Predicting Response to Depression Treatment (PReDicT)
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional

Summary: 
      Depression is a very common, serious and in some cases life-threatening condition, affecting
      around 350 million people globally. Approximately 11% of citizens in the European Union
      suffer from depression at some point in their lives. Depression is associated with
      significant socio-economic costs and has been predicted to become the greatest cause of
      disability worldwide by 2030 . In 2010 it was estimated that there were approximately 30
      million patients with depression in Europe, with aggregated economic costs of approximately
      €92 billion . Improvements in managing the treatment of depression are urgently needed to
      improve patient outcomes, contain rising healthcare costs, improve workplace productivity and
      help to address global economic and societal challenges.

      While a range of effective antidepressant medications are available to treat depression, it
      takes 4-6 weeks after starting antidepressant treatment before a physician can detect whether
      the treatment is working. However, surprisingly, more than 50% of patients fail to respond to
      the first antidepressant treatment they are prescribed. Therefore, it often takes several
      months to identify an effective antidepressant treatment for the majority of patients with
      depression. During this time a patient's ability to work and function socially is severely
      impaired. Individuals may be absent from work for many weeks or months and this places a
      substantial burden on the economy and on healthcare resources.
    

Detailed description: 
      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).
    

Intervention name(s): PReDicT Test; Treatment as Usual
Intervention type(s): Device; Other
Intervention description(s): PReDicT Test, when completed 7-9 days after starting antidepressant treatment, is able to predict a patient's subsequent response to that antidepressant treatment 4-6 weeks later; Patients treated by the clinician conventionally using signs and symptoms to determine treatment changes or medication changes.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment