What is it? Why is it important?

A risk-based approach is a decision-making process that takes into consideration ways to identify, evaluate, manage and control risks associated with some undertaking, such as a study.

Managing risks requires them to be prioritised based on expected risk occurrence and potential negative impact.

The aim is to allocate often-limited resources by implementing risk mitigation actions in areas where they are most likely needed. With the aim to prevent or mitigate the negative impact of a risk.

 

A risk based-approach means to:

More

A risk based-approach means to:

  • Communicate and train staff on those risk mitigation measures
  • Review risk control measures in order to test its ongoing efficiency
  • Document implemented risk control measures, potential deviations and improvement procedures

What do I need to do?

As a SP-INV or Site-INV familiarise yourself with how to identify, evaluate and understand potential study risks.

Focus should be on risks that result from the implementation of the study.

 

Assess how these risks impact the:

  • Safety and well-being of study participants
  • The quality and integrity of study data
  • Study significance and public interest when compared to potential research competitors
  • Overall study quality aspects (e.g. staff and resources)

 

Upon risk identification, implement appropriate measures in accordance with the level of risk.

More

Consider potential risks when planning a study. The Swiss law defines risks based on study risk category and type of intervention.

 

  • Example of risk categorisation in ClinO studies:
    • Medicinal product studies have risk categories A, B and C, with category C having the highest risk
    • Other clinical trial studies have risk categories A and B, with risk category B having the highest risk
  • Risks depend on target population, with consenting adults having the lowest risk compared to:
    • Children and adolescents 
    • Participant with or without capacity
    • Participants in an emergency situation
  • Risks are assessed based on type of intervention, such as studies:
    • With or without expected direct benefit
    • With or without minimal risks and burdens

 

Depending on risk, the required risk management and its potential strategy within a given study can vary greatly.

Where can I get help?

Your local CTU↧ can support you with experienced staff regarding this topic

References

ICH GCP E6(R2) – see in particular guideline

  • 5.0 for quality management

ISO 31000 – see in particular section

  • Risk management: Principles and guidelines (access liable to costs)

Swiss Law

HRA – see in particular article and chapter

  • Art. 12 Risks and burdens
  • Chapter 3 Requirements for research involving vulnerable persons

Document

Abbreviations
  • ClinO – Clinical Trials Ordinance
  • CTU – Clinical Trials Unit
  • HRA – Human Research Ordinance
  • ICH GCP – International Council for Harmonisation - Good Clinical Practice
  • ISO – International Organization for Standardization
  • Site-INV – Site Investigator
  • SP-INV – Sponsor-Investigator
Basic ↦ Quality and Risk ↦ Risk Management Definitions ↦ Risk-Based Approach
Study
Basic

Provides some background knowledge and basic definitions

Basic Protocol
Basic Management
  1. Study Management
    1. Definition
Basic Ethics and Laws
  1. Principles of Ethics Research
    1. Declaration of Helsinki
    2. Declaration of Taipei
  2. Authorities
    1. Ethics Committee
    2. Swissmedic
    3. Federal Office of Public Health
    4. International
  3. Swiss Law
    1. Human Research Act
    2. Transplantation Act
    3. Stem Cell Research Act
    4. Data Protection Act
  4. Clinical Trials Ordinance
    1. Aim
    2. Medicinal Products
    3. In Vitro Diagnostic Medical Device
    4. Standardized Transplant Products
    5. Gene Therapy, GMO, Pathogenic
    6. Transplantation
    7. Other Clinical Studies
    8. Ionising Radiation
  5. Human Research Ordinance
    1. Aim
    2. Projects with Data and Biological Material
    3. Further use of Data and Biological Material
    4. Further use and Informed Consent
    5. Deceased Persons Embryos and Foetuses
  6. Medical Device Ordinance
    1. Aim
    2. In Clinical Studies
    3. Notified Bodies
  7. Organisation Ordinance
    1. Aim
  8. Portals
    1. Human Research Portal
    2. Ethics Portal BASEC
    3. Swissmedic Portal
  9. Guidelines
    1. Good Clinical Practice
    2. ISO 14155
    3. ISO 20916
Basic Documents
  1. Document Management
    1. Purpose
    2. In Studies
    3. Document Identification
    4. Document Filing
  2. Standard Operating Procedures
    1. Purpose
  3. Working Instructions
    1. Purpose
  4. Logs
    1. Purpose
  5. Essential Documents
    1. Requirement
  6. Certified Copies
    1. Procedures
  7. Staff Documents
    1. Qualifications
    2. Training
Basic Safety
  1. Safety Laws
    1. Aim
  2. Safety Terminology
    1. Overview
  3. Safety Data
    1. Product Development
    2. Pre-Clinial Studies
    3. In Clinical Studies
  4. Safety Information
    1. Investigator Brochure
  5. Safety Vigilance
    1. Pharmacovigilance
    2. Materiovigilance
Basic Data Handling
  1. Data Management
    1. Purpose
  2. Study Database
    1. Clinical Data Mgmt. System
    2. Study Data
    3. Raw Data
    4. Metadata
  3. Regulatory Requirements
    1. Swiss Law
    2. General Data Protection Regulation
Basic Statistics
Basic Quality and Risk
  1. Risk Management Definitions
    1. Risk-Based Approach
    2. Risk Identification
    3. Risk Evaluation and Prioritisation
    4. Risk Evaluation Matrix
    5. Risk Control Measures
  2. Quality Management System (QMS)
    1. Risk Based
  3. Risk-Based QMS Responsibilities
    1. Sponsor-Investigator
    2. Site-Investigator
    3. Study Staff
Basic Monitoring
Basic Drug or Device
Basic Biobanking
Concept

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Protocol
Concept Management
  1. Study Idea
    1. Implementation
    2. Design
  2. Resources
    1. Study Staff
    2. Infrastructure
    3. Storage
    4. Partners
    5. Budget
Concept Ethics and Laws
  1. Study Categorisation
    1. Procedures
    2. Risk Categories
  2. Regulatory Advice
    1. Scientific Advice
    2. Pre-Submission
  3. Regulatory Advice Meeting
    1. Ethics Clarification
  4. Research Aim
    1. Advancing Science
    2. Marketing Products
  5. Research Integrity
    1. Principles
    2. Conflict of Interest
    3. Participant Protection
  6. Study Planning
    1. Ethics Requirements
    2. Laws and Guidelines
    3. Institution Requirements
  7. Study Feasibility
    1. Ethics and Laws
Concept Documents
  1. Required Documents
    1. Protocol and Synopsis
    2. Feasibility
    3. Investigator's Brochure
Concept Safety
  1. Safety in Studies
    1. Risk-Benefit Ratio
    2. Participant Risk-Benefit
Concept Data Handling
  1. Stakeholders
    1. Sponsor-Investigator
    2. Data Manager
    3. Statistician
    4. Site-Investigator
    5. Monitor
  2. Clinical Data Mgmt. System
    1. Selection
  3. Server
    1. Data Storage
    2. Back-Up and Recovery
Concept Statistics
Concept Quality and Risk
  1. Study Feasibility
    1. Aim
    2. Feasibility Questionnaire
    3. Risk Assessment Form
    4. Study Team
Concept Monitoring
  1. Monitoring
    1. Aim
    2. Study Requirement
    3. Site Feasibility
Concept Drug or Device
Concept Biobanking
Development

Starts with confidence that the study is feasible

Ends after having received ethics and regulatory approval

Development Protocol
Development Management
  1. Responsibilities
    1. Sponsor-Investigator
    2. Site-Investigator
    3. Staff Qualification and Training
    4. Good Clinical Practice Training
  2. Quality Mgmt. System
    1. Implementation
    2. Interim Analysis
  3. Study Management
    1. Oversight
    2. Tracking
    3. Infratructure and Maintenance
    4. Multi-centre Studies
    5. Insurance
    6. Outsourced Services
    7. Contract
    8. Budget
  4. Study Documents
    1. Protocol
    2. Participant Information Sheet
    3. Informed Consent Form
    4. Exemption from written Consent
    5. Informed Consent Process
    6. General Consent
    7. Essential Documents
    8. Source Data
  5. Study Approval
    1. Ethics Committee
    2. Swissmedic
    3. Fed. Off. Public Health
  6. Biobanking
    1. Management
    2. Emergency Plan
Development Ethics and Laws
  1. Ethics Application
    1. Submission
    2. Application Dossier
    3. Approva
  2. Swissmedic Application
    1. Application Dossier
    2. Early Clarification Meeting
    3. Late Clarification Meeting
    4. Approval Medicinal Products
    5. Approval Medical Device
  3. Federal Office of Public Health
    1. Submission
    2. Approval
  4. Liability
    1. Insurance
    2. Good Clinical Practice
Development Documents
  1. Required Documents
    1. Study Protocol
    2. Participant Information
    3. Insurance and Contract
    4. Study Documents
    5. Document Submission
Development Safety
  1. Safety Documentation
    1. The Protocol
    2. Study Documents
    3. Data Protection
Development Data Handling
  1. Study Database
    1. Variables
    2. Variable Specification
    3. Case Report Form
    4. Automated Data Processing
    5. Data Confidentiality
    6. Data Coding and Anonymisation
  2. Data Quality
    1. Requirement
    2. Quality Management
    3. Data Mgmt. Plan
  3. Database Lock
    1. Procedures
Development Statistics
Development Quality and Risk
  1. Study Risk Management
    1. Risk Identification
    2. Risk Evaluation and Prioritisation
    3. Risk Control Measures
    4. Process Verification and Training
  2. Quality Assurance
    1. Aim
    2. Quality Documents
    3. Audit
  3. Quality Control
    1. Aim
    2. Monitoring
    3. Non-Compliance
  4. Risk Communication
    1. Strategy
Development Monitoring
  1. Montoring Strategy
    1. Aim
    2. Risk-Based Monitoring
    3. On-Site Monitoring
    4. Central Monitoring
    5. Monitoring Plan
Development Drug or Device
Development Biobanking
Set-Up

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Protocol
Set-Up Management
  1. Registration
    1. Research Transparency
  2. Study Training
    1. Staff
  3. Document Management
    1. Requirements
  4. Investigational Product
    1. In Studies
  5. Laboratory
    1. Aim
  6. Study Ready for Conduct
    1. Requirements
  7. Study Monitoring
    1. Site Initiation Visit
Set-Up Ethics and Laws
  1. Study Set-Up
    1. Requirements
Set-Up Documents
  1. Required Documents
    1. Study Initiation
    2. Master and Site File
Set-Up Safety
  1. Safety Management
    1. Safety Management Plan
    2. Emergency Unblinding
  2. Data Safety Monitoring Board
    1. Aim
Set-Up Data Handling
  1. Database
    1. Development
    2. Access Rights
    3. Training
Set-Up Statistics
Set-Up Quality and Risk
Set-Up Monitoring
  1. Site Initation Visit
    1. Aim
    2. Prerequisite
    3. Preparation
    4. Conduct
    5. Report
Set-Up Drug or Device
Set-Up Biobanking
Conduct

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Protocol
Conduct Management
  1. Participant Recruitment
    1. Pre-Screening
    2. Screening and Consent
    3. Documentation of Recruitment
  2. Amendment
    1. Protocol
    2. Patient Information Sheet
  3. Safety
    1. Reporting
    2. Annual Safety Reporting
    3. Interim Analysis
  4. Responsibility and Oversight
    1. Site-Investigator
    2. Routine Monitoring
    3. Risk Review
    4. Drug Accountability
    5. Compliance
    6. Newsletter
    7. Essential Documents
    8. Budget
Conduct Ethics and Laws
  1. Study Conduct
    1. Ongoing Tasks
    2. Data Protection
  2. Participant Protection
    1. Requirements
    2. Consent of Vulnerable Participants
  3. Amendment
    1. Type
    2. Submission
    3. Approval
  4. Safety
    1. Requirements
  5. Inspections and Audits
    1. Inspection Conduct
    2. Audit Conduct
    3. Audit Certificate
  6. Premature Study Termination
    1. Rationale
    2. ReportingTimelines
Conduct Documents
  1. Required Documents
    1. Study Documentation
    2. Patient File
    3. Source Data
    4. Amendment
Conduct Safety
  1. Safety Risk Review
    1. Aim
  2. Safety Assessment
    1. Medicinal Product
    2. Medical Device
    3. Other Clinical Trials
    4. Research Projects
  3. Safety Reporting
    1. Procedures
    2. Responsibilities
  4. Medicinal Product Safety Reporting
    1. Adverse Event
    2. Serious Adverse Event
    3. (Serious) Adverse Drug Reaction
    4. Suspected Unexpected Serious Adverse Reaction
    5. Advanced Therapies
  5. Medical Device Safety Reporting
    1. Adverse Event / Adverse Device Effect
    2. Serious Adverse Event and Device Effect
    3. Device Deficiency
  6. Research Project Safety Reporting
    1. Serious Events
  7. Safety and Protective Measures
    1. Procedures
  8. Annual Safety Report
    1. Procedures
Conduct Data Handling
  1. Data Entry
    1. Requirement
    2. Collection
  2. Data Quality
    1. Responsibility
    2. Training
  3. Data Handling
    1. Data Import
    2. Interim Lock
    3. Intermediate Data Eport
    4. Amendment
Conduct Statistics
Conduct Quality and Risk
  1. Risk Review
    1. Re-Evaluation
    2. Risk Documentation
  2. Deviation Documentation
    1. Note to File
  3. Regulatory Inspections
    1. Conduct
    2. Findings
    3. Corrective and Preventive Actions
Conduct Monitoring
  1. Routine Monitoring Visit
    1. Preparation
    2. Conduct
    3. Findings
    4. Report
    5. Follow-Up Letter
Conduct Drug or Device
Conduct Biobanking
Completion

Starts with last study visit completed

Ends after study publication and archiving

Completion Protocol
Completion Management
  1. Study Closure
    1. Close-Out Visit
    2. Database Lock
    3. Notification of Closure
    4. Lessons Learned
  2. Clinical Study Report
    1. Regulatory Requirements
  3. Publishing
    1. Study Registries
    2. Scientific Publications
  4. Archiving
    1. Storage
Completion Ethics and Laws
  1. End of Study Notification
    1. ReportingTimelines
    2. Liability Coverage
    3. Registry Update
  2. Clinical Study Report
    1. Procedures
  3. Publications
    1. Responsibilities
  4. Inspections and Audits
    1. Procedures
  5. Archiving
    1. Requirements
    2. Duration
Completion Documents
  1. Required Documents
    1. Study Closure
    2. Doument Archiving
    3. Document Destruction
Completion Safety
  1. Clinical Study Report
    1. Procedures
Completion Data Handling
  1. Final Database Lock
    1. Procedures
  2. Data Export
    1. Data Formatting and Tranfer
    2. Data Transfer Agreement
  3. Clinical Study Report
    1. Requirement
  4. Archiving
    1. Requirement
Completion Statistics
Completion Quality and Risk
  1. Clinical Study Report
    1. Risk Reporting
    2. Lessons Learned
  2. Archiving
    1. Study Records
Completion Monitoring
  1. Close-Out Visit
    1. Preparation
    2. Conduct
    3. Report
    4. Follow-Up Letter
    5. Archiving
Completion Drug or Device
Completion Biobanking
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