What is it? Why is it important?

A protocol amendment represents changes to the protocol during study conduct and after initial EC/RA approval. Amendments can either be:

  • Substantial, or
  • Non-substantial

Substantial amendments must initially be submitted and approved by EC/RA prior to implementation. Exceptions are safety and protective measures that must be implemented immediately or as soon as possible in order to protect the safety of study participants.

Non-substantial amendments must be notified to RA as quickly as possible and to EC in the annual safety report.

More

Studies must be conducted in compliance with the EC/RA approved study protocol.

Based on problems or situations encountered during study conduct, an amendment might become necessary.

Examples where a protocol amendment might become necessary:

  • New scientific evidence becomes available requiring adaptations in study aim, safety concerns, statistical study plan
  • Data collection is inadequate requiring the collection of additional data and or material (e.g. additional blood samples, questionnaires)
  • Participant recruitment is too slow requiring changes or adaptations of study methods, design, procedures (e.g. inclusion of additional study sites, adaptations of inclusion/exclusion criteria, number of recruited participants)
  • Fluctuations in study staff requiring changes in responsibilities (e.g. substitution of Site-INV)

What do I need to do?

Based on the ongoing evaluation of your study, including participant safety, decide whether an amendment is necessary:

  • In the event safety and protective measures become necessary, immediately implement measures as required and then inform the EC/RA.
  • Wait for EC/RA approval prior to implementing any substantial amendments
  • Notify EC of any non-substantial amendment in the annual safety report
  • Notify the RA of any non-substantial amendment as soon as possible and include them in the annual safety report
  • For every protocol amendment, evaluate whether changes to the PIS/ICF would be required

For more information refer to Protocol in this Study Guide.

More

  • In the event changes to PIS/ICF are triggered by a protocol amendment:
    • Submit PIS/ICF changes to the EC for approval. Wait for approval prior to submitting to participants
    • Inform participants of respective changes and ask participants to re-consent
    • Except for necessary safety or other EC/RA required amendments, only implement changes once participants have signed and dated the adapted ICF
  • Except for safety and protective measures, initiating a protocol amendment should be well thought through as delays in study conduct are expected
  • Delays are especially the case for substantial amendments, as EC requires 30 days deliberation for mono- and 45 days for multicentre studies
  • Documentation including any jusitfication by the SP-INV regarding substantial amendments (including safety amendments) must be reported to Swissmedic for approval
  • Substantial amendments that are subject to Swissmedic approval, include in particular changes:
    • To the IMP, the route of administration, dosage form or dose administered
    • Based on new preclinical or clinical data that may affect the safety of the product
    • To the manufacturing of the IMP that may affect the safety of the product

Where can I get help?

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

External Links

Swissethics – in particular see

  • Template annual safety report
  • Notification of significant and other changes to the EC

References

ICH GCP E6(R2) – see in particular guidelines

  • 1.44 Protocol definition
  • 1.45 Protocol Amendment definition
  • 4.5 Compliance with protocol
  • 6. Clinical trial protocol and protocol amendment(s)

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

  • 6.4 Clinical investigational plan (CIP)
  • 7.5.1 Amendments
  • 10.5 Informed consent procedure
  • 10.6 Compliance with CIP
  • Annex A Clinical investigational plan

Swiss Law

ClinO – see in particular articles

  • Art. 29, 34, 55. Changes

HRO – see in particular article

  • Art. 18. Changes
Abbreviations
  • CIP – Clinical investigational plan
  • CTU – Clinical Trials Unit
  • EC – Ethics Committee
  • EC/RA – Ethics Committee / Regulatory Authorities
  • ICF - Informed Consent Form
  • ICH-GCP – International Council for Harmonisation - Good Clinical Practice
  • IMP – Investigational Medicinal Product
  • ISO – International Organization for Standardization
  • PIS – Patient Information Sheet
  • RA – Regulatory Authorities
  • Site-INV – Site Investigator
  • SP-INV – Sponsor-Investigator
Conduct ↦ Management ↦ Amendment ↦ Protocol
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 ↦ Management ↦ Amendment ↦ Protocol

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