What is it? Why is it important?

Amendments are changes to an Ethics Committee (EC) and if applicable Swissmedic. approved study protocol.

 

Amendments can either be:

  • Substantial (SA): where modifications may have a significant impact on the:
    • Safety or physical/mental integrity of participants
    • Scientific value of the study
    • Manner of study execution
    • Handling of study IMP/IMD
  • Non-substantial (N-SA): with no expected implications to the study scope (more administrative / formal changes)

 

SAs require EC and if applicable RA (e.g. Swissmedic, international) approval before implementation. Exceptions are urgent safety measures needed to protect study participants against any immediate hazard. If required, safety measures such as temporarily halting the study can be implemented without prior approval. Still, EC/RA must be notified as soon as possible.

 

Non-SAs do not require initial approval before implementation, but are submitted to:

More

 

Examples where a substantial 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)
  • The required addition of additional study sites (multi-centre study)
  • Fluctuations in study staff requiring changes in responsibilities (e.g. substitution of Site-INV)

What do I need to do?

As a SP-INV and Site-INV:

  • In the event of a required safety amendment, immediately or as soon as possible:
    • Implement preventative safety measures
    • Notify the EC and if applicable Swissmedic

 

As a SP-INV:

  • Check the Swissmedic and EC homepage in order to determine whether a planned amendment is a SA or N-SA
  • Define reason(s) why you think an amendment is necessary
  • In the event that an amendment affects study participants, adapt the Participant Information Sheet (PIS) and the Informed Consent Form (ICF)
  • Submit documents to EC (e.g. protocol, PIS, ICF) and if applicable Swissmedic (e.g. protocol)
  • Implement changes only after authorities have approved the amendment
  • If applicable, ask participants to re-consent by signing the amended ICF

 

Except for required safety amendments, initiating a protocol amendment should be well thought through, as it can significantly delay the study.

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In order to take appropriate action in the event of immediate hazard to study participants, make pre-arrangements on how to implement and handle safety measures. The SP-INV can request support from other experts such as the Data Safety Monitoring Board or another responsible person within the organisation. The protocol should identify any individual(s) who accept(s) this responsibility.

Where can I get help?

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

External References

Swissethics – see in particular

  • Substantial amendment: YES or NO or "it depends"

Swissmedic – see in particular

  • BW101_10_003e_AA Guideline Amendments and reporting in clinical trials

Swiss Law

ClinO – see in particular article

  • Art. 29 Changes

ClinO-MD – see in particular articles

  • Art. 15 Amendments to EC
  • Art. 20 Amendments to Swissmedic

HRO – see in particular article

  • Art. 18 Changes
Abbreviations
  • ClinO – Clinical Trials Ordinance
  • ClinO-MD – Ordinance on Clinical Trials with Medical Devices
  • CTU – Clinical Trials Unit
  • EC – Ethics Committee
  • HRO – Human Research Ordinance
  • ICF – Informed Consent Form
  • IMP/IMD - Investigational Medicinal Product / Investigational Medical Device
  • N-SA – Non-Substantial Amendment
  • PIS – Participant Information Sheet
  • RA – Regulatory Authorities
  • SA – Substantial Amendment
  • Site-INV – Site Investigator
  • SP-INV – Sponsor Investigator
Conduct ↦ Ethics and Laws ↦ Amendment ↦ Type
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 Drug or Device
Current Path (click to copy): Conduct ↦ Ethics and Laws ↦ Amendment ↦ Type

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