This is a systematic rapid review published in Wellcome Open Research (2023; 8:194). It analyses evidence on community engagement and informed consent in adaptive platform and alternative design trials conducted during public health emergencies (PHEs) such as Ebola and COVID-19. The review includes 49 publications and guidance documents, highlighting key ethical and communication challenges in explaining complex trial designs under emergency conditions.

The Cochrane Central Register of Controlled Trials (CENTRAL) is a database within the Cochrane Library that provides a highly concentrated source of reports of randomized and quasi‑randomized controlled trials. It contains bibliographic records with citation details and usually an abstract, but not the full text, and is updated monthly. Records are drawn from multiple sources, including PubMed/MEDLINE, Embase, CINAHL, ClinicalTrials.gov, WHO trial registries and Cochrane Review Groups’ specialized registers, and are included regardless of language or publication year. CENTRAL is developed and maintained by Cochrane and is particularly useful for investigators who need to identify controlled trials for inclusion in systematic reviews and evidence syntheses to inform clinical studies.

EUPATIConnect is a fee‑for‑service matchmaking platform that connects trained EUPATI Patient Experts with researchers for meaningful patient involvement in medicines research and development. Researchers submit a request describing their project and needs and are matched to patient experts whose profiles, experience and disease areas fit the aims of the collaboration. Engagement can include protocol and document review, advisory boards, focus groups, speaking engagements, co‑creation workshops and other patient engagement activities. The platform is operated by EUPATI, the European Patients’ Academy on Therapeutic Innovation, which coordinates a large network of trained patient experts and national platforms.

This document is a mapping and forward-looking overview of all scientific/regulatory advice mechanisms in the EU medicines system, with a strong focus on coordination, early engagement, and support for better clinical development. The document is essentially a framework overview. It explains what advice exists, how to access it and how the system is evolving.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) can issue qualification opinions or qualification advice on novel methodologies used in medicine development, such as biomarkers, imaging methods and digital tools, within a defined context of use in non‑clinical or clinical studies. 

The Protocol Development Toolkit, part of the EDCTP Knowledge Hub, is an online resource developed by the European & Developing Countries Clinical Trials Partnership (EDCTP) and The Global Health Network to support high‑quality health research protocols, particularly for clinical studies in low‑resource settings. It combines step‑by‑step guidance on protocol development with examples, templates and interactive tools, including the Concept Protocol Crowd Review Tool, the SEPTRE electronic protocol builder and the Study Walk‑through toolkit. Linked training materials cover scientific, ethical, regulatory, operational and data‑management aspects of study design, helping investigator‑initiated studies move from a research question to a complete, robust protocol.

The Patient Engagement Toolbox, developed under the IMI‑PARADIGM (Innovative Medicines Initiative – Patients Active in Research and Dialogues for an Improved Generation of Medicines) project, centralises co‑created recommendations, practical tools and background materials to make patient engagement in medicines development easier, more consistent and more impactful. The toolbox is organised around three key phases of patient engagement: planning, conduct, reporting and evaluation. 

This document is a mapping and forward-looking overview of all scientific/regulatory advice mechanisms in the EU medicines system, with a strong focus on coordination, early engagement, and support for better clinical development.The document is essentially a framework overview. It explains what advice exists, how to access it and how the system is evolving.

The SPIRIT‑Outcomes 2022 extension to the SPIRIT 2013 statement is an international, evidence‑ and consensus‑based guideline that specifies 9 outcome‑specific items to be addressed in all clinical trial protocols. Developed within the InsPECT project using the EQUATOR framework, it supplements the SPIRIT 2013 checklist with minimum essential standards for defining, justifying, measuring, and analyzing trial outcomes. Applying SPIRIT‑Outcomes can enhance trial utility, reproducibility, and transparency and may help reduce selective nonreporting of trial results, making it particularly valuable for investigator‑initiated clinical studies.

The COSMIN database of systematic reviews of outcome measurement instruments is an online, searchable collection of systematic reviews that evaluate the quality of health‑related outcome measures in humans. It is developed by the international COSMIN (COnsensus‑based Standards for the selection of health Measurement INstruments) initiative to support research and clinical practice. The database helps investigators identify existing systematic reviews on patient‑reported outcomes and other measurement instruments, see which tools have evidence on reliability, validity and responsiveness, and spot gaps in the evidence. This makes it a useful starting point when selecting and justifying outcome measurement instruments in investigator‑initiated clinical studies.

PANDA (Practical Adaptive & Novel Designs and Analysis toolkit) is an open‑access, online educational resource developed by the University of Sheffield and collaborators to support researchers in using adaptive designs, their practical application, potential benefits and limitations. Aimed at trialists across disciplines, it explains when and how to use key adaptive approaches—sample size re‑estimation, group sequential, multi‑arm multi‑stage, adaptive population enrichment and response adaptive randomisation—and outlines their practical, statistical and operational implications. It is particularly relevant for statisticians, clinicians, trial managers, data managers and grant developers working on complex or innovative trial designs.

The SPIRIT‑Outcomes 2022 extension to the SPIRIT 2013 statement is an international, evidence‑ and consensus‑based guideline that specifies 9 outcome‑specific items to be addressed in all clinical trial protocols. Together, these two guidelines create a clear reporting continuum from the trial protocol to the final trial report, helping researchers prepare protocols and reports more consistently and making it easier to assess adherence to the planned protocol. It supplements the SPIRIT 2013 checklist with minimum essential standards for defining, justifying, measuring, and analyzing trial outcomes. Applying SPIRIT‑Outcomes can enhance trial utility, reproducibility, and transparency and may help reduce selective nonreporting of trial results.

This ICH guideline (2017) outlines principles for planning multi-regional clinical trials (MRCTs) to support global regulatory acceptance by evaluating treatment effects and safety across populations. It provides a framework for designing trials that generate evidence acceptable to multiple regulators and facilitate efficient global drug development, including single multinational trials for rare diseases.

The COMET (Core Outcome Measures in Effectiveness Trials) Initiative brings together people interested in developing and applying agreed standardised sets of outcomes, known as core outcome sets (COS). These represent the minimum that should be measured and reported in all clinical trials of a specific condition, and can also be used in routine care, clinical audit and other types of research. COMET provides an international hub and searchable database of COS‑related studies, along with methodological resources to support their development and use in clinical research.

This guidance provides an overview of the scientific and regulatory support mechanisms available through the European Medicines Agency (EMA) and national competent authorities to assist medicine developers throughout the development process. It helps investigators identify the most appropriate regulatory interactions during protocol development, including innovation meetings, scientific advice, protocol assistance and qualification procedures. The resource is particularly relevant for rare disease clinical trials, where early regulatory engagement can support innovative study designs, small population methodologies and efficient protocol development.

This EMA guidance (2025) explains to users, in the form of FAQs how to request EMA scientific advice and protocol assistance, outlining the procedures, scope, and nature of these services so that applications can be prepared, validated, and evaluated efficiently. Applicants are guided through the different steps of the procedure and receive useful information on how to prepare a possible discussion meeting with the Scientific Advice Working Party (SAWP).

SPIRIT and SPIRIT extensions are internationally endorsed reporting guidelines for clinical trials that support protocol development and trial reporting across the full research lifecycle. CONSORT 2025 provides a 30-item checklist for reporting randomized trial results, including title and abstract, trial registration, protocol and statistical analysis plan, participant flow, recruitment, harms, outcomes, interpretation, limitations, and other open science elements.  

The website hosts two online tools: SEPTRE and COBWEB:

• SEPTRE: the SPIRIT Electronic Protocol Tool & Resource, is an online trial protocol writing and management tool that helps users create, register, and manage protocols in line with SPIRIT guidance.
• COBWEB: the CONSORT-based WEB tool, is an online manuscript writing aid that guides authors through structured templates to write, edit, share, and export randomised trial reports in line with CONSORT and its extensions.

Developed by the ICH Expert Working Group, the ICH E8 (R1) Guideline is an internationally recognized guidance document from the  that defines core principles and general considerations for designing and conducting clinical studies, including exploratory and confirmatory trials. It provides a broad framework for trial planning, quality‑by‑design, risk‑based approaches, ethical considerations, statistical thinking, and meaningful interpretation of study outcomes.