Standard Operating Procedure (Sop) for Local Site

SOP Number:

Version Date: June 7, 2016

STANDARD OPERATING PROCEDURE (SOP) FOR LOCAL SITE

PRINCIPAL INVESTIGATOR (PI) OVERSIGHT in PROSPECT

APPROVED BY:

Signature: ______

Date (dd/mmm/yy): ______

SOP Document Chronology:
Version Number: / Edited by: / Effective Date: (dd/mmm/yy) / Details of changes:

1.  INTRODUCTION AND PURPOSE

This standard operating procedure (SOP) defines the requirements for ensuring Local Site Principal Investigator (PI) oversight for the PROSPECT RCT. Lack of Local PI oversight and inadequate documentation of procedures could impact the data integrity as well as the rights, safety and welfare of study participants. “If it is not documented, it is difficult to validate”.

This procedure is intended to meet the Canadian Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS), Health Canada (HC), the International Conference on Harmonization (ICH) Guidelines (E6) for Good Clinical Practices and local Research Ethics Board (REB) guidelines for Investigator Oversight for clinical studies.

2.  SCOPE OF THIS SOP

2.1.  This document applies to the Local Site Principal Investigator of the PROSPECT RCT at the participating site.

2.2.  The Local Site Principal Investigator is responsible for the implementation of this SOP and ensuring that delegates are qualified and trained for their delegated responsibilities.

2.3.  The Local PI is responsible for providing and documenting ongoing involvement in the PROSPECT RCT.

3.  SUPPORTING DOCUMENTS ASSOCIATED WITH THIS SOP

Delegation of Authority Form SOP - Version 01April2015

Delegation of Authority Form - Version 08May2015

Participating Site Training Log - Version 05July2013

Research Coordinator Training - Version Log 08May2015

4.  DEFINITIONS / ABBREVIATIONS

PI Principal Investigator

SOP Standard Operating Procedure

SDM Substitute Decision Maker

TCPS Canadian Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans

ICH International Conference on Harmonization

REB Research Ethics Board

Delegate: All members of the research team involved in the PROSPECT RCT, who have a delegated responsibilities of study conduct and are listed as such on the Delegation of Authority Form.

Informed Consent: A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject's decision to participate. In critical care research, the informed consent will most often be obtained from a substitute decision maker (SDM) because of decreased level of consciousness of critically ill patients, due to their acute illness and/or medications. Informed consent is documented by means of a written, signed, and dated informed consent form.

Methods Center: PROSPECT Methods Center

Local Site Principal Investigator: An individual who actually conducts the clinical investigation. In the event that the investigation is conducted by a team of individuals, the investigator is the responsible leader of the team. (21 CFR 312.3)

Source Documents: Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, etc.)

Sponsor: McMaster University and Dr. Deborah Cook

5.  PROCEDURES

The Local Site PI will provide oversight of the PROSPECT RCT in the areas of delegation, training and supervision. Typically, the Local Site PI is assisted by delegates (a research coordinator and other support staff such as study nurses, other physicians and research assistants). The delegates may be involved in a number of research-related tasks (screening, obtaining informed consent, collecting study samples, completing case report forms, entering data, responding to queries, research ethics board documents, etc.)

When delegating a task to a member of the study team, the Local Site PI will:

·  Ensure the delegate is sufficiently qualified to perform the delegated task

·  Ensure the team member has received adequate training to perform the delegated task

·  Demonstrate ongoing involvement in the conduct of the study including assistance with protocol implementation, progress tracking, problem solving, etc.

Sufficient Qualifications

The Local Site PI will delegate tasks to members of the study team who are qualified by education, training, experience and licensing (the latter as needed). The qualifications required will depend on the delegated task. Examples of instances in which study tasks may be inappropriately delegated to members of the study team who may lack qualifications may include physical examinations and judging of adverse events.

The Local Site PI is responsible for conducting the PROSPECT RCT in accordance with the protocol and the participating site local research ethics board. In some cases the protocol may specify the qualifications of delegates who are to perform certain protocol-required tasks (e.g., physician, registered nurse), in which case the protocol must be followed.

The delegation of authority document and participating site training log will explain the delegated tasks, recognize the training that members of the study team have received that qualifies them to perform delegated tasks (i.e., may refer to a team members' CV on file), and identify the dates of involvement in the study.

Adequate Training

The Local Site PI will ensure that there is ample training for all team members involved in the conduct of the study, including any new staff hired after the study has begun (to meet unanticipated workload or to replace staff who have left). The Local Site PI will ensure that team members:

·  Review and understand the protocol

·  Understand the attributes of the product and program that is being evaluated, as needed, to perform their assigned tasks

·  Are knowledgeable of the regulatory requirements and acceptable standards for the conduct of clinical trials and the protection of human subjects

·  Are competent to perform or have been trained to perform the delegated tasks

·  Are informed of any relevant changes during the trial and receive extra training as appropriate

If the PROSPECT Methods Center/Sponsor provides training for the Local Site PI, the delegates should also receive this method of training, or any information (e.g., training materials) from that training that is relevant to their role in the PROSPECT RCT.

The Local Site PI will consider and provide additional training to members of the research team as necessary for specific study-related procedures. For example:

·  Prescribing and/or administering a study product will require the team member to review the investigational brochure and have a full understanding of the mechanism of action of the drug, possible drug interactions, potential adverse effects of the study drug, etc.,

·  Adverse event (AE) evaluation and reporting will require the delegate to have the education and experience; and have in-depth knowledge of the protocol’s specific AE reporting policies as well as local research ethics board requirements.

Ongoing Involvement

The Local Site PI is the responsible leader of all members of the research team involved in the PROSPECT RCT. The Local Site PI will ensure that she/he has sufficient time to properly conduct and supervise the PROSPECT RCT. The level of supervision will be appropriate to the staff, the nature of the study, and the study participant population. The following factors may affect the ability of a Local Site PI to provide adequate supervision of the conduct of an ongoing study at the participating site:

·  Inexperienced study staff

·  Demanding workload for study staff

·  Complex clinical trials (e.g., many observations, large amounts of data collected)

·  Large number of subjects enrolled at a site

·  A population that is seriously ill

·  Conducting multiple studies concurrently

·  Conducting a study from a remote (e.g., off-site) location

·  Conducting a study at multiple sites under the oversight of a single investigator, particularly where those sites are not in close proximity

The Local Site PI will develop and implement a plan for the supervision and oversight of the PROSPECT RCT at the participating site. Supervision and oversight will be provided for all members of the research team, even those who are highly qualified and experienced. The plan might include the following elements, to the extent they apply to a particular trial:

·  Routine scheduled meetings with staff to review study progress, adverse events, and update staff on any changes to the protocol or other procedures

·  Routine meetings with the PROSPECT Methods Center/Sponsor and Monitors

·  A procedure for the timely correction and documentation of problems identified by study personnel, outside Monitors or Auditors, or other parties involved in the conduct of a study

·  A procedure for documenting or reviewing the performance of delegated tasks in a satisfactory and timely manner (e.g., observation of the performance of selected assessments or independent verification by repeating selected assessments)

·  A procedure for ensuring that the consent process is being conducted in accordance with International Conference on Harmonization (ICH) Guidelines (E6) for Good Clinical Practices and local Research Ethics Board requirements

·  A procedure for ensuring that source data are accurate, contemporaneous, and original

·  A procedure for ensuring that information in source documents is accurately captured on the case report forms (CRFs)

·  A procedure for dealing with data queries and discrepancies identified by the study monitor

·  Procedures for ensuring study delegates comply with the protocol and adverse event assessment and reporting requirements

·  A procedure for addressing medical and ethical issues that arise during the course of the study in a timely manner

Oversight of Other Parties

The Local Site PI is responsible for members of the research team involved in the study but not directly employed by the Local Site PI. In this situation, the Local Site PI should take steps to ensure that the team members not under her/his direct employ are qualified to perform delegated tasks and have received adequate training on carrying out the delegated tasks and on the nature of the study. If not, the Local Site PI should provide such training. The Local Site PI will ensure the appropriate documentation needed to comply with the investigator’s regulatory responsibilities is developed and maintained by delegates (i.e., source documents, CRFs, drug storage and accountability records, research ethics board correspondence). The Local Site PI will supervise the study tasks performed by delegates, even if they are not in her/his direct employ during the conduct of the study. This responsibility exists regardless of the qualifications and experience of members of the research team.

Rights, Safety, and Welfare

The Local Site PI is responsible for protecting the rights, safety, and welfare of participants under their care during the PROSPECT RCT. This responsibility will include:

·  Providing reasonable medical care for study participants for medical problems arising during participation in the study that are, or could be, related to the study intervention

·  Providing reasonable access to needed medical care, either by the Local Site PI or by another identified, qualified individual (e.g., when the investigator is unavailable, when specialized care is needed)

·  Adhering to the protocol so that study participants are not exposed to unreasonable risks

During any period of unavailability, the Local Site PI will delegate responsibility for medical care of study participants to a specific qualified individual who will be readily available to participants and team members during that time (in the manner a physician would delegate responsibility for care in clinical practice).

6.  REFERENCES, APPLICABLE REGULATIONS AND GUIDELINES

ICH GCP, E6

Guidance for Industry, Investigator Responsibilies-Protecting the Rights, Safety and Welfare of Study Subjects. FDA October 2009, Section 3

Clinical Research Times, BUMC, Principal Investigator Oversight, April 2010 Issue

TCPS

4