What is it? Why is it important?

A protocol amendment is necessary if (a) change(s) is/are made in an Ethics Committee (EC), and if applicable Swissmedic (i.e. risk-category B and C) approved protocol.

 

Amendments are either substantial (SA) or non-substantial (Non-SA). SAs potentially impacting participant safety (risk-benefit ratio) and rights, or the reliability of study results, and require approval prior to implementation.   

 

Reasons for a protocol amendment may include:

  • New scientific evidence requiring an adaptation of study aim, statistical study plan
  • Missing variables requiring the collection of additional data and/or biological material
  • Slow participant recruitment (e.g. inclusion of additional study sites, adaptations of study inclusion/exclusion criteria)
  • Staff fluctuations and change in responsibility (e.g. substitution of Site-INV)

 

Example of SAs that require Swissmedic approval may include:

More

Safety amendments do not require pre-approval by EC/RA, as risk-control measures must be implemented in order to protect study participants (i.e. implementation of safety and protective measures)

What do I need to do?

As a SP-INV:

  • Apart from the protocol, identify documents that need to be adapted due to the amendment (e.g. PIS/ICF, CRF).
  • Make changes to applicable protocol sections / documents in track-change (i.e. both old and new entries must remain legible)
  • Ensure amended documents comply with document identification guidelines
  • Provide a short rational why changes are necessary
  • Approve (sign and date) the amendment together with applicable partners (e.g. Site-INV, statistician)
  • 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 partners (e.g. laboratories, monitor) are trained on the amendment (i.e. document in training-log)

 

Note:

  • Adaptations to participant documents (e.g. PIS, ICF) may require that participants re-consent to the study
  • A shift in the study`s risk-benefit ratio may require an update of the insurance policy

More

A protocol amendment can only be implemented while the study is still ongoing. An amendment is no longer possible after the last patient has had his or her last study visit.

 

Document Management:

  • Create a “document history” to list all protocol changes
  • For each amendment ensure to comply with document identification guidelines (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
  • Ensure 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 – in particular see 

  • 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

ClinO-MD – See in particular articles

  • Art. 15 Modifications
  • Art. 20 Modifications

HRO – see in particular article

  • Art. 18. Changes

 

Abbreviations
  • ClinO – Clinical Trials Ordinance
  • ClinO-MD – Ordinance on Clinical Trials with Medical Devices
  • CRF – Case Report Form
  • CTU – Clinical Trials Unit
  • HRO – Human Research Ordinance
  • ICF – Informed Consent Form
  • ICH GCP – International Council for Harmonisation Good linical Practice
  • IMP – Investigational Medicinal Product
  • ISO – International Organization for Standardization
  • PIS – Participant Information Sheet
  • Site-INV – Site Investigator
  • SP-INV – Sponsor Investigator
Conduct ↦ Protocol ↦ Protocol Amendment ↦ Procedures
Study
Basic

Provides some background knowledge and basic definitions

Basic Monitoring
Basic Drug or Device
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 Statistic Methodology
Completion Drug or Device
Current Path (click to copy): Conduct ↦ Protocol ↦ Protocol Amendment ↦ Procedures

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