What is it? Why is it important?

An amendment are changes during study conduct of an EC, and if applicable RA (e.g. Swissmedic), approved study. Amendments can either be:

  • Substantial, or
  • Non-substantial, or
  • Safety amendments (always considered a substantial amendment)


Substantial amendments require prior EC/RA approval. Exception are safety amendments where protective measures are immediately implemented (e.g. or as soon as possible) in order to protect study participants.


Apart from the protocol, an amendment might result in changes to other EC approved study documents such as the PIS and ICF.

What do I need to do?

As a SP-INV and based on problems or situations encountered during study conduct:

  • Decide whether an amendment is necessary
  • Apart from the protocol, identify documents that must be adapted as they become affected by the amendment (e.g. PIS/ ICF, CRF, etc.)
  • Prepare the amended documents and submit the request for an amendment to the EC and if applicable RA (e.g. Swissmedic)


Prepare the amended documents as follows:

  • Create the amended documents in a clean and track-change version
  • Adapt the document identification accordingly (e.g. date, version)
  • Summarize changes in the cover letter
  • Submit the amendment to EC, and if applicable RA, for approval


The amendment can only be implemented in the study after EC/RA approval has been received


For more information refer to Protocol in this Study Guide.


Except for safety amendments, carefully evaluate whether a substantial amendment is necessary. Note that preparing and submitting an amendment dossier to EC/RA, as well as implementing the amendment will require additional resources (e.g. staff, finances). An amendment might both increase the cost and the duration of the study.

Where can I get help?

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

External Links

Swissethics – see in particular

  • 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 – 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
  • CIP – Clinical investigational plan
  • ClinO – Clinical Trials Ordinance
  • CRF – Case Report Form
  • CTU – Clinical Trials Unit
  • EC/RA – Ethics Committee / Regulatory Authorities
  • HRO – Human Research Ordinance
  • ICF – Informed Consent Form
  • PIS – Participant Information Sheet
  • RA – Regulatory Authorities
  • SD – Source Data
Conduct ↦ Documents ↦ Required Documents ↦ Amendment

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 ↦ Documents ↦ Required Documents ↦ Amendment

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