The adaptive platform trial toolbox

This toolbox aims to collect the accumulated knowledge, experience, & resources from multiple projects and trials into a practical and guided toolbox to facilitate planning & conduct of future APTs in any therapeutic area.

The toolbox has been structured with different categories and subcategories to facilitate the navigation of the over 130 resources. Each tool is presented with a brief explanation indicating the tool's format and level of validation.  The tools can also be searched by their type, year of publication or more generally by keywords. The link to access the outside source is included. If you want to download a list of key references to have on hand you can select them and download them directly. 

Toolbox categories

To begin your search narrow down your key criteria here:

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A collaboration of group developing, running and reporting Multi-arm, Multi-stage (MAMS) platform trials in neurogenerative disease (ACORD)

Category
  • From recent and ongoing trials
  • Other

The  ACORD collaboration was formed in 2021 to encourage and support the development, running and reporting of Multi-arm, Multi-stage Platform Trials in four major neurodegenerative diseases: MND, Progressive MS, Parkinson’s Disease and ultimately Dementia.

Reference : ACORD | 2021
Type
Website
Trial information
Acces tool

A multinational, phase 2, randomised, adaptive protocol to evaluate immunogenicity and reactogenicity of different COVID-19 vaccines in adults ≥75 already vaccinated against SARS-CoV-2 (EU-COVAT-1-AGED): a trial conducted within the VACCELERATE network

Category
  • From recent and ongoing trials
  • COVID

VACCELERATE is a clinical research network for coordinating and conducting COVID-19 vaccine trials. The network is comprised of academic institutions from all over Europe. University Hospital Cologne, Germany, led the consortium. This protocol paper presents the design of  EU-COVAT-1-AGED, an adaptive platform conducted within the VACCELERATE network, to test different vaccine immunogenicity and reactogenicity in adults ≥75.

Reference : Neuhann | 2022
Type
Journal article
Summary of protocol
Acces tool

A Practical Adaptive & Novel Designs and Analysis toolkit (PANDA)

Category
  • Trial conduct and documents
  • Trial conduct

PANDA is a toolkit developed by a collaborative initiative in the UK funded by NIHR. It presents critical information for adaptive design development and trial conduct, and it provides resources to help researchers use adaptive design in practice, such as statistical software, guidance to enhance the reporting, and case studies/ examples of different types of adaptive design.

Reference : PANDA | 2023
Type
Website
Toolbox
Acces tool

A randomised, embedded, multi-factorial, adaptive platform trial for community-acquired pneumonia (REMAP-CAP)

Category
  • From recent and ongoing trials
  • COVID

REMAP-CAP is a randomised, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia. In addition, REMAP-CAP provides an adaptive research platform for the evaluation of multiple treatment modalities in the event of a respiratory pandemic resulting in critical illness. Sponsored by University Medical Center Utrecht.

Reference : University Medical Center Utrecht | 2015
Type
Website
Trial document
Acces tool

A trial like ALIC4E: why design a platform, response-adaptive, open, randomised controlled trial of antivirals for influenza-like illness?

Category
  • Trial conduct and documents
  • Case Study / Lesssons learned

ALIC4E is the first publicly funded, multi-country, pragmatic study determining whether antivirals should be routinely prescribed for influenza-like illness in primary care. Taking ALIC4E as an example, this article aims to provide an accessible description of crucial aspects of the platform design, response adaptation of study arms, and pragmatic aspects in open-label trials.

Reference : Butler et al | 2018
Type
Experience
Journal article
Acces tool

Accelerating adoption of complex clinical trials in Europe and beyond

Category
  • Introduction and design elements
  • Complex innovative design

Report and presentations from a multi-stakeholder workshop organised by EFPIA to develop shared solutions for the use of complex clinical trials to optimise drug development in Europe

Reference : EFPIA | 2021
Type
Website
Report
Acces tool

Accelerating clinical trial implementation in the context of the COVID-19 pandemic: challenges, lessons learned and recommendations from DisCoVeRy and the EU-SolidAct EU response group

Category
  • Trial conduct and documents
  • Case Study / Lesssons learned

This review discusses the European clinical trial, including the implementation of some EU platform trials for COVID-19, such as from DisCoVeRy and the EU-SolidAct. 

Reference : Diallo | 2022
Type
Experience
Journal article
Acces tool

Accelerating COVID-19 therapeutic interventions and vaccines (ACTIV) trials

Category
  • From recent and ongoing trials
  • COVID

A public-private partnership in the United States led by the National Institutes of Health (NIH) and coordinated by the Foundation for the National Institutes of Health (FNIH) to develop a research strategy for prioritising and speeding development of the most promising COVID-19 vaccines and treatments. Some trials including the STRIVE platform, are ongoing under this project.

Reference : STRIVE | 2022
Type
Website
Trial document
Acces tool

Adaptive design clinical trials for drugs and biologics - guidance for industry

Category
  • Statistics and data management
  • Guidance support

This FDA document provides guidance to sponsors and applicants submitting investigational new drug applications, new drug applications, biologics licensing applications, or supplemental applications on the appropriate use of adaptive designs for clinical trials to provide evidence of the effectiveness and safety of a drug or biologic.

Reference : FDA (b) | 2019
Type
Document
Guide
Acces tool

Adaptive design clinical trials: a review of the literature and ClinicalTrials.gov

Category
  • Introduction and design elements
  • Complex innovative design

The journal article reviews the characteristics of implemented adaptive design clinical trials and provides examples of regulatory experience with such trials.

Reference : Bothwell et al | 2017
Type
Journal article
Review
Acces tool

Adaptive designs for clinical trials

Category
  • Introduction and design elements
  • Complex innovative design

This journal review focuses on adaptive designs of confirmatory clinical trials. It discusses the benefits and limitations of such designs, using four case studies that highlight the statistical and operational considerations.

Reference : Bhatt and Mehta | 2016
Type
Journal article
Review
Acces tool

Adaptive designs in clinical trials: from scientific advice to marketing authorisation to the European Medicine Agency

Category
  • Regulatory
  • Europe

The journal article assesses and reviews scientific advice letters issued by EMA containing questions related to adaptive clinical trials in phases II or III. It also examines relevant regulatory aspects.

Reference : Collignon O et al | 2018
Type
Journal article
Original Research
Acces tool

Adaptive platform trials to transform amyotrophic lateral sclerosis therapy development

Category
  • From recent and ongoing trials
  • Other

The platform trial approach is now being employed more often in neurology. This paper describes a newly launched platform trial for ALS. The Healey ALS Platform Trial is testing multiple investigational products concurrently in people with ALS to identify novel treatments, biomarkers, and trial endpoints rapidly.

Reference : Paganoni et al | 2022
Type
Journal article
Summary of protocol
Acces tool

Adaptive platform trials: scalable from breast cancer to COVID

Category
  • Trial conduct and documents
  • Case Study / Lesssons learned

This video with attached slides summarises how the adaptive platform I-SPY trial has been developed for breast cancer and how it is replicated as a COVID trial. It depicts the life cycle of an adaptive platform trial with rationale, design, infrastructure, intervention selection, data collection, added value, and publications. It was hosted by NIH Collaboratory.

Reference : This video with attached slides summarises how the adaptive platform I-SPY trial has been developed for breast cancer and how it is replicated as a COVID trial. It depicts the life cycle of an adaptive platform trial with rationale, design, infrastructure | 2020
Type
Experience
Video
Acces tool

Adaptive trial designs - introduction for non-statisticians

Category
  • Introduction and design elements
  • Complex innovative design

This video introduces adaptive trial design options for non-statisticians with example trials. It is presented by Cytel.

Reference : cytel | 2019
Type
Presentation
Video
Acces tool

Adding flexibility to clinical trial designs: an example-based guide to the practical use of adaptive designs

Category
  • Introduction and design elements
  • Complex innovative design

The journal article introduces the main features of adaptive designs and commonly used terminology, highlighting their utility and pitfalls, and illustrating their use through case studies of adaptive trials.

Reference : Burnett et al | 2020
Type
Journal article
Review
Acces tool

An open-label, multicentre, randomised, adaptive platform trial of the safety and efficacy of several therapies, including antiviral therapies, versus control in mild/moderate cases of COVID-19 (ANTICOV)

Category
  • From recent and ongoing trials
  • COVID

ANTICOV is an open-label, randomised, comparative, adaptive platform trial that will test the safety and efficacy of treatments in 2,000 to 3,000 mild-to-moderate COVID-19 patients. ANTICOV aims to identify early treatments that can prevent the progression of COVID-19 to severe disease and potentially limit transmission. It is sponsored by the Drug for Neglected Diseases Initiative and others.

Reference : Drugs for Neglected Diseases Initiative et al | 2020
Type
Website
Trial document
Acces tool

An overview of platform trials with a checklist for clinical readers

Category
  • Trial conduct and documents
  • Reporting

This journal review aims to outline key considerations for general clinical readers when critically evaluating publications on platform trials and for researchers when designing these types of clinical trials. Supplementary tables provide examples of the use of the checklist for platform trials.

Reference : Park et al (a) | 2020
Type
Document
Guide
Acces tool

Capacity building and assessment handbook for site readiness. EU-PEARL work package (WP5) - Integrated research platform for tuberculosis (TB)

Category
  • Trial conduct and documents
  • Trial conduct / specific disease

This handbook represents an innovative approach that will help to prepare sites for future Integrated Research Platform (IRP) for TB, as discussed within one of the work packages of the EU-PEARL project.

Reference : EU-PEARL D5.2 | 2021
Type
Project deliverable
Summary of discussion
Acces tool

Changing platforms without stopping the train: experiences of data management and data management systems when adapting platform protocols by adding and closing comparisons

Category
  • Statistics and data management
  • Data Management

The journal article shares experiences from FOCUS4 and STAMPEDE trials from the operational aspects of running these adaptive trials, focusing on data management. Adding and closing intervention arms, a number of case report form changes, database amendments and database growth are discussed.

Reference : Hague et al | 2019
Type
Experience
Journal article
Acces tool

Choosing drugs for UK COVID-19 treatment trials

Category
  • Introduction and design elements
  • Consideration for particular field

The paper discussed how the UK government funded a portfolio of platform trials to develop new treatments for COVID-19. A key feature was the independent prioritisation of candidate drugs with central coordination to prevent duplication, accelerating recruitment to deliver definitive trial results. 

Reference : Chinnery et al | 2022
Type
Commentary
Journal article
Acces tool

Clinical network of NF sites report. EU-PEARL work package (WP7) – Integrated research platform for neurofibromatosis (NF)

Category
  • Trial conduct and documents
  • Trial conduct / specific disease

This deliverable presents our approach to defining site selection criteria for the network of sites that could run the platform trials for NF. The deliverable focuses on the network for the NF1 platform trial. 

Reference : EU-PEARL D7.7 | 2023
Type
Project deliverable
Summary of discussion
Acces tool

Clinical research network report to support future NASH IRPs. EU-PEARL work package (WP6) – Integrated research platform for non-alcoholic steatohepatitis (NASH)

Category
  • Trial conduct and documents
  • Trial conduct / specific disease

A vital aspect of the platform trials' success is establishing a Clinical Research Network (CRN) comprising healthcare providers, researchers, and relevant stakeholders. This deliverable describes the survey results to provide future directions and guidance on establishing a CRN for a future NASH platform trial.

Reference : EU-PEARL D6.6 | 2023
Type
Project deliverable
Summary of discussion
Acces tool

Collaborative platform trials to fight COVID-19: Methodological and regulatory considerations for a better societal outcome

Category
  • Introduction and design elements
  • Consideration for particular field

This paper provides corresponding regulatory perspectives on approval and reimbursement. It notes that the optimal design of a platform trial will differ through our societal objective and by stakeholders.

Reference : Collignon O et al | 2021
Type
Journal article
Review
Acces tool

Complex clinical trials - Questions and answers

Category
  • Regulatory
  • Europe

This document aims to address challenges sponsors may face regarding scientific and operational aspects of complex clinical trials in the EU/EEA and to encourage considerations in development as early as possible to generate valuable evidence and inform clinical and regulatory decision-making.

Reference : EC, EMA, HMA | 2022
Type
Document
Guide
Acces tool

Complex innovative trial design meeting program

Category
  • Regulatory
  • USA

The FDA program to facilitate drug development using complex innovative trial design met. Five cases were selected and the master protocols were discussed. This webpage presents public meeting records and discussion minutes. 

Reference : FDA (b) | 2022
Type
Website
Report
Acces tool

Concept paper on platform trial

Category
  • Regulatory
  • Europe

This is a concept paper for platform trials published by EMA.

Reference : EMA, CHMP | 2023
Type
Document
Guide
Acces tool

Costs and staffing resource requirements for adaptive clinical trials: quantitative and qualitative results from the Costing Adaptive Trials project

Category
  • Trial conduct and documents
  • Trial conduct

This article presents a mock costing exercise amongst seven clinical trial units (CTUs) in the UK. This work outlines the additional resources required to support a high-quality adaptive trial. The percentage increase in costs for supporting an adaptive trial was generally modest and should allow adaptive designs to be cost-effective in practice.

Reference : Wilson et al | 2021
Type
Document
Original Research
Acces tool

COVID-19: Master Protocols Evaluating Drugs and Biological Products for Treatment or Prevention -Guidance for Industry

Category
  • Regulatory
  • USA

The FDA issued this guidance to provide recommendations to sponsors of master protocols evaluating drugs for the treatment or prevention of COVID-19.

Reference : FDA | 2021
Type
Document
Guide
Acces tool

Data monitoring committee (DMC) charter template

Category
  • Statistics and data management
  • Data monitoring committee

This template of the Data Monitoring Committee Charter is for a platform trial. EU-PEARL developed the template.

Reference : EU-PEARL template 4 | 2023
Type
Project deliverable
Template
Acces tool

Data, data all around

Category
  • Statistics and data management
  • Data Management

This news article from the Lancet Digital Health highlights the complex routine data collection machinery behind the RECOVERY trial, simplifying site operations.

Reference : McCall | 2021
Type
Experience
Journal article
Acces tool

Decision rules for identifying combination therapies in open-entry, randomized controlled platform trial

Category
  • Statistics and data management
  • Methodology

The definition of error rates is not straightforward, as classical error rate concepts are not applicable. This article discusses error rates and operating characteristics. Then, it uses these to compare design parameters under a range of simulation assumptions for an open-entry, exploratory platform trial design comparing combination therapies to the respective monotherapies and standard-of-care. 

Reference : Meyer et al (b) | 2020
Type
Commentary
Journal article
Acces tool

Delivering complex and innovative trials: case study library

Category
  • Introduction and design elements
  • Complex innovative design

This website includes a podcast series and case studies of adaptive platform trials performed in the United Kingdom. It is hosted by the National Institute of Health Research.

Reference : NIHR | 2020
Type
Website
Toolbox
Acces tool

Designing an exploratory phase 2b platform trial in NASH with correlated, co-primary binary endpoints

Category
  • Introduction and design elements
  • Consideration for particular field

This article introduces some of the activities of the EU-PEARL consortium regarding the use of platform trials in NASH, in particular, the proposed trial design, decision rules and simulation results.

Reference : Meyer et al | 2023
Type
Journal article
Methodology
Acces tool

ECRAID (European Clinical Research Alliance on Infectious Diseases) Prime

Category
  • From recent and ongoing trials
  • COVID

ECRAID is the first network of its kind in Europe that offers a single point of access to a pan-European clinical research network for infectious diseases. ECRAID was established as a not-for-profit foundation in 2023 as an envisaged, long-term successor of the European-funded projects COMBACTE and PREPARE. The webpage presents ECRAID-PRIME, the platform trial for COVID-19 primary care patients.

Reference : ECRAID PRIME | 2023
Type
Website
Trial information
Acces tool

Effective delivery of complex innovative design (CID) cancer trials—a consensus statement

Category
  • Introduction and design elements
  • Consideration for particular field

The journal article provides ten consensus recommendations to improve the conduct, quality and acceptability of complex oncology trials. While it has been prepared for oncology within the United Kingdom setting, the recommendations could be of general use for adaptive platform trials.

Reference : Blagden et al | 2020
Type
Expert opinion
Journal article
Acces tool

Efficient adaptive designs for clinical trials of interventions for COVID-19

Category
  • Introduction and design elements
  • Consideration for particular field

This paper reviews the designs of four ongoing platform trials (REMAP CAP. AGILE, RECOVERY, CAPE-COVID)

Reference : Stallard et al | 2020
Type
Journal article
Review
Acces tool

Estimands and complex innovative designs

Category
  • Statistics and data management
  • Guidance support

While the estimand framework is relevant to any study in which a treatment effect is estimated, discussion is needed regarding its application to complex designs. This article discussed possible ways of implementing the estimand framework for different complex innovative designs.    

Reference : Collignon et al | 2022
Type
Commentary
Journal article
Acces tool

EU-PEARL patient and community engagement in platform trials (PaCEPT)

Category
  • Introduction and design elements
  • Patient engagement

This website, created by EU-PEARL, shows the information resources to support patient-centric platform trials. Resources are shown with each stakeholder category.

Reference : EU-PEARL PE | 2023
Type
Website
Toolbox
Acces tool

EU-PEARL webinar on non-concurrent controls in platform trials

Category
  • Statistics and data management
  • Methodology

This EU-PEARL webinar discusses the topics around non-concurrent controls in platform trials. It includes a statistical consideration in sharing control arms or changing standard of care during platform trials.

Reference : EU-PEARL video | 2023
Type
Summary of discussion
Video
Acces tool

EU-SolidAct – a pan-European platform for pandemic research and preparedness

Category
  • From recent and ongoing trials
  • COVID

The EU-SolidAct trial is a part of EU-Response, a pan-European research project involved with the rapid and coordinated investigation of new and repurposed medication to treat COVID-19 during the ongoing pandemic. EU-SolidAct is an adaptive platform trial sponsored by Oslo University Hospital, Norway. The master protocol is developed for evaluating treatments in hospitalised patients with COVID-19.

Reference : EU-SolidAct | 2020
Type
Website
Trial document
Acces tool

European Certification Programme for IRP Platforms

Category
  • Trial conduct and documents
  • Trial conduct

This deliverable ensures that the assessment and certification of data research platform / information and communications technology (ICT) systems are sustainable. 

Reference : EU-PEARL D1.9 | 2023
Type
Project deliverable
Summary of discussion
Acces tool

European Medicines Agency guidance for applicants seeking scientific advice and protocol assistance

Category
  • Regulatory
  • Europe

This guidance document addresses several questions that users of the scientific advice or protocol assistance procedures may have. It provides an overview of the procedure to obtain scientific advice or protocol assistance and guides applicants in preparing their requests. It will enable applicants to submit requests that align with Scientific Advice Working Party (SAWP) requirements and can be validated and evaluated quickly and efficiently.

Reference : EMA | 2022
Type
Document
Guide
Acces tool

Experiences of running a stratified medicine adaptive platform trial: Challenges and lessons learned from 10 years of thec trial in metastatic colorectal cancer

Category
  • Trial conduct and documents
  • Case Study / Lesssons learned

FOCUS4 was the first molecularly stratified trial in metastatic colorectal cancer, and it remains one of the first umbrella trial designs to be launched globally. This paper describes lessons learned from the trial delivery over the last ten years.

Reference : Brown et al | 2022
Type
Experience
Journal article
Acces tool

Experiences of the data monitoring committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19.

Category
  • Statistics and data management
  • Data monitoring committee

This paper presents the experiences of the Data Monitoring Committee (DMC) for the Randomised Evaluation of COVID therapy trial (RECOVERY), a large-scale randomised adaptive platform clinical trial of treatments for hospitalised patients with COVID-19.

Reference : Sandercock et al | 2022
Type
Experience
Journal article
Acces tool

Final Concept Paper E20: Adaptive Clinical Trials (step1, 8.8.2023)

Category
  • Regulatory
  • International

The ICH E20 expert working group is working on the development of a new E20 Guideline on “Adaptive Clinical Trials” on the design, conduct, analysis, and interpretation of adaptive clinical trials. It aims to provide a transparent and harmonised set of principles for the regulatory review of these studies in a global drug development program. These principles should also provide the flexibility to discuss innovative approaches to clinical trial design throughout the development process.

Reference : ICH E20 | 2019
Type
Document
Guide
Acces tool

Final concept paper ICH E6(R3): Guideline for good clinical practice (step3 8.8. 2023)

Category
  • Regulatory
  • International

This revision of the global harmonization regulatory guideline for GCP (ICH E6 R3) includes a risk-based approach to the design and conduct of clinical trials, increased reliance on electronic systems and non-traditional interventional clinical trials, such as pragmatic clinical trials, decentralized clinical trials, and those trials that incorporate real-world data sources.

Reference : ICH E6(R3) | 2019
Type
Document
Guide
Acces tool

Final report on Clinical Operations Best Practices

Category
  • Trial conduct and documents
  • Trial conduct

The deliverable is a project review of the current platform trial landscape to understand which challenges have the most complexity and impact. It is developed within the EU-PEARL project and includes a literature search, a website review, and an outreach survey to trial teams.

Reference : Parke et al | 2023
Type
Project deliverable
Summary of discussion
Acces tool

Flexible trial design in practice - stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial

Category
  • Trial conduct and documents
  • Case Study / Lesssons learned

In this commentary journal article, trial management and data management teams of STAMPEDE and FOCUS4 trials summarise the operational challenges and personal experiences of individual researchers to enable the broader clinical trials community to learn from their experiences

Reference : Sydes et al | 2012
Type
Experience
Journal article
Acces tool

Framework for ensuring and benchmarking acceptable data quality standards for platform trials

Category
  • Statistics and data management
  • Data Management

This deliverable covers the development of an organisational and business model for a scalable and sustainable data quality assessment service to assure future IRP studies and platforms that the data they reuse (e.g., from electronic health records –EHR – systems) is of satisfactory quality. 

Reference : EU-PEARL D1.10 | 2023
Type
Project deliverable
Summary of discussion
Acces tool

The tools have been selected for their relevance and utility, but the views and opinions expressed in the tools may not represent the specific opinions of the EU-RESPONSE and RECOVER consortia. If you would like to provide feedback or gather more information about the rationale and methodology of the toolbox, please contact us.