Personalise Antidepressant Treatment for Unipolar Depression Combining Individual Choices, Risks and Big Data

Study Overview
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Brief Summary
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PETRUSHKA is aimed at developing and subsequently testing a personalised approach to the pharmacological treatment of major depressive disorder in adults, which can be used in everyday NHS clinical settings. We have collected data from patients with major depressive disorder, obtained from diverse datasets, including randomised trials as well as real-world registries (registers that hold routinely collected NHS data from the UK). These data summarise the most reliable and most up-to-date scientific evidence about benefits and adverse effects of antidepressants for depression and have been used to inform the PETRUSHKA prediction model to produce individualised treatment recommendations. The prediction model underpins a web-based decision support tool (the PETRUSHKA tool) which incorporates the patient's and clinician's preferences in order to rank treatment options and tailor the treatment to each patient. This trial will recruit participants from the NHS within primary care in England and investigate whether the use of the PETRUSHKA tool is better than 'usual care' treatment in terms of adherence to antidepressant treatment, clinical response and quality of life, and its cost-effectiveness over a 6-months follow up.

Detailed Description
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The PETRUSHKA tool, employs a bespoke algorithm to identify the best antidepressant for each individual patient. The algorithm: (a) is based on a prediction model which uses a combination of advanced analytics (statistics) and machine learning methods (artificial intelligence); (b) uses a dataset which is a combination of real-world data (QResearch: https://www.qresearch.org/) from over 1 million primary care patients with depression in England and Wales, and individual participant data from about 40,000 patients recruited in randomised controlled trials; (c) incorporates preferences from patients and clinicians (especially about adverse events); (d) generates a ranked list of personalised treatment recommendations that will inform the clinical discussion between clinicians and patients, and the final treatment decision. The clinical decision aid tool is implemented in the form of a web-based application, accessible from any computer or tablet.

Official Title
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Personalise Antidepressant Treatment for Unipolar Depression Combining Individual Choices, Risks and Big Data

Conditions
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Depression

Intervention / Treatment
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* Other: PETRUSHKA tool
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 - 74 years inclusive; Willing and able to give informed consent for participation in the trial; Clinical diagnosis of depression (either single episode or recurrent), for which an antidepressant is clinically indicated; Willing to start antidepressant treatment as monotherapy; Able to read/understand and/or complete self-administered questionnaires online in English; Willing to meet any clinical requirements related to taking a specific medication Exclusion Criteria: Prescribed any antidepressant in the preceding 4 weeks; Current or historical diagnosis of ADHD, Alcohol/Substance Use Disorder, bipolar disorder, dementia, eating disorders, mania/hypomania, OCD, PTSD, psychosis/schizophrenia, Treatment Resistant Depression (having tried 2 or more antidepressants for the same depressive episode at adequate dose and time); Diagnosis of arrhythmias (including Q-T prolongation, heart block), recent MI, poorly controlled epilepsy, acute porphyrias; Require urgent mental care or admission (including suicidal intent/plans); Concurrently enrolled in another investigational medicinal product (IMP) trial or an interventional trial about depression; Participants who are currently pregnant, planning pregnancy or lactating; Has a medical, social or other condition which, in the investigator's opinion , may make the participant unable to comply with all the trial requirements (e.g., terminal illness - motor neuron disease).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PETRUSHKA tool<br>The intervention is the PETRUSHKA web-based App (also called PETRUSHKA tool), a clinical decision-support system that incorporates a personalised evidence-based prediction model with individual patient preferences, to prescribe the best antidepressant to adults with depression | Other: PETRUSHKA tool<br>* In the experimental arm, the PETRUSHKA tool will automatically select the antidepressants that have the best profile in terms of efficacy and acceptability for each individual participant (based on their baseline demographic and clinical characteristics) and then ask the participant to provide their preferences about common (and non-serious) adverse events. Based on patient's preferences and their individual characteristics, the PETRUSHKA tool will then identify the three best antidepressants for the participant. The clinician and the participant will be presented with an overall recommendation (in the format of a pictogram) showing how strongly each antidepressant is recommended for that individual patient. Via a shared decision-making process, the participant and the clinician will then agree on which antidepressant to choose from the shortlist.<br>|
| Placebo Comparator: Usual Care<br>Routine care delivered in the NHS (i.e. selection of the antidepressant based primarily on the clinicians' judgement) termed 'usual care' in this study. | Other: Usual Care<br>* Any antidepressant prescribed by clinician based upon their clinical judgement.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine whether using the PETRUSHKA tool to personalise antidepressant treatment, results in an increased proportion of patients continuing the allocated treatment, compared to usual care. | The number of participants who are still taking the allocated antidepressants after 8 weeks. | 8 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-rated change in depressive symptoms from baseline | Self-rated change in depressive symptoms measured using the 9-item Patient Health questionnaire | Baseline, week 2, 4, 6, 8, 12, 16, 20, 24 | 
| Observer-rated change in depressive symptoms from baseline | Change in depressive symptoms measured using the observer-rated 17-item Hamilton Depression Rating Scale | Baseline, week 2, 4, 6, 8, 12, 16, 20, 24 | 
| The number of participants who discontinue from treatment at 8 weeks due to any cause | Discontinuation from treatment due to any cause | Week 8 | 
| The number of participants who discontinue from treatment at 24 weeks due to any cause | Discontinuation from treatment due to any cause | Week 24 | 
| The number of participants who discontinue from treatment at 8 weeks due to adverse events | Discontinuation from treatment due to adverse events only | Week 8 | 
| The number of participants who discontinue from treatment at 24 weeks due to adverse events | Discontinuation from treatment due to adverse events only | Week 24 | 
| Self-rated change in anxiety symptoms from baseline | Self-rated change in anxiety symptoms measured using the 7-item Generalised Anxiety Disorder Assessment | Baseline, week 2, 4, 6, 8, 12, 20, and 24, | 
| Observer-rated change in anxiety symptoms from baseline | Observer-rated change in anxiety symptoms using the Hamilton Anxiety Rating Scale | Baseline, week 2, 4, 6, 8, 12, 20, and 24, | 
| The impact of depression on quality of life and capability wellbeing | EQ-5D-5L questionnaire (self-rated) | Baseline, week 4,8,12,24 | 
| A reduction in risk of suicidality from baseline | Columbia Suicide Severity Rating Scale (observer-rated), ranging 1-5, where 1 is least severe and 5 is most severe. | Baseline, week 8 and 24 | 
| An improvement in the functional outcome from baseline, with 0 being not at all and with 40 being very severely impaired. | Work and Social Adjustment Scale (self-rated) | Baseline, week 4, 8, 12 and 24 | 
| A change in the health/social care costs of depression (direct and indirect) from baseline | Health Economics Questionnaire (self-rated) | Baseline, week 4,8,12 and 24 |