The Clinical Trials Transformation Initiative (CTTI) brings together regulators, sponsors, investigators, sites and patients to study these problems and turn the findings into practical tools and recommendations that anyone can use. CTTI’s resources cover the full trial lifecycle—from feasibility and start‑up to recruitment, conduct and reporting—with a shared goal: higher‑quality, more efficient and more patient‑centred trials.

This article from the European Forum for Good Clinical Practice eConsent Initiative introduces the eConsent Fit‑for‑Purpose Study Framework, a stepwise method to design electronic informed consent for each individual study. It explains how to define study‑specific objectives, select the most suitable digital features and operational set‑up, involve key stakeholders, and plan metrics and analysis so that electronic informed consent can be evaluated in a consistent way. The framework is vendor‑neutral and intended for both commercial and non‑commercial sponsors, offering investigator‑initiated studies a practical way to move from technology‑driven decisions to a participant‑ and site‑centred electronic informed consent strategy that generates meaningful, comparable data.

This European Commission guidance provides recommendations on the ethical aspects of conducting clinical trials involving children and adolescents. It addresses key considerations for protocol development and trial conduct, including risk–benefit assessment, informed consent from parents or legal representatives, child assent, age-appropriate information, protection of vulnerable participants and involvement of minors in research decisions. Although developed within the European regulatory framework, the principles are broadly applicable to paediatric and rare disease clinical trials, where ethical considerations, family involvement and participant-centred approaches are essential for successful study implementation.

The Cambridge Clinical Trials Unit (CCTU) has made available its quality management documentation - including standard operating procedures, policies, and templates - covering the full lifecycle of sponsored clinical trials. Freely accessible on the CCTU governance page, these materials serve as practical reference documents for investigator‑led clinical research teams and span all trial phases: pre‑trial (planning, protocol development, set‑up), conduct (trial documentation, pharmacovigilance, data management, and statistics), and post‑study (close‑down, post‑study procedures, and archiving).

The NCCIH Clinical Research Toolbox is a web‑based information repository for investigators and staff involved in NCCIH‑funded clinical research. Developed by the National Center for Complementary and Integrative Health (US NIH), it brings together required templates, sample forms, FAQs, policies and guidance to support the development and conduct of high‑quality clinical research studies. Content is organised into sections such as clinical research start‑up, documents used during study conduct, on‑site monitoring, milestone documents and additional training and recruitment resources, making it a practical reference point for investigator‑initiated trials. Although some elements are specific to the NCCIH research, many sections on trial planning and development are also relevant to European researchers conducting investigator‑initiated studies.

The Easy Guide to Clinical Studies (Easy GCS) is an online tool developed by the Swiss Clinical Trial Organisation (SCTO) Project Management Platform, with input from all SCTO platforms and the Swiss Biobanking Platform. It provides easily accessible, phase‑specific guidance for planning and conducting clinical studies, organised in a grid that combines six study phases with key subjects such as protocol, ethics and laws, study management, safety, data management, statistics, quality and risk, monitoring, and biobanking. Each cell links to topic pages that answer three practical questions: what the topic is and why it matters, what needs to be done, and where to get help. The tool is aimed at sponsor‑investigators, site investigators, research coordinators and other clinical research professionals, and supports investigator‑initiated studies in Switzerland and beyond by clarifying regulatory requirements and operational good practice from study concept through to completion

Hosted by Trial Forge, this online library provides real‑world Participant Information Leaflets (PILs) and Informed Consent Forms (ICFs) used in randomised trials, assembled through the EXCELSIOR project. The collection allows researchers to see how key trial concepts such as randomisation, placebo use and withdrawal rights are actually explained to potential participants in practice. Investigators can review and compare wording across trials and use these examples to inform the design of their own participant information leaflets and consent forms for future studies.

A harmonised European template for agreements between trial sponsors and clinical sites that facilitates the setup of multi-country clinical trials. It standardizes key contractual provisions, reduces negotiation time and administrative burden, supports compliance with ICH Good Clinical Practice, and promotes efficient collaboration across participating sites. It is particularly useful during the trial initiation and site activation stages of clinical trial management. Developed by ECRIN within the ERA4Health project, its primary objective is to streamline and standardize contractual negotiations between trial sponsors and participating clinical sites while accommodating national legal requirements.

Endorsed by the EU Clinical Trials Coordination and Advisory Group (CTAG), this European Commission template supports sponsors and investigators in describing recruitment arrangements and informed consent procedures for clinical trials under Regulation (EU) No 536/2014. It is not mandatory, but if it is not used, all items it covers must still be addressed in the protocol as a minimum. The template guides users through how potential participants are identified and approached, how consent is obtained and documented, and how special situations such as incapacitated adults, minors, emergency research and cluster trials are handled. It is most useful for EU/EEA trials needing a structured, regulator‑aligned description of recruitment and informed consent arrangements, including investigator‑initiated CTIMPs.

The Adaptive Platform Trial Toolbox is an online resource developed by ECRIN, European Clinical Research Infrastructure Network, and partners within EU‑funded projects such as RECOVER and EU‑RESPONSE. It collates accumulated knowledge, experience and resources from multiple adaptive platform trials into a practical, guided toolbox to support the planning and conduct of future adaptive platform trials in any therapeutic area. More than 130 tools are organised into categories and subcategories, each with a short description of format and level of validation, helping researchers and sponsors quickly find relevant guidance, templates and examples for complex platform trial designs.

EU‑X‑CT initiative aims to improve safe and equitable access to clinical trials in Europe when suitable options are not available in a patient’s home country. The document shares practical approaches to cross‑border recruitment, conduct and follow‑up and is linked to the wider EU‑X‑CT online resources for patients, caregivers and clinical trial professionals, including a trial preparator and country profiles for selected European states.The initiative has developed general recommendations on key aspects of clinical trial management and conduct to address the challenges faced by participants who travel across borders to join a study. These recommendations were developed through a multi‑stakeholder process coordinated by the European Forum for Good Clinical Practice (EFGCP) and the European Federation of Pharmaceutical Industries and Associations (EFPIA).

This ERA4Health report  presents a structured mapping of organisations that can support at national or international level the planning, design, and conduct of multicountry Investigator Initiated Clinical Studies (IICS) in Europe. It compiles information on the services offered by clinical trial units (CTUs), academic clinical research centres, national coordinating centres, disease‑specific networks, and other non‑commercial infrastructures that provide services for investigator‑led clinical trials. For each organisation, the report documents core competencies, target trial phases, therapeutic focus (where applicable), geographic scope, and experience with multinational trials.

The GA4GH Regulatory & Ethics Toolkit provides internationally applicable guidance, frameworks and practical resources to support the responsible governance, ethical oversight and sharing of genomic and health-related data in research. The toolkit addresses key aspects of trial management, including consent, data access, privacy, governance and responsible data sharing. It is particularly relevant for rare disease clinical trials, where genomic information, international collaboration and secondary use of research data are often essential for improving diagnosis, developing therapies and enabling efficient multicentre studies. Although focused on genomics, the principles and resources are broadly applicable to paediatric and rare disease clinical research.

This PedCRIN guidance provides practical recommendations for obtaining informed consent in neonatal clinical trials. It addresses specific challenges related to parental decision-making, communication of study information, timing of consent discussions, and ethical considerations when enrolling newborns into research. Although developed for neonatal studies, the principles are highly relevant to paediatric and rare disease clinical trials, where families may face complex decisions, limited treatment options and emotionally challenging circumstances requiring carefully designed consent processes.

This Enpr-EMA guidance provides practical recommendations for developing informed consent and assent processes in paediatric clinical trials. It supports researchers and sponsors in preparing age-appropriate information and consent materials for children, adolescents and their parents or legal representatives, considering the specific needs of different paediatric age groups. Developed within the European paediatric research framework, the guidance is particularly relevant to rare disease clinical trials, where many conditions have a childhood onset and meaningful involvement of children and families is essential for ethical and successful study conduct.

This European Commission guidance provides recommendations on the ethical aspects of conducting clinical trials involving children and adolescents. It addresses key considerations for protocol development and trial conduct, including risk–benefit assessment, informed consent from parents or legal representatives, child assent, age-appropriate information, protection of vulnerable participants and involvement of minors in research decisions. Although developed within the European regulatory framework, the principles are broadly applicable to paediatric and rare disease clinical trials, where ethical considerations, family involvement and participant-centred approaches are essential for successful study implementation.

This PedCRIN guidance provides practical recommendations for planning participant enrolment during the development of neonatal clinical trial protocols. It addresses key factors that influence successful recruitment, including enrolment pathways, communication with parents and families, informed consent, site preparation and investigator engagement. Although developed for neonatal trials, the guidance addresses recruitment challenges that are common across paediatric and rare disease clinical research, where small patient populations and complex study procedures require careful planning to optimise enrolment and study feasibility.

Trials@Home is a public–private partnership funded by the Innovative Medicines Initiative that has developed recommendations for decentralised clinical trial approachesl.The consortium explored how to move trial activities from traditional sites to the participant’s immediate surroundings using digital and operational innovations. Investigator‑initiated studies can use these recommendations to design, implement and evaluate decentralised or hybrid trials, improve participant accessibility and retention, and ensure appropriate oversight, data protection and site support. Its main and in‑depth recommendations cover methodological, regulatory, ethical, operational and social aspects of decentralised clinical trials.

This recommendation paper provides harmonised guidance on introducing decentralised elements into clinical trials with investigational medicinal products in the EU/EEA, beyond any specific health‑crisis context. Developed under the Accelerating Clinical Trials in Europe (ACT EU) initiative by the Heads of Medicines Agencies Clinical Trials Coordination Group (HMA CTCG), the European Commission Clinical Trial Expert Group (CTEG) and the European Medicines Agency Good Clinical Practice Inspectors Working Group (EMA GCP IWG), it reflects the common view of the European medicines regulatory network but is not legally binding. The document includes investigator oversight, informed consent (including electronic methods), delivery and home administration of investigational medicinal products, trial‑related procedures at home, data collection and management, and trial monitoring in decentralised settings, supported by an appendix with an overview of national provisions per EU Member State. Investigator‑initiated and academically sponsored trials can use this paper to plan and document risk‑proportionate decentralised or hybrid designs while protecting participants and ensuring robust data.

Hosted by the Global Health Trials Knowledge Hub (TGHN), this open-access library provides over 100 ready-to-use templates and tools spanning the full clinical trial lifecycle. Categories cover protocol development, participant enrolment and retention, informed consent, IMP management, data management, site management, ethics, safety reporting, staff management, and quality assurance. Designed primarily for trials in global health settings, templates are directly adaptable for investigator-led studies.

The INCLUDE Project Guidance provides practical recommendations and resources to help researchers design and conduct more inclusive clinical studies by identifying and addressing barriers to participation for under-served populations. Developed by the UK National Institute for Health and Care Research (NIHR), the guidance covers recruitment strategies, participant communication, informed consent, study design and operational considerations that support equitable access to research. Although developed within the UK research context, its principles are broadly applicable to international clinical research and are particularly relevant to rare disease trials, where small, geographically dispersed populations and barriers to participation can significantly affect recruitment, retention and study representativeness.

The Enpr-EMA Network Database is a searchable directory of paediatric research networks and centres recognised by the European Medicines Agency for their expertise in conducting clinical studies in children. It enables researchers and sponsors to identify potential collaborators, specialised trial sites and research infrastructures based on therapeutic expertise, research experience, quality management and geographical coverage. Although developed for paediatric clinical research, the database is highly relevant to rare disease trials, as many rare diseases have a paediatric onset and require multinational collaboration between specialised centres. It provides a practical resource for identifying experienced partners to support the planning and management of multicentre rare disease clinical trials.

This PedCRIN guidance provides practical recommendations for assessing the feasibility of neonatal clinical trials and selecting appropriate investigator sites and study centres. It outlines key considerations for evaluating study feasibility, site capabilities, patient availability, infrastructure, clinical expertise and local operational requirements before trial initiation. Although developed for neonatal studies, the principles are broadly applicable to paediatric and rare disease clinical trials, where successful study delivery often depends on identifying specialised centres with the expertise, patient population and research capacity needed to conduct complex multicentre studies.

The Portico Center Toolkit Modules provide practical resources, templates and training materials to support the management and conduct of clinical trials. Developed within the context of paediatric musculoskeletal disease research, the toolkit covers key operational aspects such as participant recruitment and retention, informed consent, participant engagement, health literacy, diversity and inclusion, and decentralized trial approaches. Although developed for paediatric musculoskeletal research, the tools address common operational challenges encountered across paediatric and rare disease clinical trials and can be readily applied to support participant-centred and efficient trial conduct in a wide range of rare disease settings.

The UKTMN Guide to Efficient Trial Management is a practitioner‑written reference for those involved in managing non‑commercial, academically initiated clinical trials in the UK. Hosted by the Nottingham Clinical Trials Unit, University of Nottingham, and overseen by the UK Trial Managers’ Network Editorial Board, it describes the process of understanding and managing randomised trials and outlines the trial management framework, both legal and operational, providing pragmatic advice, hints, tips and links to external resources. It is written primarily for new trial managers as an essential reference tool, and also serves as an aide‑mémoire and induction resource for more experienced staff. Although some elements are specific to the UK national infrastructure, many sections on trial planning and development are also relevant to European researchers conducting investigator‑initiated studies.

Developed by the Good Clinical Trials Collaborative (GCTC), this guidance sets out the underpinning principles of good randomised controlled trials (RCT): reliably informative, ethical, and efficient. It  is organised around five guiding principles with detailed sub‑principles that cover design, conduct, oversight, and reporting. The guidance is accompanied by a structured evaluation tool to help users reflect on how well their trials align with these principles in their specific context. An online learning course further explores the fundamental principles of what makes a good trial and supports all those involved in planning, conducting, regulating, funding, or using the results of randomised trials to apply the guidance in practice.

This three‑hour programme familiarises investigators and site teams with the specific challenges of initiating and managing multinational rare‑disease trials. It is solution‑oriented, addressing common barriers such as differing national implementations of European clinical research Regulations and ethical requirements.

This ECRIN-developed ERDERA training course provides practical guidance on planning and managing multinational clinical trials in rare diseases. The course addresses key operational challenges, including trial preparation, stakeholder roles and responsibilities, regulatory and ethical considerations, budget planning and coordination across participating countries. Designed specifically for rare disease clinical research teams, it supports investigators, study coordinators and project managers in improving the feasibility and successful implementation of multinational trials involving small and geographically dispersed patient populations.