Implementation of a Decision Support System and Its Effect on Early Optimisation of Lipid-Lowering Therapies in Patients With Acute Coronary Syndrome: a Cluster Randomised Controlled Trial
Phase: NA
Conditions: Acute Coronary Syndrome, Myocardial Infarction
Sponsor: Imperial College London



ZODIAC 
Imperial College London 
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7.3 Causality  
The assignment of causality for adverse events should be made by the investigator 
responsible for the care of the participant using the definitions in the table below.  
If any doubt about the causality exists the local investigator should inform the study 
coordination centre who will notify the Chief Investigator. The pharmaceutical companies 
and/or other clinicians may be asked to advise in some cases.  
In the case of discrepant views on causality between the investigator and others, all parties 
will discuss the case. In the event that no agreement is made, the MHRA will be informed of 
both points of view.  
Since participants should be receiving standard of care, safety events will be recorded only 
if causality to the device is deemed definite.  
 
Unrelated: 
No evidence of any causal relationship 
Unlikely: 
There is little evidence to suggest there is a causal relationship (e.g. the 
 
 
event did not occur within a reasonable time after administration of the trial 
 
 
medication). There is another reasonable explanation for the event (e.g. 
 
 
the patient’s clinical condition, other concomitant treatment). 
Possible: 
There is some evidence to suggest a causal relationship (e.g. because the 
 
 
event occurs within a reasonable time after administration of the trial 
 
 
medication). However, the influence of other factors may have contributed 
 
 
to the event (e.g. the patient’s clinical condition, other concomitant 
 
 
treatments). 
Probable: 
There is evidence to suggest a causal relationship and the influence of 
 
 
other factors is unlikely. 
Definite: 
There is clear evidence to suggest a causal relationship and other possible 
 
 
contributing factors can be ruled out. 
 
7.4 Severity  
Mild:  
Awareness of event but easily tolerated 
Moderate: Discomfort enough to cause some interference with usual activity 
Severe: 
Inability to carry out usual activity 
 
7.5 Recording  
For the purposes of the study, ADEs will be followed up according to local practice until the 
event has stabilised or resolved. SADEs will be recorded throughout the study. 
 
7.6 Reporting of SADEs 
All SADEs occurring during the study must be reported to the Sponsor within 24 hours via 
zodiac.study@imperial.ac.uk AND RGIT@imperial.ac.uk as detailed in the study-specific 
procedure manual, and only if causality to the device is deemed definite. 
 

ZODIAC 
Imperial College London 
V.3 17 JAN 24 
 
Confidential 
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All SADEs will be reviewed by the Chief Investigator or a designated medically qualified 
representative to confirm expectedness and causality. Reporting of SADEs and review by 
the CI/medical monitor will be via the electronic CRF.  
 
In addition, in the UK all reportable SADE’s must be emailed to the MHRA at 
aic@mhra.gov.uk, using either the MEDDEV 2.7/3 SAE reporting table, or the MDCG 2020-
10/2 SAE reporting table.  
 
Events which indicate an imminent risk of death, serious injury or serious illness and 
require prompt remedial action for other patients, users or other persons or a new finding 
to it, must be reported to the MHRA by the ICTU Study Manager immediately but not later 
than 2 calendar days following the date the Sponsor is made aware. 
 
Any other reportable events should be reported immediately but not later than 7 calendar 
days following the date the Sponsor is made aware. 
In the UK, for USADEs, reports should be made to the REC within 15 days according to 
HRA website (via Investigator using specific form on website – non-CTIMP trials). 
The Study Manager should also notify the Device Manufacturer and Investigators at all 
sites of the USADE.  
 
 
In Spain and Italy, local ethical and regulatory requirements should be adhered to.  
 
7.7 Developmental Safety Update Reports / Annual Safety Reports / Quarterly 
Reports 
Developmental Safety Update Reports (DSUR) / Annual Safety will be submitted to the 
Sponsor, the Ethics Committee and Regulatory Authority in accordance with local / 
national regulatory requirements. 
In the UK, quarterly summary reports of all SADE’s must also be submitted to the MHRA 
via aic@mhra.gov.uk   in the format detailed in the study-specific procedure manual.  
In Spain and Italy, local regulatory requirements should be adhered to. 
7.8 Reporting urgent safety measures  
If any urgent safety measures are taken the CI/Sponsor shall immediately and in any event 
no later than 3 days from the date the measures are taken, give written notice to the 
regulatory authority and the relevant REC of the measures taken and the circumstances 
giving rise to those measures.