ROLES, RESPONSIBILITIES AND DELEGATION OF DUTIES IN CLINICAL TRIALS OF MEDICINAL PRODUCTS

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1 ROLES, RESPONSIBILITIES AND DELEGATION OF DUTIES IN CLINICAL TRIALS OF MEDICINAL PRODUCTS STANDARD OPERATING PROCEDURE NO SOP 09 DATE RATIFIED 4/7/13 NEXT REVIEW DATE 4/7/14 POLICY STATEMENT/KEY OBJECTIVES: To outline the division and delegation of responsibilities and clarify boundaries of responsibility within the research study team and how they should be documented. POLICY AUTHOR: Katie Helm; Research & Development Facilitator Page 1 of

2 BACKGROUND Appropriately qualified and trained personnel are required to ensure the satisfactory conduct of research studies at a site. This may include staff directly involved in the conduct of the research such as: Principal Investigator (PI) Co-investigator Research practitioners (e.g. research nurses/ practitioners/ officers/ coordinators) Study co-ordinators (e.g. data managers/ research assistants) In addition, there may be staff associated with, but not directly involved in the research study at the site, including: Clinicians and other clinical staff Specialist nurses Pharmacists Other support staff e.g. radiology, laboratory For a study to adhere to Good Clinical Practice (GCP) guidelines, Study Protocol and applicable regulatory requirements, it is essential that all staff involved are aware of their roles and responsibilities and that they are appropriate for the duties delegated to them by the PI. International conference of Harmonisation GCP (ICH GCP) guidelines define an investigator as A person responsible for the conduct of the clinical trial at a trial site. The investigator is responsible for protecting the integrity, health and welfare of the research subjects. The investigator must be: Qualified by education, training and experience Thoroughly familiar with the study protocol and any investigational product(s) Aware of, and compliant with Good Clinical Practice and any applicable regulatory requirements, e.g. Medicines for Human Use (Clinical Trials) Regulations 2004 or Research Governance Framework for health and social care 2005 Page 2 of

3 If a team of investigators conducts a study at a site, the investigator responsible for leading the team is referred to as the PI. Other investigators are referred to as coinvestigators. The Sponsor takes responsibility for the initiation, management and financing (or arranging the financing) of the study. PURPOSE To outline the division and delegation of responsibilities and clarify boundaries of responsibility within the research study team and how they should be documented. PROCEDURE Who? During the study set up, the PI, co-investigator(s) if applicable and the assigned research practitioner to be working on the study must discuss and agree on the study requirements and the delegation of duties. This may need to be conducted with a representative from the sponsor. The delegation of duties will depend on the qualifications and experience of the individuals in the team, and will vary from study to study and from staff member to staff member. Evidence of appropriateness to perform the delegated duties is generally in the form of up to date Curriculum Vitae (CV), and evidence of GCP training (certificate). The PI must be assured by these and knowledge of the study team that all team members are able to perform their delegated duties appropriately. When? The delegation of duties and roles within the study team should be discussed and documented as part of study set up and initiation. Further training and competency may be required by some members of the team which should be undertaken before commencing work on the study. Page 3 of

4 The Principal Investigator may be required to sign off their team on the delegation of duties log as part of the official initiation visit, if appropriate. How Roles of the study team The majority of studies have a PI, who has overall responsibility for the conduct of the study at their site. The responsibilities of a PI are summarised in Appendix A and include: Ensuring the welfare and medical care of study subjects Obtaining approval of and continued communication with regulatory bodies Conduct of the study in compliance with the protocol and required governance regulations and guidelines, as well as local policies/procedures Administration, management, storage of investigational product Safety reporting The accurate and timely completion of study data Archiving Evidence of appropriateness of research team Research Governance Framework for Health and Social Care state that the Chief Investigator is responsible for ensuring that; Each member of the research team, including those at collaborating sites, is qualified by education, training and experience to discharge his/her role in the study, and their qualifications are documented. A current CV for each member of the study team will fulfil this requirement for qualifications to be documented. The CV should be updated every 2 years or when there is a relevant change. Superceded versions should be maintained in the site file. National Research Ethics Service (NRES) ( gives guidance on completion of CV for researchers. This training will include study specific required training and experience. Good Clinical Practice (GCP) training should be attended and certificate of attendance will be evidence of this. These documents are essential documents and must be maintained as such within the study site file. Page 4 of

5 The frequency of GCP training must satisfy the Sponsor and Trust requirements. For Lancashire Care NHS Foundation Trust, the suggested timeframe for this is every two years. Clarification should therefore be sought from the study Sponsor. Delegation of duties The clinical trials regulations state: A sponsor of a clinical trial, in accordance with this regulation may delegate any or all of his functions under these regulations to any person but any such arrangement shall not affect the responsibility of the sponsor. The principle of delegation of duties is that the duty can be delegated but not the responsibility. This delegation may be from Sponsor to CI; CI to PI; PI to members of the site study team. At a study site, any duties that are delegated to the study team remain the responsibility of the PI. Each member of the team should perform their delegated duties adhering not only to research guidance and relevant legislation but also to local Trust and professional body requirements. Other key staff involved in the study may be delegated duties by the PI. A summary of some of these duties is shown in Appendix B however full details will be listed in each study protocol. These people must be appropriately experienced and qualified to assist in the management of the study for the task that they have been delegated. The PI can delegate duties, but never the responsibility for the study at the site. The allocation of duties to appropriately qualified persons should be recorded in a study specific delegation of duties log (Appendix C) with specimen signatures and the initials of all involved. The Sponsor may provide their own template to be used. If a large number of clinical staff are involved in a routine part of the study and their duties, e.g. delivering a study drug over many weeks, it may be more practical to include the senior staff member responsible for their conduct in the log, e.g. ward sister, rather than every single staff member. This must be agreed with the sponsor. Page 5 of

6 Documentation of delegated duties is an on-going process as circumstances may change, e.g. different members of staff may become involved in the study. The log must: List the names and roles of all staff involved and outline which duties have been delegated to them Confirm the start and end dates for each member of staff performing their delegated duties Be signed and dated by the PI they should sign off each individual member of staff, considering their evidence of training, education and experience prior to the staff member carrying out any duties for the trial. By delegating duties the PI confirms that the team member is appropriate for their delegated duties. and maintain the responsibility. Therefore active involvement in the study is not permitted for staff until they have been signed off by the PI. Be updated throughout the study. This may include new staff and staff who leave. Superseded versions must not be destroyed in order to allow an audit trail of who was performing which duties at any time point in the conduct of the study for future inspection Be filed appropriately in the Investigator Site File. If archived by a sponsor, a copy must remain at the site Be supplied to the sponsor as requested, with updated versions being supplied when updated. Contact names and roles of other individuals involved in the study (e.g. pharmacy, laboratory staff) should also be notified to the sponsor. The delegation of duties log is an essential document and must be maintained as such within the study site file. OTHER RELATED PROCEDURES, POLICIES, LEGISLATION OR GUIDANCE International Conference on Harmonisation of Good Clinical Practice 1996 Department of Health Research Governance Framework for Health and Social Care 2005 Page 6 of

7 Medicines for Human Use (Clinical Trials) Regulations 2004 NRES guidance on submission of curriculum vitae (CV) GLOSSARY Chief Investigator (CI) Principal Investigator (PI) Standard Operating Procedure (SOP) Curriculum Vitae (CV) National Research Ethics Service (NRES) APPENDICES Appendix A: Responsibilities of the PI Appendix B: Possible duties delegated to the study team Appendix C: Delegation of duties log template Page 7 of

8 Appendix A: Responsibilities of the PI POSITION Principal Investigator Overall responsibility for study at site Medical care and supervision of patients RESPONBILITIES OF THE PI Delegation of study related duties Ensuring all staff delegated to work on trial are adequately informed as to protocol requirements and trained in study procedures Familiarity with Investigator Brochure (where available) Patient recruitment strategy Screening of patients Informed consent Signing of consent form (as appropriate to local policy & practice) Randomisation (as appropriate to local policy & practice) Administration of investigational product Collection of trial related blood samples Completion and return of Case Record Forms and providing responses to data queries Prescriptions Documentation of adverse events Timely Serious Adverse Events reporting Initiation of new trial personnel Ethics committee approval/communications re: amendments Negotiation and completion of the financial agreement Indemnity, compensation and insurance Investigational Product accountability and monitoring of compliance Page 8 of

9 POSITION Available for audit and inspections RESPONBILITIES OF THE PI Archiving Appendix B: Possible duties delegated to the study team POSITION Co-investigator (s) Medical care of patients Screening of patients for eligibility DELEGATED DUTIES Informed consent Sign consent form Randomisation Responsible for administration of study drug Responsible for collection of trial specific blood samples Completion and return of Case Report Forms and providing responses to data queries Prescriptions Assessment of adverse events Timely SAE reporting Ethics committee obligations Research practitioner (e.g. Research nurse or study coordinator) Screening of patients Informed consent (according to local practice) Randomisation Completion and return of Case Report Forms Data queries Documentation of adverse events in source data Investigator/Study file set up and management Page 9 of

10 Support monitoring visits and audits and inspections Preparation of paperwork for Ethics committee and Trust R&D Notification Preparation of SAE reports for medical input and causality assessment Sample handling Data manager Data entry Completion and return of Case Report Forms Data queries Support monitoring visits, audits and inspections Clinical Trials Pharmacy staff Acknowledge receipt of trial supplies Drug accountability and monitoring of compliance Dispensing of Investigational Product to patients Complete dispensing logs Maintain Pharmacy file Monitor storage of Investigational Product Page 10 of

11 Appendix C: Delegation of duties log template Medical Directorate Protocol Title: Protocol Number: Name (please print) Signature Initials Role 1 Delegated Duties 2 (Please circle all that apply) Start Date (mmm/dd/yyyy) End Date (mmm/dd/yyyy) (specify): (specify): (specify): 1 PI=Principal Investigator; CI=Co Investigator; CRN=Clinical Research Nurse; CRC=Clinical Research Coordinator; P=Pharmacist 2 1=Confirm Eligibility; 2=Obtain Informed Consent; 3=Trial Related Medical Decisions; 4=Evaluation of Trial Lab Results; 5=Assess Adverse Events; 6=Unblinding; 7=Review Study and Informed Consent with Subject; 8=CRF Signatures; 9=Perform Physical Exams; 10=REC Communication; 11=Eligibility Screening; 12=CRF Completion/Corrections; 13=Query Resolution; 14=Randomization/Re-supply; 15=Study Drug Accountability; 16=Study Drug Dispensing; 17=Document Protocol Deviations; 18=Explain Correct Use of Investigational Product to Subject; 19=Other (please specify in Table above) The above persons are working under my supervision and have permission appropriate to their level of expertise to perform study procedures as described. Investigator s Signature: Date: Page 11 of