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:

Block
No items
Content

Randomised evaluation of COVID-19 therapy (RECOVERY)

Category
  • From recent and ongoing trials
  • COVID

An adaptive platform clinical trial design to accelerate the process of identifying effective treatments for COVID-19 patients who enter the United Kingdom’s National Health Service hospitals. It is sponsored by the University of Oxford.

Reference : University of Oxford 2020a | 2020
Type
Website
Trial document
Acces tool

Recommendation paper on the initiation and conduct of complex clinical trials

Category
  • Regulatory
  • Europe

This key document provides recommendations for sponsors regarding the authorisation and conduct of complex clinical trials. It describes the current perspective of the CTFG on these trials and outlines the major issues that sponsors should address in the process of initiating and conducting complex clinical trials in the EU/EEA.

Reference : CTFG | 2019
Type
Document
Guide
Acces tool

Recommended Ethical, Information Governance and Security Policies for IRPs

Category
  • Trial conduct and documents
  • Trial conduct

This document describes the recommended ethical, information governance and security policies for integrated research platforms (IRPs) of the IMI EU-PEARL project. The deliverable identifies the documents required and the reasons why they are needed. It also identifies existing templates within the EU-PEARL catalogue of products or elsewhere where possible.

Reference : EU-PEARL D1.7 | 2023
Type
Project deliverable
Summary of discussion
Acces tool

RECOVERY 1 year on: a rare success in the COVID-19 clinical trial landscape

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

For the first anniversary of RECOVERY in 2021, Peter Horby, co-lead on the RECOVERY platform trial, was interviewed about the history and future.  RECOVERY recruited 40000 patients into 13 treatment arms. It demonstrated the benefits of the steroid dexamethasone and tocilizumab while showing the lack of efficacy of azithromycin, colchicine, convalescent plasma hydroxychloroquine and lopinavir-ritonavir.

Reference : Mullard | 2021
Type
Commentary
Journal article
Acces tool

Reflection paper on methodological issues in confirmatory clinical trials planned with an adaptive design

Category
  • Regulatory
  • Europe

The document published by EMA outlines some general considerations for studies incorporating interim analyses. A set of minimal requirements must be fulfilled whenever confirmatory clinical trials are planned with an adaptive design. Later sections comment on specific design modifications.

Reference : CHMP | 2007
Type
Document
Guide
Acces tool

Report on Methodological Tools for Intervention Selection

Category
  • Trial conduct and documents
  • Trial conduct

A problem unique to platform trials is deciding not just which investigational medicinal product should be added to the trial but also the correct timing and procedure to avoid a negative impact on external validity and generalizability of the conclusion(s), as well as to minimise delays in the evaluation of ongoing investigational medicinal products. The EU-PEARL framework suggests that independent experts within the Investigational Medical Product Selection Scientific Committee should decide to include a new investigational medicinal product.

Reference : EU-PEARL D2.9 | 2023
Type
Project deliverable
Summary of discussion
Acces tool

Report on regulatory issues of IRPs

Category
  • Regulatory
  • Document from European project

An adaptive platform trial brings new challenges due to its increased operational, logistical and statistical complexity. Regulators, ethics committees and health technology assessment bodies face difficulties assessing these challenges. This report summarises these challenges and potential solutions, focusing on regulatory, ethical and HTA-related aspects.

Reference : EU-PEARL D2.11 | 2023
Type
Project deliverable
Summary of discussion
Acces tool

Report on terminology, references, introduction and design element scenarios for platform trials and master protocols

Category
  • Introduction and design elements
  • Complex innovative design

The project deliverable contains a selective glossary of terms for complex trials and platform trials. It also lists the current published platform trials and contains a curated and rated set of seminal publication references for platform Trials. It was developed within the EU-PEARL project.

Reference : Parke et al | 2020
Type
Project deliverable
Review
Acces tool

Review article: The need for more efficient and patient-oriented drug development pathways in NASH—setting the scene for platform trials

Category
  • Introduction and design elements
  • Consideration for particular field

Non-alcoholic steatohepatitis (NASH) constitutes a significant unmet medical need inclinical research and drug development. Platform trials might help accelerate drug development This review provides a comprehensive and nuanced assessment of the NASH clinical development landscape.

Reference : Pericàs et al (a) | 2023
Type
Journal article
Review
Acces tool

Seamless phase I/IIa platform for the rapid evaluation of candidates for COVID-19 treatment (AGILE)

Category
  • From recent and ongoing trials
  • COVID

AGILE is a multicentre, multi-arm, multi-dose, multi-stage open-label, adaptive, seamless phase I/II Bayesian randomised platform trial to determine the optimal dose, activity and safety of multiple candidate agents for the treatment of COVID-19. It is sponsored by University of Liverpool.

Reference : University of Liverpool | 2021
Type
Website
Trial document
Acces tool

Statistical analysis plan (SAP) template

Category
  • Statistics and data management
  • Guidance support

This is a template of the statistical plan for the platform trial. It is developed within EU-PEARL and based on TransCelerate Statistical Analysis Plan SAP V3.0

Reference : EU-PEARL template3 | 2023
Type
Project deliverable
Template
Acces tool

Statistical consideration when adding new arms to ongoing clinical trials: The potentials and the caveats

Category
  • Statistics and data management
  • Methodology

The journal article reviews the impact on the statistical inference of adding arms. It also covers changing the control arm and how patient eligibility would complicate the trial design and analysis, the more generic statistical literature, and statistical considerations for different phases and funders.

Reference : Lee et al | 2021
Type
Commentary
Journal article
Acces tool

Systematic review of available software for multi-arm multi-stage and platform clinical trial design

Category
  • Statistics and data management
  • Statistical software

This systematic research reviews existing software for the design of platform trials. It was developed within the EU-PEARL project.

Reference : Meyer et al | 2021
Type
Journal article
Software
Acces tool

TB final master protocol for IRP. EU-PEARL work package (WP5) - Integrated research platform for tuberculosis (TB)

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

A major outcome of the EU-PEARL Tuberculosis (TB) work package is the development of a TB master protocol outline to conduct platform trials in the context of an IRP with the final goal of expediting treatment regimen development. EU-PEARL developed a template for the master protocol that guides the protocol author(s).

Reference : EU-PEARL D5.4 | 2023
Type
Project deliverable
Summary of discussion
Acces tool

TB final report on Regulatory and Ethics Consultation. WP5 – Integrated research platform for tuberculosis (TB)

Category
  • Regulatory
  • Document from European project

This consensus document resulted from two very productive meetings held in 2022, which brought together researchers, academics, technical partners, TB drugs and regimens developers, trialists, regulators, guideline developers, programme managers, community representatives and nongovernmental organisations.

Reference : EU-PEARL D5.6 | 2023
Type
Project deliverable
Summary of discussion
Acces tool

TB operational plan to implement TB IRP. EU-PEARL work package (WP5) - Integrated research platform for tuberculosis (TB)

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

Alongside the master protocol, the EU-PEARL Tuberculosis (TB) work package developed operational standards and a set of best practices for planning, conducting, and reporting on IRPs. This report addresses the best practices, among these are crucial aspects of implementing an operational plan, mainly focusing on Community Engagement in the context of a TB IRP. 

Reference : EU-PEARL D5.5 | 2023
Type
Project deliverable
Summary of discussion
Acces tool

The Adaptive designs CONSORT Extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design

Category
  • Trial conduct and documents
  • Reporting

This CONSORT extension provides reporting guidance for any randomised trial using an adaptive design.

Reference : Dimairo et al | 2020
Type
Document
Guide
Acces tool

The adaptive platform trial - The statistical efficiencies

Category
  • Statistics and data management
  • Methodology

The video provides statistical and methodological aspects of adaptive platform trials. It also covers case studies. It was prepared by Berry Consultants.

Reference : Berry Consultants | 2015
Type
Presentation
Video
Acces tool

The COVID-19 Outpatient Pragmatic Platform Study (COPPS): Study design of a multi-center pragmatic platform trial.

Category
  • From recent and ongoing trials
  • COVID

This is a protocol paper of the COVID-19 Outpatient Pragmatic Protocol Study (COPPS), a flexible phase 2, multi-site, randomised, blinded trial based at Stanford University designed to overcome these issues by simultaneously evaluating multiple COVID-19 treatments in the outpatient setting in one common platform with shared controls.  

Reference : Bunning et al | 2021
Type
Journal article
Summary of protocol
Acces tool

The European clinical research response to optimise treatment of patients with COVID-19: lessons learned, future perspective, and recommendations

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

This review assesses the characteristics of implemented adaptive design clinical trials and provides examples of regulatory experience with such trials.

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

The evolution of master protocol clinical trial designs: a systematic literature review

Category
  • Trial conduct and documents
  • Template / guide for developing document

The journal review identifies existing master protocol studies and summarizes their characteristics. The review also identifies articles relevant to the design of master protocol trials, such as proposed trial designs and related methods.

Reference : Meyer et al. (a) | 2020
Type
Journal article
Systematic review
Acces tool

The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: An overview of network organization, procedures, and interventions

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

This paper describes the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network. The PrecISE Network was designed to conduct phase II/proof-of-concept clinical trials of precision interventions in the population with severe asthma. Using an innovative adaptive platform trial design, the PrecISE Network simultaneously evaluates up to 6 interventions in biomarker-defined subgroups of subjects. 

Reference : Georas et al | 2021
Type
Experience
Journal article
Acces tool

The UPMC OPTIMISE-C19 trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization

Category
  • From recent and ongoing trials
  • COVID

This paper presents the protocol for OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antibodies through Evaluation for COVID-19), an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization. The primary objective is to evaluate the comparative effectiveness of COVID-19-specific monoclonal antibodies (mABs) with US FDA Emergency Use Authorization (EUA), alongside UPMC Health System efforts to increase patient access to these mABs.

Reference : Huang et al | 2021
Type
Journal article
Summary of protocol
Acces tool

This is a platform alteration: a trial management perspective on the operational aspects of adaptive and platform and umbrella protocols

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

The journal article provides experiences gathered in FOCUS4 and STAMPEDE adaptive platform trials from a trial management perspective, highlighting the challenges and successes encountered in running adaptive platform trials.

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

TOGETHER clinical trial

Category
  • From recent and ongoing trials
  • COVID

The TOGETHER clinical trial started in June 2020 as an international collaboration in response to the worsening pandemic of SARS-CoV-2 / COVID-19. Utilizing an adaptive platform trial design, the international researchers and teams in Brazil, Canada, Australia, and the United States sought to identify evidence-informed therapeutics by repurposing existing medications to identify effective repurposed therapies to prevent the disease progression of COVID-19.

Reference : TOGETHER | 2020
Type
Website
Trial document
Acces tool

TRD and PRD final master protocol for IRP. EU-PEARL work package (WP4) – Integrated research platform for major depressive disorder (MDD)

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

EU-PEARL developed an adaptive platform trial for treatment-resistant depression (TRD) and partially responsive depression (PRD). This platform trial allows new treatments to be added to the trial anytime they become available for testing, increases the speed by which we can provide the best treatments, and requires fewer participants overall. The present document describes the master design of this platform trial.  

Reference : EU-PEARL D4.5 | 2023
Type
Project deliverable
Summary of protocol
Acces tool

TRD/PRD final report on regulatory and ethics consultation. WP4 – Integrated research platform for major depressive disorder (MDD)

Category
  • Regulatory
  • Document from European project

The report presents a draft of how EU-PEARL envision an integrated research platform for depression. This draft has been discussed formally with the European Medicines Agency (EMA), and feedback has been received from EMA experts to ensure that the trial yields speedy results on the benefit of any new drug tested and maintains the highest ethical and safety standards.

Reference : EU-PEARL D4.7 | 2023
Type
Project deliverable
Summary of discussion
Acces tool

Trial feasibility in federated hospital networks

Category
  • Trial conduct and documents
  • Trial conduct

This article describes the prototype tools and guidance documents created to help build the hospital network as part of an integrated research platform that can conduct platform trials. 

Reference : EU-PEARL D3.7 | 2023
Type
Project deliverable
Summary of discussion
Acces tool

Uptake of the multi-arm multi-stage (MAMS) adaptive platform approach: a trial-registry review of late-phase randomised clinical trials

Category
  • Introduction and design elements
  • Complex innovative design

This review examined the uptake of registered, late-phase MAMS platforms in the EU clinical trials register, etc., highlighting the potential scope of MAMS platform trials and may assist research teams considering using this approach in the late-phase randomised clinical trial setting.

Reference : Noor et al | 2022
Type
Journal article
Systematic review
Acces tool

WHA 75.8 resolution: Strengthening clinical trials to provide high-quality evidence on health interventions and to improve research quality and coordination

Category
  • Regulatory
  • International

These are the recommendations presented by WHA 75.8 for best practices and other measures to improve the global clinical trials ecosystem, taking into account existing initiatives. This may include the role of WHO, Member States and non-State actors. 

Reference : WHA | 2022
Type
Document
Guide
Acces tool

WHO guidance for best practices for clinical trials draft for public consultation

Category
  • Regulatory
  • International

This guidance was developed to implement the request of the Director General in the WHA resolution 75.8. It is under public consultation (accessed on 21 Sep 2023).

Reference : WHO Guidance | 2023
Type
Document
Guide
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.