Multiregional studies are now standard practice in drug and device development, and the revised Good Clinical Practice framework that took effect across the EU in July 2025 and was adopted by the FDA in September 2025 sharpens expectations around sponsor oversight. For companies running trials in countries where they hold no legal entity, the way local clinical staff are engaged has become a study start-up question with regulatory consequences, not only an administrative one.
Industry-sponsored research is no longer concentrated in a handful of established markets. Analysis published by Applied Clinical Trials in February 2026 reported that China's share of global trial starts rose from roughly 8% in 2013 to around 29% in 2023, with lower- and middle-income countries also taking on a growing number of newly recruiting studies. A separate review of registry data covering 25 years found that the share of trials including at least one site outside the United States rose from about 40% in 2000 to roughly 79% by 2024.
The operational consequence is direct. Protocols now routinely call for sites in countries where the sponsor has no subsidiary, no local payroll and no existing relationships with investigators or ethics committees. Site selection decisions taken on scientific and recruitment grounds create staffing obligations that have to be met inside the start-up timeline, and delays in filling those roles show up as delays to first-patient-in.
In the European Union, Article 74 of the Clinical Trials Regulation (EU) No 536/2014 requires a sponsor not established in the Union to appoint a legal representative established in the EU, responsible for ensuring compliance with the sponsor's obligations and acting as the addressee for all regulatory communications. Member States may waive that requirement for trials conducted solely on their own territory, provided the sponsor establishes at least a contact person there. An equivalent obligation applies to device studies under Article 62 of the Medical Device Regulation (EU) 2017/745.
Comparable expectations exist elsewhere in different forms: national regulatory representation, an importer of record for investigational medicinal product shipments, a local pharmacovigilance contact, and country-specific requirements for ethics committee submissions and informed consent documentation in the local language. These are structural obligations attached to running a trial in a jurisdiction, and they persist whether or not the sponsor considers the market commercially strategic.
Clinical research associates remain the clearest example. On-site monitoring visits, source data verification and site relationship management are difficult to run at long distance and across time zones, and monitoring continuity is closely tied to data quality. Study start-up specialists handle ethics committee submissions, site contracts and budget negotiations, work that generally requires local language and familiarity with national procedures. Regulatory affairs professionals manage interactions with national competent authorities. Drug safety personnel handle local expedited reporting obligations.
Decentralized and hybrid designs have reduced some of this burden without removing it. ICH E6(R3) explicitly recognises the growing use of decentralized trial elements, but remote data capture does not eliminate the need for people who can reach a site, resolve a query with an investigator, or respond to a national regulator in-country.
ICH issued the final E6(R3) Principles and Annex 1 on 6 January 2025. The EMA set an effective date of 23 July 2025 for trials conducted in the EU; Swissmedic followed in August 2025; and the FDA published its final guidance for industry in September 2025. Annex 2, covering non-traditional interventional trials including decentralized and pragmatic designs, reached ICH Step 4 in June 2026 and is scheduled to take effect in the EU on 15 January 2027.
E6(R3) restructures the guideline around quality by design and risk-proportionate approaches, and reinforces the principle that a sponsor may delegate trial-related activities but retains responsibility for them, including oversight of service providers. That principle has a practical staffing dimension. Whether the person performing monitoring is a sponsor employee, a contract research organisation employee or a contractor does not change the sponsor's accountability, but it does change how training records, delegation logs, oversight activities and vendor management documentation are maintained in the trial master file.
Sponsors expanding a study into a new market generally choose between three models, each with different trade-offs.
Establishing a local legal entity gives the sponsor direct employment relationships and full line management control. It is also the slowest and most capital-intensive route, carries corporate tax and permanent establishment implications, and is difficult to unwind if a programme stops at an interim analysis.
Engaging a contract research organisation or a functional service provider is the fastest route to established infrastructure and existing site relationships. The sponsor gives up direct line management in exchange, and oversight is evidenced through vendor qualification and vendor management processes rather than through internal supervision.
An employer of record sits between the two. A third party acts as the legal employer of record while the sponsor directs day-to-day work. Providers offering EOR services in over 40 countries allow a sponsor to place clinical staff on compliant local contracts without incorporating first, which can suit situations where only two or three sponsor-directed people are required in-country for the duration of a study.
Each model carries different implications for confidentiality obligations, intellectual property assignment, GCP training records and the documentation of sponsor oversight. None of them transfers regulatory responsibility away from the sponsor. The underlying employment administration — payroll, statutory benefits, working time rules, notice periods and termination requirements — varies by jurisdiction regardless of which route is chosen.
Contracting mechanics are not a substitute for clinical operations capability. Investigator relationships, realistic site feasibility assessment, therapeutic area knowledge and protocol familiarity still have to be built. Retention is a further constraint: staff engaged specifically for a single study face a visible end date, and turnover among monitoring personnel is a recognised contributor to inconsistent site oversight and protocol deviations.
There is also a scientific dimension. Trial populations are expected, absent justification in the protocol, to reflect the groups likely to use the medicinal product under investigation. Meeting that expectation depends on site selection and community engagement in the relevant markets, which in turn depends on having credible people on the ground rather than on the employment structure used to engage them.
With E6(R3) Annex 1 now in force across the major ICH regions and Annex 2 due in the EU in January 2027, sponsor oversight of distributed trial activity is likely to receive continued inspection attention. For sponsors, the practical effect is that the country staffing model is increasingly treated as a start-up decision made alongside site selection and regulatory strategy, rather than as an administrative step handled after the sites are chosen.
Trial geography has moved faster than sponsor footprints
Industry-sponsored research is no longer concentrated in a handful of established markets. Analysis published by Applied Clinical Trials in February 2026 reported that China's share of global trial starts rose from roughly 8% in 2013 to around 29% in 2023, with lower- and middle-income countries also taking on a growing number of newly recruiting studies. A separate review of registry data covering 25 years found that the share of trials including at least one site outside the United States rose from about 40% in 2000 to roughly 79% by 2024.
The operational consequence is direct. Protocols now routinely call for sites in countries where the sponsor has no subsidiary, no local payroll and no existing relationships with investigators or ethics committees. Site selection decisions taken on scientific and recruitment grounds create staffing obligations that have to be met inside the start-up timeline, and delays in filling those roles show up as delays to first-patient-in.
Local presence is a regulatory requirement, not only a convenience
In the European Union, Article 74 of the Clinical Trials Regulation (EU) No 536/2014 requires a sponsor not established in the Union to appoint a legal representative established in the EU, responsible for ensuring compliance with the sponsor's obligations and acting as the addressee for all regulatory communications. Member States may waive that requirement for trials conducted solely on their own territory, provided the sponsor establishes at least a contact person there. An equivalent obligation applies to device studies under Article 62 of the Medical Device Regulation (EU) 2017/745.
Comparable expectations exist elsewhere in different forms: national regulatory representation, an importer of record for investigational medicinal product shipments, a local pharmacovigilance contact, and country-specific requirements for ethics committee submissions and informed consent documentation in the local language. These are structural obligations attached to running a trial in a jurisdiction, and they persist whether or not the sponsor considers the market commercially strategic.
Which roles have to sit close to the site
Clinical research associates remain the clearest example. On-site monitoring visits, source data verification and site relationship management are difficult to run at long distance and across time zones, and monitoring continuity is closely tied to data quality. Study start-up specialists handle ethics committee submissions, site contracts and budget negotiations, work that generally requires local language and familiarity with national procedures. Regulatory affairs professionals manage interactions with national competent authorities. Drug safety personnel handle local expedited reporting obligations.
Decentralized and hybrid designs have reduced some of this burden without removing it. ICH E6(R3) explicitly recognises the growing use of decentralized trial elements, but remote data capture does not eliminate the need for people who can reach a site, resolve a query with an investigator, or respond to a national regulator in-country.
The revised GCP framework raises the oversight bar
ICH issued the final E6(R3) Principles and Annex 1 on 6 January 2025. The EMA set an effective date of 23 July 2025 for trials conducted in the EU; Swissmedic followed in August 2025; and the FDA published its final guidance for industry in September 2025. Annex 2, covering non-traditional interventional trials including decentralized and pragmatic designs, reached ICH Step 4 in June 2026 and is scheduled to take effect in the EU on 15 January 2027.
E6(R3) restructures the guideline around quality by design and risk-proportionate approaches, and reinforces the principle that a sponsor may delegate trial-related activities but retains responsibility for them, including oversight of service providers. That principle has a practical staffing dimension. Whether the person performing monitoring is a sponsor employee, a contract research organisation employee or a contractor does not change the sponsor's accountability, but it does change how training records, delegation logs, oversight activities and vendor management documentation are maintained in the trial master file.
Three routes to a country team
Sponsors expanding a study into a new market generally choose between three models, each with different trade-offs.
Establishing a local legal entity gives the sponsor direct employment relationships and full line management control. It is also the slowest and most capital-intensive route, carries corporate tax and permanent establishment implications, and is difficult to unwind if a programme stops at an interim analysis.
Engaging a contract research organisation or a functional service provider is the fastest route to established infrastructure and existing site relationships. The sponsor gives up direct line management in exchange, and oversight is evidenced through vendor qualification and vendor management processes rather than through internal supervision.
An employer of record sits between the two. A third party acts as the legal employer of record while the sponsor directs day-to-day work. Providers offering EOR services in over 40 countries allow a sponsor to place clinical staff on compliant local contracts without incorporating first, which can suit situations where only two or three sponsor-directed people are required in-country for the duration of a study.
Each model carries different implications for confidentiality obligations, intellectual property assignment, GCP training records and the documentation of sponsor oversight. None of them transfers regulatory responsibility away from the sponsor. The underlying employment administration — payroll, statutory benefits, working time rules, notice periods and termination requirements — varies by jurisdiction regardless of which route is chosen.
What the staffing model does not resolve
Contracting mechanics are not a substitute for clinical operations capability. Investigator relationships, realistic site feasibility assessment, therapeutic area knowledge and protocol familiarity still have to be built. Retention is a further constraint: staff engaged specifically for a single study face a visible end date, and turnover among monitoring personnel is a recognised contributor to inconsistent site oversight and protocol deviations.
There is also a scientific dimension. Trial populations are expected, absent justification in the protocol, to reflect the groups likely to use the medicinal product under investigation. Meeting that expectation depends on site selection and community engagement in the relevant markets, which in turn depends on having credible people on the ground rather than on the employment structure used to engage them.
What to watch next
With E6(R3) Annex 1 now in force across the major ICH regions and Annex 2 due in the EU in January 2027, sponsor oversight of distributed trial activity is likely to receive continued inspection attention. For sponsors, the practical effect is that the country staffing model is increasingly treated as a start-up decision made alongside site selection and regulatory strategy, rather than as an administrative step handled after the sites are chosen.