There are a number of collaborative working models for trials running on an international level. Model 1Model 2Model 3Description One host institution/sponsor within the UK responsible for co-ordinating the trial and co-ordinating both UK and international research sites One host institution/sponsor within the UK responsible for co-ordinating the trial and co-ordinating UK sites only. Use of a local spoke/CRO/lead site to co-ordinate international sites. The same or very similar protocols. Two or more host institutions each responsible for co-ordinating the trial and sites locally, feeding into a single trial analysis Case Studies IntAct ROLARR Advantages Greater control over the development and co-ordination of the trial, including data management Trial can be run entirely in line with host institution SOPs and guidelines No spoke costs Local spoke provides expertise in local regulatory and ethical environments Potential reduction in contracts if spoke contract with international research sites Local spoke will undertake work relating to obtaining local approvals, meaning the UK host/sponsor does not need to do this. Greater pool of patients to recruit from, leading to faster recruitment, analysis and dissemination timelines UK funder does not need to fund international recruitment, and vice versa therefore it may be easier to obtain funding Each sponsor could be responsible for local insurance, therefore a study wide policy covering all countries may not be required. UK host/sponsor will not be responsible for obtaining required local approvals at international sites Disdvantages Potential lack of awareness of local regulatory and ethical environments Setting up local sites likely to be both time and resource intensive Several contracts to negotiate Language barrier Courier/postage implications from international sites to the UK Compliance of sites to unfamiliar SOP If tissue samples are required to be sent to the UK, this may be difficult to implement across all sites Cost Spokes may work in a different way to organisations in the UK therefore may not be in agreement with host institution SOPs Contract with the spoke may need to be agreed prior to starting any international site set-up Trial could be at risk if one party is not able to obtain local funding, or subsequently withdraws from participating in the trial It may be difficult to develop consistent protocols between the parties Timelines are likely to vary between groups involved Potential lack of a party with overall responsibility for the trial Monitoring may be difficult to implement Key Points for Consideration Protocol development and version control Responsibility for obtaining local approvals for international sites Insurance Training of site staff Data flows and conduct Trial supplies Funding Database access for spoke Training of spoke staff Protocol development and amendments across sites Database development (single versus multiple) Clear division of responsibilities between the collaborating parties Plan for protocol development Agreement on data items and development of CRFs Database development (single versus multiple) Who will be responsible for the final analysis Publication rights