What is it? Why is it important?

Amendments are changes to the study protocol during study conduct and after initial EC and if applicable RA approval. Amendments can either be:

  • Substantial, or
  • Non-substantial

Before a substantial amendment can be implemented it must be approved by EC and if applicable by RA. Exceptions are safety amendments which are required to protect study participants. Still, EC and RA should be informed as quickly as possible.

Changes impacting the collection of study data are generally substantial amendments (e.g. the inclusion of additional study site(s) or data).

Substantial amendments require:

  • An initial protocol revision including approval by EC/RA
  • Adaptations / expansion of the study database (eCRF)
  • Validation, approval and release of the newly adapted database

More

Examples of amendments that might affect study data collection

  • New scientific evidence becomes available that require an adaptation regarding study aim, safety concerns, data collection and statistical study plan
  • The collected data is shown to be inadequate to answer the study question. The collection of additional data (variables) becomes necessary (e.g. additional blood samples, medical tests, participant feedback)
  • The total number of study participants needs to be increased. In order to gain access and recruit adequate participants the inclusion of additional study site(s) becomes necessary

What do I need to do?

Evaluate the impact of an amendment on the:

  • Study database (eCRF), pCRFs, study randomisation processes, existing data, subsequent data analysis and evaluation, adaptations regarding documentation requirements, additional data import requirements (e.g. laboratory systems), and staff trainings
  • Potential risks to data integrity, quality including data confidentiality and protection

Implement an amendment:

  • In collaboration with the DMan
  • Only once EC/RA approval has been received
  • Establish and save the database as a new updated version
  • Validate the amended database and ensure it works as intended
  • Train staff on applicable changes
  • Upon successful validation release the updated database for data entry

More

An amendment might also include the addition of additional study site(s). In that case applicable access rights will have to be updated.

Except for safety amendments aimed at protecting study participants, initiating a protocol amendment should be carefully evaluated as:

  • Delays in study conduct are expected. Especially in the event of a substantial amendment, where EC requires 30 days deliberation for mono- and 45 days for multi-centre studies
  • The quality of study data might be jeopardised, as the study might end up operating with two or more different and partly incompatible databases. This can lead to challenges during the statistical evaluation of the study

Where can I get help?

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

External Links

Swissethics – see in particular

  • Amendments – Definition of substantial and non-substantial amendments

References

ICH GCP E6(R2) – see in particular guidelines

  • 5.5. Trial Management, data handling, and record-keeping
Abbreviations
  • CTU – Clinical Trials Unit
  • DMan – Data Manager
  • EC – Ethics Committee
  • EC/RA – Ethics Committee / Regulatory Authorities
  • eCRF – Electronic Case Report Form
  • pCRF – paper Case Report Form
  • RA – Regulatory Authorities
Conduct ↦ Data Handling ↦ Data Handling ↦ Amendment
Study
Basic

Provides some background knowledge and basic definitions

Basic Protocol
Basic Statistics
Basic Monitoring
Basic Drug or Device
Basic Biobanking
Concept

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Protocol
Concept Statistics
Concept Drug or Device
Concept Biobanking
Development

Starts with confidence that the study is feasible

Ends after having received ethics and regulatory approval

Development Protocol
Development Statistics
Development Drug or Device
Development Biobanking
Set-Up

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Protocol
Set-Up Ethics and Laws
Set-Up Statistics
Set-Up Drug or Device
Set-Up Biobanking
Conduct

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Protocol
Conduct Statistics
Conduct Drug or Device
Conduct Biobanking
Completion

Starts with last study visit completed

Ends after study publication and archiving

Completion Protocol
Completion Statistics
Completion Drug or Device
Completion Biobanking
Current Path (click to copy): Conduct ↦ Data Handling ↦ Data Handling ↦ Amendment

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