The adaptive platform trial toolbox

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.

MND-SMART is a UK-wide, long-term adaptive platform trial designed to evaluate multiple repurposed drugs simultaneously for motor neuron disease (MND). This webpage includes trial information, patient materials (short videos and newsletters), a protocol paper(Wang 2022, Beswick 2021), and a statistical plan paper (Parker 2023). 

The TACTIC programme is a multi-arm, platform trial designed to test immune-modulating treatments for COVID-19 patients at risk of severe disease, aiming to reduce ICU admissions. It includes two trials: TACTIC-R, repurposing existing drugs, and TACTIC-E, testing new experimental treatments. The platform allows treatments to be added or removed based on emerging data on effectiveness or safety. This website includes some platform trials under this program, such as TACTIC -E (https://cctu.org.uk/portfolio/COVID-19/TACTIC/TACTIC-E) and TACTIC -R (https://cctu.org.uk/portfolio/COVID-19/TACTIC/TACTIC-R), including a master protocol and PIC.

EU-PEARL developed an adaptive platform trial for non-alcoholic steatohepatitis (NASH).This master protocol for phase 2b provides a framework for its implementation within the IRP structure. 

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 parent website includes educational materials and webinars for patients participating in clinical trials.

EU-PEARL developed an adaptive platform trial for neurofibromatosis (NF). 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. 

Supported by the National Institutes of Health, the NIH Pragmatic Trials Collaboratory is intended to improve the way clinical trials are conducted by creating a new infrastructure for collaborative research within healthcare systems. There are several presentations regarding APT;  REMAP-CAP(05-15-20, 04-02-21, 08-11-22), I-SPY (08-21-20), ACTIVE(07-15-22, 04-30-21), PRINCIPLE (05-21-21), TOGETHER (07-29-22, 03-18-22, 08-06-21), HEALEY-ALS (04-11-25), and RECOVERY(04-24-20)

OCTOPUS is a platform trial sponsored by University College London, aiming to identify treatments that can slow, stop, or reverse disability progression in individuals with progressive multiple sclerosis (MS). The trial began recruitment in early 2022, and as of June 2025, over 400 participants have been randomised across approximately 26 sites across the UK and internationally. It exemplifies the use of platform trial designs in MS. The official trial website provides current versions of the protocol, patient information sheets, webinars, and related publications including concept papers. The Australian extension is PLAYPUS (https://www.msaustralia.org.au/platypus/).

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 workshops delivered together with patient and community representatives. 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. The recruitment has stopped in 2024. This website includes protocol, ICF or other trial documents

The EJS ACT-PD consortium formed a patient engagement working group of patients and care partners, developed collaborative processes, and is evaluating the impact of patient engagement. This study presents results from a mixed-methods approach—including surveys, interviews, and document reviews—and offers practical insights on implementing and assessing PE in complex clinical trials.

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.

The TOGETHER Trial, took place in one state of a middle-income country (Brazil) with a more fragmented health system compared with the other platform trial such as PRINCIPLE Trial in UK. But those were similarly successful in recruiting patients. This paper describes the attributes of the TOGETHER Trial within the framework of health system resiliency.

This is the protocol paper for the PANORAMIC trial—a UK-wide, open-label, prospective, adaptive, multiarm platform randomised clinical trial evaluating the safety, effectiveness, and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated, high-risk patients in the community. Eligible participants are randomised to usual care or an antiviral plus usual care, with daily electronic symptom diaries and a primary endpoint of all-cause, non-elective hospitalisation and/or death within 28 days. The design includes multiple preplanned interim analyses to allow interventions to be stopped for futility or superiority.

This is the protocol paper for the PRINCIPLE trial, a decentralised, adaptive platform trial designed to evaluate treatments for COVID-19 in older adults in the community. The trial tests multiple interventions, including hydroxychloroquine, azithromycin, and doxycycline, with eligibility based on age, symptoms, and comorbidities. Recruitment is conducted through general practices, helplines, and online platforms, and data are collected via an online symptom diary. 

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, sponsored by the University of Oxford. Recruitment ended in 2024, but the website provides some information as trial guides, such as master protocol and glossary.

EU-PEARL developed a tool that contains 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. The summary of this tool is explained in the deliverable D2.10-Final Report on Clinical Operations Best Practices (https://eu-pearl.eu/wp-content/uploads/2023/05/D2.10-Final-Report-on-Clinical-Operations-Best-Practices-1.pdf).

Although Platform trials are particularly useful in rapidly evolving disease areas or emergencies, optimising patient numbers, costs, and timelines. They also raise complex methodological, ethical, and regulatory issues, including challenges in sponsorship, data management, and acceptability of results by authorities. This review summarises the discussions on these topics held at a round table.

This commentary reviews the experiences of several platform trials for COVID-19, such as REMAP-CAP, WHO Solidarity, RECOVER, ACTIVE, 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.

This paper by the EU/US CTAD Task Force discusses the growing importance of platform trials in Alzheimer’s disease (AD) research. It reviews examples such as DIAN-TU and other ongoing or planned initiatives, highlighting their advantages in terms of shared infrastructure, adaptive design, and the ability to study combination treatments. The authors also outline key operational challenges, such as ensuring biomarker standardisation and managing heterogeneity in trial populations. Overall, the paper serves as a strategic overview to guide the development and optimisation of platform trials in AD.

Despite an active pipeline, conventional Phase 3 trials for NASH often fail to achieve the endpoints necessary for regulatory approval. 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 website presented by Berry consulting introduced some softwares, such as FACTS, ADDPLAN, and QUOTES particulally optimasefd for complex clinical trials.There are on payment after 3 months trials. This websites also includes some examples from the current platform trials.

Master protocols—including basket, umbrella, and platform trials—are innovative trial designs aimed at accelerating drug development. Despite their conceptual advantages, uptake remains limited due to statistical and operational challenges. This article summarises master protocol types, clarifies definitions, reviews key statistical methods, and offers practical recommendations for their design and implementation.

PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma Network) is a collaborative network of medical centres, clinicians, and researchers sponsored by the U.S. National Heart, Lung, and Blood Institute (NHLBI).This paper presents the protocol for the PrecISE trial, which employs an adaptive platform design to systematically evaluate novel interventions in biomarker-defined subgroups of patients with severe asthma.

PROTECT (PROphylaxis for patIEnts at risk of COVID-19 infecTion) is a basket trial of prophylactic interventions in at-risk patients, with randomisation stratified by subpopulation (https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/protect-covid-19/?utm_source=chatgpt.com). PROTECT-V is a platform trial under the PROTECT project, designed to evaluate the efficacy of multiple interventions in individuals with primary or secondary immunodeficiency. The trial was closed in May 2023 (https://www.camcovidtrials.net/trials/view,protect_50.htm).

PROTECT(PROphylaxis for patIEnts at risk of COVID-19 infecTion) is a basket trial evaluating prophylactic interventions for at-risk patients (https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/protect-covid-19/?utm_source=chatgpt.com). PROTECT-CH is one sub-study, designed as a UK-wide platform clinical trial to evaluate COVID-19 prophylactic treatments in care home residents. The trial was not implemented due to changes in the pandemic status and the introduction of new treatments. However, the trial website includes the protocol, statistical analysis plan (SAP), informed consent forms (ICF), and training materials.

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), according to the master protocol from WHO Solidarity. The objective of the trial is to evaluate the clinical efficacy and safety of different investigational repurposed therapeutics relative to the standard of care in patients hospitalised with COVID-19.

RAMPART (Renal Adjuvant MultiPle Arm Randomised Trial) is an international investigator-led phase III multi-arm multi-stage, multi-centre randomised controlled platform trial of adjuvant therapy in patients with resected primary renal cell carcinoma at high or intermediate risk of relapse.

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. This website includes the trial documents (current PRT, SAP and DM charter), webinar, news, commentaries, and publications.

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.

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.

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.

The EU-PEARL project systematically reviewed EU and US guidelines, engaged with regulatory bodies, and gathered input from stakeholders, including ethics committees and HTA bodies, to address these challenges. A master protocol template was developed alongside the identification of unresolved issues, such as clinical trial submissions, multiplicity control, non-concurrent controls, and randomisation schemes. Early dialogue with stakeholders remains essential to effectively implement platform trials and mitigate their complexities.

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 generalisability 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.

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.

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.

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.

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 the University of Liverpool. This webpage includes essential trial document (protocol, protocol papers, ICF and lab manual), and short videos.

This study explored using response-adaptive randomisation (RAR) in the RECOVERY trial. Simulations showed RAR would have allocated more patients to dexamethasone, reduced mortality, and maintained unbiased results. Though it sometimes lowered statistical power, it could have identified effective treatments sooner. The findings highlight ethical trade-offs between benefiting current and future patients.

The Staphylococcus aureus bacteraemia Network Adaptive Platform Trial is an innovative trial to evaluate a range of interventions with the aim of improving outcomes for patients with Staphylococcus aureus bacteraemia (AKA bloodstream infections). The study includes sites from throughout Australia, New Zealand, Singapore, Canada, Israel and the UK and has the potential to include sites elsewhere in the world. This website includes trial documents, such as core protocol, the domain-specific protocol and the SAP 

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