What are the responsibilities of a sponsor?
The sponsor is responsible for ensuring that specific duties are performed, properly distributed, allocated and accepted by investigators and their employing institutions and care organisations, and for the governance of the research study from conception to final completion, including design, management, and finance. The sponsor satisfies itself that appropriate checks have been undertaken to ensure that the study meets the relevant standards, and makes sure arrangements are put and kept in place for authorisation, management, monitoring and reporting. Full details are contained in the UK Policy Framework for Health and Social Care Research and the Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 1031), which should be consulted for further information.
What are the risks attached to an organisation taking on the role of Sponsor?
A Sponsor organisation is exposed to potential risks in a number of areas. Failure to allocate responsibilities through ensuring formal arrangements around sponsorship increases these risks, while thorough procedures to define and distribute sponsor roles diminish the risk of additional liabilities falling on the sponsor:
- Financial – e.g. claims for damages from individuals who participated in the research;
- Legal – e.g. prosecution by MHRA or other regulatory authority for breach of Clinical Trials Regulations, failure to comply with conditions of ethical approval, or failures in pharmacovigilance;
- Reputation – e.g. adverse publicity arising from failure of the study, failure to meet required standards of GCP to satisfy MHRA auditors, or from prosecution as outlined above
A detailed risk assessment should always be performed when planning a new study and practical advice on risk assessment can be found on the NIHR Clinical Trials Toolkit webpage.
How can a sponsor mitigate against risk?
The following principles underpin successful risk mitigation:
- Risk assessment prior to commencement of study and avoidance of high risk activities (unless substantially outweighed by the benefits);
- Ensuring that all responsibilities listed in the Research Governance Framework and, if appropriate, the Clinical Trials Regulations have been formally
assigned to, and accepted by, specified institutions, groups or individuals;
- Ensuring the competence of the Chief Investigator and host organisation(s) to oversee and manage the study;
- Appropriate training in research methods and GCP for members of the research team;
- Audit and monitoring of studies to detect and rectify poor compliance
What is the legal status of a sponsor?
A sponsor is legally responsible for ensuring that a number of requirements of the EU Clinical Trials Directive are met. These legal responsibilities are defined in the UK Clinical Trials Regulations, Parts 3-5, and are summarised below:
Part 3: authorisation and ethics committee opinion
- Request clinical trial authorisation (CTA), amend the request
- Produce undertaking to allow inspection of premises in third countries if required
- Give notice of amendments to CTA, make representations about amendments
- Give notice of amendments to the protocol
- Give notice a trial has ended
Part 4: Good Clinical Practice and conduct
- Put and keep in place arrangements to adhere to GCP (if no other person is specified)
- Ensure Investigational Medicinal Products available to subjects free of charge
- Take appropriate urgent safety measures (with investigator)
Part 5: Pharmacovigilance
- Keep records of all adverse events reported by investigators
- Ensure recording and prompt reporting of suspected unexpected serious adverse reactions (SUSARS)
- Ensure investigators are informed of SUSARs
- Ensure all SUSARs including those in third countries entered into European database
- Provide annual list of suspected serious adverse reactions and a safety report Please refer to the Clinical Trials Regulations for further details.
Please refer to the Clinical Trials Regulations for further details.
What are the implications for indemnity with respect to sponsorship?
A sponsor is responsible for ensuring that arrangements are in place to indemnify the Investigator(s) against claims for harm arising from negligence. The employer of the Investigator(s) may also be liable for non-negligent harm to study participants. NHS bodies are unable to provide indemnity for non-negligent harm. Certain other kinds of sponsor (e.g. universities) may be able to offer indemnity for non-negligent harm but the need for insurance against this risk will be determined by an NHS ethics committee following consideration of the risks associated with a particular study. Responsibilities, liabilities and risk management in clinical trials of medicines (Universities UK and DH joint statement, May 2004). It should be noted that the Clinical Trial Regulations do not alter existing liabilities or introduce additional liabilities on the parties involved in the management of clinical trials.
Which studies require a sponsor?
All research falling under the remit of the Secretary of State for Health must have a formal sponsor. This includes all research In health and social care that involve NHS patients, their tissue or information, staff, equipment or other resources of the NHS. There are similar requirements for research involving social care practitioners, clients and resources, where this falls under the Secretary of State for Health’s remit.
Who may become a sponsor?
Any organisation that is a legal entity may declare itself as a sponsor. While the Clinical Trials Regulations allow for individuals to become sponsors, many institutions do not permit their staff to take personal responsibility in such areas because of the risks and legal liabilities involved. Sponsorship by individuals is not advocated by the Forum.
Can sponsorship be shared or delegated?
Under the Clinical Trials Regulations, a sponsor can be an individual, an institution or a group of individuals or institutions that is willing to discharge the sponsor’s responsibilities. The Regulations provide for sponsorship by:
a) a single individual or institution (sole sponsorship); or
b) a group of individuals or institutions that divide the responsibilities and liabilities out between them such that each has a defined subset of the overall responsibilities (co-sponsorship); or
c) a group of individuals or institutions that share the responsibilities jointly (joint sponsorship). Joint sponsors are jointly and severally responsible for all the duties of the sponsor, such that all are responsible in the event of a failure of any one of the joint sponsors to discharge their responsibilities.
Sole sponsorship and co-sponsorship arrangements offer the greatest degree of clarity and transparency in the allocation of responsibilities. However it should be noted that co-sponsorship is an arrangement that is not recognised in EU states other than the UK and is therefore not applicable to multi-national studies within the EU. A sponsor can delegate specific responsibilities to any other individual or organisation that is willing and able to accept them. However, the sponsor should ensure that the delegation of responsibilities to another party is formally agreed and documented. Note that responsibilities that have not been explicitly delegated to another individual or organisation are assumed to remain with the sponsor organisation, which will thus be held liable in the event of a breach of the regulatory guidelines.
Can an institution elect to sponsor particular types of studies?
Institutions are expected to review candidate studies for sponsorship on a case-by-case basis and should only accept the role of sponsor for studies that lie within their range of competence. For example, an organisation that has no experience or infrastructure for the management of clinical trials should avoid acting as a sponsor for such studies unless it can delegate the specific responsibilities to another organisation that has the required expertise, and an organisation lacking experience of managing multi-centre studies may be advised to limit itself to sponsoring single centre studies.
Who acts as the sponsor of student studies?
According to the UK Policy Framework for Health and Social Care Research, the supervisor of a student may act as the sponsor for research where the primary objective of the research is educational. However many institutions insist on institutional sponsorship of all their research and do not permit individual sponsorship by supervisors. The Forum does not advocate sponsorship by individuals because of the risks and liabilities involved.
Moreover, it is not always obvious whether the primary objective of a particular study is educational or is to derive new knowledge, nor is it always obvious whether an individual should be regarded as a ‘student’. For example, trainees in professions such as Public Health Medicine and Clinical Psychology are required to undertake a research project as part of their training but this is often designed to generate new knowledge in addition to satisfying the training (ie: educational) requirements
Who acts as the sponsor for Primary Care studies?
PCTs have legal powers to engage in and facilitate research, so research is part of their normal business. Like all other institutions therefore, PCTs can act as sponsors, but to do so they must examine their ability, capacity and expertise to discharge the relevant responsibilities for the particular research project, and to make formal arrangements with co-sponsors where sponsor responsibilities are allocated to and accepted by their research partners. Candidate studies for sponsorship should always be reviewed on a case-by-case basis to ensure that a PCT’s capacity or expertise is not exceeded. The shared arrangements for RM&G in primary care mean that a lead RM&G PCT within the partnership should normally be well-placed to gear itself to become a sponsor.
PCTs can become sponsor of research undertaken by their own staff, independent contractors or of research undertaken by third parties on patients for whom the PCT has a duty of care.
Independent contractors should be strongly discouraged from becoming sponsors because of the scope of responsibility involved. Where an independent contractor is considering becoming a sponsor, they should be urged to contact their professional body and their mutual indemnity society, to ensure that the appropriate safeguards for indemnity are in place. Independent contractors are not covered by NHS indemnity (but for further guidance on indemnity arrangements in primary care, see the Primary Care working party’s position statement on indemnity).
Is there an obligation to register as a sponsor?
There is no obligation to register as a sponsor under either the Medicines for Human Use (Clinical Trials) Regulations 2004 or the UK Policy Framework for Health and Social Care Research. However, the list of organisations that have voluntarily registered can be found on the DoH website www.ct-toolkit.ac.uk
How does an organisation declare as a sponsor?
In order to declare as a sponsor, access the Department of Health website http://www.ct-toolkit.ac.uk/routemap/sponsorship
Does the list of sponsors specify the type of study that an institution has agreed to sponsor?
“The organisations on this list have confirmed to DH that they would be willing and able to sponsor research. However, this does not imply a commitment for any particular study (sponsorship would need to be decided on a case-by-case basis) or for all areas of research. Anyone using this list will need to check locally about the kinds of research that a selected organisation on the list would be prepared to take on.”
http://www.ct-toolkit.ac.uk/routemap/sponsorship Institutions are expected to review candidate studies for sponsorship on a case-by-case basis and should only accept the role of sponsor for studies that lie within their competence
What quality assurance exists to ensure the robustness of procedures in organisations that have declared as sponsors?
At present the list reflects a self-declaration and as such does not provide any level of assurance as to the ability of the organisation to undertake the role of sponsor. However, the self-declaration contains the following statement:
- “I understand that my organisation will be removed from the list if, as part of the monitoring arrangements for compliance with this framework, it is found that it does not meet the requirements for being a research sponsor.”
Who can provide guidance on sponsorship?
The NHS R&D Forum document Sponsorship Principles outlines the basic concepts of sponsorship. Questions requiring clarification from:
- The Department of Health, Research Policy and Governance, Department of Health, Quarry House, Quarry Hill, Leeds LS2 7UE
- The MHRA http://www.mhra.gov.uk/
- NRES http://www.nres.nhs.uk/ Questions relating to specific aspects of a study may be directed to the Research Office of the organisation employing the Chief Investigator
How should sponsorship arrangements and responsibilities be documented?
The R&D Forum is engaged in the development of model agreements to assist organisations in formalising their sponsorship arrangements. Further development of these draft documents is being co-ordinated by the UKCRC under their Streamlining the Regulatory and Governance Processes workstream and copies will be placed on the Forum web site when they have been finalised
What costs will be incurred in fulfilling the role of sponsor?
These fall into two categories:
- All studies: Sponsors undertaking responsibility for set up, management, monitoring, audit and reporting may elect to recoup their costs from the funder or the employing institution.Conversely sponsors delegating specific responsibilities may reasonably be expected to pay the organisation fulfilling these functions.
- Trials involving IMPs: For studies undertaken at least partly on their own site, the NHS R&D Support Funding of the host NHS institution may be used to meet the following costs:
i. Annual MHRA registration
ii. Obtaining a Clinical Trials Authorisation (CTA)
iii. GCP adherence
v. MHRA inspection and audit
In industrially-sponsored contract research, these costs will normally be met by the sponsor company.
What sponsorship arrangements are appropriate for international studies?
N.B. Little guidance on this subject is available from the DH, MHRA or other advisory bodies and the following suggestions are based on limited experience in this area to date. It is therefore recommended that expert legal advice be sought by any UK organisation that is considering becoming a sponsor of an international study and that consideration be given to working through a CRO for such studies.
International studies fall into two categories:
- Studies that are led by a coordinating centre outside the UKwith participating sites within the European Community. The Clinical Trials Regulations advise that a legal representative of the study organiser, if they are based in the European Community, can take on the role of sponsor for such studies within the European Community. A UK centre could therefore take on sponsorship for sites within the UK but may not wish to act as sponsor for study sites elsewhere in the European Community (see next paragraph).
- Studies that are led by a UK coordinating centre with participating sites outside the European Community. In principle, the role of sponsor can be taken on by a UK organisation for study sites anywhere in the European Community. However there are concerns about the advisability and practicality of doing so for sites outside the UK, since the national regulations to enact the EU Clinical Trials Directive vary considerably in their provisions and it is unclear how the responsibilities of a UK sponsor under the Clinical Trials Regulations in the UK align with those under other national regulations. One possible solution is for a UK organisation to take on sponsorship subject to stringent, legally-binding agreements with each of the non-UK centres.
Note: The European Community means the EU countriesplus Norway, Iceland and Liechtenstein.