Predicting Response to Depression Treatment (PReDicT)

The study is a randomized, two-arm, multi-centre, open label, clinical investigation of a medical device, the Predicting Response to Depression Treatment Test (PReDicT Test) . It will be conducted in depressed patients in primary care settings in five European countries (UK, France, Spain, Germany and the Netherlands).

The study is divided into an 8 to 10 week clinical phase and a 40 week follow-up phase. Each participant will be in the study for a total of up to 48-50 weeks.

During the clinical phase, participants will attend between 2 and 4 study visits, depending on their study arm and their response to treatment. Some of these visits may be conducted by telephone. Participants will also complete weekly online questionnaires from home.

During the follow-up phase participants will complete online questionnaires from home every 4 weeks over a 40 week period. Study visits will not be required during the follow-up phase.

An electronic Patient Reported Outcomes (ePRO) system, accessed via a study website, will be used to collect questionnaire data and PReDicT Test responses. The ePRO system will be used to randomise participants and will issue email reminders to participants and study researchers when study-related activities are due.

Visit 1: Screening and PReDicT #1 The visit will take place at the study site 0 to 7 days after the SSRI was prescribed. Visit 1 may take place on the same day as the Selective Serotonin Reuptake Inhibitor (SSRI) was prescribed only if local approvals permit this to happen. Informed Consent must be obtained before any study procedures are performed. Visit duration will be approximately 90 minutes.

The following will take place at Visit 1:

• Informed Consent
• Unique participant screening number assigned
• Demographics (including age, gender, ethnicity, number of years in higher education, family history of depression)
• Depression history (as applicable), including age at first episode, number of past episodes of depression and time since last episode
• Brief medical history
• Medication history (current medication, medication taken over the past month, any available information on previous antidepressant medications)
• Entry criteria check Participants that do not meet the entry criteria ('screen failures') will leave the study.

Participants that meet the entry criteria will complete the following activities in the order below:

• Montgomery-Åsberg Depression Rating Scale (MADRS)
• Registration of participant on the Electronic Patient Reported Outcomes(ePRO) system (by study researcher)
• Participant creates ePRO system account
• PReDicT Test (which includes the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR-16) questionnaire from which baseline QIDS-SR-16 scores are obtained)
• Randomisation (by the ePRO system)
• 5 dimensional - 5 Level quality of life questionnaire (EQ-5D-5L)
• Health Economics Questionnaire (HEQ)
• Oxford CAPabilities questionnaire-Mental Health (OxCAP-MH) (UK and Germany only)
• Social Adjustment Scale - Self-Report (screen version) (SAS-SR (screen version))
• Generalised Anxiety Disorder Questionnaire, 7 item version (GAD-7)
• Digit Symbol Substitution Test (DSST)
• Adverse Events (AEs), Adverse Device Effects (ADEs) and device deficiencies will be recorded from the signing of the ICF and continue until week 8.

At the end of the visit, enrolled participants will be asked to start their prescribed SSRI. Dose and frequency will be as prescribed by their physician.

Visit 2 is only required for participants in the PReDicT arm.

• This visit will take place after PReDicT #2 has been completed. It will preferably take place within 1 day (same day is permissible). The visit may be conducted by telephone (if permitted locally) or at the study site. Visit duration will be approximately 5-10 minutes. The following will take place.
• A study researcher will review the PReDicT Test results online.
• If the PReDicT Test results indicate a positive response to the prescribed antidepressant:

• Antidepressant treatment is not changed.
• The next study visit is Visit 4 (there is no Visit 3 for this participant).
• If the PReDicT Test results indicate an insufficient response to the prescribed antidepressant:

• Antidepressant treatment is altered (by a physician) in accordance with locally appropriate guidelines and judgement of the physician (i.e. normally the dose of the current medication is increased).

Visit 3 is only required for participants in the PReDicT arm who have completed PReDicT #3. This visit will be the same as Visit 2.

Visit 4 (All Participants) The visit will take place 8-10 weeks after starting antidepressant treatment. Visit duration will be approximately 60 minutes. All participants will then continue into the online follow-up phase of the study.

The following Visit 4 activities must be completed at the study site and will take approximately 30 minutes.

• MADRS
• Number and dates of non-study clinical visits for depression since Visit 1
• Review of antidepressant medication compliance. Document all changes to dose or type of antidepressant. Refer to ePRO system data. Ensure any discrepancies between eCRF data and ePRO data are explained
• Review of concomitant medication since last visit
• Review of AEs, ADEs and device deficiencies
• Serious Adverse Events (SAEs) and device-related incidents will be followed up as set out in Section 10.0, Adverse Event Reporting. Non-serious AEs will be followed up at the study physician's discretion The following Visit 4 online questionnaires may be completed at home or at the study site. They can take place before or after the other Visit 4 activities. Questionnaires will take approximately 30 minutes to complete.
• QIDS-SR-16
• EQ-5D-5L
• HEQ
• OxCAP-MH (UK and Germany only)
• SAS-SR (screener version)
• GAD-7
• DSST
• Patient Acceptability Questionnaire An email reminder will be sent to each participant at 8 weeks. An alert will be emailed to the study researcher after 2 days if the questionnaire(s) have not been completed. Researchers should contact the participant as soon as possible and ask them to complete the missing questionnaire(s).

Participants will complete the following online questionnaires every 4 weeks for 40 weeks, starting 4 weeks after Visit 4. The questionnaires take approximately 15 minutes (total) to complete.

• QIDS-SR-16
• EQ-5D-5L
• HEQ Participants will complete the following online questionnaires at week 24 and week 48 of the study.
• OxCAP-MH (UK and Germany only)
• SAS-SR (screener version) For all online questionnaires, an email reminder will be sent to each participant on the day that completion of the questionnaires is due. The email will include a link to the questionnaires on the ePRO system.

An alert will be emailed to the study researchers after 2 days if the questionnaire(s) have not been completed. A researcher will contact the participant as soon as possible and ask them to complete the missing questionnaire(s).

To improve study participation and reduce drop-outs, participants in the PReDicT arm of the study will be able to view their QIDS-SR-16 scores on the ePRO system from Visit 4 up to and including the final online follow-up (Follow-Up #10, occurring 40 weeks after Visit 4).

Prescribing physicians and (if relevant) support staff at each study site will be asked to complete a Healthcare Provider Acceptability Questionnaire at around the time that the final participant at their study site completes Visit 4.

The Healthcare Provider Acceptability Questionnaire is a 40-item questionnaire covering their experience of taking part in the study, their experience of using the PReDicT Test in the study and their future intentions regarding the use of the PReDicT Test. Additional space is provided for free-text comments.

In England and Germany, digitally recorded semi-structured interviews will be performed with maximum variance samples of participants (patients), prescribing physicians and (if relevant) support staff. Interviews will be conducted by fluent speakers of English and/or German (as appropriate) and may be carried out face-to-face or by telephone/Skype.

Interviewees will be selected in such a way that there is appropriate representation of factors including age, gender, questionnaire responses, full- and part-time staff, urban and rural location and high/low/non-recruiting study sites.

Approximately 15 to 20 participants, 20-25 prescribing physicians and a small number of support staff (if relevant) will be interviewed. Interviews will be conducted by trained researchers and will take place during and after completion of the clinical phase of the study, depending on whether participants or study staff are being interviewed. Participants will be recruited for interview within 1 to 2 months after they have completed Visit 4. Prescribing physicians and support staff will be interviewed after the end of the clinical phase at their study site (when all participants have been recruited).

Inclusion criteria

• Male or female aged between 18 and 70 inclusive.
• Diagnosed with a depressive episode by a physician (either first episode or recurrent) and requiring treatment with a selective serotonin reuptake inhibitor (SSRI) medication (excluding fluoxetine).
• Prescribed an SSRI by a physician for the treatment of depression within 7 days prior to Visit 1, but has not yet started taking medication.
• Is intending to start SSRI treatment within 7 days of Visit 1.

Exclusion criteria

• Previous history of mania.
• Is currently taking an antidepressant medication or has stopped antidepressant treatment within 2 weeks prior to Visit 1.
• Requires immediate referral to alternative mental health services (e.g. where a patient seen in primary care is referred to secondary care services).
• Presents to a physician with significant current suicidal intent requiring enhanced care.