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 systematic rapid review published in Wellcome Open Research (2023; 8:194). It analyses evidence on community engagement and informed consent in adaptive platform and alternative design trials conducted during public health emergencies (PHEs) such as Ebola and COVID-19. The review includes 49 publications and guidance documents, highlighting key ethical and communication challenges in explaining complex trial designs under emergency conditions.

How can it be useful?

This review provides guidance for designing ethical engagement and consent processes for adaptive trials in outbreak settings. It summarises practical lessons on early stakeholder involvement, culturally appropriate communication, and clear explanation of adaptive trial features. Overall, it provides evidence-based recommendations for implementing responsive, participant-centred communication in adaptive and rapid-response trials.

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?

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?

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.

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 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?

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 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 is a special communication published in Journal of Biomedical Informatics (2023) describing innovative EHR-based methods developed by the EU-PEARL project (Work Package 3) to support the design and conduct of platform trials. The paper presents two main tools: an EHR readiness eSurvey for identifying hospitals with mature EHR systems suitable for clinical research, and interoperable proxy queries to translate trial eligibility criteria into computable formats for feasibility assessment and patient pre-screening. The methods rely on OMOP Common Data Model (CDM) and open-source OHDSI tools such as ATLAS and Cohort Diagnostics, supporting the creation of interoperable, data-driven clinical networks.

How can it be useful?

This article provides practical, open methods to leverage hospital EHR data for platform trial feasibility and participant recruitment. The eSurvey tool helps identify research-ready clinical sites, while the OMOP-based queries allow researchers to estimate potential participant numbers before launching a trial. The paper also discusses challenges in data readiness, eligibility criteria translation, and interoperability, proposing the use of NLP and open-source tools (ATLAS, Cohort Diagnostics, GitHub repositories) to improve automation and data quality. As part of the toolbox, this resource is useful for research teams planning data-driven, EHR-enabled platform trials across Europe.

What is it?

This is an informational website developed within the DART – Building Data-Rich Clinical Trials project, funded by the European Union. It presents the Basket of Baskets (BoB) trial, a European adaptive basket trial led by Cancer Core Europe. Using a histology-agnostic design, the trial groups cancer patients by shared genetic or molecular mutations rather than tumour type, testing multiple targeted therapies across different cancers.
The study includes two components: i-Profiler (genomic profiling to identify actionable mutations) and i-Basket (treatment phase matching patients to therapies). The site also outlines ethical approval, informed consent, and European collaboration, providing clear guidance for patients, caregivers, and clinicians.

How can it be useful?

The i-ENTER platform supports informed decision-making for patients considering participation in adaptive basket trials. It provides a practical overview of mutation-driven recruitment, targeted treatment allocation, and multi-centre collaboration in precision oncology. For researchers and regulators, it demonstrates how innovative trial designs can be effectively communicated and implemented within European clinical research. As part of the toolbox, it serves as a real-world example of how the DART project translates complex adaptive design concepts into accessible, patient-centred resources that promote transparency and engagement in oncology trials.

What is it?

This is a review article that discusses how the estimand framework from ICH E9(R1) can be applied to complex innovative designs in clinical trials. It examines challenges and practical solutions for integrating estimands into adaptive designs, basket trials, umbrella trials, and platform trials, as well as other innovative approaches such as Bayesian borrowing and dynamic control arms.

How can it be useful?

The article provides concrete guidance on framing estimands in master protocols and adaptive designs. It clarifies how to align objectives, populations, endpoints, and intercurrent events when trials evolve (e.g., adding or dropping treatment arms). Researchers can apply these insights to design more transparent, regulator-ready protocols that anticipate trial adaptations and maintain consistency in interpretation of treatment effects.

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 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 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 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 deliverable from EU-PEARL D1.10 Framework for Ensuring and Benchmarking Acceptable Data Quality Standards for Platform Trials, develops an organizational and business model for a scalable and sustainable data quality assessment service to ensure that data reused in Integrated Research Platform (IRP) studies (e.g., from electronic health records) meets acceptable quality standards. To validate the framework, data from four disease areas—Major Depressive Disorder (MDD), Neurofibromatosis (NF), Non-Alcoholic Steatohepatitis (NASH), and Tuberculosis (TB)—were used to design and test data quality rules.

How can it be useful?

This resource provides practical methods, rules, and tools to assess and improve electronic health record (EHR) data quality for use in platform trials. By applying structured data quality dimensions (completeness, correctness, uniqueness, consistency), it helps researchers and trial designers determine whether EHR data are reliable and fit for secondary use in clinical research. It can support trial planning, patient recruitment, data sharing, and regulatory submissions, ensuring reproducible and trustworthy outcomes

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?

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?

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.

What is it?

This is a video lecture by Dr. John Marshall (University of Toronto) made available by the Canadian Transfusion Trial Group. It explains the evolution of trial design and introduces master protocols—basket, umbrella, and especially platform trials. Using examples like REMAP-CAP and RECOVERY, it shows how adaptive platforms can test multiple interventions, add or remove arms, and deliver rapid evidence. The talk also covers Bayesian methods, response-adaptive randomization, and funding or regulatory challenges.

How can it be useful?

The video is a clear introduction to master protocols, illustrated with real clinical examples. It helps researchers and clinicians understand design choices, adaptive methods, and operational issues, making it a practical learning tool for innovative trial design.

What is it?

This meta-epidemiological study systematically reviewed 98 randomized platform trials published or registered between 2015 and 2022. Platform trials evaluate several interventions within a single protocol for a specific disease, with flexibility to add or drop interventions. The review summarizes trial characteristics, methodological features (e.g., statistical methods, randomization, blinding), and examples across diverse disease areas, notably COVID-19, oncology, and neurodegenerative disorders.

How can it be useful?

This review provides practical insights on adaptive designs, decision rules, and adding new interventions, useful for planning efficient, multi-intervention studies. It summarizes trial characteristics, methodological features (e.g., statistical methods, randomization, blinding), and examples across diverse disease areas, notably COVID-19, oncology, and neurodegenerative disorders (RECOVERY, REMAP-CAP, I-SPY, PRINCIPLE).
 

What is it?

This is a commentary article that examines the operational and human experience of researchers working on platform trials such as STAMPEDE and FOCUS4. Based on qualitative interviews, it describes challenges of workload, complexity, scale, and heightened expectations. Importantly, it shows how molecular stratification “in effect brings the patient into the trial office, as a specific individual, despite anonymisation, who is owed test results and a treatment decision,” creating a direct link between patient needs and researcher responsibilities.

How can it be useful?

The article documentis both staff and patient-related pressures in adaptive platform trials. It highlights the need for adequate resources, recognition of researcher workload, and mechanisms to protect staff well-being. At the same time, it emphasizes how staff experience a compassionate responsibility toward anonymised patients whose biomarker results and treatment options depend on their work. This dual perspective offers practical lessons on building trial environments that support both patients and the research teams delivering complex studies

What is it?

This EUPATI (European Patients’ Academy on Therapeutic Innovation) resource, developed as part of its patient engagement toolbox, explains adaptive clinical trial designs in plain language for patients and the general public. Adaptive designs allow pre-planned modifications during a trial based on interim data while maintaining validity and integrity. The resource describes three types of adaptive trial designs: group sequential designs, adaptive dose-finding designs, and biomarker-adaptive designs.

How can it be useful?

As a patient-focused educational tool, this EUPATI resource helps patients, advocates, and the public understand how adaptive trials work, why flexibility can improve efficiency, and how such trials can still safeguard scientific validity. It explains three specific adaptive design types, enabling non-specialists to better follow discussions about trial planning, especially in rare diseases. It also shows how patient input can guide researchers in choosing the most appropriate design by clarifying patient needs, and how patients can participate in Data Monitoring Committees to oversee trial conduct.

What is it?

It reviews alternative trial designs to conventional randomized controlled trials, including pragmatic trials, cluster trials, stepped wedge designs, practice-preference randomisation, adaptive designs, registry-based randomized trials, and specifically platform, basket, and umbrella trials. The article explains the strengths, weaknesses, and methodological challenges of each approach.

How can it be useful?

This article provides a concise overview of modern innovative trial designs for researchers and sponsors planning complex studies. It highlights when and why alternative methods may be appropriate, outlines practical trade-offs, and identifies challenges in implementation and analysis. As part of the toolbox, it serves as a reference for selecting and comparing trial designs, especially adaptive platform, basket, and umbrella trials, in order to improve efficiency, reduce cost, and enhance generalisability.

What is it?

This is a systematic review published in BMJ Open (2024; 14:e077132) on the operational complexities of international clinical trials. It synthesises evidence from 38 studies on challenges including sponsorship and insurance requirements, funding constraints, lack of harmonisation in ethics and regulatory approvals, lengthy contracts, site training, monitoring, communication, recruitment, data management, drug procurement and distribution, biospecimen processing, and adaptive trial-specific issues.

How can it be useful?

The review provides practical solutions for planning multinational and adaptive platform trials. It outlines strategies to address funding delays, contract bottlenecks, regulatory incompatibility, drug supply issues, and protocol amendments, offering a consolidated reference of barriers and solutions to improve the planning, coordination, and execution of international complex clinical trials.

What is it? 

This article is a real-world commentary on the plasmaMATCH platform trial, a multi-cohort, biomarker-guided study in advanced breast cancer. It explains in detail how a phase IIa platform trial was implemented, including molecular screening via ctDNA, adaptive cohort inclusion, protocol management, regulatory navigation, and data handling.

How it is useful? 

It is highly useful for clinical trial designers and research units preparing to implement complex, biologically stratified, multi-cohort trials—particularly when integrating liquid biopsy, multiple stakeholders, and adaptive trial governance. It provides practical solutions to operational hurdles, making it a valuable methodological and operational reference."

What is it? 

The EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project (2019–2023), funded under the Innovative Medicines Initiative 2, developed the Platform for Patient and Community Engagement in Platform Trials (PaCEPT). Led by the European Patients’ Forum (EPF) and Novartis, this online repository explains platform trials through training materials, tools, and guidance for engaging patients and communities in platform trials, and offers resources for Patient and Community Advisors to actively shape trial design and conduct.

How can it be useful?

PaCEPT gives researchers, sponsors, and patient/community representatives free access to practical engagement resources, including infographics, videos, recommendation documents, best practice tools, and a repository of previous platform trials. It supports involvement of patients and communities from trial design to dissemination, helping align research with patient needs, improve informed consent processes, and enhance recruitment and retention. By hosting on the Patient Focused Medicines Development-PFMD Synapse network, it connects users to over 4,700 members and 1,450 organisations for collaboration. This resource can be directly integrated into a clinical trial toolbox to guide stakeholder engagement in patient-centric platform trials.

What is it?

This is a discussion paper published in the CADTH Health Technology Review (2022; Vol. 2, Issue 7). It summarises a workshop hosted by CADTH (Canada) examining the use of platform, basket, and umbrella trials in oncology and precision medicine. The paper discusses challenges for health technology assessment (HTA), including lack of comparator arms, small heterogeneous subgroups, use of real-world data (RWD), survival analysis limitations, health economic modelling, incremental cost-effectiveness ratios (ICERs), patient preferences, and ethical issues such as informed consent, justice, and equity. While the HTA framework is Canada-specific, the methodological and ethical challenges are internationally relevant.

How can it be useful?

This paper provides practical insights into data quality, economic evaluation, patient-centred value, and ethical principles when assessing new therapeutics. As part of the toolbox, it highlights how HTA decision-making is affected by trial design limitations, heterogeneity, and uncertainty, and suggests ways to integrate real-world evidence, health economics, and patient perspectives into evaluations of complex clinical trials. The lessons can be relevant for international researchers and policy-makers, beyond Canada, facing similar challenges.

What is it?

This is a review article published in Therapeutic Innovation & Regulatory Science (2021; 55:1145–1154). It provides an overview of master protocol frameworks—basket, umbrella, and platform trials—covering their definitions, design considerations, statistical methods, operational aspects, and regulatory perspectives. The paper highlights major challenges including control arm selection, non-concurrent controls, type I error control and multiplicity, data sharing, transparency, cross-treatment comparisons, tumor agnostic indications, and operational complexity.

How can it be useful?

This article provides practical recommendations for designing and implementing basket, umbrella, and platform trials, with examples from oncology and regulatory feedback from both the US and EU. It offers guidance on managing issues such as control arm design, type I error, and data sharing, while addressing broader concerns like regulatory acceptance, transparency, and efficiency. As part of the toolbox, it supports informed decision-making on the design, conduct, and compliance of complex clinical trials.

What is it?

This is a methodology and practical guidance article published in Trials (2022; 23:757). It summarises the collective experience of six UK-based Clinical Trials Units (CTUs) in running late-phase platform protocols, including basket, umbrella, multi-arm multi-stage (MAMS), and master protocols. Based on discussions from a one-day workshop and examples such as STAMPEDE, FOCUS4, Add-Aspirin, and CompARE, it presents operational recommendations covering the entire life cycle of a platform trial. 

How can it be useful?

This paper provides practical lessons and recommendations to run late-phase platform protocols more effectively. It gives guidance on communication, funding models, regulatory engagement, database and randomisation systems, PPI involvement, staffing, and oversight structures, and highlights specific challenges compared with traditional two-arm trials. It can serve as a concise operational reference for planning, managing, and maintaining complex adaptive and master protocol trials.

What is it? 

This is a project deliverable developed by ECRIN as part of the ERA4Health project (2025). It provides an overview of master protocol frameworks—basket, umbrella, and adaptive platform trials—covering their definitions, design features, and methodological considerations. The booklet addresses challenges such as funding models, sponsorship and governance, regulatory and ethical aspects, trial and data management, biomarker assay quality, patient engagement, and statistical approaches including Bayesian methods, error control, and adaptive features.

How can it be useful?

The booklet offers practical recommendations for the planning and conduct of master protocols, focusing on infrastructure setup, governance, recruitment strategies, consent processes, and data quality assurance. It also points to relevant EU and US regulatory guidance. As part of the toolbox, it serves as a hands-on reference for navigating regulatory compliance, operational complexity, funding mechanisms, and methodological rigor in complex clinical trials.

What is it?

This deliverable (EU-PEARL D1.7) sets out the Recommended Ethical, Information Governance and Security Policies for Integrated Research Platforms (IRPs). It describes the portfolio of policy documents needed to ensure compliance in areas such as ethics, informed consent, data protection, GDPR, transparency, and internal governance when designing and running IRPs. The report also points to templates and examples (e.g., master protocol, informed consent forms, data management plans) that can be adapted for platform trials.

How can it be useful?

This resource provides a practical checklist of governance and compliance instruments needed when planning or operating Integrated Research Platforms or other master protocol trials. It helps to identify required documents (e.g., DPIAs, transparency statements, data-sharing policies), understand their rationale, and locate existing templates. It is also useful for ensuring ethical compliance, GDPR alignment, and clear governance frameworks when developing multi-sponsor, multi-arm platform trials.

What is it?

A phase II, multi-arm multi-stage (MAMS) adaptive platform trial protocol evaluating reduced-frequency dosing of immune checkpoint inhibitors (ICIs) in patients with sustained responses across various advanced cancers, including renal cancer. The article outlines trial methodology, economic modelling, biomarker sub-studies, and patient and public involvement (PPI), providing a comprehensive overview of implementing an adaptive design to assess extended-interval immunotherapy.

How can it be useful?

REFINE troal is highly applicable for trial teams designing adaptive oncology trials that test non-inferiority or duration-based interventions. It provides a framework for extending adaptive MAMS platforms to dose scheduling questions. Its inclusion of economic and pharmacodynamic components, modular expansion across indications, and intention to inform a phase III trial makes it a highly translatable and scalable model.

What is it?

This is a regulatory reflection paper developed by the European Medicines Agency (EMA), focusing on the methodological issues involved in confirmatory clinical trials using adaptive designs. It outlines regulatory expectations, defines key concepts, discusses statistical control requirements (e.g. Type I error), and evaluates potential design modifications such as sample size reassessment, early stopping, and changes to primary endpoints.

How can it be useful?

This reflection document informs us how to incorporate adaptive design elements in late-phase (confirmatory) clinical trials. It provides clear regulatory expectations and cautions against misusing adaptive flexibility without pre-planning. It emphasizes the need to preserve trial integrity, especially when modifying trial elements mid-course. Practical insights on interim analysis handling, protocol amendments, and acceptability of design modifications are include

What is it?

This article, Regulatory Issues of Platform Trials: Learnings from EU-PEARL, draws on the  EU-funded Innovative Medicines Initiative 2 Joint Undertaking (IMI2 JU) EU-PEARL project (2019–2023) to outline key regulatory considerations for platform trials. Focusing mainly on European regulations (EMA requirements, EU Clinical Trials Regulation No. 536/2014, GDPR) with some US FDA comparisons, it addresses regulator interactions, submission strategies, trial authorisations, amendments, safety reporting, data protection, and ethics.

How can it be useful?

This resource offers practical, directly applicable insights for designing and conducting platform trials in compliance with regulatory expectations in Europe. It can help trial sponsors and investigators navigate multi-country authorisation processes, manage protocol amendments, and ensure safety reporting and data protection. By including concrete lessons learned from EU-PEARL and highlighting jurisdictional differences, it serves as a ready reference for teams planning efficient, regulatorily compliant platform trials.