RSK ASSESSMENT AND MONTORNG - EXPERENCE FROM PHEMON AU UNVERSTET HEATH BRGTTE ORK SCHEMMER GCP-KOORDNATOR 22. OKTOBER 2015
Mantle Cell ymphoma Working Group: Designs and runs clinical trials
NG-MC6 - PHEMON PHase brutinib Enalidomide MONtle Cell ymphoma A phase non-randomised, open-label multicenter trial in relapsed/refractory MC Primary endpoint Maximal overall response rate with PET and CT (ORR)
PHEMON treatment outline R R R R R R R R R R R R 1 5 9 13 17 21 25 29 33 37 41 45 49 57 65 73 81 89 Weeks 12 nduction cycles Maintenance until progression
PHEMON organisation CTO Aarhus Mats Jerkeman, P und, Sponsor Sweden Mats Jerkeman National P Norway Arne Kolstad National P Finland Riikka Räty National P Denmark Martin Hutchings National P und Uppsala Oslo Trondheim Helsinki Oulu Rigshospitalet Odense Aalborg Aarhus
PHEMON in summary Phase study 4 Nordic countries, 10 sites imited budget Central coordination by CTO How do we fulfill the sponsor obligation of monitoring?
Monitoring in PHEMON Established good collaboration with local GCP unit and with several other Nordic academic units Centralised coordination preferred
TMENE FOR THE COOPERATON N PHEMON May 2014 - First PHEMON trial meeting in Aarhus (sponsor from Sweden, CTO, GCP-unit) t was decided to use the Nordic Monitoring Network, NORM Sept. 2014 - Second trial meeting in Aarhus (sponsor from Sweden, CTO, GCP-unit) The Danish risk assessment was prepared for discussion before the meeting Nov. 2014 - Third trial meeting on Skype (sponsor and CTO) t was decided that the monitoring plan should be the same in all the Nordic countries and should be prepared according to the NORM guideline March 2015 Mail correspondence with sponsor and CTO about first version of RAT (risk assessment tool for a coordinated GCP-monitoring) and the monitoring plan April 2015 Start meeting AU UNVERSTET HEATH BRGTTE ORK SCHEMMER GCP-KOORDNATOR 22. OKTOBER 2015
PHEMON TRA MEETNG MAY 2014 First meeting in Aarhus (sponsor from Sweden, Helle Toldbod from CTO, Marianne E and Birgitte S from the GCP-unit) Not only to discuss monitoring it was just a small part of the meeting But among others - it was decided to use the Nordic Monitoring Network, NORM to identify monitors in Norway, Sweden, Finland and Denmark At this point the monitoring guideline including RAT wasn t available yet t was planned that before the next meeting sponsor should send his proposal for a monitoring plan and that the GCP-unit should use this to prepare a draft for a monitoring plan AU UNVERSTET HEATH BRGTTE ORK SCHEMMER GCP-KOORDNATOR 22. OKTOBER 2015
PHEMON TRA MEETNG SEPT. 2014 Second trial meeting in Aarhus (sponsor from Sweden, Helle Toldbod from CTO, legal advisor Susanne Kudsk, Marianne E and Birgitte S from GCP-unit) Again monitoring was just a part of the agenda The Danish risk assessment template was prepared for discussion before the meeting t was filled in by Marianne and With several questions to discuss ssues to think about The documents were sent to sponsor and CTO (Helle Toldbod) ahead of the meeting AND. AU UNVERSTET HEATH BRGTTE ORK SCHEMMER GCP-KOORDNATOR 22. OKTOBER 2015
WHAT CAME UP N SEPT. 2014? ength of monitoring period: 2 yrs inclusion period (2015-2016) + 3 yrs follow-up period (2017-2019). n total 5 yrs. Organisation: A responsibility split should be prepared Data: Comparable results: Use of Deauville criteria for PET evaluations will be added to the protocol and to the CRF A comment field should be available in the CRF for registration of protocol deviations t was discussed if monitoring should be performed on any parts of the MRD data? e.g. manual data entry AU UNVERSTET HEATH BRGTTE ORK SCHEMMER GCP-KOORDNATOR 22. OKTOBER 2015
WHAT CAME UP N SEPT. 2014? Sponsor will select the inclusion/exclusion criteria which should be monitored. Biobanking was discussed Study drug was discussed Safety: An instruction for AE/SAE reporting should be prepared because this section in the protocol is complicated to read/understand due to the 2 companies requests of specific wordings. A list of contraindicated medicines which the monitors should check will be prepared by sponsor AU UNVERSTET HEATH BRGTTE ORK SCHEMMER GCP-KOORDNATOR 22. OKTOBER 2015
Contact to monitors E-mail to monitors via NORM contact list All responded positively nitial cost proposals Decision for local monitors except Sweden: 1 monitor due to economy
PHEMON TRA MEETNG NOV. 2014 Skype meeting between sponsor and CTO Not to discuss monitoring but.. Among others it was decided, that there should be one monitoring plan for all the Nordic countries That the NORM template and guideline should be used That the risk assessment should be prepared by the GCP-unit and forwarded to the participating monitors for comments and their site assessment AU UNVERSTET HEATH BRGTTE ORK SCHEMMER GCP-KOORDNATOR 22. OKTOBER 2015
PREPARATON OF RAT AND NORM MONTORNG PAN Marianne and started all over or at least that's how it felt Working with RAT was a challenge - t took a while to get through it We tried to use the risk assessment already prepared in Danish and the knowledge from the meetings with sponsor and CTO We ended up with a version that was send to sponsor and CTO with more questions to ask and more issues to think about Yes it is a very patient sponsor Nothing new came up from this risk assessment, but the wording in RAT can be used in the monitoring plan AU UNVERSTET HEATH BRGTTE ORK SCHEMMER GCP-KOORDNATOR 22. OKTOBER 2015
PREPARATON OF RAT AND NORM MONTORNG PAN This final version dated 16.03.2015 was send by CTO to all of you who are participating in PHEMON for your comments We didn t get very many comments back why? Maybe because t is always a challenge to comment on a risk assessment if you have never done one yourself You are busy with a lot of other studies and PHEMON is far ahead This was the first study using NORM s RAT Or? AU UNVERSTET HEATH BRGTTE ORK SCHEMMER GCP-KOORDNATOR 22. OKTOBER 2015
CTO thoughts Very convenient to be able to contact all monitors via the NORM network Very convenient to have only one monitoring plan National requirements in appendix 1a: very few issues
National requirements Sweden: Norway: Finland: Denmark: Specifies local SOP to use C signature by patient not any legal representative Specifies local SOP to use Timeline for response to discrepancies Assessment of site s experience Specifies local SOP to use Monitoring costs and invoicing is described Assessment of site s experience
DD WE EARN SOMETHNG? f it is possible, then a risk assessment should always be made in cooperation with sponsor We think the Danish risk assessment helped sponsor to think about some issues in the protocol and in the preparation of study procedures As we can see RAT didn t add anything extra to this, but probably would have, if it had been the first risk assessment To be able to use RAT takes some practice especially the first couple of times But it is a great guideline with a lot of explanation But be prepared it is very time consuming AU UNVERSTET HEATH BRGTTE ORK SCHEMMER GCP-KOORDNATOR 22. OKTOBER 2015
CTO conclusion Be prepared we want to do it again
AU UNVERSTET