The content of these Standard Operating Procedures (SOPs) has been registered to the Fonds de recherche du Québec - Santé (FRQS) and is duly protected under the Copyright Act of Canada.

These SOPs were created specifically for use in publicly funded institutions in Quebec and are applicable to both academic research projects as well as pharmaceutical and device regulated clinical trials. They reflect the current best practices in clinical research in accordance with Provincial and Federal regulations and guidelines.

The FRQS SOPs and available standardized training material on the SOPs can be adapted and customized for clinical research sites, research institutions or groups worldwide. Due recognition to FRQS as the source of the material should be clearly stated in the adapted version of the materials.

The FRQS assumes no responsibility for changes made to these SOPs without its prior written approval.

The Fonds de recherche du Québec - Santé (FRQS) is very pleased to share these Standard Operating Procedures to Ensure Good Clinical Practice at Clinical Research Sites with clinical research organizations, centers and sites worldwide.

The FRQS has identified Clinical Research as one of its main priorities in its current Strategic Development Plan 2007-2010. This initiative is part of the implementation process of this aspect of the Plan. Our goal is to promote, encourage and support quality clinical research practice at the local and international levels; while ensuring that Quebec becomes and remains an important player in the field of quality and ethical clinical research.

The Standard Operating Procedures (SOP) presented here are the result of a successful collaborative effort between the FRQS, the Government of Quebec, four Quebec universities (McGill University, Université de Montréal, Université de Sherbrooke, Université Laval) as well as the 19 FRQS-funded research centres. The goal of this collaboration was to create quality assurance material for clinical research activity that occurs in publicly funded institutions in Quebec (publicly funded as well as industry-sponsored). These SOPs are part of a larger quality assurance package that is currently being developed. This package includes training material on issues related to Good Clinical Research Practices.

The FRQS SOPs were developed within the context of a publicly funded initiative (the GEREQ Project) that had the mandate to improve the Quality of Clinical Research in Quebec. One of the main objectives of this initiative was to help academic clinical researchers meet internationally recognized quality standards in their field-work activity and to make these standards available to researchers at a cost that they can afford.

Within this context, quality standards were developed and 3 activities were prioritized as being critical to assure the quality of clinical research field-work. These are:

1) Training clinical research personnel in good clinical research practice (GCP)

2) Developing site specific standard operating procedures (SOP) for clinical site activity

3) Having a standard and validated information system dedicated to clinical research

The 26 FRQS SOPs were developed by a provincial expert working group (including an observer from Health Canada’s Inspectorate) and are not templates. They are complete SOPs written in a generic fashion so that they can be applied to all clinical research centers in Quebec (they are applicable to both academic research projects as well as pharmaceutical and device regulated clinical trials). They have been written as a comprehensive training resource tool for clinical research sites.

The FRQS SOPs incorporate the following standards and regulations:

-International Conference on Harmonisation (ICH) Guidelines for Good Clinical Practices, 1996;

-Health Canada Therapeutic Products Directorate Food and Drug Regulations for Clinical Trials. Division 5. Canada Gazette Part II, Vol. 135, No. 13, June 7, 2001;

-USA Food and Drug Regulations, Code of Federal Regulations Chapter 21 Part 11;

-Tri-Council Policy Statement; Ethical Conduct for Research Involving Humans; Medical Research Council of Canada; Natural Sciences and Engineering Council of Canada; Social Sciences and Humanities Research Council of Canada, August 1998;

-Quebec and Canadian Laws, as applicable

The FRQS SOPs are available in both English and French and can be adapted and customized for clinical research sites, research institutions or groups by the end-users themselves.

The available standardized training material on the SOPs assures the adequate training of clinical research staff once SOPs are implemented at the site.

SOP

Objective

SOP
General Training

	Tutorial only [195 Ko, 14 p.]

Describe the Standard Operating Procedures

SOP-01
Development, Approval and Review of Standard Operating Procedures (SOP)

	Procedure [419 Ko, 14 p.]
	Tutorial [177 Ko, 5 p.]

Define:

-The development of site standard operating procedures

-The SOP approval/validation process

-The implementation of SOPs within the institution

-The management and updating of SOPs

SOP-02
Organizing a Site for Clinical Research

	Procedure [206 Ko, 14 p.]
	Tutorial [188 Ko, 7 p.]

Describe procedures to be followed to ensure proper organization of the clinical study site.

SOP-03
Research Team: Role Definitions, Responsibilities and Task Delegation

	Procedure [263 Ko, 10 p.]
	Tutorial [182 Ko, 9 p.]

Identify all members of the research team, define their roles and responsibilities as well as record written procedures for the delegation of tasks and responsibilities.

SOP-04
Site Research Team: Competency, Knowledge and Training)

	Procedure [141 Ko, 7 p.]
	Tutorial [180 Ko, 7 p.]

Inform all members of the research team of the requirements concerning competency, knowledge and training. This SOP outlines how these requirements are to be documented.

SOP-05
Preparing the Team for a Study

	Procedure [153 Ko, 6 p.]
	Tutorial [180 Ko, 8 p.]

Explain to the research team the clinical the processes for study setup.

SOP-06
Study Feasibility Assessment

	Procedure [173 Ko, 9 p.]
	Tutorial [177 Ko, 5 p.]

Provide the research team with some tools with which to evaluate the feasibility of a clinical study in order to:

-Obtain information about the local feasibility of the study

-Identify the environment in which the clinical study will beconducted

-Confirm the study operations schedule

-Make an informed decision concerning distribution of clinical sites

-Understand and focus on the subject population targeted for recruitment into the clinical study

SOP-07
Conducting a Study in The context of a Clinical Trial Application in Canada

	Procedure [165 Ko, 9 p.]
	Tutorial [183 Ko, 10 p.]

Guide the sponsor-investigator in the conduct of a clinical trial when the trial is the subject of a Clinical Trial Application (CTA) to Health Canada.

Detailed information and forms to be used for a Clinical Trial Application are available on Health Canada’s web site at the following address: www.hc-sc.gc.ca.

SOP-08
Protocol and Protocol Amendment, submission to Research Ethics Board

	Procedure [214 Ko, 15 p.]
	Tutorial [179 Ko, 6 p.]

Ensure that all clinical study protocols or amendments implemented within the institution are in compliance with ICH Good Clinical Practice and any applicable regulations.

Ensure that all institutional personnel working in clinical research comply with the protocol or protocol amendment.

Furthermore, this operating procedure is designed to help the sponsor-investigator or investigator/qualified investigator prepare and submit a clinical study protocol or a protocol amendment to the Ethics Committee.

SOP-09
Consent Process and Subject Informed Consent Form

	Procedure [223 Ko, 16 p.]
	Tutorial [181 Ko, 8 p.]

Ensure the compliance of all informed consent forms (ICF) being used in the institution, with ICH GCP standards, as well as with applicable provincial and federal legislation.

Ensure that the consent process used in the institution, follows applicable ethical standards in order to ensure the safety and protection of study subjects.

SOP-10
Rights and Protection of Study Subjects

	Procedure [162 Ko, 9 p.]
	Tutorial [179 Ko, 7 p.]

Describe the process which ensures the rights protection and well being of subjects participating in a clinical study.

SOP-11
Conflict of Interest

	Procedure [167 Ko, 7 p.]
	Tutorial [179 Ko, 7 p.]

Define the process of managing conflict of interest within an institution.

All parties involved in clinical research should be independent, objective and loyal in their relations with subjects, sponsors, research establishments and professional corporations.

Conflicts of interest can affect various parties in a clinical study. The sponsor-investigator, investigator / qualified researcher, ethics committee, institution and even a subject participating in the clinical study can be in a situation of conflict of interest.

SOP-12
Subject Recruitment

	Procedure [145 Ko, 8 p.]
	Tutorial [178 Ko, 6 p.]

Describe the principles that govern the process of recruitment of subjects in a clinical study.

SOP-13
Subject Follow-up

	Procedure [284 Ko, 8 p.]
	Tutorial [178 Ko, 6 p.]

Ensure that the rights, the dignity and well-being of subjects are protected by proper follow-up.

In order to ensure the proper course of the clinical study and to be in conformity with ethics, the investigator/qualified investigator should make sure that all measures are in place for the best possible follow-up of subjects. Protection of human subjects requires ensuring participants in a study the same rights as users of healthcare or social services.

SOP-14
Dealing with Scientific Misconduct and Protocol Deviations

	Procedure [138 Ko, 6 p.]
	Tutorial [179 Ko, 7 p.]

Describe procedures for documenting scientific misconduct or protocol deviations and their submission to the appropriate bodies.

To ensure integrity of the data and validity of the final results of the clinical study, the investigator/qualified Investigator or those he delegates should observe the protocol requirements meticulously.

SOP-15
Research Ethics Board (REB): Ongoing communications

	Procedure [169 Ko, 10 p.]
	Tutorial [180 Ko, 8 p.]

Describe the communications process (submission, follow-up, etc.) between the investigator/qualified investigator and Ethics Committee, during the course of clinical studies.

To ensure respect for the rights, protection, safety and well-being of subjects, the institutional Research Ethics Board is responsible for reviewing and periodically checking biomedical research projects involving human subjects. For all clinical studies, communications between investigator/qualified investigator and the REB start with the preparation of documents for submission, and continue during the study until submission of the final report.

SOP-16
Management of Communication During a Study

	Procedure [121 Ko, 5 p.]
	Tutorial [179 Ko, 7 p.]

Define channels of communication and exchange of information among the investigator, the research team and subjects. It also defines principles of communication between the investigator and the sponsor and, according to applicable regulatory requirements, communications with the sponsor-investigator, investigator, Ethics Committee and regulatory authorities.

SOP-17
Management of Adverse Events - Serious Adverse Events and Adverse Reactions - Serious Adverse Reactions

	Procedure [174 Ko, 8 p.]
	Tutorial [184 Ko, 10 p.]

To ensure the safety of participants, the investigator/qualified investigator and research personnel are required to follow each subject in a clinical study with the utmost care. This SOP describes methods of collection, documentation, investigation and assessment, as well as submission and follow-up, of AE/SAEs or AR/SARs which occur in the course of a clinical study with, or without, drugs or medical devices.

This SOP also defines AE/SAEs or AR/SARs, the responsibilities of the sponsor-investigator and investigator/qualified investigator, as well as deadlines for reporting these AE/SAEs or AR/SARs.

SOP-18
Managing Investigational Products, Biological Products, Medical Devices or Radiopharmaceuticals Under Study

	Procedure [160 Ko, 9 p.]
	Tutorial [186 Ko, 13 p.]

-Define standard operating procedures which describe how investigational products are managed within the establishment.

-Provide basic standards in order to ensure compliance with applicable regulatory requirements.

-Ensure that procedures for management of research products specific to a sponsor/sponsor-investigator, are followed.

SOP-19
Management of Biological Specimens : Collection and Storage

	Procedure [162 Ko, 6 p.]
	Tutorial [178 Ko, 6 p.]

Describe the management of biological specimens, from their collection to their destruction, within the institution.

SOP-20
Preparation for Monitoring Visits

	Procedure [161 Ko, 6 p.]
	Tutorial [179 Ko, 7 p.]

Guide the research team in its preparation for a monitoring visit.

SOP-21
Preparation for an Audit or Inspection

	Procedure [172 Ko, 7 p.]
	Tutorial [181 Ko, 9 p.]

Guide the research team in its preparation for an audit or inspection visit.

SOP-22
Study Closure

	Procedure [158 Ko, 8 p.]
	Tutorial [180 Ko, 9 p.]

Guide the research team during the closing of a clinical study.

SOP-23
Management of Data and Source Documents

	Procedure [159 Ko, 8 p.]
	Tutorial [183 Ko, 11 p.]

Describe the process of collection and storage of data and source documents, and ensure that management of the process complies with the principles of GCP of the ICH. To achieve this goal, it is imperative that the case report form (CRF) represents the subject’s data precisely and that the said data are complete, accurate, precise and up-to-date.

SOP-24
Clinical Data Management, Paper or Electronic Format

	Procedure [170 Ko, 8 p.]
	Tutorial [181 Ko, 8 p.]

Define the different stages of management of clinical data entered onto the CRFs, whether on paper or electronically. This SOP describes the stages of collection, capture and storage of data, as well as quality control and corrections to clinical data collected during the study.

Ensure that the collection, follow-up, control and confidentiality of all clinical data entered in a CRF, paper or electronic, conforms to the principles of the ICH and the laws and regulations in force. In order to achieve this goal, it is imperative that the system used for applicable capture and processing of data is validated, and that the databases in which clinical data are stored accurately represent the subject’s data.

SOP-25
How to Fill In a Case Report Form and Modify Data

	Procedure [164 Ko, 7 p.]
	Tutorial [179 Ko, 6 p.]

Define the process of collection of clinical data required by the protocol in order to ensure the integrity of said data recorded on a CRF, paper or electronic. Data recorded on a CRF can be generated from source data or documents, or can be directly collected in the CRF in accordance with the protocol.

Ensure the legibility, authenticity and accuracy of all recorded clinical data collected in a paper or electronic CRF, in accordance with the principles of the ICH.

SOP-26
Security and Confidentiality of Data

	Procedure [165 Ko, 7 p.]
	Tutorial [178 Ko, 6 p.]

Describe the process that ensures the quality, integrity and confidentiality of clinical data collected within the framework of a clinical study. describe procedures for the protection of data from any risk of accidental or involuntary destruction.