The Texas Interprofessional Pharmacogenomics (IPGx) PILOT Cohort
Conditions: Adverse Drug Reaction
Sponsor: Texas A&M University

 
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Document Version:   June 13, 2023 
1. 
Protocol title:  
The Texas Interprofessional Pharmacogenomics PILOT Cohort  
 
2. 
Study team 
Principal investigator: 
Kenneth S. Ramos, MD, PhD 
Alkek Chair of Medical Genetics 
Center for Genomic and Precision Medicine 
Professor of Translational Medical Sciences, Texas A&M College of Medicine 
Executive Director, Texas A&M Institute of Biosciences and Technology 
Associate Vice President for Research, Texas A&M University Health Science Center 
Assistant Vice Chancellor for Health Services, The Texas A&M University System 
 2121 W. Holcombe Blvd 
Houston, TX. 77030 
Tel. 713.677.7440 
kramos@tamu.edu  
 
Co-Investigator(s) 
 
Gabriel Neal, MD 
Clinical Associate Professor, Department of Primary Care and Population Health 
Director, Texas A&M Health Family Care Clinic 
 
Sara Rogers, PharmD 
Clinical Assistant Professor of Pharmacy Practice, Precision Medicine – Ambulatory Care 
Irma Lerma Rangel College of Pharmacy 
 
George Udeani, PharmD, DSC, FCP, FCCP 
Clinical Professor and Department Head of Pharmacy Practice 
Irma Lerma Rangel College of Pharmacy 
 
Asim Abu-Baker, PharmD 
Clinical Professor and Associate Dean for Clinical and Professional Affairs 
Irma Lerma Rangel College of Pharmacy 
 
Rick Silva PhD, MBA 
Executive Director, Clinical | Translational | Industry Collaborations 
Texas A&M Health Science Center 
Assistant Professor, Department of Translational Medical Sciences, College of Medicine 
 
 
3. 
Objectives: 
Our primary aim is to evaluate polypharmacy-associated adverse drug reactions (ADR) in a pilot 
study of at-risk patients using state-of-the-art pharmacogenomic technology and to use this 
information to make recommendations for optimization of pharmacotherapy regimens. The data 
from the pilot cohort will be used to optimize and integrate a customized electronic decision 
support (clinical semantic network; CSN) dashboard to identify drug regimens that should be 
modified, replaced, or discontinued. A secondary objective of the pilot study is to evaluate the 
capacity/saturation of CYP P450 enzymatic pathways in polypharmacy patients. A third 

 
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objective is to determine the feasibility of the planned informatics workflows between the CLIA 
lab, the EMR, and the Family Medicine Practice.  There is no prospective comparison group 
because this is a pilot study for a registry.   
 
4. 
Background:  
We are concerned with patient safety and ADRs as these areas of clinical practice represent 
significant causes of death, ahead of many of the better recognized acute and chronic causes of 
mortality (1). While prescribing medicines can have life-altering benefits, a more precise way of 
choosing among the options on a formulary continues to lag behind existing technologies. A 
person’s drug response can vary by means of drug-drug or drug-food interactions, as well as by 
sex, age, and disease status. Large interpersonal variabilities of up to 1000-fold exist in 
response to the same dose of a given medication (2). Genetic polymorphisms help define 
pharmacokinetic and pharmacodynamic profiles, but these insights have not yet been 
consistently incorporated into clinical practice and standards of care. Several medication 
management programs have appeared in recent years, but these are mainly geared toward 
adherence, with only limited incorporation of pharmacogenomics-based medication 
management.  Precision medicine advocates that one size does not fit all medical care. How 
might the provision of care get closer to the bullseye in polychronic disease management, and 
the management of polypharmacy?  
 
There exists a polypharmacy crisis in the United States that is large in scope, especially among 
the older populations who often have diminishing renal and hepatic functions. The prevalence of 
potential hepatic cytochrome enzyme-mediated drug-drug interactions was estimated to be as 
high as 80% in one study (3), with elder adults considered to be more susceptible to problematic 
drug interactions. Conventionally, polypharmacy refers to taking five or more medications 
concurrently. An estimated 15 million patients 65 or older have been identified as facing the 
challenge. Polypharmacy patients often have at least two comorbid chronic diseases, and 
nearly 50% of older adults are using at least one medication that is not necessary (4).  
Hospitalized patients average five to eight medications, and the number surpasses nine in 40% 
of nursing home residents. In a study of patients with cognitive decline or mild Alzheimer's 
disease, 88% of these patients met polypharmacy criteria, with anticholinergic cognitive burden, 
drug-drug interactions, and drug-gene interactions all prevalent issues in these populations (5). 
In an increasing number of extreme cases, polypharmacy can approximate 20 drugs posing 
risks for adverse drug outcomes that equal nearly 100% (6). The greater the number of 
medications in a regimen, the higher the risk to patient safety and compromised clinical 
outcomes. One in twenty polypharmacy outpatients seek medical care for ADRs (6). 
Polypharmacy has also been associated with hospitalizations among the elderly (Gutierrez-
Valencia et al., 2017).  Polypharmacy is associated with decreased medication adherence, 
nutrition, urinary incontinence, reduced activities of daily living, and loss of physical and 
cognitive functions. Increased falls occur along with accompanying morbidity and mortality (7). 
Financially, the impact of polypharmacy has been associated with a 30% increase in health care 
expenditures (8), and a major factor in ultrahigh healthcare utilizers (9).   Analysis of the 
Observational Health Data Sciences and Informatics data set showed that 10% of diabetes 
patients, 24% of hypertension patients, and 11% of depression patients followed a treatment 
pathway that was unique among a population of 250 million cases (10), illustrating the need for 
electronic decision support (11) to flag drug interactions resulting from patient specific care 
plans and implement corrective measures.  
 

 
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Electronic health records continue to fall short regarding their level of interoperability, with 
significant deficiencies enabling a care plan and medication management that can draw data 
and decision support from across the provider continuum. This is a suboptimal situation in the 
provision and refinement of precision and personalized medical care. The clinical burden of 
polypharmacy and medication reconciliation often impacts primary care clinicians who may not 
have the necessary data at the point of service, a nidus for polypharmacy management 
problems. Innovative approaches to managing the polypharmacy challenge include the creation 
of medical management clinics with focused efforts on mitigating the cost and healthcare 
burden of polypharmacy and to systematically evaluate the incremental clinical changes that 
accompany medication alterations, modification or discontinuation where indicated. 
 
Utilizing an interprofessional care team that includes physicians, pharmacists, nurses, case 
coordinators, along with telemedicine and digital tools, we can engage patients and garner 
information such as phenotypic, functional, and social determinants of disease profiles. These 
data can be entered as computable actionable data prior to a visit in order to better track what 
happens in-between visits (adherence to the care plan, or lack thereof). We posit that this 
information is as important as what happens at an appointment, and this is especially true in 
clinical cases of polypharmacy. In the end, this information can become more readily available 
to both patient and provider utilizing the Interprofessional Pharmacogenomics (IPGx) care 
model.   
 
Figure 1 Interprofessional Pharmacogenomics (IPGx) Model.  1. Referral of polypharmacy patient to the IPGx clinic. 2. 
Interprofessional team collects relevant medical history with an emphasis on information related to chief complaints, which also 
includes a transition of care history from primary care to the IPGx. This information is analyzed using the Clinical Semantic 
Network to identify complaints of possible pharmacological root cause.  3a. When warranted, pharmacogenomic profiling is 
performed. 3b. When warranted, pharmacokinetic profiling is performed.  4.  A medication management report citing complaints 
of potential pharmacological root causes and suggested alternative medications or adjustments to drug regimen is provided to 
the referring physician.  5. If patient chooses to give informed consent, all clinical data, bioanalytic data and biological specimens 
are entered into a pharmacogenomic research registry (clinical-genomic database). 

 
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We are developing a care decision support protocol and pharmacogenomic/ pharmacokinetic 
dashboards that augment the capacity for primary care clinicians to manage medication more 
precisely for individual cases and that is minimally disruptive.  
 
 
The dashboards (12) will be useful to providers and patients, helping to identify clinical cases 
where there might be benefit from proactive medication management to identify those who may 
not respond and those at heightened risk of ADRs. The dashboards would be informed by a 
growing library of clinical cases with a clinical data warehouse. The dashboard would generate 
and iteratively refine novel care decision trees (algorithms) centered on medication 
management. The data structure and care protocol are designed to enable concomitant and 
longitudinal observation (research) of the clinical activities toward validation of the CSN and 
dashboards as a useful tool for patient-centric clinical research. The ideal databank will include 
drug blood levels (not relevant to this PILOT), drug list and other relevant modifier data that may 
impact medication use and effectiveness. This approach would also provide a means to learn 
more about drug adherence and help to systematically identify patients who may be candidates 
for a pharmacogenomic evaluation and longer-term participation in a medication management 
program.  
 
Specific questions that this GENERALIZED approach might inform:  
• 
Does a drug level near zero mean non-adherence, or is the patient metabolizing a drug 
extensively such that blood or urine levels become undetectable after administration? 
Our phenotypic questionnaire coupled with drug blood or urine level measurements will 
inform that question.   
• 
Is a protocol needed to determine when to order a pharmacogenomic test? Our data 
platform, powered by the CSN, can validate the clinical and cost-effectiveness of those 
decisions.   
• 
What is the best use pharmacogenomic data? If a patient has had a pharmacogenomic 
test, blood or urine drug levels might help refine knowledge about the metabolic activity 
for pertinent enzymatic pathways and help craft key questions to identify what 
constitutes an overloaded CYP P450 pathway in the setting of polypharmacy.  
 
 
ADRs might be preventable in the psychotropic domain by applying the knowledge derived from 
a medication management consultation (18). For instance, in the case of antidepressants, 
weeks may go by before a clinical response can be evaluated after initiating medication based 
on standard dosing and trial and error.  In a precision medication management scenario, the 
provider would know at the outset if the patient were an ultra-rapid metabolizer for a relevant 
CYP P450 enzymatic pathway and be better equipped to identify the drug of choice and to 
optimize dose titration. If the clinical dashboard reveals a patient that is receiving several 
medications competing for a common pathway, proper medication adjustments can also be 
made, as needed. 
 
The CSN to be used here is a proprietary computable health record system containing millions 
of interrelated medical findings that arc with each other to create a knowledge network. As data 
is entered, weighted arcs are used to build clinical decision support and differential diagnoses. 
This provides a potentially strong environment for a pharmacogenomic profile to create a 
precision drug and dosing regimen tool while taking advantage of clinical workflows currently in 
practice. The pharmacogenomic dashboard is contained within the CSN.   
 
 

 
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5. 
Inclusion and Exclusion Criteria: 
 
Inclusion  
We plan to recruit at most 50 volunteers from the Texas A&M affiliated community health family 
medicine program.   
• 
People taking 5 or more medications, including over the counter drugs, supplements, 
natural products, cannabis produces, or other recreational drugs  
• 
Ability to give and comprehend the consent process. 
• 
Consent to donate urine samples, genetic data through buccal swabs, undergo a 
comprehensive history and physical examination. 
• 
All genders.  
• 
Age 45 and over.  
 
Exclusion 
• 
Subject has been diagnosed or is being treated for any cancer other than basal cell 
cancer in the last 5 years.  Patients with metastatic melanoma in the last 5 years will be 
excluded.   
• 
Admitted to hospice. 
• 
Patient has ever been diagnosed with Hepatitis B or C. 
• 
Patient has ever been diagnosed with active liver disease, hepatomegaly, grossly 
abnormal liver function.  Meld score >10, ALT or AST >100U/L or an AST/ALT ratio >2 
• 
Patients taking imidazole antifungal medication.  
• 
Declines to participate or interact with staff/share their medical status. 
• 
A diagnosis of Alzheimer’s disease 
• 
Pregnant patients will be excluded 
• 
Unable/unwilling to consent.  
• 
Unable to verbally communicate and comprehend English/Spanish language. 
 
While ADRs are an important endpoint in the proposed study, ADRs are not an inclusion or 
exclusion criterion for enrollment.  As such, under the polypharmacy inclusion criterion, severe 
side effects are expected in the enrolled population, but not a criterion for enrollment.  Clinical 
efficacy of existing therapies will be indirectly informed by the disease specific quality of life 
questionnaires in the electronic health record of patients referred and enrolled.   
 
Severe side effects are not uncommon in a polypharmacy population and severe side effects 
will not disqualify subjects from participation in the study.   
 
 
 
6. 
Number of Participants: 
Up to 50 
 
7. 
Multi-Site Research: 
 

 
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Texas A&M Health Family Care Clinic and the Texas A&M Interprofessional 
Pharmacogenomics Clinic (IPGx) (12) is co-located within facilities made available by the 
Department of Primary Care and Population Health. Patients will be referred to the IPGx 
exclusively from the Texas A&M Family Medicine Clinic.  working closely with our laboratory 
collaborators, InnovativeGx, located in San Antonio, TX,  IC42 in Aurora Colorado. A  research 
collaboration agreement has been be promulgated among Texas A&M and Goldblatt systems to 
ensure data sharing and reporting is compliant with all relevant regulations.  InnovativeGx, and 
IC42 will receive specimens labeleed with a code thathe TAMU research team will use ot 
reidentify the reports when they come back to TAMU.  InnovativeGx, and IC42 will not have 
access to the codes . 
 
Research activities will occur at all of the sites mentioned, but patient recruitment will be limited 
to Texas A&M Health Family Care Clinic and the Texas A&M Interprofessional 
Pharmacogenomics Clinic (IPGx). 
 
All sites will have the most current version of this Pilot Study Protocol, informed consent 
documentation, and HIPAA authorization. All required approvals will be obtained at each 
location including the site’s IRB of record (or affirmation to recognize the TAMU IRB as the IRB 
of record, or documentation of exemption from IRB approval). All planned modifications to the 
Protocol will be communicated to the various primary care sites in addition to the site’s IRB of 
record and implemented, upon IRB approval if required. All engaged participating sites will 
safeguard data as required by their local information security policies and in compliance with 
HIPPA and General Data Protection Regulation standards.  Through regular dialogue and open 
communication will be made so that all local site investigators conduct the study appropriately. 
All non-compliance with the study protocol or applicable requirements will be reported in 
accordance with local policy and as specified in the Protocol. 
 
8. 
Study Timelines: 
 
The duration of individual participation period in the study is limited to their medical 
encounter in the IPGx clinic, and any subsequent medication management visits their 
primary care physician refers back to the IPGx. No more than 180 days from the date of 
their enrollment in the study.   
 
9. 
Variables and outcome measures: 
 
• 
Frequency and nature of ADRs on the Naranjo Scale (19)  
• 
Emergency department visits 
• 
Hospital admissions 
• 
Serum/plasma drug concentrations 
• 
Pharmacogenomic genotype with corresponding ADR phenotype  
• 
Drug-drug interactions, drug gene interactions, drug-drug-gene interactions 
 
10. 
Procedures Involved: 
 
Patients will be referred to the Texas A&M Interprofessional Pharmacogenomics Clinic (IPGx) 
by their primary care physicians to evaluate polypharmacy status, genotyping, pharmacokinetic/ 
pharmacodynamic (PK/PD) assessment, and monitoring of potential for ADR.  
 

 
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An assessment at the IPGx will start with the pharmacist or physician doing a pharmacologic 
consultation to evaluate medications or other drugs currently being used by the patient and to 
identify any potential issues related to toxicity, drug interactions, or side effects that might be 
relevant to the clinical presentation. A physician or ambulatory pharmacist in the IPGx clinic or 
Family Care Clinic will obtain a complete medical history, physical examination, and validate the 
patient’s current concomitant medication list at the IPGx during the office visit. Other clinical 
team members may include house staff or medical students, a clinical coordinator, and a nurse. 
Those patients who are eligible for inclusion in the research study would be offered enrollment. 
Patients who choose not to participate in the study are still eligle to receive care, without 
prejudice.  After detailed educational instruction and informed consent, including risks and 
benefits of the study, patient medical information would be input into the CSN, which functions 
as a computable EHR. The attached informed consent obtains permission from every 
individual to use their clinical, genetic, and lab data.  
 
Medical record analysis will be conducted as follows (Excerpt from Silva et al., 2021 (12)):  
 
Polypharmacy patients and patients demonstrating symptoms and 
complaints that might be indicative of possible medication interactions are 
referred to the IPGx clinic for evaluation by the attending clinician (Figure 
1, step 1). Patients are not required to consent to the registry to receive the 
bioanalytic workup and medication management care; registry 
participation is optional and not a condition of care. The program entails a 
process of stepwise progression of electronic medical record analysis 
toward pharmacokinetic ground truth to inform primary care practitioners.  
The first step consists of a clinically aware computational analysis such that 
entry of complaints into the patient’s record, updates the rendering of 
complaints that match the known side effects (from First Data Bank) of 
drugs taken by the patient.  The second step strengthens these associations 
if a pharmacokinetic model of the medications renders potential instances of 
pathway overload (Epocrates).  Next the CSN can further strengthen these 
associations by identification of pharmacogene variants of known clinical 
significance that are consistent with the list of candidate side-effects or 
pathway overload.  Finally, pharmacokinetic data is incorporated to 
distinguish among and validate instances of drug-gene or drug-drug 
interactions. 
3.2 Medical Record Analysis and the Clinical Semantic Network 
The first step is a computational and semantic comparison of case history to 
the medications the patient is taking. This is powered by DrugBank (13), 
Epocrates (14), and Lexicomp (15) to tally the subset of symptoms that are 
present and known to occur as side effects of the medications the patient is 
taking. At a clinical informatics level, cough with fever might be connected / 
mapped to curated ontologies such as SNOMED (Systematized 
Nomenclature of Medicine (16)) about SARS COV2, or pneumonia in a 
weighted fashion, by subject matter experts who then have the capability to 
markedly enhance this highly navigable information. A net result is that a 
SNOMED identification can be established with multiple attributes built 

 
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into the CSN system. Other analogies in the CSN include instances when a 
chief complaint is entered such that the system knows which history of 
present illness questions should be used to interrogate. The technology 
works much in the same manner as Google can predict shopping 
preferences based on user actions.  
For the purposes of this communication, we created a virtual patient with 
medication, pharmacogenomic and side effect profiles that were aggregated 
drawing from previous experiences with a number of real-life clinical cases. 
The clinical characteristics assessed included: 
• 
Number of side effects / complaints / diagnoses identified in the patient 
and believed to be related to his/her current medication regimen, 
• 
Number of medications possibly contributing to the identified / 
diagnosed side effects, 
• 
Number of drug metabolic pathways identified as being potentially 
overloaded, 
• 
Number of drug metabolic pathways identified as borderline 
overloaded, 
• 
Number of medications with pharmacogenomic profiles, 
• 
Number of medications putting the patient at risk for serotonin 
syndrome, 
• 
Number of medications putting the patient at risk for QT prolongation, 
• 
Number of anticholinergic medications.    

 
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Figure 2: Side Effects Dashboard. List of symptoms indicating potential 
pharmacological origin.  
At this step, a side-effects dashboard is created by the CSN utilizing any 
drug in the First Databank to distill complaints that could be of 
pharmacological origin. Figure 2 provides a summary of selected 
computational clinical findings for the virtual patient which are also a 
rendering of the complaints from Table 1, that correspond to the subset of 
complaints that are also known side effects of the medications the patient is 
taking.  Those side effects, as initially rendered prior to pharmacogenomic 
profiling, may not inherently be of pharmacological origin, or may arise due 
to drug-drug interactions, or as a result of drug-gene interactions.  
Pharmacogenomic testing and pharmacokinetic testing can reveal whether 
these complaints are rooted in drug-gene or drug-drug interactions.  . The 
CSN can be contrasted from step-and-fetch functionality of most electronic 
medical records by the interconnectivity of medical terms. Those medical 
terms are connected in a neural-like network of semantic associations that 
effectively represent knowledge and contextual awareness of potentially 
related data elements in a patient record. The network consists of nodes 
representing objects and arcs which describe the relationship between those 
objects. Semantic networks can categorize the objects in various forms and 
can link those objects making it particularly useful in an electronic health 
record which can utilize and act on computable data. Interconnecting a 
patient’s clinical content (phenotypes) with this form of health care 
knowledge gives the data in these relationships actionable context. There is 
a pharmacokinetic modeling dimension in this analysis that examines the 

 
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repertoire of medications a patient has been prescribed and that models 
these data based on known pathways for those medications to assess drug-
drug interactions that might result from pathways that are excessively taxed 
by virtue of the combination of medications (Figure 3).  
 
 
Figure 3. Medication and Pharmacokinetic Pathway Summary. The green rectangles are 
a few salient transporters, and the light blue box represents anticholinergic burden. 
The left most vertical column denotes the patient’s medications. Vertically the 
column beneath named alleles in red indicate that the respective pathway could be 
overloaded. Panel B Key 
This dashboard can incorporate correlative associations (complaints-drug 
side effects) and bioanalytic associations (PGx genotypes and predicted or 
measured pharmacokinetic). As such, this computationally rendered 
dashboard provides useful insight on the potential root cause of complaints 
both before and after bioanalytic analysis is entered into the CSN case 
record. 
3.1 Bioanalytics 

 
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Pharmacogenomics 
is 
used 
to 
assess 
the 
impact 
of 
individual 
pharmacogenomic variants on how subjects respond to their medication by 
evaluating specific medication receptor targets as well as transporter 
functionality (17).  The informatics design incorporates all Clinical 
Pharmacogenetics Implementation Consortium (CPIC) guidelines and the 
knowledgebases contained in PharmGKB and PharmVar to provide a cogent 
front-end presentation of case-relevant and actionable pharmacologic 
considerations for use by the clinician at point-of-care. The point of care 
dashboard  only renders CPIC Level 1 and Level 2, Pharm GKB Level 1 and 
2, the FDA Table of PGx Biomarkers, and  FDA Table of PGX Association In 
summary, the digital dashboard from the CSN reflects a comprehensive 
analysis of known pharmacogenomic knowledge through the filter of 
established consensus medical guidelines. For illustrative purposes Table 3 
presents a list of CYP2D6 haplotypes that the CSN is configured to 
dynamically incorporate into the rendering of the pharmacogenomic 
analysis.  The CSN is capable of incorporating all variants of known clinical 
significance per CPIC guidelines.  The patient scope varies and is 
dynamically adjusted to the variants that are presented by the 
instrumentation. The CYP2D6 haplotype call is made from the core variants 
for each haplotype and all other variants are verified as constant relative to 
that haplotype so variants of unknown significance are not presented as 
normal. 
 
The dashboards (12) will be useful to providers and patients, helping to identify clinical cases 
where there might be benefit from proactive medication management to identify those who may 
not respond and those at heightened risk of ADRs. The dashboards would be informed by a 
growing library of clinical cases with a clinical data warehouse. The dashboard would generate 
and iteratively refine novel care decision trees (algorithms) centered on medication 
management. The data structure and care protocol are designed to enable concomitant and 
longitudinal observation (research) of the clinical activities toward validation of the CSN and 
dashboards as a useful tool for patient-centric clinical research. The future, generalized 
databank will include drug blood or urine levels, drug list and other relevant modifier data that 
may impact medication use and effectiveness. This approach would also provide a means to 
learn more about drug adherence and help to systematically identify patients who may be 
candidates for a pharmacogenomic evaluation and longer-term participation in a medication 
management program.  
 
 
Clinical staff will obtain a buccal swab to collect DNA for a pharmacogenomic evaluation 
pursuant to the sample collection kits from the CLIA lab, which will occur at the start of the study 
period. Blood chemistry will be taken from the EMR.  Any blood taken for clinical chemistry 
during this visit is purely for clinical care and as warranted by the provider and not mandated by 
the research protocol. For measurement of drug levels, urine will be collected in kits provided by 
IC42 at room temperature will be shipped to IC42 each day via FedEx in provided biosafety 
shipping kits. Buccal swabs need no special preparation, and will  be shipped each day via 
FedEx in provided biosafety shipping kits.  
 
A single pharmacogenomic test will be conducted using DNA from the initial buccal swab. An 
assay for pharmacogenomic variants of known clinical significance for the drug-gene pairs 

 
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specified in Exhibit  A [insert table or online reference to genotypes interpreted] will be 
conducted and a report generated (per the CPIC guidelines (20, 21)).  In certain instances, 
blood or urine levels of drug or metabolites may need to be re-assessed periodically if 
warranted by standard clinical practice, on a case-by-case basis. If the physician wishes to 
determine whether a change in dose or a change in medication has resolved undesirable steady 
state levels of medications or their metabolites, a followup urine or blood sample (depending on 
the drug being measured and the specifications for the corresponding CLIA test for that drug) 
may be ordered in accordance with drug labels where dose titration is warranted, or where an 
actionable pharmacogenomic variant (under FDA and CPIC guidelines) indicates a change in 
dose or medication should be considered.  The sample will be obtained in a timeframe the 
physician determines as medically prudent.  Patients will be seen in the clinic after the final 
report is submitted to the referring physician.  
There are inherent risks of morbidity and mortality associated with taking, changing or 
discontinuing medications in whatever standards-of-care are applicable to an individual’s case. 
These risks are routinely weighted by the physician in the practice of medicine, and no actions 
beyond the exercise of physician judgments are prescribed under this protocol.   IPGx will 
forward specific recommendations to the referring physician who in turn will make changes to 
the regimen, as desired. It is expected that changes made to mitigate a polypharmacy burden 
would reduce risk of ADRs. We do not expect these risks to differ from those inherent to the 
medication of choice and adjustments thereto during standard medical care.  
 
It should be noted that standard of care for changing most medications is simply trial and error 
(22), with a few exceptions warranting pharmacogenomic testing.  However, consensus medical 
guidelines for actions based on results of pharmacogenomic tests for a number of drug gene 
pairs exist and are endorsed by Association for Molecular Pathology, American Society for 
Clinical Pharmacology and Therapeutics, and the American Society of Health-System 
Pharmacists.  The working principle for this program is that the risks of being a polypharmacy 
patient without medication management care are greater than the risks of trying to ameliorate 
that burden with pharmacogenetic and drug level testing to inform medication management. Put 
another way, the status quo presents greater risk of adverse drug reactions to the patient than 
participation in the protocol.   In many respects that study can be viewed as a quality 
improvement project for participating clinics. For these reasons, the proposed study is one of 
minimal to no risk. 
 
The Pilot Study will track and document any change in medication, but changes are not a 
condition of participation, and it is plausible some subjects will not have a change in medication 
recommended by the referring physician or may choose against a medication change 
recommended by the physician.  
 
Any risk will be minimized by exercising the same level of clinical decision prudence that any 
active medical practice would take during clinical care delivery to monitor a patient’s safety and 
condition. Licensed practitioners would be taking care for patients in compliance with standards 
of care, state licensure regulations and any rules of safety practices associated with the United 
States, the State of Texas, and Texas A&M University. Clinicians would make all final clinical 
decisions, in accordance with standard of care practices for the medical conditions in each 
clinical case.  This protocol is observational in that it does not dictate a specific course of action 
in choosing which medications to prescribe. As is the case in medical practice, patients will be 
encouraged to contact the physician’s office if they require medical advice and attention.  
 
In the initial patient engagement (Figure 1), patients will present to the IPGx clinic with a 
detailed list of all their prescriptions and over the counter medications, supplements or 

 
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substance use. If available, the exact medication list will be acquired into the CSN through 
Surescripts and validated in the initial IPGx encounter. (23).  Any alternative medication 
prescribed would be medications that a licensed pharmacy would fill, such as medications 
described in First Databank (FDB). At the primary care physician or IPGx physician’s discretion, 
they may choose to further inform their decision making, utilizing additional tools such as the 
CSN, pharmacogenomic results at Innovative Gx, blood work, questionnaires. These steps will 
also serve to mitigate risk. The care delivery model will generally be for the IPGx physician or 
pharmacist to assess the patient and analyze the case before and after genotyping and/or 
clinical pharmacokinetics and provide medication management recommendations for the 
primary care physician to consider.   Should a primary care physician and a patient elect to go 
forward with therapy modifications as recommended, it would be based on the standard of care 
in medical practice and the clinical judgement of the referring physician. IPGx will actively 
participate in medication management at the request of the referring physician. No intervention 
is mandated by the protocol.  Neither the physician nor the patient are required to change 
medication in order to participate in the study, but it should be clear that the purpose of 
participation is to enable the patient and physician to have a more informed discussion about 
the best standard-of-care medicines choices among the medications the patient is taking to treat 
chronic health problems.  Overall, the clinical decision-making process will be conducted in 
accordance with standard of care and the statutory scope of practice for primary care 
physicians. It is possible that timing of ADRs may be gleaned from patterns captured in prior 
health records and the referral. The source of prior medical records would come from the 
referring physician as would be the practice in any specialized clinic such as recent, evaluation 
and management notes, allergies, hospital records, procedures, past medical-surgical, and 
family history. Patient protection would include HIPPA compliance. 
Upon IRB approval of changes to the PILOT PROTOCOL, Drs. Neal and Rogers will be 
provided a copy of the revised protocol via email and updated on changes via Zoom.  Study 
changes will also be summarized in the Quarterly IPGx investigators meeting.  Investigators 
unable to attend will receive minutes as is standard practice.   
 
Self-reported or documented ADRs.  Documented ADRs will be classified in accordance with 
NCI USNCI Cancer Therapy Evaluation Program: Common Terminology Criteria for Adverse 
Events (CTCAE) v3.0. Available online: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_8.5x11.pdf (accessed on 4 February 2020). 
• 
Off-schedule, ED/Urgent care visit notes. 
• 
Hospital visits 
• 
Clinical Data Architecture documents, including but not limited to  
o OVS – Office visit summary document  
o VDT – View download transmit summary  
o TOC—Transfer of Care ambulatory summary  
 
11. 
Data and Specimen Management: 
 
Clinical Lab.  
• 
CAP (College of American Pathologists) 
• 
CLIA (Clinical Laboratory Improvement Amendments) 
• 
ABFT (American Board of Forensic Toxicology) 
• 
ANAB (ANSI National Accreditation Board) pending 
• 
ISO (international standards organization) pending 

 
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The building that houses the lab has video surveillance, a log of personnel. Authorized access 
to the building is designated to specific personnel. Keypad security access is used. 
 
Specimens 
Until use, clinical specimens will be kept at  
InnovativerGx 
5410 Fredericksburg Road 
Suite 304 
San Antonio, TX 78229 
(210) 352-5175 
ruben.bonilla@innovativegx.com 
 
__________ 
Research specimens will be kept at 
Texas A&M 
2121 W. Holcombe Blvd 
Houston, TX 77030 
 
Monitoring, refrigeration or freezing of samples as needed will be available.  
 
Pharmacogenomic assays 
Like most pharmacogenomic tests, the assays used in this IPGx are laboratory developed tests 
(LDT) conducted in CLIA certified, CAP accredited clinical laboratories. The tests will not be 
submitted by the collaborating organizations for reimbursement by Medicare or private 
insurance, Buccal swabs for pharmacogenomics: Six samples will be obtained. The first four are 
discarded after DNA is extracted. The second two samples will be a back-up in case enough 
DNA cannot be extracted from the first sample and destroyed after 180 days.  
 
Clinical Data Center 
Goldblatt Systems Clinical Semantic Network (CSN). 
5151 East Broadway Blvd 
Tucson AZ 85711 
Telephone 520 495-1009 
 
Goldblatt Systems CSN, as an EHR the data “lives forever” in the EHR. It is a web-based 
system with security policies and procedures meeting the same standards of commercial EHRs 
regarding, security, encryption firewalls, access and authorization.  
 
Servers have software control. There are firewalls and encryption. In addition to software 
controls, there are physical controls/barriers to entry. There are procedures for offsite recovery.  
An authorized clinical user can sign in with a username and password and access patient’s 
data, when warranted. The clinical annotation and phenotypic data (information obtained in 
examinations and physician consultations, not including genetic data) will be collected on site in 
Texas by the clinical team and entered into the CSN (part of Goldblatt Systems) through a cloud 
portal to a data center housed in Tucson AZ.  Goldblatt Systems CSN has completed a Security 
Assessment Phase 1 by TAMU IT.   
 
The frequency of data collection is estimated to be once or twice per month, in each clinical 
case, daily across the cohort. 
 
Data Sharing 

 
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The IPGx will receive PHI from the Family Care Clinic through import of Health Level Seven 
International (HL7) Clinical Document Architecture (CDA) documents under the patient 
authorization, HIPPA waiver, and informed consent specified in the Protocol. Clinical data 
generated by the IPGx, the CSN, and  IC42, and InnovativeGxwill be managed in the Goldblatt 
systems CSN electronic health record.   
 
The care team  
will receive a copy of a precision medication management dashboard report summarizing 
germane information about drug concentrations and relevant CYP variants.   
 
 
The following data elements are expected to be collected and shared among the collaborators 
(and de-identified where appropriate): 
 
Clinical EHR 
• 
Demographics (age, race, zip code, sex)  
• 
Medication history 
• 
Diagnoses 
• 
Hospitalizations 
• 
Physician notes 
• 
Pharmacy 
 
Lab 
• 
Genotypes and raw sequence data, when available 
Figure 1- Clinical and data care pathway of a case through the referring clinic (Texas A&M Family Medicine) care, 
the Texas A&M Health Interprofessional Pharmacogenomics Clinic, and the associated IPGx Data Repository 
program.  Update InnovativeGx 

 
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• 
Clinical chemistry 
• 
Drug concentrations 
 
Patients will be referred to the IPGx for evaluation and “consultation”. After the IPGx performs 
its evaluation, the document created in the CSN will be transmitted back to the referring 
physician. 
 
There are several methods of accomplishing this. 
• 
Initial phone call to discuss salient aspects of the evaluation 
• 
A CSN-generated PDF will be transmitted to referring physician via fax 
• 
Clinical Data Architecture (CDA) 
• 
Create a screen sharing session so that referring clinics can see the IPGx Medication 
Management dashboards review what is being used to inform IPGx decisions 
 
All clinically actionable variants (per CPIC guidelines) obtained from the pharmacogenomic and 
steady-state pharmacokinetic assays will be compiled into the IPGx report and shared with the 
referring physician. These genotyping reports are commonplace in the field of 
pharmacogenomics and the formatting of these reports whether in a paper form or electronic 
rendering, are not treated as experimental.  No experimental interventions will be utilized at any 
time in the IPGx clinic.  Medication changes or dosing adjustments will be ordered by licensed 
physicians, in accordance with standards of care for a given drug or class of drugs and 
evidence-based recommendations, and within the applicable medical guidelines at the 
discretion of the physician. Specific medication or interventional protocols are NOT 
prospectively prescribed by this protocol.  The IPGx test result, report, software rendering are 
not prescriptive and only provide analytic information from a lab test to a physician under CLIA 
regulations.  This means that the menu choices of medications that a physician uses in the 
provision of standard of care remains the same. The IPGx report (whether in paper form or 
electronic rendering) is among all the other information (i.e., the patient’s chart) that informs the 
choice of medication. The physician retains full control to consider or ignore the IPGx report 
when making medication choices, just like any other lab report order or any other piece of 
information in the EMR a physician normally considers when continuing, deprescribing, or 
prescribing a new medication.  
 
At the point the patient signs an informed consent to participate in the IPGx Pilot Study, 
research activities (data collection only, there is no prescribed, randomized assignment to an 
intervention) will begin (Fig. 1). Any PHI within the Pilot Study will be managed in accordance 
with the attached consent, and applicable contractual and statutory requirements restricting its 
use of sharing will be applied at all times.  
 
12. 
Data Analysis: 
 
The data will be used by TAMU in implementation of informatics workflows for the IPGx.  Lab 
results will be used in clinical management during clinical quality assessment and review and 
inform medication decisions by Dr. Neal and/or the PCP.  Samples and clinical data will not be 
used for any analysis beyond the scope or timeframes specified in this protocol. 
 
13. 
Participant Safety: 
(This section is required when research involves more than Minimal Risk to participants.) 

 
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The study likely poses minimal-to moderate risk since it is not interventional: there is no 
prescriptive intervention and no requirement  for patients or physicians to change medications  
The protocol will involve a standard of care medication management approach, albeit informed 
by drug metabolism and pharmacogenomics information. While polypharmacy patient 
populations with co-morbidities are at elevated risk of ADRs, the proposed protocol involves 
similar or lower risk to participating patients compared to routine clinical practice. Study 
participants will benefit from standard of care medication management decisions made by 
clinicians who will be better informed about an individual’s pharmacogenomic ability to 
metabolize the drugs they are taking, and any issues related to drug metabolism that could be 
affirmed by direct measurement of drug levels (and their metabolites) in blood (in clinical care, 
outside this study protocol, at the discretion of the provider). In short, the protocol is likely to 
enhance the safety of research subjects relative to patients receiving standard of care in a 
primary care setting without the information this study will provide. In this vein it should be noted 
that the FDA has a current posture of not regulating physician facing clinical decision support 
tools (24).  However, the FDA has issued nonbinding guidance (25) for Software as a Medical 
Device (SaMD) that recommends design control and clinical evaluation standards, including the 
use of third-party certifications, for SaMD.  While the CSN and the pharmacogenomic 
dashboards being used in this protocol are not subject to FDA regulation under the SaMD 
framework (like most electronic medical record readouts), the CSN platform has received 
certification from rigorous third party (ONC-Authorized Certification Bodies) evaluation. These 
established standards in the health informatics industry establish low tolerances for 
computational or design flaws in software that can render erroneous information for clinical 
decision making that poses risks to patients. 
 
It should be noted that standard of care for changing most medications is simply trial and error 
(22), with a few exceptions warranting pharmacogenomic testing though consensus medical 
guidelines for actions based on results of pharmacogenomic exist and are endorsed by 
Association for Molecular Pathology, American Society for Clinical Pharmacology and 
Therapeutics, and the American Society of Health-System Pharmacists.  The working principle 
for this program is that the risks of being a polypharmacy patient without medication 
management care are greater than the risks of trying to ameliorate that burden with 
pharmacogenetic and drug level testing to inform medication management. In many respects 
that study can be viewed as a quality improvement project for participating clinics. For these 
reasons, the proposed study is one of minimal to no risk. 
 
It is expected that study participants remain engaged with the primary care clinic from where 
they were referred. Since the period of study is 180 days and the recommendation calls for 
periodic re-evaluation of the enrollee, if concerns arise the referring clinician would help address 
the need to monitor safety. Lab data will be reviewed as it becomes available. We will establish 
a safety monitoring board constituted by team members to oversee and report any adverse 
events issues or episodes to the IRB. Because medication management is expected to align 
with standard of care and within normal parameters of physician judgment, the risk of adverse 
outcomes is minimal relative to a care plan that omits a medication management element and 
the polypharmacy and pharmacogenomics information that will be made available to the care 
team.   
 
Data Safety Monitoring Plan.   
 
Clinical study staff and investigators, under the supervision of the PI will review all data on an 
ongoing basis for data completeness and accuracy as well as protocol compliance.  All data will 
be appended to the CSN Medical record and reconciled by Dr. Rogers, Abu-Baker, or Udeani, 

 
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under the supervision of Dr. Ramos and Dr. Neal when each subject first presents to the IPGx.    
Drs. Ramos, Neal, and Rogers will review the safety and progress of the study quarterly, after 
medication changes occur in at least 5 subjects. Study reports, including patient recruitment, 
retention/attrition, and AEs, will be produced following each of the quarterly reviews.  Study 
reports will be compiled for each subject at the closeout of this pilot study, with a study report for 
each case appended to the CSN for record keeping. 
 
Items to be in the closeout report and reviewed by the PI include: 
• 
Interim/cumulative data for evidence of any study-related adverse events and serious 
adverse events; 
• 
Summary of data quality, completeness, and timeliness; 
• 
Adequacy of compliance with goals for recruitment and retention, including those related 
to the participation of women and minorities; 
• 
Adherence to the protocol; 
• 
Factors that might affect the study outcome or compromise the confidentiality of the trial 
data (such as protocol violations); and, 
• 
Factors external to the study such as scientific or therapeutic developments that may 
impact participant safety or the ethics of the study. 
 
AEs will be noted in the CSN categorized according to the likelihood that they are related to the 
study intervention. Specifically, they will be labeled definitely unrelated, definitely related, 
probably related, or possibly related to the study intervention.  AEs will be labeled according to 
severity, which is based on their impact on the patient. An AE will be termed “mild” if it does not 
have a major impact on the patient, “moderate” if it causes the patient some minor 
inconvenience, and “severe” if it causes a substantial disruption to the patient’s well-being.  In 
the final study report, the PI will attest that they have reviewed all AE reports 
 
A serious adverse event (SAE) is any adverse event that results in one or more of the following: 
• 
Death 
• 
A life-threatening event 
• 
Inpatient hospitalization or prolongation of existing hospitalization 
• 
A persistent or significant disability/incapacity 
• 
A congenital anomaly or birth defect 
 
Any SAEs will be documented and reported to the TAMU IRB in accordance with HRP-029 (5 
business days or less).   
 
The PI will codify each review with their actionable recommendations to IPGx as to whether the 
study should continue without change, be modified, or be terminated.  
 
Recommendations regarding modification of study could include: 
• 
Changes of the study protocol raised by the review of the safety data; 
• 
Suspension or early termination of the study because of serious concerns about 
subjects’ safety, inadequate performance, or rate of enrollment;  
• 
Corrective actions regarding a study center whose performance appears unsatisfactory 
or appears to raise questions regarding the conduct of the study. 
• 
 
Immediate Action Report: The clinical Investigators will notify the PI and TAMU HRPP/IRB of 
any observations of a serious and immediate nature or recommendations to discontinue all or 
part of the study.   In addition to verbal communications, recommendations to discontinue or 

 
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substantially modify the design or conduct of a study must be conveyed to the PI and the TAMU 
HRPP/IRB in writing by e-mail, fax, or courier within 5 business days of occurrence.  
 
The study period is limited (one visit and 12 months of chart analysis), the number of subjects is 
small (n=22), and the risks to subjects are of low likelihood and low magnitude of harm, so 
stopping for futility is not justified.   
 
 
 
 
14. 
 Withdrawal of Participants: 
 
An individual can be suspended or removed from the research protocol due to non-compliance 
with visits. Issues such as pregnancy, admission to hospice, death, will be evaluated by clinical 
staff in consultation with the principal investigator. Adverse Drug Responses (ADRs) as defined 
by Aronson:  “ arise when a compound (e.g. a drug or metabolite, a contaminant or adulterant) 
is distributed in the same place as a body tissue (e.g. a receptor, enzyme, or ion channel), and 
the encounter results in an adverse effect (a physiological or pathological change), which results 
in a clinically appreciable adverse reaction.” (26).  For clarity, ADRs will not necessarily be a 
reason for removal of a subject from the study. An orderly termination procedure would include 
written notice and or documented phone call between the subject, their  legal guardian, if 
appropriate, and a member of the care team. Enrollees will be given a two-week notice. The 
only safety reason for termination is the determination by the medical staff the patient’s 
condition necessitates discontinuation of participation in the study. An example would be a 
determination by the physician that continued participation in the study would be deleterious to 
the enrollees’ health. If a patient withdraws from the research, they will still be able to continue 
to be a patient at the IPGx. 
 
15. 
 Risks to Participants: 
 
Risks involved:  
• 
ADRs consistent with standard of care for their disease burdens. 
• 
Complications associated with a change in medication dose frequency or discontinuance 
of a medication. PL (probability low), see below 
• 
Medication associated side effects such as nausea or vomiting, diarrhea, constipation, 
gastrointestinal, genitourinary, psychiatric, cardiac, or other medical system problems. 
PM MM DS (probability moderate, magnitude moderate, duration short) and so forth. 
• 
Medication allergy such as rash, difficulty breathing, or as life-threatening as a Steven 
Johnson syndrome. PL, MM / L DS / M 
• 
Other discomfort, hazards or inconveniences, taking into consideration physical 
psychological, social legal, and economic risk. ML 
• 
Scheduling an appointment. 
• 
Traveling to appointment. 
• 
Transportation. 
• 
Time spent in clinic. 
• 
Phlebotomy along with its associated risks ranging from ecchymoses, hematoma, nerve 
injury, infection. PL 

 
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• 
Pharmacy and physician visit copay. 
• 
Medication management in pregnant women, medication changes may carry significant 
inherent risk to the fetus. Pregnancy is both a reason for exclusion and being withdrawn 
from the protocol. 
 
Key 
Probability P  |  Magnitude M  |  Duration D  |  Short S   |  Low L  |  Moderate M  Extensive E 
 
The use of the PGx dashboard of the PGx test results does not alter the magnitude of risks to 
subjects whose medications are changed from one standard of care medication to another 
standard of care medication.  These choices are made by physicians, within their professional 
discretion and statutory scope of practice, and regrettably, it is common for medications to be 
harmful because of the unknown genetics of the patient or unrevealed drug interactions.  These 
choices are routinely made by primary care physicians (and specialists) without the benefit of 
understanding whether a patient may be experiencing adverse drug reactions and 
understanding whether those reactions may be a result of drug-drug interactions to drug-gene 
interactions.  Put another way, the menu of choices of medications is not altered under the 
Protocol or by virtue of Pilot Study participation, only that the physician is more informed.   
 
The likelihood of new risk is slightly increased in that test results could be erroneous or 
improperly rendered by the CSN.  In such a case, the physician may choose a new standard of 
care medication while misinformed about the genotype of a patient.  This is no worse than 
choosing a new standard of care medication while uninformed about the genotype of a patient.  
The likelihood of such errors is inherent in all CLIA tests that are used pervasively in the 
practice of medicine, and the probability and magnitude of risk to the patient is miniscule.  One 
of the two principle of beneficence in the Belmont Report is to “maximize the possible benefit 
and minimize possible harms.”  In the present case, the benefits of informing medication 
management far outweigh the inherent risks of making suboptimally informed medication 
management decisions (or doing nothing) when the medications the patient is currently taking 
are suspected of currently inflicting harm.  Subjectively, the likelihood and magnitude of harm to 
subjects are low while the potential benefits are highly probable. 
 
17. 
Potential Benefits to Participants: 
 
The study is designed in alignment with the principles of Standards in the Conduct of Registry 
Studies for Patient-Centered Outcomes Research – Report to PCORI [11].  A description of the 
scope of the polypharmacy problem is described in more detail in Sections 3:  Objectives, 4: 
Background, 9: Outcome measures, 13: Participant Safety.  
 
Additionally, we seek to understand how and when polypharmacy begins the cascade of ADRs 
such as ED visits, falls, or expression of another comorbidity. Our expectation is that a patient 
will experience reduced polypharmacy burden, and that participation in a medication 
management program with pharmacogenomic and informed drug dose titration (when 
warranted), will reduce ADRs that are common and frequent in these populations. We also 
expect that participation will improve adherence.   
 
The clinical burden of highly prevalent anticholinergic medications can be quantitatively 
monitored such that refined use of this class of drugs has substantial potential to inform and 
impact this major contributor to polypharmacy burden. 
 

 
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Benefits of the study for the healthcare and scientific communities 
 
The potential benefit and reason for requesting this study is to develop a polypharmacy solution 
utilizing electronic clinical decision support, pharmacogenomic studies, and blood drug levels 
(derived from urine drug levels in this study).  We might understand the impact of comorbidities 
such as depression or cognitive problems due to non-compliance. These phenomena are major 
drivers of high healthcare utilization, with genetic and social determinants. This care team 
strategy enables the collection of data underlying these factors. It can help inform clinical 
decision making (medication adjustments) in a manner that improves quality of life (reduced 
side effects), and clinical outcomes for patients (improved efficacy).   
 
As the enrolled population and our database grow, we might identify novel genotypes for drug 
metabolism that inform precision dosing and improve risk management through medication 
management programs. Our informed consent form, collaborative structure, and contracts will 
thoughtfully account for the best way to allow for compliant and deidentified sharing of the data 
collected under this protocol with the clinical and scientific community, including but not limited 
to peer-reviewed publication. 
 
18. 
Vulnerable Populations: 
Not eligible. 
 
19. 
Sharing of Results with Participants: 
 
The results of the IPGx’s evaluation and management, such as lab data, pharmacogenomics, 
and drug blood levels (inferred from urine drug levels in this study), will be shared with the 
referring physician in Texas A&M Family Care Clinic  and patients as soon as it is practical 
during the course of care, referred back to the referring physician with a report to explain 
medication management recommendations. Results may be shared, utilizing all means of 
communication commonly available to physicians in the practice of medicine. For example, at 
the time of visit or by phone. The rationale for this is that clinical decisions will be made 
regarding medication management, and the patient will be an engaged participant in that 
process. Results in the form of a precision medication management dashboard report 
summarizing germane information about drug concentrations and relevant CYP variants, will be 
shared with the ordering physician and the referring physician/primary care physician in written 
form. 
 
20. 
Setting: 
 
Texas A&M University.  Research participants will be recruited from the patients referred to the 
iPGX clinic from their primary care physician for polypharmacy problem consultation. The out-
patient IPGx clinical site will be a clinic owned and managed by Texas A&M Health. Participants 
will be recruited from Texas A&M primary care clinics. Collaboration with the primary care 
component would involve patients who meet inclusion criteria prescribed by this protocol. In 
some instances, as requested by the referring physician, IPGx clinicians will make medication 
change recommendations, and keep the referring clinic apprised of these recommendations. If a 
patient wishes to be seen at the IPGx but does not meet inclusion criteria, all recommendations 
will be directly reported to the referring primary care clinic for review and determination. The 
research will be performed at the clinic site designated by Texas A&M, but some bioanalytic 

 
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Document Version:   June 13, 2023 
sample analysis will occur offsite.  Please see section 7 above regarding multi-site. The CSN 
decision support will be handled either on-site in the Texas A&M clinic and or with assistance 
from CSN Tucson, AZ. 
No community advisory review board other than what is customary for Texas A&M is considered 
at this time. If the decision is made that a community advisory board is indicated, members 
might include those who represent the referring physicians, a community pharmacy, and a 
patient advocate. 
 
21. 
Personnel and Resources Available: 
 
Dr. Ramos MD, PhD, PharmB- Principal Investigator 
 
Dr. Ramos is a licensed physician-scientist with training and certifications in clinical 
pharmacology, toxicology, forensic medicine, and pulmonary medicine. He is an inductee in the 
National Academy of Medicine and a tenured professor at Texas A&M Health Science Center. 
Dr. Ramos also is Associate Vice President for Research at the Texas A&M University Health 
Science Center and Assistant Vice Chancellor for Health Services for the Texas A&M University 
System. Previously, Dr. Ramos was founding director of the University of Arizona Health 
Sciences Center for Applied Genetics and Genomic Medicine and chief medical and scientific 
officer of the Arizona Precision Medicine Initiative, and has been instrumental in developing 
precision health strategies, diagnostic technology, and clinical data strategies to improve health 
care delivery.  Dr. Ramos will be the Principal Investigator and be the ultimate decision maker 
and have supervisory authority for the conduct of the protocol and management of the Pilot 
Study.  Dr, Ramos will also participate in data analysis. 
 
Dr. David Jacobs MD, Co-Investigator 
Dr. Jacobs is Chief Medical Information Officer for Goldblatt Systems, a health science 
company in Arizona that focuses on using a clinical semantic network with electronic health 
records and laboratory-based data focused on pharmacogenomics.  He has been with the 
company since 2016 involved in the development and execution of a polypharmacy solution at 
the point of service for clinicians. Prior to that Jacobs practiced medicine in the areas of in-
patient post-acute care and outpatient interventional pain management. During his tenure as 
medical director of an acute inpatient rehabilitation hospital, Jacobs became acutely aware and 
interested in the challenge of polypharmacy to the senior rehabilitation population and its impact 
on their functional outcomes, where he developed system-wide approaches to this issue prior to 
having tools and technology, such as electronic decision support or pharmacogenomic testing.  
Dr. Jacobs will consult with Family Medicine and IPGx on clinical workflows and clinical 
informatics implementation and coordinate the activities of Goldblatt systems to be optimally 
configured in support of the data collection and management strategies of the future IPGx 
Registry. Dr. Jacobs will mediate the decisions about which cases warrant additional 
pharmacokinetic assays (or no pharmacokinetic analysis) and will have access to identifiable 
data. He will not consent patients or provide care.  
 
Dr. Gabriel Neal MD, Co-Investigator 
 
Dr. Gabriel Neal is board certified in Family Medicine and received his MD from the University of 
Oklahoma in 2001. Dr. Neal first joined the Department of Family Medicine in 2008 and is 
faculty in the Texas A&M Family Medicine Residency. Over the past decade he has taught in 
numerous pre-clinical and clinical courses for the College of Medicine. He is the Family 
Medicine Clerkship Director for the A&M Integrated Medicine Program at the Bryan-College 

 
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Document Version:   June 13, 2023 
Station College of Medicine Campus. His teaching illuminates applied evidence-based medical 
care and ethics. He was awarded Clinical Faculty Preceptor of the Year in 2011 and 
Outstanding Faculty in Family Medicine in 2019. He is Director of the Texas A&M Family Care 
Clinic and involved in several clinical research projects.  
Dr. Neal will assist in the recruitment and consenting of patients who might be eligible for, and 
benefit from, participation in the IPGx pharmacogenomic program. Dr. Neal will also participate 
in data analysis. 
 
Sara Rogers, PharmD, BCPS 
Sara Rogers is a Clinical Assistant Professor of Pharmacy Practice at Irma Lerma Rangel 
College of Pharmacy, Texas A&M University. Dr. Rogers has served as co-investigator for a 
pilot study to identify ethical values and priorities related to pharmacogenomics. Her research 
focuses extensively on patient access to and reimbursement for pharmacogenetics testing. 
Rogers serves an organizational member of the NIH National Human Genomics Research 
Institute Inter-Society Coordinating Committee for Practitioner Education in Genomics (ISCC-
PEG), Pharmacogenomics Working Group and a member of the Clinical Pharmacogenetics 
Implementation Consortium (CPIC), Dissemination Working Group. Rogers co-leads the 
Standardizing Laboratory Practices in Pharmacogenomics (STRIPE) Collaborative Community, 
a public-private multidisciplinary initiative to develop consensus-based industry standards for 
pharmacogenetics testing. She will be a healthcare provider in the IPGx clinic and assist in the 
recruitment and consenting of patients who might be eligible for, and benefit from, participation 
in the IPGx pharmacogenomic program 
 
 
Rick Silva PhD, MBA Co-Investigator 
 
Dr. Rick Silva is Executive Director Executive Director, Clinical | Translational | Industry 
Collaborations at Texas A&M Health Science Center and holds an academic appointment as 
Assistant Professor of Translational Medical Sciences in the Texas A&M Institute of Biosciences 
and Technology. He has scientific training in physiology and neuroendocrinology, with 
significant experience in implementation and management of clinical and translational research 
programs, including dimensions of regulatory science, diagnostic technology development, 
cohort strategy, and clinical data strategies in clinical translational collaborations among 
academic medical centers and industry.  Dr. Silva will serve as coordinator of the Registry and 
implementation of its data strategy with the IPGx and Family Medicine Clinics.  Dr. Silva will also 
participate in data analysis. 
 
George Udeani, PharmD, DSc, FCP, FCCP Co-Investigator 
 
Dr. George Udeani is a Clinical Professor and Head of the Department of Pharmacy Practice at 
Irma Lerma Rangel College of Pharmacy, Texas A&M University. Dr. Udeani completed 
postdoctoral training in anticancer drug discovery and development with the National Cancer 
Institute-National Institutes of Health, Bethesda, MD. He is a Fellow of the American College of 
Clinical Pharmacology, and Fellow of the American College of Chest Physicians. Dr. Udeani has 
served as principal investigator for numerous pre-clinical, as well as Phase III and Phase IV 
clinical trials. Dr. Udeani has published extensively on the use of Clinical Decision Support 
Systems in Medicine and Pharmacy, as well as in the areas of pharmacokinetics, and 
pharmacodynamics.  Dr. Udeani will consult on interpretation of pharmacogenomic and 
pharmacokinetic results and provide input on data collection and program strategies for the 
IPGx Registry. Dr, Udeani will also participate in data analysis. 
 

 
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Asim Abu-Baker, PharmD Co-Investigator 
Dr. Abu Baker is Clinical Professor and Associate Dean of Clinical and Professional Affairs at 
Texas A&M University Irma Lerma Rangel College of Pharmacy.  Dr. Abu-Baker previously held 
appointments at California Health Sciences University College of Pharmacy as Associate 
Professor of Clinical Sciences and Chair of the Department of Clinical and Administrative 
Sciences (2014-2017), St. John Fisher College Wegmans School of Pharmacy (2007-2014) as 
Tenured Associate Professor of Pharmacy Practice and Assistant Director of Experiential 
Education; and Assistant Professor of Pharmacy Practice at Lake Erie College of Osteopathic 
Medicine School of Pharmacy (2004-2007).  He completed his PharmD and an Ambulatory 
Care Residency with a focus on Endocrinology and Internal Medicine at the Albany College of 
Pharmacy. Dr. Abu-Baker completed the American Association of Colleges of Pharmacy 
(AACP) Academic Leadership Fellowship in 2014 and the Accreditation Council for Pharmacy 
Education (ACPE) Accreditation Reviewer training in 2012.  His research experience is in 
clinical outcomes and practice research. Dr. Abu Baker will consult on interpretation of 
pharmacogenomic and pharmacokinetic results and provide input on program strategies for the 
IPGx Registry. Dr, Abu Baker will also participate in data analysis. 
 
John Kriak, Pharm.D, Co-Investigator  
Dr. Kriak is a clinical pharmacist at MolecularDx and Goldblatt Systems with expertise in 
pharmacogenomics.  He will consult on interpretation of pharmacogenomic and 
pharmacokinetic results and provide input on research analysis for clinical cases.  Dr, Kriak will 
also participate in data analysis.  Dr. Kriak completed his Doctor of Pharmacy degree in 1996 
from Duquesne University in Pittsburgh PA. Since that time, he has become the president and 
CEO of CAMMCO, LLC, which is a clinical and strategic business consulting company. Dr. Kriak 
has over 25 years of experience providing clinical, medical education and business consulting 
services by authoring numerous educational programs, courses, and grants. Following 
graduation, he taught clinical pharmacology and biostatistics at Saint Francis University as well 
as worked as an author and subject matter expert for Kaplan educational centers in New York. 
Since 2007, Dr. Kriak has primarily been working with clinicians and technical engineers to help 
develop the clinical components of the Goldblatt Systems Clinical Semantic Network (CSN). He 
also currently works with MolecularDx scientists, clinicians, and technical architects on the 
development of genomic and therapeutic databases, business development for clinical testing 
services, writing of institutional review board (IRB) protocols, and clinical pilot program 
management. 
 
 
Jim Garliepp, Co-Investigator 
Jim Garliepp currently leads MolecularDx scientists, clinicians and Goldblatt systems technical 
architects on the development of genomic and therapeutic databases.  He will supervise clinical 
informatics integration between Goldblatt Systems, and Texas A&M; develop steady state drug 
level modeling and dashboards; IPGx report formatting; and clinical data curation. 
 
Reuben Guerrero, MD, DABMG, FACMG, MB(ASCP), CGMBS 
Dr. Ruben Bonilla-Guerrero serves as Innovative Genomics (IGx) Laboratories’ Chief 
Medical Officer. He is a laboratory professional, who is Mayo Clinic trained in Clinical 
Pharmacology, Clinical Biochemical Genetics, and Molecular Biology, a Fellow of the 
American College of Medical Genetics, the American Association of Clinical Chemistry, 
and is an active member of several distinguished professional organizations. Dr. Ruben 
Bonilla-Guerrero board certified in Clinical Biochemical Genetics by the American 
Board of Medical Genetics (ABMG) and in Molecular Biology by the American Society 

 
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for Clinical Pathology (ASCP), with expertise in clinical pharmacology, inborn errors of 
metabolism, genetics, vaccine development, and clinical pharmacogenomics. Having 
authored several peer-reviewed medical publications including book chapters, Dr. 
Bonilla-Guerrero is also the winner of the Henry Christian Award from the American 
Federation for Medical Research (2002) and the Mayo Clinic Department of Internal 
Medicine Outstanding Research Fellow Award (2003). Previously, Dr. Bonilla-Guerrero 
simultaneously served as Laboratory Director, Associate Medical Director, and Medical 
Director of Medical Affairs for the department of Genetics at Quest Diagnostics, as 
well as concurrently served as the Medical Director and Vice President of Medical 
Affairs at Admera Health. He is responsible for the clinical genomic-based testing at 
Innovative Gx Laboratories and leads the Medical Affairs team. 
 
 
Institutional 
 
The roles of Goldblatt Systems and Texas A&M Health for this limited scope pilot study is be 
codified in a Beta Testing Agreement, in which each party will have specified rights to terminate 
their involvement in the study.   A limited data and nondisclosure agreement for deidentified 
data will be promulgated with Innovative Gx, and IC42,. In the event of termination of the 
collaboration the protocol and informed consent will be revised and submitted for approval of the 
amendments. 
 
Collaborating organizations 
Goldblatt Systems LLC.  The Goldblatt Systems LLC CSN Electronic Health Record will be 
used in the Precision Medication Management Practice and PHI/ePHI will be housed by 
Goldblatt in accordance with the BAA. The CSN in Tucson is HIPPA and ONC (Office of the 
National Coordinator for Health Information compliant). Goldblatt Systems LLC, as a small 
company, maintains no formal scientific/ethics policy. In the Tucson Office Goldblatt Systems 
has a staff of approximately 20 people, some of whom have worked with Dr. Goldblatt for many 
years prior, including Chief Technical Officer Jim Garliepp and the Director of Engineering. The 
team includes software engineers, content subject matter experts, implementation staff, and 
quality control and assurance staff. In Pennsylvania, Dr. Goldblatt employs approximately 20 
people as well, which consist of world-class PhD’s from places such as Johns Hopkins who 
have expertise in genomics, toxicology, mass spec, and includes operating various genetic 
arrays. At InnovativeGxin San Antonio, and IC42 in Aurora CO, there are several pathologists 
who have laboratory, toxicology, or forensic expertise. Goldblatt systems LLC has a clinical 
pharmacist (PharmD) on staff, in addition to business development legal and support personnel. 
 
InnovativeGx is a CAP/CLIA and ABFT certified clinical diagnostics laboratory.  In terms of 
research related activity outside the institution, please see 12.0 Data and Specimen Banking. 
The Texas lab is CAP CLIA, and ABFT certified.  Lab specimens for pharmacogenomics would 
be handled off-site in Innovative Gx’s San Antonio, TX clinical lab.   
 
 
IC42 is a CAP/CLIA and ABFT certified clinical diagnostics laboratory.  In terms of research 
related activity outside the institution, please see 12.0 Data and Specimen Banking. The 
Colorado lab is CAP CLIA, and ABFT certified.  Lab specimens for drug blood levels (derived 
from urine levels in this study) would be handled off-site in IC42’s  Aurora, Colorado clinical lab.   

 
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22. 
Prior Approvals 
IRB approval of this protocol, and amendments hereto, will be obtained from Texas A&M IRB, 
and any IRB of future collaborative health systems and research institutions. 
 
23.  Confidentiality 
Please see above 7, 11, 12, 13 and 19 
- Where and how data or specimens will be stored locally? Any samples will be 
collected at the Texas A&M Family Medicine Clinic using biosafety compliant 
collection kits provided by IC42, and InnovativeGx, and shipped immediately standard 
shipping. Then the samples will be handled at IC42 and InnovativeGx, in accordance 
with a fully certified lab. Specimens for this pilot study will not be entered into a 
biorepository.  
-  
- How long the data or specimens will be stored locally? Specimens will be 
confidentially stored at IC42 and InnovativeGx, until analysis and destroyed after 
usable results are generated. 
 
- Who will have access to the data or specimens locally? Nobody will have access to 
the specimens locally other than the phlebotomy staff at the TAMU phlebotomy lab. 
Data within the CSN is available to authorized providers and personnel with a 
password. 
- Who is responsible for receipt or transmission of the data or specimens locally? A 
phlebotomy staff member at the TAMU phlebotomy lab will ship specimens using the 
kits provided by IC42 and InnovativeGx. .  Test results will be sent directly to TAMU 
Family Medicine and uploaded into the CSN by an investigator on this protocol or 
authorized staff under his/her supervision and accessed by TAMU staff and 
Investigators through secure access to the CSN . 
- How data and specimens will be transported locally? There will be no local transport 
of specimens.  Data will be stored in the CSN on the cloud. 
- This CSN Module is 2015 Edition compliant and has been certified by an ONC-ACB in 
accordance with the applicable certification criteria adopted by the Secretary of Health 
and Human Services.   
- https://www.goldblattsystems.com/wp-content/uploads/2020/01/Goldblatt-2015-
Edition-Certificate-1.pdf   
 
24. 
Provisions to Protect the Privacy Interests of Participants: 
 
We will obtain written informed consent for participation, interaction, and collection of medical 
data from a patient. No participant will be required to interact with anyone or share personal 
information with anybody other than their care team providers at their referring clinic and the 
Texas A&M IPGx staff. See exclusion criteria about unwillingness to participate or consent.  
Participants will be made to feel at ease through open communication with Texas A&M IPGx 
staff and explanation of data use sharing and limitations thereof in the informed consent form. 
Participants should feel no more or less uncomfortable than when presenting to any general 
medicine clinic. There is nothing invasive to worry about other than giving urine and a buccal 
swab. Discomfort about sharing DNA information can be addressed in the informed consent 
form and consultation. Participants will be advised that their information will always be handled 

 
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confidentially. Data will be protected by the lab, and within their medical record, in accordance 
with federal privacy laws. The genetic material obtained (see 12 above) will only be used to 
determine a patient’s enzymatic handling of medications. The test to be administered will not 
delve into someone’s heritage, or other sensitive information, beyond what they consent to. 
Authorized members of the research and care team will have a password so that they can 
access the secured electronic health record.  
 
25. 
Compensation for Research-Related Injury 
N/A 
Medication management decisions are up to the referring physician or the IPGx clinic 
physician (if appropriate).  
 
While outcome data will be collected, this protocol is not intended to evaluate or 
propose any experimental intervention outside standard of care (i.e., drugs for FDA 
approved indications, or off label use at the discretion and direction of the prescribing 
physician).  
 
26. 
Economic Burden to Participants 
Transportation to the clinic.  The possible need to go to a pharmacy and pick up a new 
prescription. The costs of the tests will be supported by Texas A&M.  Doctor visits will be billed 
to their health insurance carrier. 
 
27. 
Recruitment Methods 
(Describe when, where, and how potential participants will be recruited.) Dr. Neal has identified 
22 of his patients who might benefit from participation in this IPGx Pilot study.  Research 
recruiting will be performed by Drs. Neal and Rogers and their staff using email, telephone calls, 
or in-clinic discussion as warranted for each patient.  The collateral materials used will include a 
call/in person script, an email script, and a general brochure about clinical research 
participation.   
 
Subject compensation not contemplated. 
 
28. 
Consent Process 
 
We will obtain consent in a basic informed consent form [Appendix 1].  
 
An individual team member authorized by the principal investigator and IRB can obtain consent 
from patients. Regardless of who is obtaining consent, the Principal Investigator is responsible 
to ensure the correct procedures are carried out.) 
- Where will the consent process take place? At the designated IPGx (Interprofessional 
Pharmacogenomics Clinic) or Family Care Clinic. 
- Any waiting period available between informing the prospective participant and obtaining 
the consent? It would be at the discretion of the patient to consent when they decide 
they are comfortable participating.  

 
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- Any process to ensure ongoing consent? If any material changes to the research or 
significant findings that could affect their willingness to continue participation in the 
study, subjects will be notified. Participants may end their participation at any time.  
- The role of the individuals listed in the application as being involved in the consent 
process. The role of the PI would include: answering an enrollee’s questions, discussing 
risk - benefit options and alternatives, and reporting back to the team. A patient consent 
to participate will be obtained in writing. 
- The time that will be devoted to the consent discussion. As much as needed, 1 hour 
estimated, inclusive of medical history and prescription information collection. 
- Steps that will be taken to minimize the possibility of coercion or undue influence. We 
can make it clear at the outset that this is completely voluntary, and the consent form will 
emphasize this. It will not in any way jeopardize the patient’s relationship with their 
doctor or anyone else. No financial inducements will be used. 
- Steps that will be taken to ensure the participants’ understanding.) Patient will 
acknowledge in writing they understand.   There can be a translator if needed for 
Spanish speaking subjects on select clinic days. 
 
Waiver or Alteration of Consent Process: 
NA. 
 
Participants who are not yet adults (infants, children, teenagers) 
N/A. 
This study will focus on older adults. 
Cognitively Impaired Adults 
Consent of such subjects will be done in accordance with Texas A&M policies, ethics, culture, 
and legal considerations.  
Adults Unable to Consent 
N/A, to be excluded.  See inclusion/exclusion criteria 
 
30. 
Process to Document Consent in Writing: 
See Appendix 1- Informed Consent Form 
 
31. 
Drugs or Devices: 
Electronic Medical record 
It should be noted that the FDA has a current posture of not regulating physician facing clinical 
decision support tools (24).  However, the FDA has issued nonbinding guidance (25) for 
Software as a Medical Device (SaMD) that recommends design control and clinical evaluation 
standards, including the use of third-party certifications, for SaMD.   While the CSN and the 
pharmacogenomic dashboards being used in this protocol are not subject to FDA regulation 
under the SaMD framework (as for electronic medical record readouts), the CSN platform has 
received certification from rigorous third party (ONC-Authorized Certification Bodies) evaluation.   
 
Pharmacogenomic Testing  

 
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The pharmacogenomic tests being conducted by I InnovativeGx, are  lab developed tests (LDT) 
marketed under the Clinical Laboratory Improvement Amendments (CLIA) under the jurisdiction 
of the Centers for Medicare and Medicaid Services.  Most medical decision making is based on 
LDT tests marketed under the CLIA framework, which covers about 260,000 laboratories in the 
US, and interpreted by physicians (and pharmacists) within the statutory scope of practice and 
accepted medical guidelines.  Most clinical DNA sequencing and especially, pharmacogenomic 
are commonly made available under the LDT-CLIA regulatory framework and used in 
accordance with established consensus medical guidelines.  Consensus medical guidelines for 
actions based on results of pharmacogenomic exist, are curated by the Clinical 
Pharmacogenetics Implementation Consortium (CPIC), and are endorsed by Association for 
Molecular Pathology, American Society for Clinical Pharmacology and Therapeutics, and the 
American Society of Health-System Pharmacists.   
Clinical Pharmacokinetic Tests 
The pharmacogenomic tests being conducted by IC42 and InnovativeGx,   are  lab developed 
tests (LDT) marketed under the Clinical Laboratory Improvement Amendments (CLIA) under the 
jurisdiction of the Centers for Medicare and Medicaid Services.  Most medical decision making 
is based on LDT tests marketed under the CLIA framework, which covers about 260,000 
laboratories in the US, and interpreted by physicians (and pharmacists) within the statutory 
scope of practice and accepted medical guidelines. CLIA and CAP documentation is available 
upon request. 
 
32. 
Waiver of IND or IDE 
Not relevant 
33. 
Community-Based Participatory Research* 
Describe involvement of the community in the design and conduct of the research. N/A 
 
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