An Observational Post-Marketing Safety Registry of Sativex®

The objectives of this multi-centre, observational program are to evaluate the long-term safety of Sativex® with special regard to the following:

• The potential for addiction, abuse and misuse for illegal purposes
• The potential for long-term psychiatric effects including suicidality and psychosis
• The potential for mood changes / psychological effects (such as confusion / disorientation)
• The potential for memory impairment
• The effect on driving ability
• The potential for falls
• The use of MS concomitant medications

All physicians who are prescribing Sativex® in the UK and those from specialist neurology centres in Germany and Sweden will be invited to participate in the registry and will be provided with information regarding the background and objectives of the study. The prescribing physician will be asked to enter the following information via electronic Case Report Forms (CRF) at 6 monthly intervals for up to 24 months for any one patient:

Sativex® Use:

• Was Sativex® prescribed for Spasticity in MS? (Yes/No). If no, specify then indication for prescribing Sativex®
• Year of Spasticity diagnosis (Germany/Sweden only)
• Sativex® start date
• Sativex® daily dose (average, minimum and maximum)
• Date of last prescription
• Is Sativex® providing worthwhile benefit? (Yes/ No/ Don't Know)
• Has Sativex® been stopped permanently? (Yes /No). If yes, reason for stopping is to be provided.
• Sativex® stop date

Adverse Events (AE):

• Have any clinically significant adverse events been reported for this patient since they started taking Sativex® (initial record); did any clinically significant adverse events occur, or were ongoing, during this period (follow-up records) (If yes, the details are recorded on an AE form)
• Has the patient sought medical attention because of a fall related injury; since they started taking Sativex® (initial record); during this period (follow-up records) (If yes, the details are recorded on an AE form)
• Has the patient experienced any suicidal thoughts or attempted suicide; since they started taking Sativex® (initial record); during this period (follow-up records) (If yes, the details are recorded on an AE form)
• Has the patient experienced any other significant psychiatric or psychotic events; since they started taking Sativex® (initial record); during this period (follow-up records) (If yes, the details are recorded on an AE form)
• Has the patient reported any change in their driving ability; since they started taking Sativex® (initial record); during this period (follow-up records)
• Improved
• No change
• Deteriorated
• Not appropriate

Supporting Information:

• Medical History relevant to adverse events
• What other Spasticity medications have previously been used and are now stopped permanently (baclofen, tizanidine, benzodiazepines, gabapentin, botulinum toxin) (Germany/Sweden only)
• Changes to other MS symptom medications; since they started taking Sativex® (initial record); during this period (follow-up records)?

Survival status:

• Is the patient currently alive? If no, date of death and cause of death.
• Was the death due to suicide (Yes/No)

Paper CRF will also be available and will subsequently be entered into the electronic CRF database.

The data from the Registry will be analysed descriptively and collated into summary tables and listings.

A Registry report based upon the data summaries will be included within the Periodic Safety Update Reports for Sativex® and the results will be submitted to the appropriate Regulatory Agencies within 60 days of the data summaries tables and listings becoming available.

Each six monthly report and the data tables and listings will be reviewed by an independent Sativex® Registry Advisory Board and a summary overview will be prepared by the committee.

A final Registry report will be assembled within 180 days of the final study data being available.

Any significant safety issues identified will be communicated to the relevant Regulatory Agencies immediately.