What is it? Why is it important?

A protocol amendment is an implemented change to an approved protocol during study conduct (i.e. approved by Ethics Committee (EC) and if applicable Regulatory Authorities (RA) such as Swissmedic (risk-category B or C) and FOPH.


An amendments can either be:

  • Substantial (SA): include changes to the risk-benefit ratio of the study or study conduct. SAs must be approved by EC/RA  prior to implementation (i.e. EC requires 30 days deliberation for single centres; 45 days for multicentre studies; Swissmedic requires 30 days deliberation)
  • Non-substantial (Non-SA): Include minor aspects such as the coordination of the study (e.g. changes among study nurses regarding delegated tasks).  EC is informed through the annual safety report; Swissmedic is notified as soon as possible, while


Safety amendments do not require pre-approval by EC/RA, as risk-control measures must be implemented to protect study participants. Still, the implementation of safety and protective measures must be reported to EC/RA within 7 days.

What do I need to do?

As a SP-INV:

  • Make changes to applicable protocol sections in track-change (i.e. both old and new entries must remain legible)
  • Provide a short rational why changes are necessary
  • Identify documents, which because of the protocol amendment need an adaptation (e.g. PIS/ICF, CRF).
  • Approve the amendment together with potential Site-INV(s) or other involved parties by dating and signing the signature page
  • Submit the amended protocol, including other adapted documents, to the EC and if applicable Swissmedic for approval
  • File the amended protocol / documents in the ISF to ensure they are available to site staff
  • Ensure study staff, Site-INV(s), and other relevant study collaborators (e.g. laboratories, statistician, monitor) are trained on the amendment (i.e. document in a training-log)


Document Management:

  • Create a “document history” to list all protocol changes
  • Following each protocol amendment, update applicable document identifications accordingly (e.g. document release date, document version)
  • Sort or save (electronically) protocols according to protocol version and date of the amendment
  • Ensure the current and approved protocol / document(s) are accessible to study staff, and that archived protocol / documents are clearly identifiable from current or active ones

Where can I get help?

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

External Links

Swissethics – see in particular

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


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 (access liable to cost) - see in particular sections

  • 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
  • CIP – Clinical investigational plan
  • ClinO – Clinical Trials Ordinance
  • CRF – Case Report Form
  • CTU – Clinical Trials Unit
  • EC – Ethics Committee
  • FOPH – Federal Office of Public Health
  • EC/RA – Ethics Committee / Regulatory Authorities
  • HRO – Human Research Ordinance
  • ICF – Informed Consent Form
  • ICH-GCP – International Council for Harmonisation - Good Clinical Practice
  • ISF – Investigator Site File
  • ISO – International Organization for Standardization
  • Non-SA – Non Substantial Amendment
  • PIS – Patient Information Sheet
  • RA – Regulatory Authorities
  • SA – Substantial Amendment
  • Site-INV – Site Investigator
  • SP-INV – Sponsor-Investigator
Conduct ↦ Management ↦ Amendment ↦ Protocol

Provides some background knowledge and basic definitions

Basic Monitoring
Basic Drug or Device

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Drug or Device

Starts with confidence that the study is feasible

Ends after having received ethics and regulatory approval

Development Drug or Device

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Ethics and Laws
Set-Up Quality and Risk
Set-Up Drug or Device

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Drug or Device

Starts with last study visit completed

Ends after study publication and archiving

Completion Statistics
Completion Drug or Device
Current Path (click to copy): Conduct ↦ Management ↦ Amendment ↦ Protocol

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