Pharmacogenomic Testing to Optimize Antidepressant Drug Therapy

Study Overview
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Brief Summary
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A randomized controlled trial comparing pharmacogenomic guided versus standard pharmacist care to optimize antidepressant drug therapy. This study evaluates the effectiveness of pharmacists utilizing pharmacogenomic testing in the community pharmacy setting to help patients find the most appropriate drug therapy option(s) and minimize the risk of side effects in collaboration with prescribing physicians.

Detailed Description
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Physicians and pharmacists have long been aware of subtle differences between patients in their responses to medications, but until recently did not have the tools to predict a patient's response to a drug before prescribing it. Many commonly prescribed medications are either ineffective or cause significant side effects for some patients. Individual variation in response to prescription drugs due to genetic factors (pharmacogenetics) is a substantial part of this serious clinical issue. Such variation in patient response ranges from failure to benefit from a drug, to adverse drug reactions, and drug-drug interactions when several drugs are taken at the same time. After years of uncertainty over the value of personalized medicine, recent studies show promising approaches for incorporating pharmacogenetics (PGx) data into routine patient care in order to reduce medication issues due to genetic factors. Over the last decades, clinical PGx research has made significant progress in defining which genetic variations are important for influencing inter-patient variability in drug response. Evidence-based consensus therapeutic guidelines for multiple drug-gene pairs are available and promoted by the Clinical Pharmacogenetic Implementation Consortium (CPIC). Although the primary focus of PGx testing has been on improving drug selection and dosing, a secondary benefit of testing is the improvement of medication adherence. GeneYouIn has developed the Pillcheck® drug response test that provides personalized insights on a patient's predicted response to medications. To implement the Pillcheck test, GeneYouIn is working with pharmacists who are adept in understanding pharmacogenetic terminology and can consult with prescribing physicians and patients within current scope of practice. GeneYouIn will provide educational seminars on the latest advances in pharmacogenetics and using the Pillcheck report. This demonstration project will provide critical education to clinical pharmacists to enable utilization of patients' pharmacogenetic data for evidence-base treatment optimization. The Pillcheck report has been carefully designed to make it easy to interpret and integrate in the clinical pharmacy setting. The study will provide insights on the impact of pharmacogenetics testing on solving Drug Therapy Problems. The Pillcheck test assesses variations in 14 genes responsible for drug transport and metabolism for over 140 commonly prescribed medications. The Pillcheck report can enable pharmacists to effectively identify Drug Therapy Problems and advise physicians on personalized treatment options thus allowing for more rational medication choices and/or dosing.

Official Title
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A Randomized Controlled Trial of Pharmacogenomic Guided Versus Standard Pharmacist Care to Optimize Antidepressant Drug Therapy in a Community Pharmacy Setting

Conditions
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Depression, Anxiety, Major Depressive Disorder, Generalized Anxiety Disorder, Mood Disorders

Intervention / Treatment
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* Other: Pharmacogenomic Testing
* Other: Pharmacist Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prescribed one or more antidepressants Diagnosed with major depressive disorder and/or generalized anxiety disorder Newly initiated on antidepressant therapy or a recent change in therapy and dissatisfied with therapy. Experiencing adverse drug reaction(s) or suboptimal response or dissatisfaction with therapy Demonstrated dissatisfaction based on a 9-item prescreening questionnaire. Scoring range from 0='not at all' to 4='very much'. If any scores for Q1-3 on side effects >2, or if any scores for Q4-6 on effectiveness <2, or if any scores for Q7-9 on overall opinion of therapy <2. [Q1. Side effects interfere with my physical activity, Q2. Side effects interfere with my leisure activities, Q3. Side effects interfere with my daily activities, Q4. The medicine I am taking reduces my symptoms, Q5. I am satisfied with the time it takes for the medicine to start to have an effect, Q6. I feel better now than I did before starting the treatment, Q7.I intend to continue using this treatment, Q8. I feel happy with my treatment, Q9. In general, I feel satisfied with the treatment.] Exclusion Criteria: Patients with poor command of English or who are unable to provide fully informed consent Liver transplant patient (cheek swab won't detect liver DNA) Non-adherent to prescribed drug therapy due to reasons outside of not feeling better (non-medical influencing factors) Diagnosis of schizophrenia, bipolar disorder, dementia Patients under 18 years old

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: Enrolled subjects will be randomly assigned to either the control arm (pharmacist standard of care) or intervention arm (pharmacogenetic guided decision making by the pharmacist) in optimizing antidepressant drug therapy. Randomization is done by the primary investigator who isn't directly involved with patient consultations.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention<br>Pharmacist optimizing antidepressant therapy using the patient's personalized pharmacogenomic report to make recommendations. | Other: Pharmacogenomic Testing<br>* pharmacogenomic drug response test provides personalized insights on a patient's predicted response to medications based on metabolism<br>* Other names: Geneyouin;|
| Placebo Comparator: Control<br>Pharmacist optimizing antidepressant therapy based on standard of care | Other: Pharmacist Standard of Care<br>* Pharmacist providing standard of care as per usual practice<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Satisfaction with Medicines Questionnaire (SATMED-Q) - general measure of satisfaction to drug therapy | This scale evaluates patient satisfaction of drug treatment for with any chronic disease. It's a brief, self-administer multidimensional generic questionnaire comprising 17 items. There are six categories of questions assessing satisfaction of (1) drug efficacy, (2) side-effects, (3) convenience of use, (4) medical care, (5) impact on activities of daily living and (6) general satisfaction. Scores of individual items range from 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A higher total score is an indication of greater satisfaction with drug therapy. Only scores from the side effects category would be summed as negative values. There is no recommended cutoff score, however is used to monitor the overall satisfaction to treatment over the period of the study. | Change of score from baseline to 6 months | 
| Patient Health Questionnaire (PHQ-9) - measure/monitor the severity of depression | PHQ-9 is a clinical evidence-based scale used to assess the severity of depression. There are nine diagnostic criteria for major depression based on the Diagnostic and Statistical 4th Ed. (DSM-IV) which are scored '0' (not at all), '1' (several days),'2' more than half the days, '3' (nearly every day). The nine items cover experience of pleasure, feeling down, sleep disruption, energy levels, appetite, feeling a failure, trouble concentrating, speaking slowly or being fidgety and having negative thoughts around suicide or self-harm over the previous 2 weeks. The total sum indicates depression severity: 0-4 none, 5-9 mild, 10-14 moderate, 15-19 moderately severe, 20-27 severe. | Change of score from baseline to 6 months | 
| Generalized Anxiety Disorder-7 (GAD-7) - measure/monitor the severity of anxiety | Evidence-based questionnaire used to monitor the severity of generalized anxiety. The GAD-7 score is calculated by assigning scores of '0' (not at all), '1' (several days),'2' more than half the days, '3' (nearly every day). Questions assess the tendency of feeling nervous, not being able to stop or control worrying, worrying too much about different things, trouble relaxing, being so restless that it's hard to sit still, becoming easily annoyed or irritable, feeling afraid as if something awful might happen. Total sums of 5, 10, and 15 represent mild, moderate, and severe anxiety, respectively. | Change of score from baseline to 6 months | 
| Sheehan Disability Scale - measure of functional impairment in work/school, social life, and family life | This scale assesses functional impairment using three 0 to 10 point visual analog scales. This can also be interpreted as percentages. Each of the three scales would have the patient represent how have their symptoms disrupted (1) work/school life, (2) social life, and (3) family life/responsibilities. The points from the 3 scales are summed as a global functional impairment score ranging from 0 (unimpaired) to 30 (highly impaired). There is no recommended cutoff score, however is used to monitor the response to treatment over the period of the study. In general, a score of 5 or greater on any of the three scales is associated with significant functional impairment. | Change of score from baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of pharmacist identified drug therapy problems | Total number of Drug Therapy Problems related to antidepressant use identified by the pharmacist include the following types (1) Dose too high/overuse/abuse, (2) Dose too low, (3) Unnecessary drug therapy/duplication, (4) Adverse drug reaction / drug interaction, (5) Requires additional drug therapy, (6) Non-adherence, (7) Inappropriate drug for indication | Analysis done at the completion of study ( 1 year) | 
| Prescriber acceptance rate of pharmacist's recommendations | Percentage of prescriber accepted pharmacist recommendations in the intervention group vs. control group | Analysis done at the completion of study ( 1 year) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacogenetics, pharmacogenomics, antidepressants, pharmacy, pharmacist, community