The adaptive platform trial toolbox

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. 

This document explains the feasibility of protocol for patient recruitment using Communication Technology (ICT). This tool enables the reuse of Electronic Health Record (EHR) data, supporting an industry or public platform trial sponsor and contributing research organisations to undertake platform trials. 

Recruiting participants remains crucial to research efficiency in platform trials with more extensive and complicated trial designs. This document describes a proposal for a generic process for gaining an estimate of patient numbers that match the clinical study inclusion criteria at hospitals, based on the analysis of hospitals' Electronic Health Records (EHR)

Global Coalition for Adaptive Research (GCAR) is a non-profit organisation in the US, committed to uniting stakeholders and developing and sponsoring Master Protocols and adaptive platform trials such as GBM AGILE for brain cancer, REMAP CAP US (for COVID) to speed the discovery of treatments for rare and deadly diseases. The website presents several sets of information about platform trials with short video presentations. 

Guidance for a cover letter outlines the critical point when submitting a platform trial application to the regulatory authority. This guideline applies to the companion protocol templates, Master Protocol Template and Intervention Specific Appendix Template prepared within the EU-PEARL consortium.

A national platform trial jointly sponsored by Cambridge University Hospitals NHS Foundation Trust and The University of Cambridge. It aims to evaluate the impact of treatments on longer-term morbidity, mortality, re-hospitalisation, symptom burden and quality of life associated with COVID-19.

This Users’ Guide is intended to help clinicians and readers understand articles reporting on interventions evaluated using platform trial designs.

Adaptive platform phase 2 trials family with a Bayesian design to investigate treatments for COVID-19. It is sponsored by QuantumLeap Healthcare Collaborative.

This document describes internationally accepted principles and practices in conducting individual clinical trials and overall development strategies for new medical products. R1 contains statements for a wide range of study designs (platform trials etc.) and various data sources.

Between 2001 and 2019, 16 platform trials were initiated globally for the COVID-19 pandemic. This review was conducted to quantify and describe platform trials used in COVID-19.

This journal article presents the Bayesian, adaptive, platform trial INSIGhT to develop precision medicine approaches in glioblastoma. Detailed information on the statistical model, simulations, and randomization algorithm is provided with expected benefits and challenges.

European Federation of Pharmaceutical Industries and Associations (EFPIA) Clinical Research Expert Group developed this white paper as a landscape review of innovation in clinical trial design, such as adaptive designs.

Clinical Trial Design Software for calculating sample size for basket and platform trials developed by the university of Texas MD Anderson Cancer Center.

This FDA document guides to sponsors and applicants in interacting with the FDA on complex innovative trial design proposals for drugs or biological products. It also covers some critical aspects of complex trial designs.

This intervention-specific appendix (ISA) template for platform trials contains instruction text, common / suggested text, variable text and examples. It is downloadable as a Microsoft Word document for readers' editing. This template is used with the Master Protocol Template, developed within the EU-PEARL project, based on TransCelerate Common Protocol Template CPT V8.0.

Adaptive platform phase 2 trials family with a Bayesian design to investigate treatments for breast cancer. It is sponsored by QuantumLeap Healthcare Collaborative.

This deliverable describes the value proposition of the IRP for NASH, the lessons learned during the project duration that affect the options available to fund and set up the IRP, and the proposed plan to implement such lessons in the future. 

This deliverable explains several tools developed by the EU-PEARL project to sustain the integrated research platform (IRP) for TB. Tools are a master protocol template including a design proposal for TB adaptive trials, an operational plan (a community engagement plan),  the Capacity Building and Assessment Handbook for sites to conduct TB drug development trials within the IRP environment, and a systematic review to identify and assess host and bacterial biomarkers able to predict end of treatment outcomes.

The video with slides discusses the accumulated experience from the REMAP-CAP COVID-19 platform trial, focusing on design, Bayesian statistical model, data management, interpretation of results, funding, and challenges for publication and trial logistics. It was hosted by NIH Collaboratory. 

The EU-PEARL project aims to develop an adaptive platform trial for difficult-to-treat depression. This report gives the public information about observational research on difficult-to-treat depression that is a part of this new framework of platform design.  LMHS enables us to recruit a large and continuous number of participants and promote a sustainable model for conducting clinical trials in this field.

This CTTI website includes a step-by-step tool for developing master protocols. It also contains guides for implementing the protocol and statistical considerations.

This template of the master protocol (MPT) for the platform trial contains instructional text, common / suggested text, variable text and examples, and it is downloadable as a Microsoft Word document for readers' editing. It is developed within the EU-PEARL project, based on TransCelerate Common Protocol Template CPT V8.0.

This FDA guidance provides advice to sponsors of drugs and biologics for cancer treatment regarding the design and conduct of clinical trials, other than first-in-human trials, intended to simultaneously evaluate more than one investigational drug and/or more than one cancer type within the same overall trial structure (master protocols) in adult and pediatric cancers.

This review summarises published platform trials and examines specific methodological design features among these studies, including the basics of methodological and statistical considerations.

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.

FOCUS4 is an adaptive, molecularly stratified trial that aims to improve the efficiency with which new novel agents can be tested in colorectal cancer. It has a multi-arm, multi-stage design with a master protocol. It is sponsored by University College London.

Motor Neuron Disease Systematic Multi-Arm Adaptive Randomised Trial (MND-SMART) aims to evaluate the efficacy of drugs efficiently and definitively in a multi-arm, multi-stage, adaptive trial. The first two drugs selected for evaluation in MND-SMART are trazodone and memantine.

One of the work packages of the EU-PEARL project developed a master protocol to conduct platform trials (phase 2b) for NASH.

This document presents the process of eliciting feedback from regulatory (EMA innovation task force) and ethics stakeholders for the master protocol for a NASH platform trial.

R-package NCC (https://CRAN.R-project.org/package=NCC) is for the design and analysis of platform trials using non-concurrent controls. NCC allow for simulating platform trials and evaluating the properties of analysis methods that use non-concurrent controls in various settings. This paper describes the main NCC functions and shows how to use the package to simulate and analyse platform trials through specific examples.

The document and attached presentation discuss adaptive design elements for clinical trials, including advantages, disadvantages, rare diseases, and involvement of patients. It was prepared by EUPATI.

The platform trial for NF developed by EU-PEARL will consist of an observational and a treatment phase. In the observational phase, patients will not be treated with an investigational agent and will provide data on the natural course of the disease. If patients need treatment and a drug is available, patients will be randomised to a treatment arm. This deliverable aims to report the finalised master protocol for the platform trial for NF. 

This report results from a collaboration between the EU-PEARL clinicians, patients, industry, regulatory experts, and Erasmus Universitair Medisch Centrum Rotterdam (EMC) regulatory and ethics review. It also includes a brief produced for an EMA Innovation Task Force meeting in close collaboration with the Global Coalition for Adaptive Research (GCAR), which is expected to play an essential role in the sustainability of the NF platform trials. 

This article discusses the use of non-concurrent controls in adaptive platforms. In addition to concurrent controls, non-concurrent controls can improve the trial’s efficiency by increasing power and reducing the required sample size but can introduce bias due to time trends.

EU-PEARL has designed two platform trials for NF, one for NF1 and the other for Schwannomatosis tumours. This report explains the steps needed to make these trials happen.

This document serves as a template for a Clinical Operations Plan  to support the proposed integrated research platform (IRP) for NASH. It provides specific details regarding where different sets of instructions can be found, who should take on specific activities, and what information needs to be recorded from the beginning to the end of the trial. 

EU-PEARL has developed an Integrated Research Platform for Major Depressive Disorder (MDD). This report shows an overview of the stakeholder interaction and consultation, including regulators, ethics committees, the biopharmaceutical Industry, clinicians/academics, and patient or community representatives. 

Within EU-PEARL, several Patient and Community Engagement workshops and sessions were organised with different aims, evolving as the project progressed. This deliverable informs on the EU-PEARL Platform for Patient and Community Engagement in Platform Trials (PaCEPT) and the outcomes of the patient and community engagement (PCE) workshops delivered together with patient and community representatives. Lastly, it covers the design and development of the PaCEPT platform.

PANORAMIC is a NIRH-funded, national priority adaptive platform trial in the UK, designed as a platform clinical trial for the early treatment of the COVID-19 community.

This deliverable describes how and why one of the working groups of the EU-PEARL project developed an online repository, the EU-PEARL Platform for Patient and Community Engagement (PaCEPT). PaCEPT enables researchers to learn how to engage with patients and communities in platform trials, explains what platform trials are in lay language to patients and affected communities, and provides resources for Patient and Community Advisors who want to actively shape platform trials.

This study is a national priority, country-wide  platform, randomised controlled trial in primary care that can rapidly test low-risk treatments for people at higher risk of complications from COVID-19. The intent is to establish an on-going trial infrastructure within a master protocol. It is sponsored by the University of Oxford.

The tool contains the main tasks involved in planning a clinical trial, highlighting the special considerations that arise when designing a platform trial on top of those typical for a conventional trial.

This article discusses the platform trials in clinical psychology. It could have a transformative effect by increasing the speed with which treatment effects are estimated, getting effective interventions into clinical care more quickly, and providing much-needed comparisons between different interventions for the same condition.

This commentary reviews the experiences of several platform trials for COVID-19, such as REMAP-CAP, WHO Solidarity, RECOVER, ATTACC, PRINCIPLE, AGILE, COPPS, and OPTIMISE C-19, and focuses on the basic concepts and methodological keys of platform trials using some of the recent developments in COVID-19 treatment to illustrate the potential of these trial designs.

This paper provides an overview of platform trials and discusses the possibility of this design for clinical trials in anaesthesia.

Although the pipeline for drug development in NASH, active conventional Phase 3 trials often fail to achieve the endpoints necessary for approval by regulatory agencies. Adaptive trials might be an attractive complement or alternative to conventional clinical trials by using a master protocol that allows evaluation for multiple investigational medicinal products concurrently or sequentially with a single, shared control arm. The possibility of using adaptive platform trials in NASH drug development is discussed.

This paper provides an overview of the master protocol framework, unifies the definitions with some examples, reviews the statistical methods for the designs and analyses, and focuses its discussions on some practical considerations and recommendations for master protocols to help practitioners better design and implement such studies.

PrecISE, or Precision Interventions for Severe and/or Exacerbation-Prone Asthma Network, is a network of medical centres, doctors, and scientists sponsored by the U.S. National Heart, Lung, and Blood Institute (NHLBI) established to design and execute a trial that uses adaptive platform design techniques. This paper systematically evaluates novel interventions in biomarker-defined subgroups of severe asthma.

The EU-PEARL established an Integrated Research Platform (IRP) for Neurofibromatosis, including Neurofibromatosis type 1 (NF1). Patients for the treatment arms of the NF1-IRP will be selected from an underlying longitudinal natural history study (LNHS), forming the backbone of the IRP. This document presents a detail of LNHS.

This is a protocol paper for the DISCOVERY trial, a multi-arm randomised controlled trial for COVID-19, developed by the French National Institute for Health and Medical Research (Inserm). The objective of the trial is to evaluate the clinical efficacy and safety of different investigational re-purposed therapeutics relative to the standard of care in patients hospitalised with COVID-19.