Determining the Feasibility, Acceptability, and Preliminary Effectiveness of Pharmacogenomic Testing in Primary Care
Phase: NA
Conditions: Antidepressants Causing Adverse Effects in Therapeutic Use
Sponsor: University of Michigan

 
 
 
 
 
 
 
Determining the Feasibility, Acceptability, and Preliminary Effectiveness of PGx Testing in 
Primary Care  
Funding Source: University of Michigan MCubed Program 
Principal Investigator: Lorraine Buis, PhD 
Approval Date: 9/7/2018 
NCT03270891 
 
 
 

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Abstract 
 
Background: Antidepressants are commonly prescribed by primary care providers for treating 
depression, anxiety, and other conditions. A trial and error approach is typically used to identify 
effective therapy. Treatment efficacy and safety of many antidepressants can vary based on 
the presence of certain diseases and metabolism gene types. Pharmacogenomic (PGx) testing 
provides phenotypic classification of individuals as poor, intermediate, extensive, and ultra-
rapid CYP450 metabolizers. This allows more accurate drug selection for efficacy and dosing 
to minimize toxicity. 
 
Objective: To determine the preliminary effectiveness of PGx testing for selection of effective 
antidepressant, medication adherence, depressive symptoms, and healthcare utilization. To 
determine acceptability of PGx testing in primary care among patients and providers. 
 
Methods: 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 and if they 
have had PGx testing in the past.  
 
Physician participants will complete a baseline survey to assess demographics, and 
knowledge, acceptability and utility of PGx testing for this population. At the conclusion of the 
study, physician participants will complete a semi-structured interview to assess knowledge, 
satisfaction, feasibility, acceptability, effectiveness, barriers to widespread adoption, and utility 
of PGx testing.  
 
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 reasons for antidepressant use, 
depression and anxiety symptoms and severity, functional health status (SF-12), PGx 
knowledge, work status changes, demographic information, physician and emergency 
department visits, adverse effects, and medication alterations and adherence.  
 
 
 

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Contents 
Determining the Feasibility, Acceptability, and Preliminary Effectiveness of PGx Testing in 
Primary Care ............................................................................................................................... 4 
1.0 
Study Personnel ............................................................................................................... 4 
2.0 
Introduction ....................................................................................................................... 5 
3.0 
Objectives ......................................................................................................................... 5 
4.0 
Resources and Personnel ................................................................................................ 6 
4.1 Setting ................................................................................................................................ 6 
4.2 Staff Roles and Responsibilities ........................................................................................ 6 
4.3 External Partners ............................................................................................................... 7 
5.0 
Study Procedures ............................................................................................................. 7 
5.1 Study Design ...................................................................................................................... 7 
5.2 Recruitment Methods ......................................................................................................... 9 
5.3 Informed Consent Procedures ......................................................................................... 10 
5.4 Inclusion/Exclusion Criteria .............................................................................................. 11 
5.5 Study Evaluations ............................................................................................................ 11 
5.6 Data Analyses .................................................................................................................. 14 
5.7 Withdrawal of Subjects .................................................................................................... 14 
6.0 
Project Timeline .............................................................................................................. 14 
7.0 
Reporting ........................................................................................................................ 15 
8.0 
Privacy and Confidentiality ............................................................................................. 15 
9.0 
Communication Plan ....................................................................................................... 15 
10.0 
References ..................................................................................................................... 16 
 

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Determining the Feasibility, Acceptability, and Preliminary 
Effectiveness of PGx Testing in Primary Care 
 
1.0 
Study Personnel 
 
Principal Investigator  
Lorraine Buis, PhD 
University of Michigan Medical School  
Department of Family Medicine  
buisl@med.umich.edu  
 
Co-Investigators  
Vicki Ellingrod, PharmD 
University of Michigan College of Pharmacy  
Department of Clinical, Social and Administrative Science  
vellingr@umich.edu 
 
Karen Farris, PhD 
University of Michigan College of Pharmacy  
Department of Clinical, Social and Administrative Science  
kfarris@umich.edu 
 
Michael Klinkman, MD, MS  
University of Michigan Medical School  
Department of Family Medicine  
mklinkma@med.umich.edu  
 
Mack T. Ruffin IV, MD, MPH 
Penn State Hershey Medical Center 
Department of Family and Community Medicine 
mruffin@hmc.psu.edu  
 
Research Staff 
Beatriz Manzor Mitrzyk, PharmD 
University of Michigan College of Pharmacy 
bmitrzyk@med.umich.edu  
 
Reema Kadri, MIS 
University of Michigan Medical School  
Department of Family Medicine  
rkadri@umich.edu  
 
Melissa Plegue, MA 
University of Michigan Medical School  
Department of Family Medicine  
petrelim@umich.edu  
 

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2.0 
Introduction 
According the Centers for Disease Control and Prevention, between 2011 and 2014, 10.7% of 
Americans reported taking at least one antidepressant in the past month. [1] Antidepressants 
were the third most commonly used medication after cholesterol and pain medications. 
Antidepressants are prescribed for the management of depression, anxiety, and other 
conditions. Given that the time from initiation of pharmacologic treatment to clinical effect takes 
two to four weeks,[2, 3] coupled with the fact that the initial medication may not be effective, 
thus necessitating adjustments to dosages or medications, treatment with an antidepressant 
can be a long and complicated process, during which patients still experience symptoms. 
Strategies to improve treatment often include switching patients to a different antidepressant or 
prescribing an additional antidepressant.[4]  
One reason for poor response to antidepressants can be attributed to the drug metabolism 
process. Many of the most commonly prescribed antidepressants undergo phase one 
xenobiotic metabolism by a class of enzymes in the P450 superfamily. This family of enzymes 
exhibits a high degree of genetic polymorphism, resulting in variable metabolism. Because of 
this variation in P450, we can classify individuals as poor, intermediate, extensive, and ultra-
rapid metabolizers. The consequence of this population heterogeneity is that medications are 
metabolized at different rates and plasma concentrations of specific drugs can be outside of 
the optimal range, which may result in adverse drug events or lack of therapeutic effect. 
Because of these two medication outcomes, treatment may be discontinued.  
Pharmacogenomic (PGx) testing of several cytochrome P450 genes and the most frequently 
described functional variants (CYP2D6, CYP2C9, CYP2C19, and CYP1A2) can be used to 
predict the metabolic capacity of an individual. For example, it is estimated that 5-10% of 
Caucasian individuals are poor metabolizers and 1-2% are ultra-rapid metabolizers based on 
CYP2D6 phenotypes.[5] By knowing a patient’s genetic information and the drug’s major 
metabolic pathway, we can prospectively assess the appropriateness of specific medications, 
modifying the dosing or using enhanced monitoring. By identifying the approximately 10% of 
individuals who will not metabolize antidepressants properly via the CYP2D6 pathway, we may 
be better able to identify effective treatment options and minimize adverse effects.  
While the promise of this personalized medicine approach has been high, clinical uptake of 
PGx testing has lagged behind due to a combination of factors, including but not limited to 
provider confusion, lack of expertise, lack of studies confirming clinical utility, cost of testing, 
and a lack of an integrated approach.[6]  
3.0 
Objectives 
PGx testing could greatly improve the use of antidepressants by aiding prescribers in 
identifying proper medications for individual patients; thus potentially improving medication 
adherence, as well as reducing symptoms and antidepressant side effects.  
This pilot study will explore the use of PGx testing in primary care, and is guided by several 
specific aims: 

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Specific Aim 1: To determine the effect of PGx testing on the primary outcome of physician 
treatment decisions, as measured by the change in the proportion of patients who are 
prescribed medications at baseline that are contraindicated according to the PGx test, 
compared to the proportion at six-month follow-up.  
Specific Aim 2: To determine the effect of PGx testing on secondary outcomes measures of 
interest, including change in symptoms and severity and medication adherence from baseline 
to six-month follow-up.  
Specific Aim 3: To determine the acceptability of PGx testing in primary care among patients 
and physicians.   
4.0 
Resources and Personnel 
4.1 Setting 
This study will be conducted with physicians and patients recruited from the University 
of Michigan (UM) Department of Family Medicine (DFM), which has six clinical sites; 
Briarwood (Ann Arbor), Domino’s Farms (Ann Arbor), Ypsilanti, Chelsea, Dexter, and 
Livonia.  
 
4.2 Staff Roles and Responsibilities 
 
 
Buis 
Ellingrod 
Farris 
Klinkman 
Ruffin 
Mitrzyk 
Kadri 
Statistician 
Study 
Design 
X 
X 
X 
X 
X 
 
 
 
Recruitment 
 
 
 
 
 
X 
X 
 
Consenting 
Participants 
 
 
 
 
 
X 
X 
 
Data 
Collection 
 
 
 
 
 
X 
X 
 
Consulting 
with 
Physicians 
on PGx Test 
Results 
 
X 
 
 
 
X 
 
 
Access to 
PHI 
X 
X 
 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Data 
Analysis 
X 
 
 
 
 
X 
X 
X 
Report 
Preparation 
X 
X 
X 
X 
X 
X 
X 
X 

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4.3 External Partners 
All blood specimens will be sent for analysis to Progenity, a CLIA-accredited molecular 
diagnostics laboratory in Ann Arbor, MI. Progenity will provide a report for each sample 
to the study staff via MiShare or other secure transmission method, who will in turn 
release the results to physicians, along with any treatment recommendations based on 
the test results, via MiChart. The arrangement between UM and Progenity is covered by 
a contract.  
5.0 
Study Procedures 
5.1 Study Design 
This study will include two different populations of participants; primary care physicians 
and their patients who have been recently prescribed and taking one of the following 
antidepressants: 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, Effexor XR), nortriptyline (Aventyl, Pamelor), bupropion (Forfivo, 
XL, Wellbutrin, Wellbutrin SR, Wellbutrin XL), mirtazapine (Remeron,  Remeron Soltab), 
or vortioxetine (Trintellix). We will recruit and enroll approximately 30 UM DFM 
physicians to participate in this study. For physician participants, we will obtain consent 
and then conduct assessments of baseline PGx knowledge, as well as semi-structured 
interviews and surveys regarding their experiences at the conclusion of the study. 
Please see Figure 1 for physician participant study flow. 
From those participating physicians, we will recruit 100 of their adult patients who have 
been newly prescribed one of the antidepressants listed above. These patient 
participants will be enrolled in a six-month randomized wait-listed control pilot study.  
Patient participants will meet with study staff for consent and baseline data collection at 
a Michigan Clinical Research Unit (MCRU) in either Domino’s Farms or the 
Cardiovascular Center. Once consent and baseline data collection are complete, 
participants will have their blood drawn by MCRU laboratory staff. A single 4 mL 
Lavender top EDTA tube of blood will be drawn. Once the blood draw is complete, 
study staff will send the sample to Progenity for analysis. After the baseline assessment 
is complete, patient participants will be randomized equally to either have their test 
results sent immediately to their participating primary care physicians once available, or 
to have their test results sent in three months. Randomization will be stratified by 
physician in ten block units to ensure balance by physician. PharmDs on the research 
team (Ellingrod and Mitrzyk) will be available to consult with physician participants at 
any time during the study; however, our study PharmDs will meet with each 
participating physician at least once, when their first patient PGx test results are 
available to provide general, as well as patient specific education about the PGX test 
and results. These consultations will help physicians to interpret PGx test results, and 
may help to guide treatment decisions, if necessary. Study pharmacists or staff will not 

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provide PGx results to patients; it is up to the patient’s physician to provide this 
information if he/she feels it is appropriate. Likewise, although study pharmacists may 
make treatment recommendations based on the PGx test results, it is up to the treating 
physician to decide whether to act on those recommendations. All intervention patient 
participants will be followed for a total of 6 months, with phone-based follow-up 
assessments occurring at 3- and 6-months. All control patients will be followed for 9 
months, with phone-based follow-up assessments occurring at 3-, 6-, and 9-months. 
Please see Figure 2 for patient participant study flow.  
Figure 1. Physician Participant Study Flow 
 
 
 
 
 
 
 
 
 
 

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Figure 2: Patient Participant Study Flow 
 
Physicians and patients enrolled in this study will be exposed to minimal risk. 
Participants in both arms of the study will undergo PGx testing. Physicians for 
intervention group participants will receive PGx test results as soon as they are 
available, whereas those participants in the waitlisted control group will receive their 
test results three months after enrollment. Because the current standard of care does 
not involve the use of PGx testing, our waitlisted control group is not exposed to any 
additional risk above and beyond usual care. To clarify, the intervention under 
investigation in this study is the PGx test. We will not directly intervene in the clinical 
care of a patient, as all clinical decision making is at the discretion of the physician 
managing a patient’s care. All participants in this study may benefit because their 
antidepressant medication may be tailored to their pharmacogenomic profile. Although 
both populations of participants run risks associated with breaches of privacy due to 
electronic storage of study data, every effort will be made to minimize these risks.  
5.2 Recruitment Methods 
To conduct this pilot RCT, we will recruit from two populations of participants; primary 
care physicians, and 100 patients of those physicians who have been newly prescribed 
a certain antidepressant.  
5.2.1 Physician Participants 
Physician participants will be recruited through presentations of the study at UM 
DFM Grand Rounds and faculty business meetings, clinical site staff meetings, 
and targeted emails and letters to all UM DFM physicians who treat patients. 

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Study staff may also call providers who have not responded to recruitment 
letters/emails up to two times. In the event that a potential participant is eligible 
to participate in the study, except for the fact that their primary care provider is 
not yet participating, we will attempt to recruit the provider through up to two 
additional emails and two additional phone calls. Any provider who indicates that 
they are not interested in participating will not be contacted further. Provider 
participants will receive no incentives for their participation in this study. 
5.2.2 Patient Participants 
For patient participant recruitment, once UM DFM physicians have been 
consented and enrolled, we will recruit their patients who have new prescription 
for an antidepressant(with the past 4 weeks prior to screening) from the 
following list: 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, Effexor XR), nortriptyline (Aventyl, Pamelor), bupropion 
(Forfivo, XL, Wellbutrin, Wellbutrin SR, Wellbutrin XL), mirtazapine (Remeron, 
Remeron Soltab), or vortioxetine (Trintellix). These potential patient participants 
will be identified through direct provider referral via flags to providers in MiChart 
and patient brochures, signs and brochures posted in the UM DFM clinical sites, 
and targeted recruitment letters, followed by recruitment phone calls, to patients 
who meet eligibility criteria as identified in MiChart.  
To facilitate the delivery of targeted recruitment letters to potential patient 
participants, we will obtain lists of potentially eligible participants from the Data 
Office on a rolling basis. Letters will be batched and sent in waves.  
To thank patient participants for their participation in this study, we will provide a 
$20 check after each data collection assessment (up to $60 for intervention 
group participants, and up to $80 for waitlisted control group participants). All 
incentives will be pro-rated for partial study completion. Incentives will be 
distributed by the UM Treasurer’s office through the Human Subjects Incentive 
Program.  
5.3 Informed Consent Procedures 
We will obtain written informed consent from both groups of participants in this study 
(physicians and their patients). First, research staff (including project coordinators and 
research assistants) will describe the study to physician participants and obtain written 
informed consent. Once physician participants are consented and enrolled, we will then 
recruit patients of those physicians who are newly prescribed a certain antidepressant. 
Research staff (including project coordinators and research assistants) will explain the 
study to patient participants and written informed consent will be obtained. Any 
participant who is unable to provide consent for himself/herself will be excluded from 
this study. Whenever possible, study staff will seek to conduct consent and baseline 
data collection at the MCRU site in order reduce burden on participants.  

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5.4 Inclusion/Exclusion Criteria 
5.4.1 Physician Participants 
To be included in this pilot trial, physician participants must: 
• 
Be a practicing physician at one of the six UM DFM clinical sites 
• 
Be willing to utilize PGx test results to adjust antidepressant therapy 
for their participants enrolled in the study  
• 
Be willing to allow study staff to contact their patients 
• 
Self-report that they are willing to prescribe antidepressants 
• 
Be at least 21 years old 
 
 
Physician participants will be excluded from this pilot trial if they: 
• 
Do not meet inclusion criteria 
 
5.4.2 Patient Participants 
To be included in this pilot trial, participants must: 
• 
Be a patient of a participating physician 
• 
Have a new prescription for a certain antidepressant recorded in 
MiChart (within the previous 4 weeks prior to screening) 
• 
Be currently taking the new antidepressant  
• 
Be willing to undergo PGx testing via single tube blood draw 
• 
Be at least 18 years old 
 
Participants will be excluded from this pilot trial if they: 
• 
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 targeted antidepressant for longer than 4 
weeks (prior to screening)  
 
5.5 Study Evaluations 
5.5.1 Physician Participants 
Physician participants will be screened for inclusion/exclusion criteria prior to 
consent and enrollment. After enrollment, all physician participants will complete 
a baseline survey that assesses demographics and participant characteristics, 
knowledge of PGx testing, as well as perceptions of the acceptability and utility 
of PGx testing in primary care. At the conclusion of the study, physician 
participants will complete a semi-structured interview and survey that will assess 

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knowledge of PGx testing, whether they recommended PGx testing to other 
physicians, or ordered PGx testing on patients not included in this study; as well 
as perceptions of the feasibility, acceptability, effectiveness, and utility of PGx 
testing in primary care, including barriers to widespread adoption, as well as 
satisfaction. Surveys/interviews will be audio recorded when permitted by 
participants. Please see Table 1 for physician participant measures and timing 
of assessment.  
Table 1: Physician Participant Measures 
 
 
 
 
 
 
 
 
5.5.2 Patient Participants 
Patient participants will be screened for inclusion/exclusion criteria prior to 
consent and enrollment. After enrollment, all patient participants will complete a 
baseline, 3-, and 6-month assessment. Control patients will have an additional 
9-month assessment of the previously mentioned items. All baseline data will be 
collected via paper forms and then transferred into REDCap, whereas 3-, 6-, 
and 9-month assessments will be conducted via phone and entered directly into 
REDCap by study personnel. The constructs, measures, and data collection 
times are shown in Table 2. In addition to these measures collected during data 
collection visits, data will be extracted from MiChart to document treatment, 
including medication changes, and healthcare utilization for patient participants 
during the study. We will also extract any available PHQ-9 and GAD-7 data, 
which is now collected as a part of routine clinical practice. Surveys/interviews 
will be audio recorded when permitted by participants.  
 
 
 
 
Construct 
Measure 
Assessment Time 
Baseline 
Post-Study 
Demographic information 
and characteristics of 
physicians 
Investigator 
Developed Semi-
Structured 
Interview and 
Survey 
X 
 
Knowledge of PGx testing 
X 
X 
Acceptability of PGx testing 
X 
X 
Utility of PGx testing 
X 
X 
Effectiveness of PGx testing 
X 
X 
Feasibility of PGx testing 
X 
X 
Barriers to PGx testing 
X 
X 
Satisfaction with PGx testing 
X 
X 

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Table 2. Patient Participant Measures  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Construct 
Measure 
Assessment Time 
Baseline 
(via 
paper 
survey) 
3 
months 
(via 
phone) 
6 
months 
(via 
phone) 
9 months 
(Control 
Only; 
via phone) 
Reason 
antidepressant 
was prescribed 
 
X 
X 
X 
X 
Depression 
Symptoms and 
Severity 
Personal Health 
Questionnaire 
Depression Scale 
(PHQ-8)  
X 
X 
X 
X 
Anxiety 
Symptoms and 
Severity 
Generalized Anxiety 
Disorder 7-Item Scale 
(GAD-7) 
X 
X 
X 
X 
Functional Health 
Status 
12-Item Short Form 
Survey (SF-12) 
X 
X 
X 
X 
PGx Knowledge 
Investigator 
Developed 
X 
 
 
X 
Missed days of 
work 
Work Productivity and 
Activity Impairment 
Questionnaire (WPAI) 
X 
X 
X 
X 
Demographic 
information 
 
X 
 
 
 
Health history 
Smoking history, BMI 
X 
 
 
 
Healthcare 
utilization 
Physician visits, 
hospital and ER 
admissions 
X 
X 
X 
X 
Adverse Drug 
Reactions 
  Antidepressant Side-
Effect Checklist 
(ASEC) 
X 
X 
X 
 
X 
Medication and 
medication 
changes 
Medications 
prescribed and 
number of medication 
changes 
X 
X 
X 
X 
Medication 
Adherence 
Adherence to Refills 
and Medication Scale 
(ARMS)  
X 
X 
X 
X 
Pill count 
X 
X 
X 
X 
Three-Item Self-rated 
Adherence Scale 
X 
X 
X 
X 

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5.6 Data Analyses 
In this study, we expect to enroll up to 30 physician participants and expect a retention 
rate of 90-100%. We also expect to enroll about 100 patient participants and expect a 
retention rate of 80% at the completion of this study.  
Data from this study will be analyzed by the study statistician. Survey data will be 
analyzed using descriptive statistics. Multiple-choice questions will be analyzed using 
standard quantitative techniques including Chi square and t-test. Open-ended 
responses will be independently coded using qualitative methods, including any 
transcripts that result from the recorded survey responses. 
Independent sample t-tests will be used to compare outcomes between 
intervention and control groups at each time point, as well as at similar time 
points after test results were released to physicians (i.e. baseline for intervention 
vs. 3 month for control group). Linear mixed models will assess the change in 
outcomes, as well as whether the change is similar between groups. This will be 
done by including time, study group, and a time by study group interaction as 
predictors of each outcome. Time will be considered in two ways, first as the 
time in study, and secondly as time since test results were released to 
physicians. In the latter, only data from 3-month to 9-month will be included for 
the control group, and baseline to 6-month for intervention group, due to timing 
of test result release. Models will be adjusted for patient demographics.  
 
5.7 Withdrawal of Subjects 
Participants may be withdrawn from the study without their consent if the PI feels that it 
is unsafe for the participant to continue to participate, or if they refuse the blood draw. 
Participants may withdraw from the study at any time by contacting study staff either in 
writing or by calling the study hotline. 
6.0 
Project Timeline 
  
Year 1 – 2016 
Year 2 – 2017 
Year 3 – 2018 
  
(quarter) 
(quarter) 
(quarter) 
  
3 
4 
1 
2 
3 
4 
1 
2 
3 
4 
Protocol development, 
IRB approval, personnel 
hiring/training 
X 
X 
 
 
  
  
  
  
 
 
Contracting with Progenity 
 
X  
 
 
  
  
  
  
 
 
RCT recruitment and 
enrollment 
  
 
 X 
X 
X 
X 
X 
X 
 
 
RCT data collection (9 
month follow-up) 
  
 
 
 
 
 
X 
X 
X 
 
RCT data analysis 
  
  
  
  
  
  
 
 
 
X 
Final report preparation 
  
  
  
  
  
  
  
  
 
X 

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7.0 
Reporting 
Participants will be requested to call the study hotline to report any adverse events (AEs) or 
unanticipated problems. All staff will be directed to report any serious (SAEs), protocol 
deviations, and unanticipated problems to the Project Coordinator as soon as possible. The 
Project Coordinator or the PI will submit the appropriate documentation to the UM IRB or other 
department as required. 
8.0 
Privacy and Confidentiality 
This study will utilize PHI including the following elements: name, date of birth, full mailing 
address, clinic dates, phone numbers, email addresses, social security numbers, medical 
record numbers. All study staff-generated electronic study data including participant identifiers 
will be securely maintained in REDCap, or a UM restricted server, in an access-limited folder, 
with access given only to specified project staff. All participants will be assigned a study ID, 
which will be associated with their survey data. Although we will maintain a file that links patient 
MRN and study ID, this will be kept separate from other study data, in a manner consistent with 
UM policies for PHI. The results of the Progenity Informed PGx tests will be transmitted back to 
study staff via secure means such as MiShare and stored securely in access-limited folders. All 
paper records and audio recordings and equipment with patient identifiers will be kept in a 
locked office, in locked file cabinets. Access to the file cabinets will be restricted to approved 
study personnel.  
 
PHI sent to Progenity as part of ordering the PGx test is protected as required by the contract. 
9.0 
Communication Plan 
Prior to the start of this study, the research team will complete the process for obtaining 
approval to recruit participants from UM DFM clinical sites, which includes obtaining permission 
from the UM DFM Associate Chair for Research (Dr. Caroline Richardson), as well as clinical 
site medical directors.  
Any proposed changes to the study protocol which would change the role of the recruitment 
sites will be communicated via email to UM DFM Associate Chair for Research and the clinical 
site medical directors and agreed upon prior to seeking IRB approval. 
UM DFM Associate Chair for Research and the relevant clinical site medical director will be 
informed via email once recruitment at each individual site has been closed. 
 
 
 

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10.0 References 
 
. 
1. Center for Disease Control and Prevention website. Table 80 (page 1 of 3). Selected 
prescription drug classes used in the past 30 days, by sex and age: United States, selected 
years 1988–1994 through 2011–2014. Accessed on 4-10-18 at: 
https://www.cdc.gov/nchs/data/hus/2016/080.pdf 
2. 
Cameron, C., et al., Optimizing the management of depression: primary care 
experience. Psychiatry Res, 2014. 220 Suppl 1: p. S45-57. 
3. 
Papakostas, G.I., et al., A meta-analysis of early sustained response rates between 
antidepressants and placebo for the treatment of major depressive disorder. J Clin 
Psychopharmacol, 2006. 26(1): p. 56-60. 
4. 
Posternak, M.A. and M. Zimmerman, Is there a delay in the antidepressant effect? A 
meta-analysis. J Clin Psychiatry, 2005. 66(2): p. 148-58. 
5. 
Hicks, J.K., et al., Clinical Pharmacogenetics Implementation Consortium guideline for 
CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin Pharmacol 
Ther, 2013. 93(5): p. 402-8. 
6. 
Patel, H.N., et al., Stakeholder views on pharmacogenomic testing. Pharmacotherapy, 
2014. 34(2): p. 151-65.