his guideline should be read in conjunction with other ICH guidelines relevant to the
conduct of clinical trials (e.g., E2A (clinical safety data management), E3 (clinical study
reporting), E7 (geriatric populations), E8 (general considerations for clinical trials), E9
(statistical principles), and E11 (pediatric populations)).
This ICH GCP Guideline Integrated Addendum provides a unified standard for the European
Union, Japan, the United States, Canada, and Switzerland to facilitate the mutual acceptance
of data from clinical trials by the regulatory authorities in these jurisdictions. In the event of
any conflict between the E6(R1) text and the E6(R2) addendum text, the E6(R2) addendum
text should take priority.
6677 ANMAT Regulation dated November 2010 has recently replaced previous regulations covering studies in clinical pharmacology: Clinical Trial Application Process, ANMAT Inspection Process and ANMAT`s explicit incorporation of GCP guidelines into the regulation.
In this PPt contain the E6 R1 and E6 R2 information , and the GCP training material for the Good prectice. and end of the ppt there is a ink which is use for your online training and generate certificate.
This document describes the detailed information of clinical trial protocol and protocol design. The protocol includes the key information of study designs. This document is downloaded as a PDF and viewed online.
CSR Automation: Streamlining Clinical Study ReportingClinosolIndia
Clinical Study Reports (CSRs) play a pivotal role in communicating the results and findings of clinical trials. The traditional process of creating CSRs is resource-intensive and time-consuming. The integration of automation technologies offers a transformative solution to streamline CSR generation, enhancing efficiency, accuracy, and overall study reporting. This article explores the key aspects, benefits, and considerations associated with CSR automation.
6677 ANMAT Regulation dated November 2010 has recently replaced previous regulations covering studies in clinical pharmacology: Clinical Trial Application Process, ANMAT Inspection Process and ANMAT`s explicit incorporation of GCP guidelines into the regulation.
In this PPt contain the E6 R1 and E6 R2 information , and the GCP training material for the Good prectice. and end of the ppt there is a ink which is use for your online training and generate certificate.
This document describes the detailed information of clinical trial protocol and protocol design. The protocol includes the key information of study designs. This document is downloaded as a PDF and viewed online.
CSR Automation: Streamlining Clinical Study ReportingClinosolIndia
Clinical Study Reports (CSRs) play a pivotal role in communicating the results and findings of clinical trials. The traditional process of creating CSRs is resource-intensive and time-consuming. The integration of automation technologies offers a transformative solution to streamline CSR generation, enhancing efficiency, accuracy, and overall study reporting. This article explores the key aspects, benefits, and considerations associated with CSR automation.
End of Internship Presentation Slides (Geomatika University College)Darshini Perumalsivam
Overall, this internship was a useful experience. I have gained new knowledge, skills and met many new people. I achieved several of my learning goals, however for some the conditions did not permit.
Throughout my internship, I could understand more about the definition of Good Clinical Practice and the way of applying it in the Clinical Study as well as the importance of Drug Regulation. This provide me to prepare myself to become a responsible and an ambitious Clinical Research Associate (CRA) in the future. Along my training period, I realise that observation and time management is a main element in order to identify and to complete the study.
During the task assigned, I corporate with my colleagues to determine the problems. This indirectly helped me to learn independently, discipline myself, be considerate/ patient, self-trust, take initiative and ability to solve problems. Besides, my communication skill is strengthened as well when communicating with others. During training period, I have received advices from supervisors and colleagues when mistakes were made. Those advices are useful guidance for me to change myself and avoid myself making the same mistakes again.
In sum, the activities and tasks assigned that I have done as well as learned during my industrial training are really useful for me in future to face challenges in a working environment.
Document Control Effectiveness in ISO 15189 Accredited Laboratoriesinventionjournals
ISO 15189 is the global quality management standard published by the International Organization for Standardization (ISO). Document control is one of the Key requirements of ISO 15189. It is considered Document control is the major quality element to establish a quality management system. The research study was carried out to understand the effectiveness of a document control system followed in accredited medical laboratories. It was the key objective to identify the importance of document control system hypothesis vs practical implementation and Challenges of Document control system implementation. It was really hard to categorize the implementation status of document control, but I have tried to analyze it. In the study volume of up to date control document usage in functional area is estimated. Various effects of document control are also analyzed before implementing the accreditation system and post accreditation system. A structured document control system is also observed and compared with pre and the post accreditation system. In the study all reported events are analyzed to find out out the reported event in related to document control system. Risk analysis of document used in the laboratory is also analyzed. Total risk scoring is done based on the document risk involvement. Major challenges observed in the manual document control system. A suggestive idea is prescribed in the improvement of a document control system.
What is ICH- GCP?
Why is GCP important?
Outline the goals of GCP
Provide a historical perspective on GCP
WHO Principles of GCP
Principles: Defines, Application & Implementation.
Quality management systems: Good Laboratory Practice (QMS GLP)Dr Ajay Kumar Tiwari
Fundamental knowledge on pharmaceutical
product development and translation from laboratory to market.
Quality management systems: Quality management & Certifications.
1. Introduction to GLP
2. Definition of GLP
3. Fundamentals of GLP
4. GLP Principles
5. Aim of GLP
Definition. A clinical research protocol is a document that describes the background, rationale, objectives, design, enrollment criteria, methodology, data recording requirements, statistical considerations, and organization of a clinical research study.
Here's a list of steps on how to write a research protocol:
Write a project summary. ...
Create a section for basic information. ...
Offer the rationale for your research study. ...
State the study's goals and objectives. ...
Detail the study design. ...
Define the methodology. ...
List safety considerations. ...
Create steps for the follow-up process.
Role of protocol in clinical research.
The protocol should outline the rationale for the study, its objective, the methodology used and how the data will be managed and analyzed. It should highlight how ethical issues have been considered, and, where appropriate, how gender issues are being addressed.
PMI Proper Material Identification of Alloy Material. X-Ray Production or fabrication processes can include dozens of stages to convert raw materials into finished goods. Regardless of the raw material or the finished product, one factor is constant - - most metals look alike.
HealthIT.gov
National Learning Consortium logo
Advancing America's Health Care
Continuous Quality
Improvement (CQI)
Strategies to Optimize
your Practice
Primer
Provided By:
The National Learning Consortium (NLC)
Developed By:
Health Information Technology Research Center (HITRC)
The material in this document was developed by Regional Extension Center staff in the
performance of technical support and EHR implementation. The information in this document is
not intended to serve as legal advice nor should it substitute for legal counsel. Users are
encouraged to seek additional detailed technical guidance to supplement the information
contained within. The REC staff developed these materials based on the technology and law
that were in place at the time this document was developed. Therefore, advances in technology
and/or changes to the law subsequent to that date may not have been incorporated into this
material.
�
Illustration titled the EHR Implementation Lifecycle shows 6 arrows, arrow 6 is highlighted. Step 6: Continue Quality Improvement
NATIONAL LEARNING CONSORTIUM
The National Learning Consortium (NLC) is a virtual and evolving body of knowledge and resources
designed to support health care providers and health IT professionals working toward the implementation,
adoption, and Meaningful Use of certified electronic health record (EHR) systems.
The NLC represents the collective EHR implementation experiences and knowledge gained directly from
the field of ONC’s outreach programs (REC, Beacon, State HIE) and through the Health Information
Technology Research Center (HITRC) Communities of Practice (CoPs).
The following resource can be used in support of the EHR Implementation Lifecycle. It is recommended
by “boots-on-the-ground” professionals for use by others who have made the commitment to implement
or upgrade to certified EHR systems.
EHR Implementation Lifecycle
EHR Implementation Lifecycle illustration shows 6 arrows. Step 1 Access; Step 2 Plan; Step 3 Select; Step 4 Implement; Step 5 Meaningfully Use; Step 6 Improve Quality.
DESCRIPTION AND INSTRUCTIONS
Continuous Quality Improvement (CQI) is a quality management process that encourages all health care
team members to continuously ask the questions, “How are we doing?” and “Can we do it better?”
(Edwards, 2008). To address these questions, a practice needs structured clinical and administrative
data. EHRs can, if properly designed and implemented, capture these data efficiently and effectively,
thereby transforming patient care in ways that might have been difficult or impossible with paper records
alone.
This Primer introduces CQI concepts, strategies, and techniques a practice can use to design an effective
CQI strategy for EHR implementation, achieve Meaningful Use of the system, and ultimately improve the
quality and safety of patient care. A practice can use CQI throughou ...
Guidelines for Preparation of Documents, Clinical Study Report Clinical Trial...Dinesh Gangoda
Contents
Guidelines for Preparation of Documentation
Clinical Study Reports
Clinical Trial Monitoring
Safety Monitoring in clinical trials
Introduction
Proper documentation is critical to the success of a clinical study.
Every aspect of the study must be documented in order to obtain useful data and demonstrate compliance with Good Clinical Practice (GCP) guidelines and with all applicable regulations.
Investigator’s Brochure (IB)
List of Abbreviations
Contents & Summary
Introduction provides the chemical name (and generic and trade names, if approved) of the investigational product.
Physical, chemical and pharmaceutical properties and formulation of the medicinal product. Non-clinical studies & Clinical Studies and their results.
The Investigator's Brochure should be reviewed at least annually and revised as necessary in compliance with a standard procedures established by drug development company.
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
End of Internship Presentation Slides (Geomatika University College)Darshini Perumalsivam
Overall, this internship was a useful experience. I have gained new knowledge, skills and met many new people. I achieved several of my learning goals, however for some the conditions did not permit.
Throughout my internship, I could understand more about the definition of Good Clinical Practice and the way of applying it in the Clinical Study as well as the importance of Drug Regulation. This provide me to prepare myself to become a responsible and an ambitious Clinical Research Associate (CRA) in the future. Along my training period, I realise that observation and time management is a main element in order to identify and to complete the study.
During the task assigned, I corporate with my colleagues to determine the problems. This indirectly helped me to learn independently, discipline myself, be considerate/ patient, self-trust, take initiative and ability to solve problems. Besides, my communication skill is strengthened as well when communicating with others. During training period, I have received advices from supervisors and colleagues when mistakes were made. Those advices are useful guidance for me to change myself and avoid myself making the same mistakes again.
In sum, the activities and tasks assigned that I have done as well as learned during my industrial training are really useful for me in future to face challenges in a working environment.
Document Control Effectiveness in ISO 15189 Accredited Laboratoriesinventionjournals
ISO 15189 is the global quality management standard published by the International Organization for Standardization (ISO). Document control is one of the Key requirements of ISO 15189. It is considered Document control is the major quality element to establish a quality management system. The research study was carried out to understand the effectiveness of a document control system followed in accredited medical laboratories. It was the key objective to identify the importance of document control system hypothesis vs practical implementation and Challenges of Document control system implementation. It was really hard to categorize the implementation status of document control, but I have tried to analyze it. In the study volume of up to date control document usage in functional area is estimated. Various effects of document control are also analyzed before implementing the accreditation system and post accreditation system. A structured document control system is also observed and compared with pre and the post accreditation system. In the study all reported events are analyzed to find out out the reported event in related to document control system. Risk analysis of document used in the laboratory is also analyzed. Total risk scoring is done based on the document risk involvement. Major challenges observed in the manual document control system. A suggestive idea is prescribed in the improvement of a document control system.
What is ICH- GCP?
Why is GCP important?
Outline the goals of GCP
Provide a historical perspective on GCP
WHO Principles of GCP
Principles: Defines, Application & Implementation.
Quality management systems: Good Laboratory Practice (QMS GLP)Dr Ajay Kumar Tiwari
Fundamental knowledge on pharmaceutical
product development and translation from laboratory to market.
Quality management systems: Quality management & Certifications.
1. Introduction to GLP
2. Definition of GLP
3. Fundamentals of GLP
4. GLP Principles
5. Aim of GLP
Definition. A clinical research protocol is a document that describes the background, rationale, objectives, design, enrollment criteria, methodology, data recording requirements, statistical considerations, and organization of a clinical research study.
Here's a list of steps on how to write a research protocol:
Write a project summary. ...
Create a section for basic information. ...
Offer the rationale for your research study. ...
State the study's goals and objectives. ...
Detail the study design. ...
Define the methodology. ...
List safety considerations. ...
Create steps for the follow-up process.
Role of protocol in clinical research.
The protocol should outline the rationale for the study, its objective, the methodology used and how the data will be managed and analyzed. It should highlight how ethical issues have been considered, and, where appropriate, how gender issues are being addressed.
PMI Proper Material Identification of Alloy Material. X-Ray Production or fabrication processes can include dozens of stages to convert raw materials into finished goods. Regardless of the raw material or the finished product, one factor is constant - - most metals look alike.
HealthIT.gov
National Learning Consortium logo
Advancing America's Health Care
Continuous Quality
Improvement (CQI)
Strategies to Optimize
your Practice
Primer
Provided By:
The National Learning Consortium (NLC)
Developed By:
Health Information Technology Research Center (HITRC)
The material in this document was developed by Regional Extension Center staff in the
performance of technical support and EHR implementation. The information in this document is
not intended to serve as legal advice nor should it substitute for legal counsel. Users are
encouraged to seek additional detailed technical guidance to supplement the information
contained within. The REC staff developed these materials based on the technology and law
that were in place at the time this document was developed. Therefore, advances in technology
and/or changes to the law subsequent to that date may not have been incorporated into this
material.
�
Illustration titled the EHR Implementation Lifecycle shows 6 arrows, arrow 6 is highlighted. Step 6: Continue Quality Improvement
NATIONAL LEARNING CONSORTIUM
The National Learning Consortium (NLC) is a virtual and evolving body of knowledge and resources
designed to support health care providers and health IT professionals working toward the implementation,
adoption, and Meaningful Use of certified electronic health record (EHR) systems.
The NLC represents the collective EHR implementation experiences and knowledge gained directly from
the field of ONC’s outreach programs (REC, Beacon, State HIE) and through the Health Information
Technology Research Center (HITRC) Communities of Practice (CoPs).
The following resource can be used in support of the EHR Implementation Lifecycle. It is recommended
by “boots-on-the-ground” professionals for use by others who have made the commitment to implement
or upgrade to certified EHR systems.
EHR Implementation Lifecycle
EHR Implementation Lifecycle illustration shows 6 arrows. Step 1 Access; Step 2 Plan; Step 3 Select; Step 4 Implement; Step 5 Meaningfully Use; Step 6 Improve Quality.
DESCRIPTION AND INSTRUCTIONS
Continuous Quality Improvement (CQI) is a quality management process that encourages all health care
team members to continuously ask the questions, “How are we doing?” and “Can we do it better?”
(Edwards, 2008). To address these questions, a practice needs structured clinical and administrative
data. EHRs can, if properly designed and implemented, capture these data efficiently and effectively,
thereby transforming patient care in ways that might have been difficult or impossible with paper records
alone.
This Primer introduces CQI concepts, strategies, and techniques a practice can use to design an effective
CQI strategy for EHR implementation, achieve Meaningful Use of the system, and ultimately improve the
quality and safety of patient care. A practice can use CQI throughou ...
Guidelines for Preparation of Documents, Clinical Study Report Clinical Trial...Dinesh Gangoda
Contents
Guidelines for Preparation of Documentation
Clinical Study Reports
Clinical Trial Monitoring
Safety Monitoring in clinical trials
Introduction
Proper documentation is critical to the success of a clinical study.
Every aspect of the study must be documented in order to obtain useful data and demonstrate compliance with Good Clinical Practice (GCP) guidelines and with all applicable regulations.
Investigator’s Brochure (IB)
List of Abbreviations
Contents & Summary
Introduction provides the chemical name (and generic and trade names, if approved) of the investigational product.
Physical, chemical and pharmaceutical properties and formulation of the medicinal product. Non-clinical studies & Clinical Studies and their results.
The Investigator's Brochure should be reviewed at least annually and revised as necessary in compliance with a standard procedures established by drug development company.
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
2. Introduction
On 15 December 2016, the International Council for Harmonistion (ICH) adopted the revised E6 guideline,
entitled “Integrated Addendum to Good Clinical Practice (GCP).” Now, regulatory implementation is carried out
according to the same national/regional procedures that apply to other regulatory guidelines and
requirements (ICH 2017).
www.citiprogram.org
Who does the new guideline affect?
The ICH E6 addendum affects the full clinical trial cycle and research enterprise. The revisions to the guideline
mainly affect sponsors, stipulating a more proactive approach to study design, as well as risk management and
study monitoring. However, Contract Research Organizations (CROs), that often delegated trial-related tasks by
the sponsor, need to learn about the revised practice points in the guideline. Sponsor-investigators also
need to be aware of the changes and their responsibilities associated with being a sponsor. The changes
Why revise the guideline?
Research has modernized in the thirty years since the original E6(R1) guideline. However, E6(R2) still has the
same goal of standardization.
The European Medicine Agency (EMA) submitted a report in 2014 summarizing 398 GCP inspections of clinical
trial sponsors, sites, and CROs from 2000-2012. The report’s critical and major findings were mostly in relation
to:
This was good news, in that, most critical findings were not directly related to informed consent or human
subject safety. However, the report identified concerns and areas for improvement in the design and conduct
of clinical trials. It was clear that the ICH E6 guidelines that originally provided a standardized framework for
harmonization needed to be modernized for the current research landscape and address these GCP inspection
findings.
Standardization ensures that marketing applications to various
regulatory agencies around the world can occur without
redundant testing. Many pharmaceutical companies conduct
multi-site international clinical trials. Repeating trials in different
markets to comply with slightly different regulations is
inefficient and unnecessarily delays bringing new drugs to
patients.
“Lack of harmonisation may not only slow
the adoption of innovative approaches to
clinical trial design, management, oversight,
conduct, documentation, and reporting,
but may also lead to inconsistency in
approaches sponsors use among the ICH
regions which could add cost and time to
the development of needed drug products”
(ICH 2014b).
2
Monitoring Cinical study reports
Data management Source documentation
associated with being a sponsor. The changes are important to investigators, Institutional Review Board/
Independent Ethics Committee (IRB/IEC) members and administrators, study monitors, clinical research
coordinators and professionals, and institutions/sites.
3. The ICH convened an expert working group to create an addendum to the existing E6 guideline. The expert
working group was consisted of ICH members from both industry and regulatory agencies, as well as
observers, to address current research topics like quality by design, quality risk management, and focus on
technological tools to ensure robust conduct, oversight, and reporting.
www.citiprogram.org
Format of Revised Guideline
The revised guideline uses an addendum-integrated format. This format embeds the revisions
into the current E6(R2) guideline, identifying the change as “ADDENDUM” above the new text (below the
The revised guideline also includes a document history with dates and versions of the guideline, as well as a
table that displays the current E6(R2) sections that were revised.
3
old text) and using edge marks to show the changes.
4. What are the revisions?
The focus of the revisions is on increasing human subject protections and data integrity mainly through
better study design and conduct. Therefore, most of the changes affect the sponsor. As seen below, the
sponsor section was the most revised. No revisions were made to IRB/IEC, Investigator’s Brochure, or the
clinical trial protocol and protocol amendment(s) sections.
Introduction
Glossary
The Principles of ICH GCP
Institutional Review Board (IRB) / Independent Ethics Committee (IEC)
Investigator
Sponsor
Clinical Trial Protocol and Protocol Amendment(s)
Investigator’s Brochure
Essential Documents for the Conduct of a Clinical Trial
ICH E6 Sections Revisions Made To:
Introduction
1.63, 1.64, 1.65
2.10, 2.13
None
4.2.5, 4.2.6, 4.9.0
5.0, 5.0.1, 5.0.2, 5.0.3, 5.0.4,
5.0.5, 5.0.6, 5.0.7, 5.2.2, 5.5.3 (a),
5.5.3 (b),5.5.3 (h), 5.18.3,
5.18.6 (e), 5.18.7, 5.20.1
None
None
8.1
www.citiprogram.org
The focus of the revisions includes:
• Using a risk management approach in designing studies
• Promoting the use of risk-based and centralized monitoring in managing studies
• Addressing the reporting and follow-up of significant noncompliance (including conducting a root
cause analysis, and creating a corrective and preventative action plan)
• Addressing technology issues (for example, specifying that electronic systems should be validated,
backed-up, and safeguarded)
• Specifying oversight responsibilities of sponsors and investigators
• Improving data integrity (for example, requiring that source data are attributable, legible,
contemporaneous, original, accurate, and complete)
• Ensuring both investigators and sponsors have access to study data and documents
The revisions aim to balance efficiency in clinical trials while retaining human subject protections and data
integrity. Analysis of progress following implementation may provide sponsors and investigators with
insight into areas that require further clarification.
4
5. ICH (2016) E6(R2) Revisions by Section
www.citiprogram.org
Introduction
The introduction section revisions explain the purpose of the revisions to the guideline, refer to other ICH
guidelines relevant to clinical trials (for example, E2A Clinical Safety Data Management and E3 Clinical Study
Reporting), and clarify that the E6(R2) addendum should replace E6(R1).
Section 1 - Glossary
ICH E6 adds the following definitions to the glossary:
• Certified copy (section 1.63)
• Monitoring plan (section 1.64)
• Validation of computerized systems (section 1.65)
Section 2 - The Principles of ICH GCP
Reflecting modernization from paper-based documentation to electronic systems, section 2.10 includes a
minor clarification to indicate that clinical trial information (irrespective of the type of media used) should be
recorded, handled, and stored in a way that allows its accurate reporting, interpretation, and verification.
The emphasis on data integrity is seen through a minor revision to section 2.13, which added that quality
assurance systems should focus on human subject protection and reliability of trial results.
Section 3 - Institutional Review Board (IRB) / Independent Ethics Committee (IEC)
No changes were made to this section.
Section 4 - Investigator
The investigator continues to be ultimately responsible for conducting the trial. No changes were made to the
“Investigator’s Qualifications” section and the investigator is still allowed to delegate trial-related
responsibilities. “Adequate Resources” revisions specify that the investigator is responsible for supervision
(oversight) of persons with delegated tasks. Further, the investigator should ensure research staff are
capable and trained for their assigned trial-related tasks. This is aligned with the U.S. Food and Drug
Administration (FDA) regulations (Investigational New Drug Application 2016) and FDA (2009) guidance.
The added text in “Records and Reports” also mirrors the FDA in specifying that “source data should be
attributable, legible, contemporaneous, original, accurate, and complete” (ICH 2016). The commonly used
acronym is ALCOAC. Records and reporting may be written or electronic.
5
6. www.citiprogram.org
Attributable
Legible
Contemporaneous
Original
Accurate
Complete
The record identifies who created or modified the record, when
the record changed, and why it changed.
The record and dates of an entry are clear and can be interpreted
and understood.
The data are recorded in real-time, the data are observed, and
records are signed (or initialed) and dated accurately.
The record is original as it is captured, collected, or is an exact
facsimile of the original.
The record is collected and recorded honestly and completely to
demonstrate transparency.
Up-to-date and with no omissions.
6
Example of “Attributable”
A study team member who performed the assessment/procedure should sign his/her name/initials
when documenting the assessment/procedure that was performed. If someone else is present
during the assessment/procedure and recording on behalf of the principal investigator, that person
should also sign his/her name/initials.
Example of “Contemporaneous”
A late data entry should be noted as such. If a study team member forgets to enter data at the correct
time and must go back and do it later, the study team member should note this fact and include a date
and time when entering the data.
Example of “Original”
Study team members should not use pencil. It is important to use pen for originals. To make changes
to an original entry, draw a single line through the error, then initial and date with an explanation for
the correction. No correction fluid or writing over an original entry is permitted.
7. www.citiprogram.org
Section 5 - Sponsor
The most extensive changes to ICH E6 were made to the sponsor’s section, beginning with a new section on
quality management.
Quality Management
ICH E6 requires sponsors to implement a “quality management system” from trial design to trial conduct to
close-out. A well-designed protocol is the most important tool for ensuring human subject protection and
high-quality data (FDA 2011). The addendum adds that the sponsor should use a risk-based approach to
develop the protocol and study materials. This process is outlined in section 5.0 as risk identification, risk
evaluation, risk control, risk communication, risk review, and risk reporting.
Active Oversight
As stated in the previous guideline, the sponsor is still permitted to delegate trial-related responsibilities to
others (for example, contractors and vendors), but the sponsor is ultimately responsible for the quality and
integrity of the trial data. The revised guideline adds, in section 5.2.2, that the sponsor should ensure oversight
of trial-related duties and functions carried out on its behalf, even for those responsibilities subcontracted to
another party by the sponsor’s contracted CRO (ICH 2016). The sponsor must plan and describe how this will
be assessed. This is typically done through the sponsor’s qualification/requalification audit of the CRO. This
revision to ICH is a clarification of expected trial conduct to reduce misinterpretation of oversight responsibilities.
Electronic Systems
ICH E6 recognizes that sponsors routinely use electronic systems for trial data. Further changes were added in
section 5.5, “Trial Management, Data Handling, and Record Keeping,” to include
that the sponsor should use a risk assessment in validating electronic trial
data handling and/or remote trial data systems. As before, the
guideline requires the sponsor to maintain standard operating
procedures (SOPs) for using these electronic data systems. The addendum
adds specific requirements that the SOPs must include systemsetup, installation, use,validation and functionality
testing, data backup, recovery, and training for users. The addendum also clearly puts the responsibility for
reliable data on the sponsor, requiring in section 5.5.3(h) that the sponsor ensure the integrity of the data, even
when making changes to the computerized systems (such as, software upgrades or migration of data) (ICH 2016).
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8. www.citiprogram.org
g
Monitorin
Effective monitoring is critical to ensuring both subject protections and high quality trial data. Monitoring
continues to be the sponsor’s responsibility. By far, the most substantial changes to ICH E6 are related to study
monitoring. The addendum incorporates elements from the FDA’s (2013) risk-based monitoring guidance,
which supports alternative approaches (specifically, risk-based and combination activities) to monitoring.
The revised ICH E6 requires that the sponsor develop:
Per section 5.18.6(e), "monitoring reports," including both centralized reports and on-site monitoring visit
reports, are now required to be provided to the sponsor (including appropriate sponsor management
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follow up, if needed. This allows and requires the sponsor to follow-up on
identified serious noncompliance. In section 5.20, the addendum adds the
sponsor should perform a root cause analysis and implement appropriate
corrective and preventive actions (for example, a corrective and preventative
action plan) if noncompliance is or may be serious.
Finally, each study now requires a study-specific monitoring plan. The plan should take into consideration
potential risks of harm to human subjects and data integrity. The monitoring plan should not only include how
the study will be monitored, but a rationale. Additionally, the monitoring plan should also emphasize the
monitoring of critical data and processes, especially those that are not routine clinical practice and require
extra training (ICH 2016).
8
A systematic, prioritized, risk-based approach to monitoring clinical trials. The flexibility in the
extent and nature of monitoring described in this section is intended to permit varied approaches
that improve the effectiveness and efficiency of monitoring. The sponsor may choose on-site
monitoring, a combination of on-site and centralized (off-site) monitoring, or, where justified,
centralized monitoring (only). The sponsor should document the rationale for the chosen monitoring
strategy (e.g., in the monitoring plan).
Note: If the sponsor is planning to
perform off-site reviews of source
documents (centralized monitoring),
this should be established and
agreed to by the site, well before
studyinitiation.Centralizedmonitoring
may be more time-consuming for
sites than typical on-site visits.
The ICH E6 addendum defines centralized monitoring and
distinguishes it from on-site monitoring. Centralized monitor-
ing allows the real-time review of accumulating trial data,
which helps to identify missing or inconsistent data, examine
trends, identify data errors, analyze sites/investigators, and/or
select sites for targeted on-site monitoring.
9. www.citiprogram.org
Section 6 - Clinical Trial Protocol and Protocol Amendment(s)
No changes were made to this section.
Section 7 - Investigator’s Brochure
No changes were made to this section.
Section 8 - Essential Documents for the Conduct of a Clinical Trial
ICH E6(R2) adds in the introduction section a requirement to specify that both the sponsor and investigator/
institution (site) conducting the trial should maintain their respective essential documents in a system that
provides processes for locating the document, as well as providing for document identification, version history,
search, and retrieval.
ICH E6(R2) adds more about document control, specifying that the sponsor should not have exclusive
control of case report form (CRF) data submitted by the investigator, and that the investigator/institution
should have control of all their own essential documents before, during, and after the trial. ICH E6(R2)
clarifies that the sponsor should ensure that the investigator has continuous access to the CRF data
reported to the sponsor (ICH 2016). Also, ICH E6(R2) states that copies used to replace original documents
must meet the definition of certified copies.
Law or guidance?
Summary
The ICH E6(R2) guideline continues to provide practical standardization for the conduct of clinical trials. The
revisions reflect a modernizing and evolving research landscape and do not
change the core of the guideline. Sponsors, investigators, and others in the
research enterprise should be aware of the integrated addendum and new
procedures in order to continue to design and conduct clinical trials that
protect human subjects and ensure data integrity.
9
The FDA adopted ICH E6(R1) and subsequently ICH E6(R2) as guidance. Therefore,
the ICH E6 guidelines do not have the force of law in the U.S. and are not regulations.
In the Federal Register Notice, FDA stated that the ICH E6 guideline "does not
create or confer any rights for or on any person and does not operate to bind FDA
or the public. An alternative approach may be used if such approach satisfies the
requirements of the applicable statutes, regulations, or both" (FDA 2018, 8882-3).
Health Canada implemented ICH E6(R1) in 1997. The revised ICH E6(R2) has not
yet been implemented by Health Canada. Health Canada did advise of its intent to
implement with a target date of 1 April 2019.
The European Commission adopted ICH E6(R2) on 15 December 2016 and has set
an effective date of 14 June 2017.
10. References
• European Medicines Agency (EMA). 2014. “Classification and analysis of the GCP inspection findings of
GCP inspections conducted at the request of the CHMP.” Accessed January 20, 2017.
• International Council for Harmonisation (ICH). 2014. “Final Business Plan Addendum for ICH E6: Guideline
for Good Clinical Practice.” Accessed June 6, 2017.
• International Council for Harmonisation (ICH). 2015. “Addendum to ICH E6(R2) presentation.” Accessed
January 20, 2017.
• International Council for Harmonisation (ICH). 2016. “Integrated Addendum to ICH E6(R1): Guideline for
Good Clinical Practice E6 (R2).” Accessed January 20, 2017.
• International Council for Harmonisation (ICH). 2017. “Formal ICH Procedure.” Accessed January 20.
• Investigational New Drug Application, 21 CFR § 312 (2016).
• U.S. Food and Drug Administration (FDA). 2009. “Guidance for Industry: Investigator Responsibilities —
Protecting the Rights, Safety, and Welfare of Study Subjects.” Accessed January 20, 2017.
• U.S. Food and Drug Administration (FDA). 2011. “Oversight of Clinical Investigations: A Risk-Based
Approach to Monitoring (Draft Guidance).” Accessed January 20, 2017.
U.S. Food and Drug Administration (FDA). 2013. “Guidance for Industry: Oversight of Clinical Investigations
— A Risk-Based Approach to Monitoring.” Accessed January 20, 2017.
Additional Resources
www.citiprogram.org
• International Council for Harmonisation (ICH). 2014. “Final Concept Paper Addendum for ICH E6: Guide
line for Good Clinical Practice.” Accessed June 6, 2017.
• International Council for Harmonisation (ICH). 2015. “Addendum to ICH E6 (R2) presentation.” Accessed
January 20, 2017.
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• U.S. Food and Drug Administration (FDA). 2018. “E6(R2) Good Clinical Practice: Integrated Addendum
to E6(R1); International Council for Harmonisation; Guidance for Industry.” Federal Register 41(83):8882-3.
•