Substantial
Amendments
Emma Barsoum, University of Birmingham
19th May 2014
Substantial Amendments
For Clinical Trials of Investigational Medicinal Products (CTIMPS), a
substantial amendment is defined as a change to the terms of the
approvals given by either:
» Competent authority (MHRA)
» Research Ethics Committee (REC) or;
» Protocol change or change to any other
documentation submitted with the applications
which significantly affects one of the following:
» The safety, or physical or mental integrity of trial
subjects
»The conduct or management of the trial
»The scientific value of the trial
»The quality or safety of any IMP
used in the trial
Who to Notify about an
Amendment
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It is the responsibility of the sponsor to determine whether an
amendment is substantial.
– Cosponsors: University of Birmingham and Central Manchester
University Hospitals NHS Foundation Trust
Substantial and non-substantial amendments should both be notified to
the Lead R&D.
– Lead R&D: Greater Manchester Comprehensive Research Network
(GMCRN)
Substantial amendments should be notified to the REC and/or MHRA.
– REC: North West GM Central (CMFT)
Substantial and Non-Substantial
Amendments
Substantial
Non-substantial
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Changes to the design or methodology
of the study, or to background
information affecting its scientific value
Changes to the procedures
undertaken by participants; any
change relating to the safety or
physical or mental integrity of
participants, or to the risk/benefit
assessment for the study
Significant changes to study
documentation i.e. PIS, consent forms
Change of PI at existing centre
Addition of a new trial site
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Minor changes to the protocol or other
study documentation e.g. correcting
errors, typos
Updates of the investigator’s brochure
(unless there is a change to the
risk/benefit assessment for the trial)
Changes in the documentation used
by the research team for recording
study data
Changes to the research team at trial
sites (other than change of PI)
Changes in funding arrangements
Extension of the study beyond the
period specified in the application form
NRES (2014) Examples of substantial and non-substantial amendments
http://www.nres.nhs.uk/applications/after-ethical-review/notification-of-amendments/examples-of-substantialand-non-substantial-amendments/ [accessed 13/05/2014]
Submitting a Substantial
Amendment
Collate information to be included in the Substantial Amendment
BCTU complete Substantial Amendment form on IRAS
European Commission Notification of Substantial Amendment (Annex 2)
Sponsor to authorise Substantial Amendment form
Substantial Amendment is submitted to R&D, and REC and/or MHRA
REC and R&D (MHRA if required) review the amendment
REC and R&D (MHRA if applicable) approve the amendment
Releasing a Substantial
Amendment
Lead R&D inform participating NHS R&D
departments of amendment
BCTU inform all investigators on
behalf of the CI
Sites will be instructed on how to update
the Site File
BCTU will notify all Investigators and Research Staff at site
of ALL Substantial Amendments
Releasing a Substantial
Amendment (2)
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BCTU will circulate the following documents and information following
amendment approval:
– Important numbers and dates sheet
– Current REC approved documents list
– Summary of changes and actions needed
– MHRA acknowledgement and approval letter
– REC approval letter(s)
– Signed substantial amendment form
– New approved versions of REC approved documents
Latest Amendments
PREDNOS
Substantial Amendment 13:
- Change of PI (at two existing sites)
- Extension to the recruitment period
- IMP shelf life expiry statement
- Protocol amendment to Protocol Version 2.1 (1st September
2013)
- MHRA, R&D and REC approved (released 9th January 2014)
 Substantial Amendment 14:
- New site
- Change in PI
- R&D and REC approved (released 10th March 2014)
Latest Amendments
PREDNOS 2
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Substantial Amendment 4:
- Change of PI (at two existing sites)
- New sites (addition of two new sites)
- Protocol amendment to Protocol Version 1.2 (25th September
2013)
- MHRA, R&D and REC approval (released 20th February 2014)
Substantial Amendment 5:
- New site
- Change of PI
References
http://www.hra.nhs.uk/research-community/during-your-researchproject/amendments/preparing-amendments/
http://www.nres.nhs.uk/applications/after-ethical-review/notification-ofamendments/examples-of-substantial-and-non-substantial-amendments/
http://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/
Clinicaltrials/ManagingyourCTA/Amendments/Generalinformation/index.ht
m
Thank you
Thank you for listening.
Any Questions?