Conduct↦Management↦Amendment↦Protocol
What is it? Why is it important?
A protocol amendment is an implemented change to an approved protocol during study conduct (e.g. approved by Ethics Committee (EC) and if applicable Regulatory Authorities (RA) such as Swissmedic and FOPH).
An amendments can either be:
- Substantial, or
- Non-substantial
Studies must be conducted in compliance with an EC/RA approved protocol. Still, due to problems or situations encountered during study conduct, a protocol amendment might become necessary.
Consequently, a substantial amendment must be submitted and approved by EC/RA prior to implementation. Exceptions are safety amendments that require the implementation of protective measures (e.g. risk control-measures) in order to protect study participants.
Non-substantial amendments are notified to:
- RA as soon as possible
- EC in the annual safety report
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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?
As a SP-INV and Site-INV, based on the ongoing evaluation of your study decide whether an amendment is necessary.
- Prepare amended documents and include the SP-INV`s justification for a required substantial amendment
- In the event of a safety amendment, immediately implement protective measures and inform the EC and as applicable 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 amendments as soon as possible, and include them in the annual safety report
- For every protocol amendment, evaluate whether changes to the PIS/ICF would also be required (PIS/ICF amendments)
Except for safety amendments, a substantial protocol amendment should be well thought through as delays in study conduct are expected (e.g. EC requires 30 days deliberation for mono-, and 45 days for multi-centre studies)
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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
External Links
Swissethics – see in particular
- Template annual safety report
- 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 (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