What is it? Why is it important?
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:
- Swissmedic as soon as possible
- The EC in the annual safety report
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?
- 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.
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
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
- Substantial amendment: YES or NO or "it depends"
Swissmedic – see in particular
- BW101_10_003e_AA Guideline Amendments and reporting in clinical trials
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