What is it? Why is it important?

Findings are inconsistencies or problems found during monitoring, such as:

  • Data enterd into the eCRF of the study database (CDMS) does not match the Source Data (SD
  • Data is incomplete or missing
  • Study staff is not trained
  • Responsibilities are not clear
  • Documents are used that are outdated or have not been approved by the Ethics Committee (EC), and if applicable RA (e.g. Swissmedic)
  • Irregularities exist in the Informed Consent (IC) process
  • Safety documentation is missing, or there is an unacceptable delay in safety reporting
  • The therapeutic product under investigation (IMP / IMD) is incorrectly handled (e.g. incorrect temperature storage, unrestricted access, incomplete product accountability-log)

 

The severity of a finding depends on its potential negative impact on:

More

Findings can be:

What do I need to do?

If you are the study monitor:

  • Document all findings in the monitoring report that are to be reviewed and assessed by the SP-INV
  • Ask the site staff to make immediate corrections to simple findings
  • Consult with the site to understand the root cause of more complicated findings and discuss applicable strategies to correct findings and prevent any reoccurrence (e.g. CAPAs)
  • Discuss findings with the SP-INV. Findings that systematically remain unresolved during subsequent RMVs may lead to a protocol amendment

 

Findings to be reviewed by the SP-INV of the study are listed in the monitoring report. It is up to the SP-INV to determine the seriousness of any findings and define appropriate steps. In the event of serious findings, jeopardising participant safety and or data quality, the SP-INV may decide to close a study site..

More

Findings might result in a protocol amendment. It is important to note that a protocol amendment, especially a substantial one, can have unwanted consequences on how a study is run.

An amendment can seriously delay the study because an amendment:

  • Must be approved by the Ethics Committee (EC) and, if applicable, the RA (e.g. Swissmedic) prior to implementation. This will delay the study as well as generate additional costs
  • Requires relevant staff to be retrained
  • May require participants to re-consent to study procedures, which carries a risk that participants drop-out of the study

 

Make sure to invest sufficient time needed to develop the study protocol. This can avoid unnecessary amendments later on during study conduct.

Hasty and inadequate planning, significantly increase the risk of introducing inconsistencies in the study protocol.

Example of a protocol amendment

Based on an implemented study protocol, collected blood volumes were found to be inadequate for the planned analysis. In order to be able to collect additional blood from participants, the SP-INV must first complete both a protocol and a PIS/ICF amendment. In addition, prior to implementation the amendments will have to be approved by EC and if applicable RA. In addition, participants have to consent to the extra blood draw.

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

  • Glossary: definition monitoring
  • Glossary: definition monitoring report
  • 3.10.1.3 Risk control
  • 3.11.4 Monitoring
  • 3.11.4.5 Monitoring activities
  • 3.11.4.5.1 Communication with parties conducting the trial

ICH E8 – see in particular guideline

  • 6.1 Study conduct
  • 6.2.1 Safety monitoring

ISO 14155 Medical Device – see in particular section (access liable to costs)

  • 9.2.4 Monitoring
Abbreviations
  • CAPA – Corrective and Preventive Actions
  • CDMS – Clinical Data Management System
  • ClinO – Clinical Trials Ordinance
  • ClinO-MD – Ordinance on Clinical Trials with Medical Devices
  • CTU – Clinical Trials Unit
  • EC – Ethics Committee
  • eCRF – electronic Case Report Form
  • GCP – Good Clinical Practice
  • GMO - Genetically Modified Organisms
  • HRA – Human Research Act
  • HRO – Human Research Ordinance
  • ICH – International Council for Harmonisation 
  • ICH GCP – International Council for Harmonisation Good Clinical Practice
  • IC – Informed Consent
  • ICF – Informed Consent Form
  • IMD – Investigational Medical Device
  • IMP – Investigational Medicinal Product
  • ISO – International Organisation for Standardisation
  • PIS – Patient Information Sheet
  • RA – Regulatory Authorities
  • RMV – Routine Monitoring Visit
  • SD – Source Data
  • SP-INV – Sponsor-Investigator
Conduct ↦ Monitoring ↦ Routine Monitoring Visit ↦ Findings
Study
Basic

Provides some background knowledge and basic definitions

Basic Monitoring
Concept

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Statistic Methodology
Concept Drug or Device
Development

Starts with confidence that the study is feasible

Ends after having received ethics and regulatory approval

Development Drug or Device
Set-Up

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Ethics and Laws
Set-Up Statistic Methodology
Set-Up Quality and Risk
Set-Up Drug or Device
Conduct

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Statistic Methodology
Conduct Drug or Device
Completion

Starts with last study visit completed

Ends after study publication and archiving

Completion Drug or Device
Current Path (click to copy): Conduct ↦ Monitoring ↦ Routine Monitoring Visit ↦ Findings