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
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.
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.
- 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 multi-centre 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
Basel, Departement Klinische Forschung, CTU, dkf.unibas.ch
Lugano, Clinical Trials Unit, CTU-EOC, www.ctueoc.ch
Bern, Clinical Trials Unit, CTU, www.ctu.unibe.ch
Geneva, Clinical Research Center, CRC, crc.hug.ch
Lausanne, Clinical Research Center, CRC, www.chuv.ch
St. Gallen, Clinical Trials Unit, CTU, www.kssg.ch
Zürich, Clinical Trials Center, CTC, www.usz.ch
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
ClinO – see in particular articles
- Art. 29, 34, 55. Changes
HRO – see in particular article
- Art. 18 Changes