HOW TO SCREEN PATIENTS AND BOOK THE BASELINE VISIT APPOINTMENT? Trial protocol code: ISRCTN30952488 Version 2, 19 Oct 2017

StatinWISE Patient Recruitment 200 patients will be enrolled 58 GP practices in England and Wales Potentially eligible patients identified from medical records search, opportunistically, and direct advertising

Patient Recruitment A trial designed to investigate if atorvastatin 20mg causes more muscle symptoms than placebo Is your patient complaining/has complained of muscle symptoms due to statins? Does your patient want to stop/has stopped statins because of muscle symptoms? Does your patient think statins are the cause of their muscle symptoms? YES? Your patient may be eligible for the StatinWISE trial Your patient could participate if s/he: is an adult aged 16 or over was prescribed statin treatment in the last 3 years stopped OR is considering stopping statin treatment due to muscle symptoms has normal CK and ALT test results within 3 months of enrolling is able to provide fully informed consent is willing to take a daily capsule for 12 months and report symptoms

Patient Recruitment Overview Site trial staff conduct database search to identify potentially eligible patients (repeated every 1-2 months to identify new patients) + Patients can be identified opportunistically, or respond to direct advertising List of potentially eligible patients is given final approval by StatinWISE practice PI Site trial staff use Docmail to send “mail outs” to patients with trial information and reply slips (expressions of interest – EOIs) which are sent to the CTU CTU informs site trial staff of EOIs or patient contacts practice directly Site trial staff conduct screening call to discuss study and eligibility If patient is interested, and does not have recent CK + ALT results, a blood test is scheduled Site trial staff check for CK + ALT results. If acceptable, they call patient to book Baseline Visit

Identifying patients EMIS database search Eligibility Those stopped statins and [database search], Those considering stopping (waiting room adverts [log at reception] / GP consultation / database search) Issues cant really capture patients considering stopping (opportunistic patients) Questions: Who will run the search How will you manage the Eligibility checking Has this already been sent to you – How many preliminary results came up?

3. Posting the PIS to Patients DOCMAIL instructions are in Folder 1, Section 6 “Data Handling” of the ISF

Docmail: scheduled mailings Instructions – Folder 1, Section 6 “Data Handling” of the ISF mail out 0 (Invitation / newsletter & reply slip ) Be sure to personalise the letters with practice letterhead and contact details mail out 2 (Invitation / PISs & reply slip) mail out 3 (Invitation / PIS / newsletter & reply slip) Questions Do you use Docmail - Log in will be confirmed once we receive your delegation log Who should we sent EOI’s to? All mail packs contain reply slip and return envelope to CTU

Questions Do you use Docmail - Log in will be confirmed once we receive your delegation log Who should we sent EOI’s to?

Screening call guidance Questions Do you use Docmail - Log in will be confirmed once we receive your delegation log Who should we sent EOI’s to?

Baseline visit * Confirming eligibility * Patient attends the site for the Baseline visit with Nurse/GP Nurse/GP goes through PIS, re-explains the trial and answers any questions Informed consent must be recorded on Informed Consent form provided in Section 13 of the Investigator Site File Baseline data is recorded on the database Patient meets all eligibility criteria Patient is randomised Complete the Screening / Randomisation logs Patient changes their mind Patient does not meet all eligibility criteria Patient is not randomised Complete the Screening log * If patient consents to participating in the optional genetic study (separate ICF), a single blood sample is taken and posted using the Safebox provided (see separate presentation) A separate presentation for taking informed consent is available. Question – Who will perform this – are there any questions? Please remember that patients do not have to consent to the genetic study: the consent form is in 2 parts. They can simply consent to the main StatinWISE study only A separate presentation explaining the optional genetic study and its procedure is available. A separate presentation for access to the trial database and how to enter data is available. General Medical Information and re-checking eligibility The trial treatment is posted to patients by the CTU

Baseline visit Detailed instructions on all aspects of conducting the Baseline Visit are included in the MOP A separate presentation for taking informed consent is available. Question – Who will perform this – are there any questions? Please remember that patients do not have to consent to the genetic study: the consent form is in 2 parts. They can simply consent to the main StatinWISE study only A separate presentation explaining the optional genetic study and its procedure is available. A separate presentation for access to the trial database and how to enter data is available. General Medical Information and re-checking eligibility

Baseline visit Detailed instructions on all aspects of conducting the Baseline Visit are included in the MOP A separate presentation for taking informed consent is available. Question – Who will perform this – are there any questions? Please remember that patients do not have to consent to the genetic study: the consent form is in 2 parts. They can simply consent to the main StatinWISE study only A separate presentation explaining the optional genetic study and its procedure is available. A separate presentation for access to the trial database and how to enter data is available. General Medical Information and re-checking eligibility

Baseline visit Detailed instructions on all aspects of conducting the Baseline Visit are included in the MOP A separate presentation for taking informed consent is available. Question – Who will perform this – are there any questions? Please remember that patients do not have to consent to the genetic study: the consent form is in 2 parts. They can simply consent to the main StatinWISE study only A separate presentation explaining the optional genetic study and its procedure is available. A separate presentation for access to the trial database and how to enter data is available. General Medical Information and re-checking eligibility

Baseline visit – guidance Folder 1, Section 6

Statinwise Treatment Atorvastatin 20 mg and matched placebo capsule to swallowed whole anytime once daily double blind 3x 2 months taking statins and 3x 2 months on placebo predetermined random order Treatment will be posted to patients by CTU in 2-months treatment packs – triggered by CTU data base The treatment packs fit through a standard letterbox. A self-addressed envelope is enclosed with each treatment packs for patients to return their used treatment packs at the end of each treatment period

Data Collection: Day 50-56 Daily Symptoms Questionnaire

Data Collection: Day 56 End of Treatment Period Questionnaire

Patient Eligible Overview Patient meets all eligibility criteria Patient provides full informed consent Patient is randomised Train the patient on data collection Complete the Screening log Complete the Randomisation log

Patient Ineligible Overview Patient does not meet all eligibility criteria Patient does not provide full informed consent Patient is not randomised Update the Screening log

CONTACT US London School of Hygiene & Tropical Medicine Room 180, Keppel Street, London WC1E 7HT Tel +44(0)20 7299 4684 Fax +44(0)20 7299 4663 Email: statinwise@Lshtm.ac.uk