GA-103: Investigators Responsibility &
Delegation of Responsibility
|SOP No.: 103 INVESTIGATOR RESPONSIBILITY AND DELEGATION OF RESPONSIBILITY|
|Author: Office of Human Research|
|Effective Date: October 1, 2007||Supercedes document dated: N/A|
|Last Reviewed on: N/A||Results of Review: N/A|
|This SOP pertains to: : Any investigation product (drug, biologic, medical device)
|Responsibility for executing this SOP: Investigator and Designated Research Personnel|
J. Bruce Smith, MD
Associate Vice President for Research
(signature on file at OHR)
Steven E. McKenzie, MD, Ph.D.
Vice President for Research
(signature on file at OHR)
1. INTRODUCTION AND PURPOSE
Research studies will be conducted according to FDA and HHS regulations to protect the safety and welfare of study subjects that must be ensured by a research team knowledgeable about ongoing study protocols and investigational articles.
Investigators and all key members of the research team who are working on or overseeing programs that conduct research on humans will receive initial and ongoing training regarding the responsible conduct of research.
This standard operating procedure (SOP) describes the process and documentation required by this the institution for the initial and ongoing education of the principal investigator and research staff in Good Clinical Practices (GCPs) and the ethical conduct of research conducted at this research site.
3. SPECIFIC PROCEDURES
3.1 Investigator Responsibilities
- Consults with the Office of Human Research (OHR) for clinical study activities prior to proceeding.
- Follows standard operating procedures (SOP’s) to ensure that the conduct of FDA-regulated human subject research proceeds in compliance with GCP Guidelines and all applicable regulations and institutional requirements are met (Reference Investigator SOP Manual).
- Ensures that critical documents are developed, reviewed, approved, and modified in a controlled and accountable manner (Reference SOP 101, Standard Operating Procedure Preparation and Maintenance and SOP 102, Document Development and Change Control).
- Ensures that responsibilities and activities in the conduct of FDA-regulated human subject research that are delegated to others are understood by those who carry them out and are delegated to individuals who are qualified by training and experience to carry out those responsibilities and activities, with appropriate documentation of that delegation.
- Follows training policies and procedures to provide all designated individuals with the opportunity to maintain and enhance their ability to carry out delegated responsibilities; and ensures all individuals engaged in clinical research have met their training requirements.
- Ensures that financial and professional conflicts of interest are recognized, reported to appropriate authorities, and any applicable management plans are followed (Reference SOP 105, Prohibition of Financial Conflicts).
- Should establish criteria for selecting qualified outside contractors to conduct study-related activities when necessary and appropriate, and document those selection criteria and delegated responsibilities.
- Facilitates and coordinates effective written and oral communications with the FDA, including regulatory submissions, responses to questions and meetings, and maintains active FDA status with respect to conducting clinical studies using investigational drugs/biologics/medical devices, e.g., IND, IDE
- Reviews and periodically evaluates the evidence relating to the safety and effectiveness of the investigational product and ensures that all relevant reports (e.g., clinical study reports, adverse event reports, safety reports and annual reports) are submitted to the FDA and other affected parties (e.g., the IRB, Investigators) in a timely manner..
- Ensures that clinical investigations are performed according to the general investigational plans and clinical protocols contained in the IND/IDE, and that changes to protocols or participant treatment are reported to appropriate regulatory and institutional authorities.
- Submit to the IRB for approval prior to implementation of the change
- Submit to the FDA for non-objection prior to the implementation of the change (if applicable)
- Keeps Investigators informed by means of Investigator Brochures, published literature, observations, and general information concerning the clinical investigation and any significant, new adverse events or risks associated with the investigational product.
- Selects qualified Investigators, on the basis of qualifications, clinical research experience, and knowledge of subject matter, and maintains files on those Investigators involved in the study, including notifying the FDA of their participation.
- For research conducted under an IND, the Investigator should ensure that the (Principal) Investigator signs the Investigator Statement for each protocol and signs and adheres to the requirements stated on Form FDA 1572 (See SOP 103 Attachment C: Form FDA 1572 for IND studies).
- Ensures that Investigators and their study staff are adequately prepared to conduct a clinical investigation through site training on the regulations, the protocol and the investigational product.
- Ensures regular, timely, effective and well-documented communication among all individuals participating in the conduct of clinical research.
- Ensures the investigational products are manufactured under appropriate controls, are properly labeled and released only to qualified Investigators, and are distributed, stored and disposed of in a manner that permits full accountability of all investigational product, via appropriate record keeping.
- Maintains all required documents and records in the appropriate location and for a period of time specified by regulatory requirements.
- Monitors the progress of the investigation by performing periodic reviews of participant records and data collected as part of the clinical investigation, including investigational product accountability records, case report forms, other participant records, protocol adherence, adverse event reporting, informed consent, and regulatory documentation.
- Terminates an investigation that is determined to present an unreasonable or significant risk to subjects, or for recurring violation of the investigational plan.
- Protects the rights and well being of study participants and ensures initial and ongoing review by a Thomas Jefferson University Institutional Review Board, other designated IRB, and other relevant institutional research safety committees, e.g., Radiation Safety, IBC.
- Ensures that each participant signs the current version of Thomas Jefferson University approved informed consent form and continues the process of informing participants about their ongoing participation throughout the duration of the study.
- Safeguards the scientific, ethical and regulatory validity of the clinical study by requiring strict adherence to participant enrollment criteria, participant identification methods (protection of confidentiality), and biological specimen collection and handling requirements.
- Ensures the management of participants' medical care while enrolled and that adverse events are recorded and, if serious, are promptly investigated and reported to the FDA and other relevant institutional and regulatory authorities.
- Maintains a system for recording and managing data and observations from clinical studies, including required safeguards for electronic data collection systems.
- Employs quality assurance practices that ensure scientific, ethical and regulatory compliance by permitting the independent review and assessment of policies, procedures and records for quality improvement purposes.
- Cooperates with regulatory authorities (e.g., FDA, OHR) in their assessment of the clinical research program's compliance with applicable regulations.
3.2 General Responsibilities of the Study Team
- Communicate effectively with participants, other study team members, the IRB, and the Investigator.
- Support required training activities through their own professional development in relevant content areas.
- Communicate all adverse events and abnormal laboratory results to the Investigator for an assessment of severity and reports non-serious adverse events or serious adverse events to the IRB, and Investigator appropriately.
- Meet regularly with the Investigators and other study team members to discuss subject participation and protocol progress.
- Prepare for and attend Investigator and study start-up meetings.
- Participate in monitoring visits and audits as appropriate.
- Make available to Monitors, Auditors, the IRB and regulatory authorities all requested study-related records.
- Ensure accuracy, completeness, legibility and timeliness of case report forms (CRFs).
- Ensure that CRFs accurately reflect source documents, explain any discrepancies between source documents and CRFs, and endorse changes or corrections to the CRFs.
- Ensure documentation of study-related procedures, processes and events.
- Comply with written SOPs to document changes to data and/or CRFs.
- Maintain study documents and files as required by the regulations for the appropriate time frame and under secure conditions.
3.3 Delegation of Responsibility and Signature Authority
- The Investigator has the authority to delegate any study-related task and duty to any member of the study team who has been properly trained to carry out the designated function.
- The Investigator or his/her designee must identify the individual by name and/or by title, to which significant study-related functions have been assigned.
- Designated personnel may sign various documents when the Investigator has delegated to them this authority.
- The Investigator may sign any document in the absence of designated personnel.
- If a designated individual signs in place of another whose name is typed or printed near the space for signature, the signatory shall sign his or her name followed by the word "for" indicating they are signing for that person.
- For instances in which the signatory is signing a totally blank space, that person shall simply sign his or her name and provide a date.
3.4 Transfer of Responsibility to Contractors
- The Investigator has the authority to delegate any study-related task and duty to a qualified contractor (e.g., consulting firm, independent consultant, Contract Research Organization) that has been properly trained to carry out the designated function.
- The Investigator or his/her designee must identify the individual(s) by name and/or by title to which significant study-related functions have been assigned in a properly executed vendor contract.
The Investigator will maintain a file documenting the qualifications of such vendors as part of the study file.
4. APPLICABLE REGULATIONS AND GUIDELINES
|21 CFR 312.60||General responsibilities of investigators|
|45 CFR 46||46DHHS Part 46 Protection of Human Subjects|
|21 CFR 812||Subpart E Responsibilities of Investigators|
|May 1997||ICH Good Clinical Practice: Consolidated Guideline (E6 4.2.4)|
|September 1993||FDA Internal Compliance Program Guidance Manual for Clinical Investigators: 7348.811|
|June 5, 2000||NIH Notice OD-00-029: Required Education in the Protection of Human Research Participants|
|September 12, 2000||Clarification on June 5, 2000 Notice (OD-00-39)|
5. REFERENCES TO OTHER APPLICABLE SOPs
All SOPs are applicable to this SOP.
The following definitions from the International Conference on Harmonisation, Good Clinical Practice: Consolidated Guideline apply to this SOP.
Good Clinical Practice (GCP): A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected