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 does not match 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  • Documents are used that are outdated or have not been approved by the EC and RA
  • Irregularities exist in the IC process
  • Safety documentation is missing, or there is an unacceptable delay in safety reporting
  • IMP/MD is handled inappropriately (e.g. incorrect temperature storage, unrestricted access to IMP/MD)

More

Findings are classified as minor, major or critical depending on the potential negative impact on participant safety and on the quality of study data.

Findings can be:

  • GCP deviations: the finding does not follow guidelines as stated in GCP (ClinO studies)
  • Deviations from the study protocol: tasks required by the protocol are not done, or alternative tasks not covered by the protocol are performed
  • Deviations from local law and regulations: in Switzerland the following laws would apply
    • The Human Research Act (HRA)
    • The Ordinance on Clinical Trials in Human Research (ClinO)
    • The Ordinance on Human Research with the exception of Clinical Trials (HRO)

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
  • Discuss findings with the SP-INV. Findings that systematically remain unresolved during subsequent RMVs might lead to a protocol amendment

More

The monitoring reports any findings to be reviewed by the study SP-INV. It is up to the SP-INV of the study to determine the seriousness of any findings and define appropriate steps. In serious cases, the SP-INV might conclude that the most appropriate action would be to close the study site.

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 EC and, if applicable, the RA 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, 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.

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 guidelines

  • 4.5 Protocol compliance
  • 5.18 Monitoring activities
  • 6.10 Access to source data / documents

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

  • 9.2.4 Monitoring
Abbreviations
  • CTU – Clinical Trials Unit
  • EC – Ethics Committee
  • GCP – Good Clinical Practice
  • IC – Informed Consent
  • ICF – Informed Consent Form
  • IMP/MD – Investigational Medicinal Product/Medical Device
  • 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 Protocol
Basic Statistics
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 Statistics
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 Statistics
Development Drug or Device
Development Biobanking
Set-Up

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Protocol
Set-Up Ethics and Laws
Set-Up Statistics
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 Statistics
Conduct Drug or Device
Conduct Biobanking
Completion

Starts with last study visit completed

Ends after study publication and archiving

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

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