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?

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 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?

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 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 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 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 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 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.

What is it?

A review introducing master protocols—platform, basket, and umbrella trials—as innovative clinical trial designs for evaluating multiple therapies or diseases under a single overarching structure. These designs enable testing in biomarker-defined subgroups and support features like shared control arms and adaptive randomization.

Why is this tool useful?

It offers foundational guidance on complex trial designs, emphasizing their growing use in oncology, where advances in identifying tumor subtypes and mutations have made biomarker-driven approaches especially valuable. Real-world examples like I-SPY 2 and Lung-MAP illustrate how these designs improve efficiency, coordination, and adaptability in modern clinical trials.

What is it?

An official FDA guidance document introducing master protocols—umbrella, basket, and platform trials—as streamlined frameworks for evaluating multiple therapies and/or cancer types within a single overarching protocol. These designs incorporate biomarker-driven patient selection, shared control arms, and adaptive features to enable faster, more flexible clinical development, particularly in oncology.

Why is this tool useful?

It provides regulatory clarity and practical recommendations for designing and conducting complex oncology trials. The guidance emphasizes how master protocols enhance trial efficiency, support evidence generation for multiple substudies simultaneously, and facilitate regulatory approval. With reference to real-world studies like Lung-MAP, NCI-MATCH, and Pediatric MATCH, this tool helps sponsors navigate challenges related to trial design, biomarker integration, and safety monitoring—making it highly valuable for anyone developing modern oncology therapeutics.

What is it?

This is a methodological overview of major NCI-sponsored precision oncology trials—including NCI-MATCH, LungMAP, ALCHEMIST, MPACT, and Pediatric MATCH—that use basket, umbrella, and master protocol designs. These trials match patients to targeted therapies based on genomic alterations, often regardless of tumor histology.

Why is it useful?

The article provides practical insights into designing and running biomarker-driven, tumor-agnostic trials. It discusses adaptive protocols, genomic screening, stakeholder collaboration, and trial infrastructure. It is especially useful for researchers planning complex innovative trials in precision oncology across both adult and pediatric settings.
Type: Journal Article

What is it? 

This is a peer-reviewed journal article that reviews novel clinical trial designs in thoracic oncology. It explains adaptive, basket, and umbrella trials with examples and regulatory context.

How is it useful? 

The paper is highly useful for trial planners developing biomarker-driven or genomics-informed studies in oncology, offering both theoretical insights and practical trial frameworks.

What is it?

This review explores novel trial designs in neuro-oncology, particularly for glioblastoma and early phase research. It highlights Bayesian design, external control arms, and endpoints other than survival, including progression-free survival, patient-reported outcomes, neurocognitive function, tumor growth rate, and objective response rate, within externally augmented clinical trial designs.

How can it be useful?

It presents adaptive strategies using examples from INSIGhT, GBM AGILE, VE-BASKET, NCI-MATCH, NCI-MPACT, N2M2, and INDIGO. Additional trials include NRG CC001, MDNA55, Lung-MAP, and Alliance A071701. The article outlines innovations shaping future precision trials in neuro-oncology.

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?

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 systematic review evaluates how 278 published trials have reported master protocols, including platform, basket, and umbrella trials, and whether they align with FDA definitions. It highlights reporting inconsistencies and proposes improvements to enhance clarity and consistency in classification. Although the review includes various indications, oncology trials are the most frequently represented.

How can it be useful?

The review identifies areas for improving the classification and reporting of master protocol designs. It supports the development of reporting standards by highlighting inconsistencies in terminology and alignment with FDA definitions.

What is it?

This article explores statistical controversies in precision oncology by reviewing master protocols such as basket, umbrella, and biomarker-driven trials. It discusses the integration of molecular profiling, targeted therapies, and adaptive design through Bayesian and frequentist statistics design approach.

How can it be useful?

It examines randomization strategies, regulatory impact, and features of efficient design using trial examples: I-SPY 2, BATTLE, BATTLE-2, NCI-MATCH, LUNG-MAP, SHIVA, FOCUS4, and GBM AGILE. The article provides practical insights into modern clinical trial design under complex master protocol frameworks.

What is it?

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

How can it be useful?

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

What is it?

A methodological research article that critically examines the Trials within Cohorts (TwiCs) design, also known as the cohort multiple randomized controlled trial, using detailed oncology-based case studies. It highlights both practical applications and statistical considerations in complex clinical trials, including staged-informed consent, non-compliance, efficacy estimands, intention-to-treat, and instrumental variable analysis. It compares TwiCs with related frameworks like pragmatic RCTs and platform trials. The article provides an overview of applied TwiCs studies in oncology, including UMBRELLA FIT, RECTAL BOOST, TILT, VERTICAL, MEDOCC-CrEATE, and HONEY.

How can it be useful?

It provides a real-world example of converting a traditional RCT into a flexible, multi-stage platform trial in oncology. The article offers practical guidance on trial adaptation, type I error control, multi-arm randomisation, and regulatory navigation. It offers practical insights into trial management, regulatory and ethical processes, and maintaining Type I error control. It can be valuable for teams implementing multi-arm clinical trials using platform approaches in oncology.

What is it?

A systematic review and landscape analysis of master protocols in radiotherapy. The article identifies 12 trials using platform, basket, and umbrella trial designs, and presents three detailed cases—CONCORDE, PLATO, and SMART. These protocols evaluate dose personalization, novel drug–radiotherapy combinations, and radiotherapy devices, particularly in rare cancers and radiotherapy interventions.

How can it be useful?

It shares best practices in trial design and implementation for multicenter trials, emphasizing quality assurance, biomarker stratification, and support for translational research. These frameworks improve coordination, accelerate innovation, and enable adaptive approaches in radiation oncology.

What is it?

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

How can it be useful?

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