What is it? Why is it important?

Based on the Monitoring Plan (MP) of the study, the Close-Out Visit (COV) represents the last monitoring visit of the study. The COV thereby completes study monitoring.

 

The site is ready for closure once the following criteria are met:

  • The last study participant has completed his/her last study visit (Last Patient Last Visit, LPLV)
  • Required study data are collected and (e)CRF entries are complete
  • Queries / findings are resolved and eCRF / database irregularities are corrected
  • The study database is ready for final closure
  • Essential documents are signed and filed in the Investigator Site File (ISF) and Trial Master File (TMF) and ready for archiving

 

Once the database is locked, the data can be exported and forwarded to the statistician for data analysis.

More

The study SP-INV and participating Site-INV(s) are responsible for the correct closure and archiving of the study. This will allow for the reconstruction of the study at some later date (i.e. Swissmedic may request the inspection of an archived study).

What do I need to do?

As a monitor, prepare the visit for the monitoring COV.

During the COV visit ensure that:

  • Drug accountability is complete and correct, (e.g. all used or unused investigational product (IMP / IMD) are accounted for)
  • Unused IMP/IMD and lab supplies are ready for return to the SP-INV, or are destroyed at the site
  • All CRF queries are solved with no more changes possible
  • Notification of study closure is communicated to the Ethics Committee (EC) and, if applicable, to RA (e.g. Swissmedic, international)
  • ISF and TMF are complete and up to date
  • All note-to-files are correctly filed
  • Site-INV is reminded of pending responsibilities (e.g. archiving). Study documents destined for archiving can be returned to the SP-INV for safe keeping. Still, site specific documents (e.g. participant informed consent, participant-identification-log) must remain at the site during the archiving period (i.e. can last for up to 25 years)

More

The COV should be well prepared as it is the last monitoring visit to the site. Study relevant aspects must end, and the site must prepare for archiving.

 

SP-INV pending responsibilities after study COV include to:

  • Submit a Clinical Study Report (CSR) to the Ethics Committee (EC) and if applicable to RA (e.g. Swissmedic) within one year
  • Update study applicable registries
  • Publish study results (e.g. scientific journals)
  • Potentially summarize the study in a final newsletter to be distributed to relevant interest groups
  • Archive study documents according to a defined archiving SOP. Instructions include the definition of required archiving premises (e.g. access-, fire-, humidity-, and rodent protection)
  • Ensure that archiving material remains accessible and legible during the entire archiving period
  • Remain prepared for the possibility of an audit or inspection by regulatory authorities

Where can I get help?

Your local Research Support Centre↧ can assist you with experienced staff regarding this topic

  • Basel, Departement Klinische Forschung (DKF), dkf.unibas.ch

  • Lugano, Clinical Trials Unit (CTU-EOC), ctueoc.ch

  • Bern, Department of Clinical Research (DCR), dcr.unibe.ch

  • Geneva, Clinical Research Center (CRC), crc.hug.ch

  • Lausanne, Clinical Research Center (CRC), chuv.ch

  • St. Gallen, Clinical Trials Unit (CTU), h-och.ch

  • Zürich, Clinical Trials Center (CTC), usz.ch

References

ICH GCP E6(R3) – see in particular guidelines

  • 3.11.4.5 Monitoring activities
  • Appendix C. Essential records for the conduct of a clinical trial

ISO 14155:2020 Medical devices (access liable to cost) - see in particular sections

  • 8.3 Routine close out
  • Annex E – Essential clinical investigation documents

Swiss Law

HRA – see in particular article

  • 46 Notification of completion/ discontinuation of study

ClinO – see in particular article

  • Art. 38 Notification upon completion, discontinuation, interruption of study

ClinO-MD – see in particular article

  • 36 Notification of completion/ premature termination/ interruption of a clinical trial

HRO – see in particular article

  • Art. 22, 36, 40, 43 Specifications regarding notification upon completion or discontinuation of a research project
Abbreviations
  • COV – Close Out Visit
  • CTU – Clinical Trials Unit
  • CSR – Clinical Study Report
  • eCRF- electronic Case Report Form
  • EC – Ethics Committee
  • EC/RA - Ethics Committee / Regulatory Authorities
  • ICH GCP – International Council for Harmonisation Good Clinical Practice
  • ICF – Informed Consent Form
  • IMP/IMD – Investigational Medicinal Product / Investigational Medical Device
  • ISF – Investigator Site File
  • ISO – International Organization for Standardization
  • LPLV –Last Patient Last Visit
  • MP – Monitoring Plan
  • PIS – Patient Information Sheet
  • RA – Regulatory Authorities
  • Site-INV – Site-Investigator
  • SP-INV – Sponsor-Investigator
  • TMF – Trial Master File
  • RA – Regulatory Authority
Completion ↦ Management ↦ Study Closure ↦ Close-Out Visit
Study
Basic

Provides some background knowledge and basic definitions

Basic Protocol
  1. Research and Ethics
    1. Principles
    2. Ethical Dilemma
  2. Study Protocol
    1. Aim
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 Product Studies
    3. Other Clinical Studies
    4. Transplantation
    5. Transplant Products
    6. Gene Therapy, GMO, Pathogenic
    7. Ionising Radiation
  5. Clinical Trials with Medical Device Ordinance
    1. Aim
    2. Medical Device Studies
    3. In Vitro Diagnostic Medical Device Studies
    4. Ionising Radiation
  6. Medical Device Ordinance
    1. Aim
    2. Notified Bodies
  7. 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
  8. Organisation Ordinance
    1. Aim
  9. Human Research Coordination Portal
    1. Human Research in Switzerland
  10. Submission Portal
    1. Ethics Portal BASEC
    2. Swissmedic eGov Portal
  11. 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
Basic Safety
  1. Safety Laws
    1. Aim
  2. Safety Terminology
    1. Overview
  3. Safety Data
    1. Product Development
    2. Pre-Clinical Studies
    3. In Clinical Studies
  4. Safety Information
    1. Investigator Brochure
  5. Safety Vigilance
    1. Pharmacovigilance
    2. Materiovigilance
Basic Data Management
  1. Data Management in Studies
    1. Aim
  2. Study Database
    1. Clinical Data Management System
    2. Study Data
    3. Raw Data
    4. Metadata
  3. Regulatory Requirements
    1. Swiss Law
    2. EU Regulation
Basic Statistic Methodology
  1. Statistics
    1. Definition
    2. Statistician Role
    3. Statistical Software
  2. Research Question
    1. Definition
    2. The Population
    3. Intervention and Control Group
    4. Placebo and Comparator
    5. Study Outcome Endpoint
    6. Outcome Endpoint Description
  3. Study Design
    1. Definition
    2. Sample Size Calculation
    3. Randomization
    4. Study Blinding
    5. Interim Analysis
  4. Data Collection
    1. Planning
    2. Predictor Variable
    3. Confounding Variable
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
  1. Therapeutic Products
    1. Definition
    2. Generic Products
    3. Complementary and Herbal Medicine
    4. Orphan Drugs
    5. Product Development
    6. Good Manufacturing Practice
    7. Market Surveillance
    8. In Studies
  2. Medicinal Product
    1. Definition
    2. Market Authorization
    3. Manufacturing and Distribution
  3. Medical Device
    1. Definition
    2. Conformity Assessment
    3. Manufacture Responsibility
  4. In Vitro Diagnostic Device
    1. Definition
Basic Biobanking
  1. Definition
    1. Biobank
    2. Biological Material
    3. Specimen / Sample
    4. Pre-Analytical Phase
    5. Data Coding / Anonymisation
    6. Incidental Findings
  2. Donor
    1. In Research
  3. The Swiss Law
    1. Human Research Ordinance
    2. Research with Biological Material
    3. Further Use of Biological Material
    4. Further Use and Informed Consent
  4. Ethics Principles
    1. Declaration of Taipei
  5. Biobanking Standards
    1. ISO Biobanking
  6. Swiss Biobanking Platform
    1. Aim
    2. Services
    3. Quality Labels
Concept

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Protocol
  1. Research Question
    1. Feasibility
Concept Management
  1. Study Idea
    1. Feasibility
    2. Implementation
    3. Design
  2. Resources
    1. Study Staff
    2. Infrastructure
    3. Storage
    4. Partners
    5. Budget
Concept Ethics and Laws
  1. Research Aim
    1. Advancing Science
    2. Marketing Products
  2. Research Integrity
    1. Principles
    2. Conflict of Interest
    3. Participant Protection
  3. Ethics and Regulatory Requirements
    1. Ethics Requirements
    2. Laws and Guidelines
    3. Institution Requirements
    4. Study Compliance
  4. Ethics and Regulatory Advice
    1. Ethics Clarification
    2. Swissmedic Scientific Advice
    3. Swissmedic Pre-Submission
Concept Documents
  1. Required Documents
    1. Protocol and Synopsis
    2. Investigator's Brochure
Concept Safety
  1. Safety in Studies
    1. Risk-Benefit Ratio
    2. Participant Risk-Benefit
  2. Study Risk Categorisation
    1. Procedures
    2. Risk Categories
Concept Data Management
  1. Stakeholders
    1. Sponsor-Investigator
    2. Data Manager
    3. Statistician
    4. Site-Investigator
    5. Monitor
  2. Clinical Data Mgmt. System
    1. Selection
    2. Computer System Validation
  3. Server Management
    1. Data Storage
    2. Back-Up and Recovery
Concept Statistic Methodology
  1. Study Feasibility
    1. Research Question
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 Qualification
Concept Drug or Device
Concept Biobanking
  1. Biobanking in Studies
    1. Requirement
    2. Quality of Biological Material
  2. Management of a Biobank
    1. Biobank Goverance
    2. Biobank Regulation
    3. Material Transfer Agreement
Development

Starts with confidence that the study is feasible

Ends after having received ethics and regulatory approval

Development Protocol
  1. Formal Structure
    1. Requirements
    2. Protocol Template
  2. Writing the Protocol
    1. Content
    2. Responsibilities
  3. Study Participants
    1. Participant Risks and Benefits
    2. Participant Right
Development Management
  1. Responsibilities
    1. Sponsor-Investigator
    2. Site-Investigator
    3. Staff Qualification and Training
    4. Good Clinical Practice Training
  2. Study Quality
    1. Implementation
  3. Study Safety
    1. Requirement
  4. Study Management
    1. Oversight
    2. Tracking
    3. Infratructure and Maintenance
    4. Multicentre Studies
    5. Insurance
    6. Outsourced Services
    7. Contract
    8. Budget
  5. Study Documents
    1. Protocol
    2. Participant Information Sheet
    3. Informed Consent Form
    4. General Consent
    5. Essential Documents
    6. Source Data
  6. Informed Consent Process
    1. Procedures
    2. Exemption from written Consent
  7. Study Approval
    1. Ethics Committee
    2. Swissmedic
    3. Fed. Off. Public Health
  8. Biobanking
    1. Management
Development Ethics and Laws
  1. Ethics Application
    1. Submission
    2. Application Dossier
    3. Approval
  2. Swissmedic Application
    1. Submission
    2. Application Dossier
    3. Early Clarification Meeting
    4. Late Clarification Meeting
    5. Approval Medicinal Products
    6. 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 Management
  1. Database Development
    1. Variables
    2. Specification
    3. Case Report Form
    4. Calculated Fields
    5. Data Coding and Anonymisation
    6. Data Confidentiality
  2. Data Quality
    1. Requirement
    2. Quality Assurance
    3. Data Mgmt. Plan
    4. Data Monitoring
    5. Data Transfer Agreement
  3. Database Lock
    1. Procedures
Development Statistic Methodology
  1. Statistics in the Protocol
    1. The Hypothesis
    2. Data-Analysis-Set
    3. Primary and Secondary Analysis
    4. Analysis Method
    5. Missing Data
    6. Study Termination Criteria
  2. Analysis Plan
    1. Procedures
  3. Sample Size
    1. Justification
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. Verification
    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 Data Monitoring
    5. Off-Site Monitoring
    6. Monitoring Plan
Development Drug or Device
Development Biobanking
  1. Biobank Set-Up
    1. Biobank Database
    2. Facilities and Materials
    3. Collection / Storage Containers
    4. Storage Equipment
    5. Equipment Maintenance
    6. Freezer Emergency Plan
  2. Donor Consent
    1. In Clinical Studies
    2. In Research Projects
    3. For Further Use
    4. Communication
  3. Handling of Biological Material
    1. Sample Workflow
    2. Sample Collection
    3. Sample Transport
    4. Sample Reception
    5. Sample Processing
    6. Sample Storage
    7. Sample Distribution
    8. Sample Analysis
  4. Documentation
    1. Forms and Logs
    2. Non-Conformities
  5. Safety
    1. Risk-Based Approach
    2. Donors
    3. Biobanking Staff
  6. Quality Control
    1. Quality Control Indicators
    2. Data Monitoring
    3. Method Validation
Set-Up

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Protocol
  1. Protocol Training
    1. Requirements
Set-Up Management
  1. Registration
    1. Research Transparency
  2. Study Training
    1. Staff Delegation
  3. Document Management
    1. Requirements
  4. Investigational Product
    1. Definition and Handling
  5. Laboratory
    1. Purpose and Requirement
  6. Study Ready for Conduct
    1. Requirements
Set-Up Ethics and Laws
  1. Study Set-Up
    1. Requirements
Set-Up Documents
  1. Required Documents
    1. Staff Training
    2. Staff Qualification
    3. 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 Management
  1. Database Release
    1. Requirement
    2. Access Rights
    3. Training
Set-Up Statistic Methodology
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
  1. Regulatory Affairs
    1. Requirement
  2. Staff Management
    1. Requirement
  3. Sample Management
    1. Sample Traceability
    2. Packaging and Shipment
  4. Biobanking in Studies
    1. Procedures
  5. Data Integrity
    1. Data Accuracy
Conduct

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Protocol
  1. Protocol Amendment
    1. Procedures
Conduct Management
  1. Participant Recruitment
    1. Pre-Screening
    2. Screening and Consent
    3. Documentation
  2. Amendment
    1. Protocol
    2. Patient Information
  3. Responsibility and Oversight
    1. Sponsor and Site-Investigator
    2. Drug and Device Accountability
    3. Compliance
    4. Newsletter
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. Oversight 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 Management
  1. Data Entry
    1. Requirement
    2. Collection
  2. Data Quality
    1. Responsibility
  3. Amendment
    1. Requirement
    2. Adding Stakeholders
  4. Data Processing
    1. Data Import
    2. Interim Lock
    3. Data Translation
Conduct Statistic Methodology
  1. Interim Analysis
    1. Procedures
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
Conduct Drug or Device
Conduct Biobanking
  1. Biobanking Operation
    1. Processes
Completion

Starts with last study visit completed

Ends after study publication and archiving

Completion Protocol
  1. Administrative Tasks
    1. Procedures
Completion Management
  1. Study Closure
    1. Close-Out Visit
    2. Database Lock
    3. Notification of Closure
    4. Lessons Learned
  2. Clinical Study Report
    1. Requirement
  3. Publishing
    1. Study Registries
    2. Scientific Publications
  4. Archiving
    1. Storage
Completion Ethics and Laws
  1. End of Study Notification
    1. Reporting and Liability
    2. Registry Update
  2. Clinical Study Report
    1. Requirement
  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 Management
  1. Final Database Lock
    1. Procedures
  2. Data Export
    1. Data Formatting
    2. Data Sharing
  3. Clinical Study Report
    1. Requirement
  4. Archiving
    1. Requirement
Completion Statistic Methodology
  1. Data Quality Check
    1. Procedures
  2. Data Preparation
    1. Procedures
  3. Data Analysis and Reporting
    1. Procedures
  4. Quality Controls
    1. Procedures
  5. Publication
    1. Statistician Responsibility
  6. Data Sharing
    1. Data Preparation
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
    5. Archiving
Completion Drug or Device
Completion Biobanking
  1. Leftover Biological Material
    1. For Further-Use
    2. Destruction
  2. Publication
    1. Analytical Results
Current Path (click to copy): Completion ↦ Management ↦ Study Closure ↦ Close-Out Visit

Please note: the Easy-GCS tool is currently under construction.