapse network, helping integrate patient engagement into complex trial designs efficiently.

What is it?

This guidance from the European Medicines Agency (EMA) explains how applicants can request Scientific Advice or Protocol Assistance for the development of medicines, including complex trials such as platform or master protocol trials. The procedure is managed by the Scientific Advice Working Party (SAWP) and involves submission of a briefing package via the IRIS platform, validation by EMA, and evaluation within either 40 days (no meeting) or 70 days (with discussion meeting). The outcome is a formal advice letter, which, while not legally binding, provides authoritative direction on regulatory, scientific, and methodological aspects of trial design.

How can it be useful?

This resource is directly useful for researchers and sponsors designing platform or master protocol trials in the EU. It explains how to obtain early feedback on trial design and regulatory requirements, increasing the likelihood of future approval. Full details, templates, and meeting calendars, are available on the EMA Scientific Advice webpage. This page also has online trainings videos, on how to submit initial and follow-up scientific advice application using IRIS and how to register for access to IRIS, what are Research Product Identifiers (RPI) and how we can use them? 

What is it?

This article presents key learning points from the 10-year FOCUS4 trial—an adaptive, multi-arm multi-stage (MAMS) clinical trial using a complex innovative design in metastatic colorectal cancer. As one of the first molecularly stratified trials in this setting, it details challenges in biomarker testing, recruitment, and statistical methodology. Insights are drawn from extensive stakeholder feedback, including investigators, funders, data managers, and site staff.

How can it be useful?

It provides a methodological and operational overview of long-term stratified trials in oncology, highlighting governance, recruitment dynamics, biomarker logistics, and design adaptations relevant to modern clinical trial infrastructure.

What is it?

This is a clinical trial report and methodology article describing the FOCUS4 trial, the first molecularly stratified umbrella platform trial in metastatic colorectal cancer. It reports on 10 years of experience, covering trial design, biomarker stratification, recruitment, drug testing, site engagement, stakeholder feedback, and operational challenges. 

How can it be useful?

The article gives practical guidance on trial design, resource planning, biomarker testing, patient stratification, and engagement with pharma. It  synthesizes lessons learned and provides 20 recommendations for improving delivery of stratified adaptive platform trials. It also highlights the importance of adequate funding, efficient regulatory processes, and patient-centred approaches, providing a roadmap for planning and running future complex innovative design trials. 

What is it?

This is a commentary article that summarises the experiences of the Data Monitoring Committee (DMC) overseeing the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19. It describes key operational aspects of the DMC, including strategic planning, communication, safety monitoring, and regulatory interactions. It explains the role of the Data Monitoring Committee (DMC) in safeguarding the interests of patients assess the safety and efficacy of the interventions during the trial and monitor the overall conduct of the study. 

How can it be useful?

This article provides practical insights into the role of independent DMCs in large adaptive platform trials, particularly during a public health emergency. It highlights lessons learned in managing multiple treatment arms, maintaining confidentiality, working with regulators, and ensuring patient safety. The article highlights that regular reviews of unblinded data allowed the DMC to identify emerging evidence of benefit or harm and ensure that participants were not exposed to treatments shown to be ineffective or unsafe. It further stresses that maintaining confidentiality of interim data was essential to protect trial integrity and patient safety. 

What is it?

This methodological paper details the implementation of the STAMPEDE trial—a UK-led, multi-arm, multi-stage (MAMS) randomized controlled trial for evaluating systemic therapies in advanced prostate cancer. It showcases adaptive features such as early stopping for lack of benefit and adding new treatment arms mid-trial.

Why is it useful?

The MAMS design improves efficiency, reduces costs, and accelerates treatment evaluation. The authors share operational insights into trial governance, real-time decision-making, regulatory navigation, and site activation strategies. Although focused on prostate cancer, the flexible framework and logistics can inform adaptive trial designs across various diseases and settings.

What is it? 

This is a two-page Q&A guidance document issued by the Clinical Trials Coordination Group (CTCG) (version 1.0, 14 March 2023). It provides clarifications on the submission of Complex Clinical Trials (CCTs) in the EU Clinical Trials Information System (CTIS) under the EU Clinical Trials Regulation (CTR, Regulation (EU) No 536/2014). The Q&A addresses practical points such as whether to submit a CCT as a single trial or multiple trials, handling of master and sub-protocols, co-sponsorship responsibilities, naming of documents, transparency and deferral rules, and procedures for transitioning trials from the previous Clinical Trials Directive (CTD) to the CTR framework.

How can it be useful?

This concise Q&A answers questions on how to prepare submissions of complex and adaptive designs in CTIS. It provides hands-on instructions for complying with EU CTR requirements, avoiding errors in protocol submission, and ensuring consistency across multinational and multi-protocol trials. It serves as a practical compliance reference for navigating regulatory procedures in Europe.

What is it?

This is a methodology and implementation article describing a clinical trial design strategy for embedding a biomarker-stratified sub-study within the STAMPEDE platform trial, a multi-arm multi-stage (MAMS) framework for prostate cancer. It outlines the integration of rucaparib for HRD-positive patients using a precision medicine approach, with detailed discussion on stratification, assay validation, and control arm use. The study draws on practical experience from the ongoing trial to inform the design of future biomarker-enabled sub-protocols.

How can it be useful?

It offers a practical guide for incorporating low-prevalence biomarkers into large platform trials, addressing feasibility, bioassay performance, and protocol adaptability within precision oncology platforms.

What is it?

This paper outlines the INSIGhT trial, a Bayesian adaptive platform trial for evaluating targeted therapies newly diagnosed glioblastoma. It uses biomarker-driven groupings and response-adaptive randomization to evaluate multiple therapies in parallel, with flexibility to add or drop treatment arms.

Why is it useful?

It provides a in-depth statistical framework for building Bayesian adapative trials using biomarker-driven patient assignment, progression-free survival for interim adaptation, and biomarker stratification. Suitable for clinical trial methodologists and statisticians, it offers practical examples of adaptive algorithms and power simulations but is not intended for non-specialist or general clinical audiences.

What is it?

Integrated Platform for Designing Clinical Trials, is an open-access clinical trial design software platform developed by University of Texas, MD Anderson Cancer Center team, provides a suite of web-based and desktop tools for designing and simulating clinical trials. The website hosts applications such as the BOIN Suite, CRM & BMA-CRM, Keyboard Suite, Simon’s Two Stage Design, Bayesian Phase 2 Design with Delayed Outcomes, and modules for Bayesian toxicity monitoring, dose-finding, efficacy monitoring, and basket and platform trial design.

How can it be useful?

The platform enables researchers, clinicians, and statisticians to directly access trial design tools online for phase I and phase II trials, dose optimization, basket and platform trials, and decentralized trial designs. It provides practical, ready-to-use software to evaluate endpoints, optimize sample sizes, assess futility, and design adaptive Bayesian trials. As part of a toolbox, it offers hands-on resources to support decision-making and improve efficiency in planning and conducting innovative trials.

What is it?

This guidance document from the U.S. Food and Drug Administration (FDA) provides recommendations to sponsors on how to interact with the FDA when proposing complex innovative trial designs (CID) for drugs and biologics. It describes meeting opportunities, required elements of proposals, use of simulations, and considerations specific to Bayesian designs. It also presents examples such as master protocols, leveraging data from Phase 2 to Phase 3, and sequential multiple assignment randomized trials (SMARTs).

How can it be useful?

This guidance document from FDA gives recommendations how to engage with the FDA through formal meetings, outlines the information to include in CID proposals, and highlights regulatory expectations on statistical methods, prior distributions, and decision criteria. By following this guidance, sponsors can improve the likelihood of successful FDA interactions and facilitate regulatory acceptance of novel designs, including master protocols and Bayesian approaches. The Master Protocol Toolbox has a European focus for the resources included, this document has been exceptionally added as a consultative resource to take into consideration FDA non-binding advice on Complex Innovative Trial Designs. 

What is it?

A trial methodology article describing the multi-arm multi-stage (MAMS) design used in the STAMPEDE trial for prostate cancer. It outlines key considerations including randomisation, recruitment, sample size, outcome measures (OM) and target difference, and stopping arms, with refers to specific analysis issues encountered during implementation.

How can it be useful? 

It offers foundational principles for designing adaptive multi-arm cancer (MAMS) trials, including how to control type I error, manage shared control arms, sequence treatment evaluation using pre-planned stopping points, and calculate sample sizes under evolving hypotheses.

What is it?

This is a ready-to-use template (docx format) developed  within the EU-PEARL project as a tool for designing master protocol trials. It provides a structured framework for writing clinical trial protocols that involve multiple therapies, diseases, or sub-studies under a single overarching protocol. The template covers all standard protocol elements and adds guidance specific to master protocols, including governance, statistical design, data management, and regulatory considerations.

How can it be useful?

This tool can be useful in planning to design and implement master protocols. It offers a ready-to-use protocol structure, harmonised with regulatory requirements, and tailored to the complexities of platform trials. Using this template can improve consistency, transparency, and regulatory compliance, while reducing time and resources needed for protocol development.

What is it?

This article proposes adapting master protocol designs—commonly used in basket, umbrella, and platform trials—to the evaluation of radiation oncology devices (RODs). It presents a phase I/II trial of MR-guided adaptive radiotherapy (MR-Linac) as the first known example of this approach applied to therapeutic devices.

How can it be useful?

The paper demonstrates how feasibility, external controls, toxicity, patient-reported outcomes, and centralized credentialing can be coordinated across substudies. It emphasizes statistical efficiency, rigorous quality assurance, and alignment with regulatory approval to streamline and strengthen trial designs for complex device evaluation.

What is it?

In the context of immuno-oncology (IO), Mazzarella et al. argue that traditional trial models are no longer sufficient to address the biological and clinical complexity of modern therapies. Immunotherapies often produce variable, delayed, or atypical responses and toxicities, which challenge the rigid structure of conventional trials. Master protocols—whether umbrella, basket, or platform trials—respond to this by allowing adaptive features such as continuous treatment arm modifications, biomarker-based stratification, and shared control groups. 

How can it be useful? 

This article can be useful as a foundational reference for designing or evaluating innovative clinical trials in the IO field. It provides conceptual clarity on why master protocols are not just methodologically novel but practically necessary. Researchers, sponsors, and regulators can use it to justify protocol adaptations, guide safety oversight structures, and align trial design with modern drug development realities—especially where biomarker complexity and therapeutic uncertainty intersect.