Protocol Title : A Randomised, open labelled study in anti ... - EME
Protocol Title : A Randomised, open labelled study in anti ... - EME
Protocol Title : A Randomised, open labelled study in anti ... - EME
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6.6 Urgent Safety Measures<br />
The CI may take urgent safety measures to ensure the safety and protection of the cl<strong>in</strong>ical trial<br />
subjects from any immediate hazard to their health and safety, <strong>in</strong> accordance with Regulation 30.<br />
The measures should be taken immediately. In this <strong>in</strong>stance, the approval of the Licens<strong>in</strong>g<br />
Authority Approval prior to implement<strong>in</strong>g these safety measures is not required. However, it is the<br />
responsibility of the CI to <strong>in</strong>form the sponsor, Ma<strong>in</strong> Research Ethics Committee (via telephone) and<br />
the MHRA (via telephone for discussion with the medical assessor at the cl<strong>in</strong>ical trials unit) of this<br />
event immediately.<br />
The CI has an obligation to <strong>in</strong>form both the MHRA and Ma<strong>in</strong> Ethics Committee <strong>in</strong> writ<strong>in</strong>g with<strong>in</strong> 3<br />
days, <strong>in</strong> the form of a subst<strong>anti</strong>al amendment. The sponsor (JRMO) must be sent a copy of the<br />
correspondence with regards to this matter.<br />
6.7 Development Safety Update Report<strong>in</strong>g (DSUR)<br />
The Annual Safety Reports (ASR) will be sent by the CI to the sponsor, the MREC and MHRA (the<br />
date of the anniversary is the date on the “notice of acceptance letter” from the MHRA) us<strong>in</strong>g the<br />
ASR form. The CI will carry out a risk benefit analysis of the IMPs encompass<strong>in</strong>g all events hav<strong>in</strong>g<br />
arisen on the trial.<br />
The CI will send the Annual Progress Report to the ma<strong>in</strong> REC us<strong>in</strong>g the NRES template (the<br />
anniversary date is the date on the MREC “favourable op<strong>in</strong>ion” letter from the MREC) and to the<br />
sponsor.<br />
6.8 Overview of the Safety Report<strong>in</strong>g and Pharmacoviligance responsibilities<br />
The CI/PI has the overall pharmacovigilance oversight responsibility. The CI/PI has a duty to<br />
ensure that pharmacovigilance monitor<strong>in</strong>g and report<strong>in</strong>g is conducted <strong>in</strong> accordance with the<br />
sponsor’s requirements.<br />
Please outl<strong>in</strong>e the process/organisation with<strong>in</strong> the <strong>study</strong> team to ensure that all SAE/SUSAR<br />
report<strong>in</strong>g is conducted <strong>in</strong> accordance with the sponsor’s timel<strong>in</strong>es. Display this <strong>in</strong>formation with<strong>in</strong><br />
an organogram to be located <strong>in</strong> the appendices <strong>in</strong> section 15 to ensure that there is a clear and<br />
dist<strong>in</strong>ct report<strong>in</strong>g process outl<strong>in</strong>ed with the <strong>study</strong> members detailed with<strong>in</strong> this process.<br />
6.9 Pregnancy<br />
If a patient becomes pregnant whilst <strong>in</strong>volved <strong>in</strong> a CTIMP, it is not considered to be an SAE or an<br />
AE. However, it is an event that requires monitor<strong>in</strong>g and follow up. If a patient, or his partner,<br />
becomes pregnant whilst enrolled <strong>in</strong> a CTIMP <strong>in</strong> which the foetus has been exposed to an<br />
<strong>in</strong>vestigational medic<strong>in</strong>al product, immediate report<strong>in</strong>g to the sponsor is required (with<strong>in</strong> one<br />
work<strong>in</strong>g day of the PI/CI becom<strong>in</strong>g aware of the event) us<strong>in</strong>g a JRMO pregnancy template form.<br />
The CI/PI has the responsibility to ensure that the pregnancy form is completed and sent to the<br />
sponsor with<strong>in</strong> the agreed timel<strong>in</strong>es. Please state whether the patient can cont<strong>in</strong>ue on the <strong>study</strong> or<br />
whether the patient has to be prematurely withdrawn from the <strong>study</strong> here.<br />
The PI/CI also must follow up the pregnancy until delivery as well as monitor<strong>in</strong>g the development<br />
of the newborn for the appropriate time (please <strong>in</strong>dicate for this IMP) after birth. Any events that<br />
occur dur<strong>in</strong>g this time that could be considered to be a SAE must be reported to the sponsor <strong>in</strong> l<strong>in</strong>e<br />
with section 6.2.1, utilis<strong>in</strong>g the sponsor SAE report<strong>in</strong>g form.<br />
7 STATISTICAL CONSIDERATIONS<br />
7.1 Primary Endpo<strong>in</strong>t Efficacy Analysis<br />
Treatment response assessed us<strong>in</strong>g the Cl<strong>in</strong>ical Disease Activity Index (CDAI) at 6 months, and at<br />
each monthly assessment to 12 months follow up. Section 5.7.3, def<strong>in</strong>es treatment response /<br />
failure criteria. The primary analysis will focus on whether there is a superiority of Tocilizumab over<br />
Rituximab <strong>in</strong> histologically def<strong>in</strong>ed ‘B cell poor patients’.<br />
Study: R4RA EudraCT: 2012-002535-28 30 / 34