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Domain 4: Clinical Study Operations (Good Clinical Practice)

Encompasses study management and GCP compliance; safety management (adverse event identification and reporting, post-market surveillance, and pharmacovigilance), and handling of investigational product


4.1

Explain how the design, purpose, and conduct of individual clinical studies fit into the goal of developing a new intervention

Fundamental Level:

A1.       Identify the link between developing a new intervention and the interrelated trial goals and design by reading and comprehending a clinical trial protocol

Example: Identifies the study protocol methods for avoiding selection bias in a clinical study so that the results are considered reliable and valid.

Skilled Level:

B1.       Review and comment on trial protocols to ensure the links between the objective of developing a new intervention and the related trial goal and design is accurate

B2.       Provide input and share ideas, proactively and reactively, on trial design

Example: Reviews and provides substantive editorial comments for a clinical study protocol during its initial development.

Advanced Level:

C1.       Design a clinical trial independently to ensure an accurate link between the goal of developing a new intervention and the trial goal

C2.       Train, supervise, and coach junior trial designers

Example: Independently designs a feasible clinical trial per applicable regulatory requirements, within budget, to provide proof of unbiased safety and efficacy.


4.2

Describe the roles and responsibilities of the clinical investigation team as defined by Good Clinical Practice Guidelines

Fundamental Level:

A1.       Describe basic principles of GCP

A2.       Describe own role and is aware of roles of others in the site clinical investigation team as set forth by the institution or organization, regulations and GCPs

A3.       Understand the concepts of delegation of authority and scope of practice

Example: Clearly articulates own role responsibilities and describes limits of one’s role in the performance of clinical study activities.

Skilled Level:

B1.       Describe how GCP principles are incorporated into clinical research

B2.       Describe roles and responsibilities of IRB and sponsors as set forth in federal regulations and GCPs

B3.       Performs role in accordance with GCP guidelines

Example: Accurately identifies and reports situations when clinical investigation team members are not able to fulfill responsibilities and who to contact for support.

Advanced Level:

C1.       Apply GCP Guidelines to the conduct of clinical research

C2.       Review and assess all roles in the clinical investigation team

C3.       Supervise clinical investigation team members

C4.       Perform audits of clinical research performance to ensure compliance with GCPs

Example: Assembles, supervises and manages an appropriate investigational team for multiple clinical research studies


Fundamental Level:

A1.       Following training, describe how the ICH Good Clinical Practice Guidelines are incorporated into the design of a research protocol, the procedures followed during the conduct of a clinical study and the collection of data relating to the study

Example: Describes the concepts contained in the Declaration of Helsinki and how they are incorporated into clinical protocols and implemented during research on human subjects to ensure ethical and quality standards are maintained.

Skilled Level:

B1.       Successfully participate in the implementation of a clinical research protocol and assure that, with minimal supervision, the ICH Good Clinical Practice Guidelines are being followed during the conduct of research procedures and the collection of data

Example: Leads a team that is generating and collecting data in a clinical research protocol in a manner that ensures the conduct, reporting and recording of the clinical study is occurring utilizing internationally accepted guidelines.

Advanced Level:

C1.       Ensure that the operationalization of a clinical research study complies with ICH Clinical Practice Guidelines,

C2.       Appropriately resolve any compliance related issues which arise during the conduct of the clinical study,

C3.       Ensure that the personnel conducting the study are appropriately trained

Example: Assesses and ensures that ICG GCP compliance is maintained throughout the conduct of a clinical research study and when appropriate mentor and train individuals in the ethical and quality concepts required during the conduct of a clinical research study.

4.3

Evaluate the design, conduct and documentation of clinical studies as required for compliance with Good Clinical Practice Guidelines


Fundamental Level:

A1.       Describe the role of global regulatory bodies in the conduct of clinical studies

A2.       Identify the various global regulatory agencies and their respective country-specific regulations

A3.       Recognize the differences in the global regulation of drugs, biologics, and medical devices

Example: Identifies the differences between the regulations and guidelines in the US and Europe for the development and marketing of investigational medicinal products.

Skilled Level:

B1.       Assist in the identification of country-specific regulations which apply during the conduct of a clinical study

B2.       Apply current processes and procedures for the global regulatory agency application requirements for clinical studies

Example: Applies knowledge of local and global regulations in performing initial feasibility studies for the conduct of global multicenter clinical studies.

Advanced Level:

C1.       Create processes and procedures to determine feasibility for global studies

C2.       Determine and schedule the proper regulatory application requirements and timeframes for study applications

C3.       Provide mentoring and educate others on the global regulatory landscape with respect to the identification of potential clinical sites and the initiation and conduct of clinical studies

Example: Establishes workflows that promote optimal planning for future clinical study applications, data-sharing and clinical sample acquisition for a global multicenter clinical trial.

4.4

Compare and contrast the regulations and guidelines of global regulatory bodies relating to the conduct of clinical studies


4.5

Describe appropriate control, storage and dispensing of investigational product

Fundamental Level:

A1.       Understand that investigational products require specific control, storage and dispensing

A2.       Identify and follow existing Standard Operating Procedures for control, storage, and dispensing of IP

Example: Locates and applies an SOP for the receipt, storage and usage of investigational product for a clinical study at the clinical research site.

Skilled Level:

B1.       Articulate the specific procedures and elements for control, storage and dispensing of investigational product

B2.       Determine deviations in the process of handling study medication and report /solve the issue

Example: When given a variety of scenarios, implements maintenance of proper environmental storage conditions, security, inventory control, and IP accountability (ordering, receipt, inventory, disposal, transfer) to ensure adequate and safe supplies for clinical study participants.

Advanced Level:

C1.       Develop SOPs that include specific procedures and elements for control, storage and dispensing of investigational product

C2.       Develop CAPAs when issues in the handling of study medication are detected in order to avoid further deviations

Example: Performs audits, generates CAPAs and adjusts SOPs for the management of investigational products according to FDA regulations and GCPs.


4.6

Differentiate the types of adverse events (AEs) that may occur during clinical studies and explain the identification process and reporting requirement to IRBs/IECs, sponsors and regulatory authorities

Fundamental Level:

A1.       Recognize the differences between the different types of adverse events

A2.       Recognize when an SAE occurs during the conduct of a clinical trial and report it within the appropriate time frame per the regulatory regulations

Example: Applies accurate classification of adverse events from sample cases (AE, SAE, Serious and Unexpected AE, Adverse Drug Reaction, etc.)

Skilled Level:

B1.       Differentiate the reporting timelines and requirements for an SAE and SUSAR across various international guidelines (e.g., FDA, EMA, ICH, etc.)

B2.       Execute the reporting of an SAE to the appropriate entity (sponsor, regulatory agency, IRB/IEC) based on their respective role (e.g., investigator, CRA, sponsor)

Example: Demonstrates an ability to recognize and report an SAE to the appropriate entity within the appropriate time frame during the conduct of a clinical trial.

Advanced Level:

C1.       Critique the SUSAR reporting requirements across various agencies and entities and formulate new recommendations to enhance the harmonization of reporting requirements

Example: Investigates the impact of a lack of harmonization of SUSAR reporting requirements on the timeliness of reporting in a global clinical trial and constructs a new SOP to govern reporting requirements for their organization.


Fundamental Level:

A1.       Understand that human research subjects are entitled to protection and privacy and that global regulations are in place to protect research subjects during the conduct of clinical studies

A2.       Locate the specific regulations associated with the protection and privacy of human research subjects

Example: Accurately describes safeguards for human research subject protection and privacy in global, national and local regulations and guidelines.

Skilled Level:

B1.       Apply appropriate protection and privacy safeguards when conducting clinical studies

B2.       Report situations when human research subjects may require protection and privacy

B3.       Recognize the existing global regulations and local rules which differ among countries regarding to protect human research subjects and their privacy?

Example: Describes study visit activities, and identifies actions required for subject protection and privacy appropriate for the regulatory body and regulation for different countries (e.g., CFR (FDA, US), EU directive and regulation (EMA, EU), J-GCP (PMDA, Japan), C-GCP (CFDA, China) and guidelines for privacy protection for research participants.

Advanced Level:

C1.       Create strategies to protect human research subjects and guard their privacy in clinical studies

C2.       Evaluate whether protection and privacy strategies are appropriate

C3.       Develop and implement a global investigation strategy with global and local regulations to protect human research subjects and their privacy

Example: Plans a new clinical study that includes a comparison of local, national and international health care settings, norms and ethnicities that may impact human subject protection and privacy.

4.7

Describe how global regulations and guidelines assure human subject protection and privacy during the conduct of clinical studies


Fundamental Level:

A1.       Recognize and understand the rationale for clinical monitoring and the appropriate regulations and ICH guidance that applies

A2.       Adhere to the monitoring plan and applicable standard operating procedures

A3.       With guidance and oversight, perform monitoring tasks per the monitoring plan and inform others when confronted with issues not detailed in the monitoring plan

Example: Participates in local QA audits of clinical studies in preparation of a CRO monitoring visit.

Skilled Level:

B1.       Employ and implement the clinical monitoring plan to complete monitoring tasks/activities

B2.       Address complex monitoring issues with minimal supervision or guidance

B3.       Provide guidance to others to resolve simple and moderately complex monitoring issues

Example: Applies prospective risk-based approaches to ensure quality data and rapid and accurate responsiveness to clinical monitoring queries.

Advanced Level:

C1.       Lead the monitoring effort by mentoring others in the planning and conduct of monitoring site visits

C2.       Oversee the creation and planning of study-specific monitoring plans that assure sufficient resources are allocated to ensure timely review of data while maintaining established standards for study participant safety and data integrity

Example: Creates clinical study monitoring plans, provides leadership, mentoring and guidance to ensure all monitoring activities and workflows are in compliance and are ‘audit-ready’

4.8

Describe the role and process of monitoring a clinical study


4.9

Describe the role and purpose of clinical study audits

Fundamental Level:

A1.       Describe the steps taken to prepare for an audit/inspection

A2.       Name the entities which have authority to conduct audits

A3.       Locate and explain the federal regulations governing audits and inspections

Example: Assists with preparation for clinical study audits and understands roles of the team during an audit.

Skilled Level:

B1.       Distinguish between scope of audits conducted by sponsors, IRB and regulatory authority

B2.       Identify research components inspected during a clinical study audit

B3.       Distinguish between routing and for-cause audits and inspections

Example: Given a clinical study protocol, classifies and categorizes the specific information and sources of data required by auditors and inspectors.

Advanced Level:

C1.       Supervise preparation for an audit/inspection conducted by a sponsor or regulatory authority

C2.       Develop policies and SOPs in response to audit/inspection findings

Example: Given an audit report, creates a comprehensive CAPA plan to respond to audits/inspections, and develop appropriate SOPs.


4.10

Describe the various methods by which safety issues are identified and managed in clinical studies

Fundamental Level:

A1.       Understand that safety is a central issue in clinical trials and that lack of safety oversight can jeopardize participants in numerous ways

A2.       Recognize the tools and processes implemented in a clinical trial to protect participants

A3.       Remember to report suspicious activities or events which might compromise safety

Example: Identifies safety issues, risk mitigation and action plans for diabetic patient who are required to be fasting for a lengthy study visit.

Skilled Level:

B1.       Execute safety reporting within required timelines through appropriate channels

B2.       Classify safety issues and report them to regulatory authorities and IRBs

B3.       Implement international guidelines and requirements across relevant agencies (e.g., FDA, EMA, ICH, etc.)

B4.       Relate safety issues according to monitoring and pharmacovigilance plans

Example: Generates SOPs for the handling of safety hazards in the clinical research site and detecting and reporting adverse events.

Advanced Level:

C1.       Anticipate possible safety issues during the clinical study implementation

C2.       Institute measures to minimize risks

C3.       Critique and improve monitoring and pharmacovigilance plans

C4.       Recommend and conduct safety training for study teams

Example: Develops a CAPA plan and staff training for monitoring findings of under-reported adverse events.