Pharmacogenomic Testing in Primary Care

Study Overview
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Brief Summary
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This is a 6-month randomized, wait-listed, controlled pilot trial conducted in 6 department of family medicine (DFM) clinics at the University of Michigan (UM). Physicians practicing at a UM DFM clinical site who are willing to utilize pharmacogenomic (PGx) test results to manage antidepressant use will be enrolled. Patients of these DFM physicians who are adults with a new prescription for a target antidepressant will also be enrolled.

Detailed Description
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This is a 6-month randomized, wait-listed, controlled pilot trial conducted in 6 department of family medicine (DFM) clinics at the University of Michigan (UM). We will enroll physicians practicing at a UM DFM clinical site who are willing to utilize PGx test results in conjunction with treating patients prescribed certain antidepressants. We will also enroll patients of these DFM physicians who are adults with a new prescription for an antidepressant (within the past 4 weeks) including patients who have switched to a new antidepressant from another antidepressant or have added on a new antidepressant to current antidepressant therapy. Patients are excluded if taking an antidepressant for more than 4 weeks or if they have had PGx testing in the past. Patients will be randomized to either an intervention or control group. Patients in the intervention group will have PGx test results available soon after enrollment while the control patients will have test results available 3 months after the first visit. All patients will complete a baseline, 3-, and 6-month assessment; control patients will have an additional 9-month assessment. Data to be collected include symptoms and severity (PHQ-8, GAD7), functional health status (SF-12), PGx knowledge, work status changes, demographic information, physician and emergency department visits, adverse effects, and medication alterations and adherence.

Official Title
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Determining the Feasibility, Acceptability, and Preliminary Effectiveness of Pharmacogenomic Testing in Primary Care

Conditions
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Antidepressants Causing Adverse Effects in Therapeutic Use

Intervention / Treatment
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* Diagnostic Test: PGx test


Participation Criteria
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Eligibility Criteria
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Physician participants Inclusion criteria: Be a practicing physician at a University of Michigan Department of Family Medicine clinic Be willing to use PGx test results for their patients enrolled in the study Be willing to allow study staff to contact their patients Self-report that they are willing to prescribe antidepressants Exclusion criteria: -Do not meet inclusion criteria Patient Participants Inclusion: Be a patient of a participating physician Have a new prescription for one of the following antidepressant medications: citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Prozac Weekly, Rapiflux, Sarafem, Selfemra), fluvoxamine (Luvox, Luvox CR), paroxetine (Paxil, Paxil CR), sertraline (Zoloft), duloxetine (Cymbalta, Irenka), venlafaxine (Effexor), venlafaxine XR (Effexor XR), nortriptyline (Aventyl, Pamelor), bupropion (Forfivo XL, Wellbutrin, Wellbutrin SR, Wellbutrin XL), mirtazapine (Remeron, Remeron Soltab), or vortioxetine (Trintellix) Be willing to undergo PGx testing via single tube blood draw Exclusion: Do not speak English Have previously undergone PGx testing Are unable to provide their own consent to participate in the study Have been taking the new antidepressant prescription for longer than 4 weeks (prior to screening)

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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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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Delayed intervention (control arm)<br>Patients in this arm will have PGx test results made available to physicians 3 months after study enrollment | Diagnostic Test: PGx test<br>* A laboratory developed genetic test that differentiates common and uncommon alleles in genes that have been previously identified as being involved in either the metabolism or response of drugs used in the treatment of depression and/or anxiety. The results are provided as a report that contains information related to the allele status of the patient's genes, translates this into a phenotype, and relates this phenotype to recommendation classes for drugs.<br>* Other names: Progenity Informed PGx test;|
| Experimental: PGx Test<br>Patients in this arm will have PGx test results made available to physicians as soon available after enrollment. | Diagnostic Test: PGx test<br>* A laboratory developed genetic test that differentiates common and uncommon alleles in genes that have been previously identified as being involved in either the metabolism or response of drugs used in the treatment of depression and/or anxiety. The results are provided as a report that contains information related to the allele status of the patient's genes, translates this into a phenotype, and relates this phenotype to recommendation classes for drugs.<br>* Other names: Progenity Informed PGx test;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Participants Prescribed Antidepressant Medication | Count of participants who have been prescribed antidepressant medications which are not contraindicated | Baseline, 3 months, 6 months, and 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Symptom Severity - Patient Health Questionnaire (PHQ-8) | Change in PHQ-8 scores. The PHQ-8 is an 8-item participant-report measure for screening for depression and for establishing depression severity. The total score ranges from 0-24, with a higher score indicating greater depression symptom severity. | Baseline and 6 months | 
| Change in Symptom Severity - General Anxiety Disorder - 7 (GAD 7) | The GAD-7 is a self-administered assessment for general anxiety disorder. The total score for the seven items ranges from 0 to 21. Higher values represent a worse outcome. | Baseline and 6 months | 
| Change in Adherence to Refills and Medication Scale (ARMS) Scores | Change in medication adherence: The Adherence to Refills and Medication was scored by summing together the 14 items after first reversing the final item to be consistent in direction with the others. Individuals were allowed to have up to 2 missing values present which were imputed with the mean of the remaining answered items, only a handful of individuals answered 13 of the 14 questions resulting in a single item within their scale being imputed across the time periods. The questionnaire has 14 items with each item being recorded on a four-point Likert scale. The total score ranges from 14-56 with the lower score indicating better adherence. | Baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacogenomics, Primary care physicians