Guidance

Clinical trials for medicines: roles and responsibilities

Published 16 April 2026

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Legal status of this guidance

The following guidance accompanies the Medicines for Human Use (Clinical Trials) Regulations 2004, as amended by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025. These amendments come into force on 28 April 2026 and any reference to “the amended Clinical Trials Regulations” in this guidance should be construed as referring to the amended version.

Part 2 of Schedule 1 to the amended Clinical Trials Regulations requires that the investigator and sponsor have regard to all relevant guidance with respect to commencing and conducting a clinical trial.

Investigators and sponsors (and any individual or organisation that the sponsor delegates trial-related activities to) must, therefore, ensure that they are fully aware of the information within this guidance and act accordingly to achieve and maintain regulatory compliance.

Under the amended Clinical Trials Regulations, the definition of who may act as an investigator in a clinical trial has been expanded. This reflects a broader recognition of professional competencies across healthcare disciplines, whilst maintaining safeguards for participant safety and trial integrity. Health care professionals may now act as investigators and chief investigators assuming they have appropriate qualifications, experience and training and are supported by medically trained professionals where they do not have this qualification similar to how a medically trained investigator is supported by professionals with differing training and education.

This page also includes guidance associated with delegation of activities, training, and in response to the phased implementation of the Human Medicines Authorisation by Pharmacists and Supervision by Pharmacy Technicians Order 2025 (UK Statutory Instrument 2025/1249.

Eligible professions to act as Investigators

An investigator is defined in regulation 2 (1) of the amended Clinical Trials Regulations as:

“the health care professional who is responsible for the conduct of that trial at that trial location, or if more than one, the trial locations; and who is, if the trial is conducted by a team of health care professionals at that location or locations, the leader responsible for that team.”

A health care professional is defined in regulation 2 (1) of the amended Clinical Trials Regulations as:

a) a doctor

b) a dentist

c) a registered nurse as defined in regulation 8 (1) of the Human Medicines Regulations 2012

d) a pharmacist

e) a person registered in the register of optometrists maintained under section 7(a) of the Opticians Act 1989

f) Professionals registered with the Health and Care Professions Council (HCPC)

) register, excluding social workers as defined in regulation 8 (1) of the 2012 Regulations). This includes:

• biomedical scientists
• clinical scientists
• dietitians
• occupational therapists
• paramedics
• physiotherapists
• radiographers
• speech and language therapists
• other professions listed in Schedule 3 of the Health Professions Order 2001 other than a social worker

g) a registered osteopath as defined by section 41 of the Osteopaths Act 1993

h) a registered chiropractor as defined by section 43 of the Chiropractors Act 1994

i) a person registered under the Anaesthesia Associates and Physician Associates Order 2024

j) a registered midwife in regulation 8 (1) of the Human Medicines Regulations

“A doctor” means a registered medical practitioner.

The addition of professions who would be classified as a health care professional under the Medicines for Human Use (Clinical Trials) Regulations can only be via addition of the profession to the HCPC register or via amendment of the Medicines for Human Use (Clinical Trials) Regulations 2004.

The appointment of an investigator is the responsibility of a sponsor, and the sponsor must ensure that each investigator is appropriately trained (regulation 3B of the amended Clinical Trial Regulations) to undertake the role, as well as being qualified by education and experience, having the scientific background and experience in participant care required for that role in the clinical trial.

It is strongly suggested that organisations conducting clinical trials consider what training and support is required for investigators, especially where they do not have prior experience. Consideration should be given to participation in suitable training and provision of mentoring support, for example. The type and level of training for an investigator should facilitate knowledge and understanding of the relevant regulations and guidance, and expectations associated with the role, whilst being proportionate to the type of trial being conducted e.g. knowledge of dose escalation expectations may not be relevant in trials where this is not a feature.

Sponsors should also note that a qualified doctor (or, where appropriate, a qualified dentist) who is an investigator for the trial should have the overall responsibility for trial-related medical care and decisions on behalf of participants. Therefore, where a trial includes investigators who meet criteria c-j above, a doctor or dentist (as appropriate) should also be included as a member of the trial team and be delegated medical oversight for the trial. 

Chief Investigator (CI)

Chief investigator is described in regulation 2 (1) of the amended Clinical Trials Regulations as meaning:

“(a) in relation to a clinical trial conducted at a single trial location, the investigator for that location, or

(b)   in relation to a clinical trial conducted at more than one trial location, the health care professional health professional, whether or not that health care professional is an investigator at any particular location, who takes primary responsibility for the conduct of the trial.”

This role is called “Coordinating Investigator” in ICH E6 (R3), defined as “An investigator assigned the responsibility for the coordination of investigators at different investigator sites participating in a multicentre trial”, and is synonymous with Chief Investigator.

The role of the CI may be undertaken by a sponsor’s representative (for example, the sponsor’s medical director or similar) or it may be contracted out to another investigator (who may or may not be involved in the recruitment and treatment of participants at an investigator site). It is not uncommon for the sponsor to appoint a CI per country or region to facilitate the oversight of many investigator sites and to assist in the identification and management of local requirements. It should be noted that only one CI can be nominated to be responsible for the conduct of the trial in the UK and this cannot be a shared role between multiple individuals.

The additional responsibility of a CI, according to the amended Clinical Trial Regulations (regulation 31A(7)), is to ensure the trial master file (TMF) and the medical records are retained for at least 25 years in conjunction with the sponsor.

Under the previous version of the Clinical Trial Regulations the CI was responsible for submission of the initial application to the Research Ethics Committee (REC) and to appeal against an unfavourable REC opinion, but these activities have been transferred to the trial sponsor under the amended Clinical Trial Regulations.

Principal Investigator (PI)

The amended Clinical Trials Regulations do not specifically define the term ‘Principal Investigator’, although the title is commonly used to describe the lead investigator at a trial location as stated by ICH E6 (R3) (“If a trial is conducted by a team of individuals, the investigator is the responsible leader of the team and may be called the principal investigator”).

The PI is responsible for the conduct of the trial and for the leadership of the trial team at their location, although activities can be delegated to appropriate members of the trial team.

The role of the PI would need to be permanently based in the UK due to their personal responsibility for the conduct of the trial at a trial location. The role of PI requires day to day knowledge and management of the delivery of the trial at the location and the ongoing oversight of treatment and safety of trial participants.

Co-Investigator or Sub-Investigator

The amended Regulations do not specifically define the term ‘co- investigator’ or ‘sub-investigator’. ICH E6 (R3) defines a sub-investigator as “Any individual member of the clinical trial team designated and under the oversight of the investigator to perform significant trial-related procedures and/or to make important trial related decisions (e.g., associates, residents, research fellows)”.

Checks on professional status

It is expected that fitness to practise checks are conducted as part of the selection of an investigator, (including sub-investigators), i.e. that the individual is in good standing with their professional body and that there are no relevant restrictions on their ability to practise. If the professional status of the individual changes during the conduct of a clinical trial, then appropriate action should be taken to support the ongoing conduct of the trial e.g. provision of additional support to address a restriction of activities. Where professional registration is no longer in place then that individual may no longer act as a PI or CI and a replacement should be found or action taken to end that location’s participation in the trial.

It is expected that any restrictions to practise, or where an individual loses their professional registration (rather than it lapsing due to leaving the profession), for a period of five years after the conclusion of the trial are communicated to the trial sponsor. Where the reason behind the restriction or loss of registration is considered by the sponsor to impact the safety of trial participants or scientific value of the clinical trial then this should be communicated to the MHRA via the clinical trial helpline.

Licensed and registered vs registered only

An investigator who is medically qualified needs to be both registered and licensed to practise in order to undertake any medical activities in accordance with regulation of their relevant profession such as the assessment of eligibility, causality and seriousness decisions in relation to adverse event reporting or prescribing of medication (unless governed by alternative provisions similar to those used for nurse and pharmacist prescribers).

According to the General Medical Council website, registration without a license allows doctors to show that they remain in good standing with the GMC and acknowledges their primary medical qualification permitted entry to the medical register but a license to practise is required “to legally practise any activities in the UK which are restricted by law to those holding a licence (such as signing death certificates and writing prescriptions).”

It is therefore possible for a medically qualified individual to act as a CI taking primary responsibility for the conduct of the trial (rather than making medical decisions or treating patients) without being licensed but extreme care must be taken on the activities undertaken to ensure that no activities are undertaken that require the individual to be both licensed and registered.

It is also possible for a medically qualified individual to act as a medical monitor without being licensed but extreme care must be taken on the activities undertaken to ensure that no activities are undertaken that require the individual to be both licensed and registered. For example, a non-licensed medical monitor may answer a question about the general interpretation of a particular inclusion/exclusion criteria but not using patient specific information provided by the site to make the decision about an individual patient (rather than checking that the site had made the correct decision).

Where a professional body for other roles requires both registration and licensing prior to undertaking clinical duties then the principles defined above also apply to that role.

Personal professional indemnity

Professionals acting as an investigator should determine whether they are required to hold medical malpractice and/or professional indemnity alongside the insurance or indemnity provision associated with the clinical trial and that provided by their employer.

Additional requirements for non-medically trained investigators

Medical oversight

Where the PI is not a doctor or dentist, a qualified doctor or dentist must be delegated as an investigator for the provision and/or oversight of trial-related medical care and medical decision making. This ensures that medical oversight is maintained for participant safety.

Eligibility

The ability of a non-medical professional to determine eligibility should:

• be consistent with standard clinical practice or prior relevant experience and any legislative requirements
• be acceptable to the organisation e.g. NHS Trust where eligibility decisions will be made and in line with any local processes, permissions, and practices
• be acceptable to the trial sponsor and the requirements of the trial protocol
• be based on their being appropriately qualified, trained and experienced with the information and assessments required to make the eligibility decision
• be supported by oversight by a medically qualified doctor from the trial location in case of queries or assistance being required (but this could be remote).

Where interpretation of a patient’s condition or future health is required which requires medical insight then this should only be done by a medically qualified individual.

If the member of the research team determining eligibility is unsure then then the participant should not have eligibility determined until medical assistance in the decision has been obtained.  

Prescribing

It is expected that medically qualified doctors or dentists make prescribing decisions however, under certain circumstances, this can be delegated to non-medically qualified members of the research team by the Principal Investigator.

The ability of a non-medical professional to prescribe should:

• be consistent with standard clinical practice and any legislative requirements
• be acceptable to the organisation e.g. NHS Trust where prescribing decisions will be made and in line with any local processes, permissions, and practices
• be acceptable to the trial sponsor and the requirements of the trial protocol
• be based on their being appropriately qualified, trained and experienced with the information and assessments required to make the prescribing decision
• be supported by oversight by a medically qualified doctor from the trial location in case of queries or assistance being required (but this could be remote).

If the member of the research team prescribing is unsure then then the participant should not have medication prescribed until medical assistance in the decision has been obtained.  

Safety reporting

Reference should also be made to Clinical trials for medicines: collection, verification and reporting of safety events - GOV.UK for further information regarding safety reporting.

A key part of the role of a medically qualified professional within a clinical trial is the identification, management, and reporting of adverse events. Where the role of the PI is held by a non-medically trained health care professional then it is expected that support from a medically qualified investigator, as a member of the trial team, is readily available to assist with the identification, management, and reporting of adverse events.

Seriousness assessment of adverse events

The judgement as to whether an adverse event is serious is usually made by the investigator. Where the investigator is not a doctor or dentist, assessment of the seriousness of the event should be evaluated with respect to the usual remit of the investigator. For example, if a nurse prescriber evaluates seriousness of an adverse event as part of their regular duties, then it may be appropriate to have them evaluate this in the trial. However, where assessment of seriousness of an adverse event is not part of their regular duties, or if the nature of the IMP means other safety considerations may need to be considered, then the decision should be delegated to the doctor or dentist member of the team, as they have responsibility for medical oversight.

Causality assessment of adverse events

The assessment of whether there is a reasonable possibility of a causal relationship of the IMP and the adverse event is usually made by the investigator. Where the investigator is not a doctor or dentist, causality assessment should be evaluated with respect to the usual remit of the investigator. For example, if a nurse prescriber evaluates causality as part of their regular duties, then it may be appropriate to have them evaluate causality in the trial. However, where causality assessment is not part of their regular duties, or if the nature of the IMP means other safety considerations may need to be considered, then causality should be delegated to the doctor or dentist member of the team, as they have responsibility for medical oversight.

Expectedness assessment of adverse events

The regulatory determination of expectedness based upon the approved reference safety information for the IMP is usually the responsibility of the sponsor.  Investigators are not required to make this determination. Should the sponsor decide to obtain an opinion from the investigator, they should be appropriately qualified and trained in the regulatory requirements for assessing expectedness of an adverse event. 

Training expectations

Both the HRA and the MHRA advocate a proportionate approach to the application of GCP to the conduct of clinical trials and the appropriate training of staff involved.

Training needs may range from a detailed knowledge of GCP principles and associated UK Clinical Trial Regulations, to an awareness of particular GCP principles and knowledge of the UK Clinical Trial Regulations, and training can be tailored accordingly.

If an activity is part of an individual’s normal clinical role and all other protocol activities are undertaken by a member of the research team, then no GCP training may be required; however, this should be reviewed as part of the local risk assessment for that trial.

The PI, via the delegation of trial related duties to an individual, is responsible for ensuring that the individual is appropriately trained and qualified and has been made aware of the requirements of the protocol and their assigned trial activities.

Any individual involved in the conduct of a clinical trial should be qualified by education, training, and experience to perform their respective tasks(s).

It is expected that:

• Individuals have appropriate knowledge, experience and training for the role and responsibilities assigned to them.
• Individuals should be aware of the roles and responsibilities delegated to them, both in relation to the organisational set-up and as they relate to the conduct of clinical trials.
• Training is appropriate and proportionate for the role and responsibilities held by that individual, covering technical, regulatory and GCP training, and is updated on a periodic basis particularly when changes to regulations or associated guidance occur. Training should be tailored to the specific roles and responsibilities being undertaken by an individual.
• Training and experience are documented and justified where necessary. Training records should be periodically updated and reviewed by both the individual and their manager.

For certain trials it may be necessary for staff involved in trial activities to be aware of other regulatory requirements outside those of GCP. For example, healthcare professionals retaining tissue samples should be aware of relevant legislation such as the Human Tissue Act, The Blood Safety and Quality Regulations (BSQR, 2005) etc. or seek advice from others with appropriate knowledge and experience.

Training on amended Clinical Trial Regulations and ICH E6 R3

It is expected that organisations involved in the conduct of clinical trials have considered staff training needs in regard to the amended Clinical Trial Regulations and ICH GCP E6 R3 (and E8 R1 where relevant).

It is not expected that all individuals involved in clinical trials have undergone training in these requirements by 28 April 2026. Sites should adopt a risk-based approach, prioritising compliance for roles that have the greatest impact on trial conduct.

Delegation associated with routine clinical practice

If knowledge about the protocol, investigator’s brochure or other trial-related document is necessary to perform a trial-related activity, this activity should be performed by delegated persons or parties who are under appropriate oversight of investigator and have been appropriately trained.

Where clinical activities are undertaken that are considered to be consistent with routine clinical practice and do not require knowledge about the protocol, investigator’s brochure, or other trial-related document to perform a trial-related activity then centralised delegation could be considered. This is commonly seen in large departments such as (not an exhaustive list):

• chemotherapy administration
• imaging/radiology
• laboratories
• pharmacy
• phlebotomy

This concept may also be extended to phase 1 units for the conduct of non-trial specific activities such as cannulation, blood draws, collection of vital signs for example where trial specific knowledge is not required.

Implementation of centralised delegation relies upon:

• Performance of a risk assessment to determine the acceptability of this approach for the trial including the nature of the activities, the potential impact and the level of investigator oversight, training and knowledge required
• Where appropriate, having one, or more, named persons such as the clinical trials pharmacist, ward sister, Head of Department or similar who then takes responsibility for the conduct of that activity by the department, who is GCP trained (applicable to the work being undertaken) and must be appropriately trained on the trial and its requirements
• The named person(s) being delegated activities on the trial specific delegation log by the PI. Assumed delegation by the PI is not considered acceptable.
• Role based centralised delegation may be appropriate for some organisations (e.g. Phase 1 Units) and would be supported by documented procedures in the quality management system. This would specify which activities can be undertaken by particular roles when deemed trained and competent to undertake them and that persons in such roles are considered delegated by the PI.
• Staff to be included in centralised activities are required to be deemed to be competent to perform the activity, and this should be evident in training records or similar and listed on a central delegation log managed by the named person which is non-trial specific.
• Staff involved in the performance of routine clinical activities having a suitable risk proportionate level of awareness of GCP requirements. This may range from research awareness, i.e. that clinical trial activities are conducted within their area and who to report any issues to, through to tailored GCP training for their area depending on the level and type of activities being undertaken.
• Attribution of performance of the activity to an individual therefore a signature sheet, or incorporation of the signature and initials onto the central delegation log, must be maintained. The exception to this is where only true, individual specific, electronic signatures are used and that the identity of the individual is obvious.

An Organisation using such central delegation should ensure monitors and auditors understand how the process works and can access the relevant central records, including training records to verify competence of staff in that role and who have undertaken it on the trial.

Pharmacy supervision

The Regulation 37 exemption for hospitals and health centres has been updated by the Human Medicines (Authorisation by Pharmacists and Supervision by Pharmacy Technicians) Order 2025 (UK Statutory Instrument 2025/1249). This Order makes provision enabling pharmacists to authorise others, in particular pharmacy technicians,

• to perform tasks that would otherwise need to be performed by pharmacists or under their supervision,
• to take primary responsibility for the preparation and assembly of medicinal products in hospital aseptic facilities.

Some of the provisions of this Order came into force on 7th January 2026 (those related to handing out of checked and bagged prescriptions), whilst the remaining provisions come into force on 10th December 2026. In addition, Pharmacy technicians are not a registered profession in Northern Ireland, therefore only the measures concerning the handing out of checked and bagged prescriptions will apply in NI. 

In relation to clinical trials the changes, under this Order, permit a pharmacy technician to supervise the assembly of investigational medicinal products following authorisation from a pharmacist. This comes into effect on the 10th December allowing time for the development of guidance and standards. The Order requires that the authorising pharmacist have due regard to patient safety when delegating this responsibility. Likewise, the technician delegated the activity must also have due regard to patient safety when undertaking the delegated responsibility. Both pharmacists and technicians are reminded that, in accordance with the regulations 28 and 29, they must also comply with:

• the conditions and principles of good clinical practice
• the clinical trial protocol
• the terms of the request for authorisation of the clinical trial
• the terms of application for an ethics committee opinion
• the terms of any particulars or documents accompanying the request for authorisation or application

It is expected that for clinical trial activities any delegation from a pharmacist to a technician is clearly documented within the pharmacy records. Verbal delegation is not considered acceptable as it is highly unlikely that clinical trial activities are required to be conducted in emergency situations or without prior planning that allows time for formal delegation. Where there is such a need then the decision and supporting rationale should be documented as soon as possible within the investigator site file.