Patient and Provider Confidence and Satisfaction With the Clinical Use of CYP Genetic Variability Analysis to Guide Analgesic Treatment: A Randomized, Controlled Pilot Study Using the Pain Medication and Mental Health DNA InsightTM Test.
Phase: EARLY_PHASE1
Conditions: Pain
Sponsor: Defense and Veterans Center for Integrative Pain Management

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 1 of 34 
 
Application and Request for Approval of Study Proposal 
 
 
1.0 PROTOCOL TITLE:  Patient and provider confidence and satisfaction with the 
clinical use of CYP genetic variability analysis to guide analgesic treatment: A randomized, 
controlled pilot study using the Pain Medication and Mental Health DNA InsightTM  test. 
 
2.0 PRINCIPAL INVESTIGATOR: 
   
Name:       Dr. Michael Bartoszek, MD 
Title:      Staff Anesthesiologist  
Department:      DOS/AO 
Name/Address of Institution: Womack Army Medical Center, Fort Bragg, NC 
Phone: 910-907-7209 
Email: Michael.w.bartoszek.mil@mail.mil  
 
2.1 ASSOCIATE INVESTIGATORS:  
 
Name: Dr. Anthony R. Plunkett, MD 
Title: Director of Research 
Department: Anesthesiology 
Name/Address of Institution: Womack Army Medical Center, Fort Bragg, NC 
Phone: 910-643-2423 
Email: anthonyrplunkett@gmail.com 
 
Name: MAJ Min Ho Chang, MD 
Title: Staff physician IPMC  
Department: IPMC 
Name/Address of Institution: Womack Army Medical Center, Fort Bragg, NC 
Phone: 910-907-7209 
Email: Min.h.Chang.mil@mail.mil 
 
Name: Dr. Robert N. Agnello, D.O. 
Title: Primary Care Pain Champion (PCPC) 
Department: IPMC 
Name/Address of Institution: Womack Army Medical Center, Fort Bragg, NC 
Phone: 910-570-3375 
Email: Robert.n.agnello.civ@mail.mil  
 
Name: Dr. Melissa M. Roberts, MD 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 2 of 34 
 
Title: Co-Chair of the CLER Committee 
Department: Womack Family Medical Clinic 
Name/Address of Institution: Womack Army Medical Center, Fort Bragg, NC 
Phone: 910-907-9619 
Email: melissa.m.roberts23.civ@mail.mil 
 
2.2 COLLABORATORS:  
. 
Name: Amy M. McCoart RN BSN CCRC 
Title: Research Manager DVCIPM /Henry M. Jackson Foundation 
Department: Clinical Investigations/Anesthesiology 
Name/Address of Institution: Womack Army Medical Center, Fort Bragg, NC 
Phone: 910-907-6239 
Email: amy.m.mccoart.ctr@mail.mil 
 
Name: Elizabeth Dennison  
Title: Research Coordinator 
Department: Clinical Investigations 
Name/Address of Institution: Womack Army Medical Center, Fort Bragg, NC 
Phone: 910-907-9516 
Email:elizabeth.m.dennison5.ctr@mail.mil 
 
 
Name: Dr. Krista Highland, PhD 
Title: Senior Scientist  
Department: DVCIPM/ Henry M. Jackson Foundation 
Name/Address of Institution: Defense and Veterans Center for Integrative Pain Management 
(DVCIPM), Rockville, MD 
Phone: 301-816-4732 
Email: khighland@dvcipm.org 
 
 
2.3 ROLES AND RESPONSIBILITIES:  
 
 The PI will be involved in patient recruitment, design and oversight of experimental 
methodology, literature review and manuscript writing. Dr. Plunkett will assume the roles and 
responsibilities of PI in the event Dr. Bartoszek is unavailable to carry out his responsibilities. 
AIs will be involved in patient recruitment and screening and potential manuscript writing. Ms. 
McCoart and/ or Ms Dennison will be involved in recruitment, performing patient consent, 
interviews and administering surveys, specimen collection, shipping of samples and regulatory 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 3 of 34 
 
communications.   Ms McCoart will also participate in protocol development.  
 
3.0 RESPONSIBILITIES OF THE PRINCIPAL/ASSOCIATE INVESTIGATOR IN 
HUMAN SUBJECTS RESEARCH:   
 
The principal investigator is the individual who is primarily responsible for the actual execution of 
the clinical investigation.  He/she is responsible for the conduct of the study, obtaining subjects' 
consent, providing necessary reports, and maintaining study documents. The Associate Investigator 
will assist the Principal Investigator with the responsibilities stated below.    
 
As the Principal Investigator or Associate Investigator:  
 
A. 
I will not enroll a subject into a study until the study has been approved by the appropriate 
authority and, when appropriate, the subject's primary care provider has granted approval for him/her 
to enter a study. 
 
B. By signing this protocol, I warrant that any use of Protected Health Information (PHI) for reviews 
preparatory to research met the following requirements: 
i. 
The review of PHI was done solely to prepare a research protocol, or for similar purposes 
preparatory to research;  
ii. 
No PHI was taken outside the Military Health Care System or disclosed to persons not 
having a need for this information; and  
iii. 
This review of PHI was necessary for research purposes 
 
C. 
I am responsible for assuring that the prospective volunteer is not participating as a subject in 
other research that will significantly increase the research risks to the subject. 
 
D. 
I am responsible for assuring the quality of each subject's consent in accordance with current 
federal regulations.  This will include ensuring that any "designee" that obtains consent on my behalf 
is completely conversant with the protocol and is qualified to perform this responsibility. 
 
E. 
I will obtain the WAMC IRB approval for advertisements used to recruit research subjects. 
 
F. 
I will not accept any outside personal remuneration for implementation of a study. 
 
G. 
I will take all necessary precautions to ensure that the study does not generate hazardous 
chemical waste. 
 
H. I will obtain the proper WAMC clearance prior to all presentations, abstracts, and publications.  
The following require WAMC approval: 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 4 of 34 
 
i.   Reports involving WAMC subjects and/or patients. 
ii. Reports that cite WAMC in the title or byline. 
iii. Reports of WAMC approved clinical investigation or research. 
iv. Reports of research performed at WAMC. 
v. Reports of research conducted by WAMC assigned personnel. 
 
I. 
I will obtain proper Office of the Surgeon General (OTSG) publication clearance prior to all 
presentations, abstracts, and 
publications that involve: 
i. Traumatic brain injury 
ii. Post-traumatic stress disorder 
iii. Poly-pharmacy 
iv. Pain 
 
(For assistance with publication clearance contact Ms. Jenkins, IRB Secretary at 
linda.j.jenkins.civ@mail.mil ) 
 
J. 
I must submit to the Clinical Investigation Service (CIS): 
 
i.    Any source of outside funding. 
ii.   An annual Continuing Review Report (CR), due in the anniversary month of the protocol’s 
initial approval or due in the month as determined by the IRB for continuing review and approval. 
iii. Reports of adverse effects occurring in subjects as a result of study participation or of any 
protocol deviations and submit these reports to Research Monitor if there is one for the study. 
iv. An Addendum, prior to any changes made to the study or a change in the funding status.  
v. Listing of presentations, abstracts, and publications arising from the study for inclusion in the CR. 
 
K. 
I will maintain a Study File that must be kept for six years following completion of the study 
if no IND/IDE used (32 CFR 219.115(b).  If IND medication or IDE appliances are used, the file 
must be kept for 2 years after FDA approval and can then be destroyed; or if no application is filed 
or approved, until 2 years after the study is discontinued and FDA notified (21CFR 312.62(c).  The 
records should be kept in the Department/Service where the research took place (AR 40-38).  If I am 
scheduled to PCS or ETS, I will notify the Clinical Investigation Service as soon as I am aware but 
at least 3 months prior to departure. Records will be given to a new WAMC PI or the 
Department/Service Chief.   
 
L. 
I will be familiar with all applicable regulations governing research, and will adhere to all of 
the requirements outlined in the WAMC’s DOD Assurance and Federal-Wide Assurance granted by 
the Office for Human Research Protections, Department of Health and Human Services. 
 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 5 of 34 
 
I. Research Monitor 
If it is determined that a Research Monitor is assigned to the research study, I agree to provide 
the name, human subject protection training and curriculum vitae of the research  monitor.  I 
acknowledge that this individual will be qualified (e.g., Medical Doctor, Nurse Practitioner, etc.).  
The research monitor will review all unanticipated problems involving risk to the subjects or 
others, serious adverse events and all subject deaths associated with the protocol and provide an 
unbiased written report of the event.  At a minimum, the research monitor will comment on the 
outcomes of the event or problem, and in the case of a serious adverse event or death, comment 
on the relationship to participation in the study.  The research monitor will also indicate whether 
he/she concurs with the details of the report provided by the study investigator.  Reports for 
events determined by either the investigator or research monitor to be possibly or definitely 
related to participation and reports of events resulting in death will be promptly forward to the 
WAMC IRB.  
 
J. Active Duty Military Personnel as Study Subjects 
Special consideration will be given to the recruitment process for military personnel.  The Chain 
of Command will not be involved in the recruitment of military personnel and will not encourage 
or order soldiers to participate in research study.   An ombudsman will be used when conducting 
group briefings with active duty personnel to ensure that volunteers understand that participation 
is voluntary.  Restrictions on compensation for active duty military members will be adhered to 
as applicable.  
 
K. Title 10 United States Code 980 
I acknowledge the requirements of Title 10 United States Code 980: “Funds appropriated to the 
Department of Defense may not be used for research involving a human being as an 
experimental subject unless-(1) the informed consent of the subject is obtained in advance; or (2) 
in the case of research intended to be beneficial to the subject, the informed consent may be 
obtained from a legal representative of the subject.” 
 
If an individual cannot give his or her own consent (e.g., incapacitated individuals, incompetents, 
minors) to participate in the research study, consent of the individual’s legally authorized 
representative will be obtained prior to the individual’s participation in the research.  Moreover,  
such subjects will not be enrolled in Dodd sponsored research unless the research is intended to 
benefit each subject enrolled in the study. 
 
4.0 LOCATION OF STUDY: Single site: Womack Army Medical Center, Fort Bragg, NC 
 
5.0 EXPECTED COMPLETION DATE: October 2016 
 
6.0 BACKGROUND AND LITERATURE REVIEW:   

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 6 of 34 
 
 
Date of Search: December 01, 2014 
Period Searched: January 1990-December 2014 
Sources Searched: Periodicals, journals, google scholar, PubMed internet 
Keywords Searched: Genomics, Genetics, Pain, DNA, translational medicine, personalized 
medicine 
 
Military service members are often injured during training (sprains, strains, etc.) or in combat 
(battle as well as non-battle injuries).1  The need to effectively manage pain and its impact on 
rehabilitation and recovery with minimal side effects led to the formation of the Pain 
Management Task Force (PMTF) by the Office of The Surgeon General (OTSG).2  This tri-
service report defined both the problem and the general lack of training for providers of patients 
who have pain. Pain is often referred to as the “fifth vial sign” and its importance has lead the 
Joint Commission on Accreditation of Healthcare Organizations (JCAHO) to evaluate adequate 
pain control as an important marker in quality.3 Opioids have been a mainstay of pain 
management since morphine was first discovered in the 1800s.  Opioids, however, can be 
associated with various adverse side effects including postoperative nausea and vomiting, 
constipation, ileus, and respiratory depression.4 Treatment of acute pain may help prevent the 
development of chronic pain and lower the risk of addiction. 
Chronic pain is the leading cause of disability in the United States, with the top 2 reasons being 
back pain and arthritis.19 In the military, it is the leading cause of medical evaluation board 
initiation, and a major reason for evacuation from theaters of operation.20-24 The annual cost to 
treat chronic pain in the U.S. costs hundreds of millions of dollars, and the proportion of 
individuals on disability has nearly doubled over the past 20 years.  Interventional treatments for 
pain are expensive and have done little to reduce the rates of disability or need for surgery.25 
Analgesic medications such as opioids and adjuvants all possess significant adverse effects, 
including sedation and cognitive impairment, which can be particularly detrimental in service 
members.  This indicates a strong need for safe, effective treatments for chronic pain. 
 
The extraordinary variation in patients’ response to medications has been attributed to genetic as 
well as environmental factors. However, genetic variations are generally believed to account for 
up to 95 % of the observed variability in drug disposition and effects.5 The inter-individual 
variability in both pain sensitivity and response to medication is both fascinating and frustrating.  
It has long been the primary care providers biggest challenge to identify the most effective 
analgesic regimen in each patient.  Unfortunately, beyond an individual provider’s experience 
with analgesic medications, typically little objective data are available to assist healthcare 
providers in predicting an individual’s response to a given medication.  Several studies have 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 7 of 34 
 
suggested specific genetic variations as responsible for the vast inter-individual differences seen 
in patients.6-10 A review of cancer-related pain identified a number of genetic variations that are 
current targets of both diagnosis and treatment.11 The narrow therapeutic dosing range of opioid 
medications combined with the highly stressful military working environment has brought 
significant attention to the field of pain and opioid dependence management.  The concept of 
personalized or precision medicine, based on the human genome, is considered the next major 
breakthrough in healthcare.  Currently the FDA has approved pharmacogenetic information for 
over 100 medications including popular analgesics such as tramadol, codeine and carisoprodol.12 
Normal genetic variations in genes that encode drug metabolizing enzymes or drug receptors can 
result in inter-individual variations in drug response, i.e., the degree to which an individual 
metabolizes a drug or triggers a biological response can have a large effect on the success of the 
drug therapy. Therefore, genetic tests that determine gene variations can be useful in adjusting 
drug dosage based on patients’ individual gene variations.  This information allows medication 
plans to be tailored to the individual patient, maximizing drug efficacy while minimizing drug 
associated adverse effects. The CYP (Cytochrome P450 gene) superfamily is one of the most 
important groups of enzymes involved in the oxidation of therapeutic drugs, xenobiotics and 
endogenous compounds.13 Many CYP isoforms are expressed polymorphically because of 
mutations in the CYP genes (Figure 1). The CYP2D6, CYP2C9 and CYP2C19 genes are 
particularly polymorphic.14 Many of these polymorphisms have functional significance, resulting 
in altered enzyme activity or complete loss of enzyme expression.14 Individuals can be classified 
into distinct metabolizer classes based on the CYP variants in their genome.  For example, 
individuals can be classified based on their CYP2D6 enzyme activity into four metabolizer 
groups: Ultrarapid Metabolizer (UM, higher than normal enzyme activity), Extensive 
Metabolizer (EM, normal enzyme activity), Intermediate Metabolizer (IM, intermediate enzyme 
activity) and Poor Metabolizer (PM, low or no enzyme activity, Figure 2).  Clinical studies have 
demonstrated that individuals that were PMs for CYP2D6 metabolized drugs and taking codeine 
had very low systemic exposure to the active compound morphine compared to EMs.15,16  
Therefore, PMs may experience little to no pain relief from codeine.16,17 In contrast, UMs are at 
high risk of severe toxicity because of above average systemic exposure to the active compound 
morphine.18  In summary, the use of genomic information has the potential for improving the 
utility, efficacy and safety of pain management. 
In this pilot study the variability in CYP metabolism will be analyzed in a group of chronic pain 
patients taking opioids, using the  FDA exempt Pain Medication DNA InsightTM test and Mental 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 8 of 34 
 
Health DNA Insight™ test .  The study will identify both clinician and patient confidence and 
satisfaction with the use of this test to guide a potential change in their analgesic regimen. 
 
 
 
Figure 1: Relative contribution to drug metabolism by CYP type 
 
 
Figure 2. Variation in CYP activities has an impact on drug pharmacokinetics 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 9 of 34 
 
 
 
 
 
 
6.1 REFERENCES:   
 
1. Cohen, S.P., et al., Presentation, diagnoses, mechanisms of injury, and treatment of soldiers 
injured in Operation Iraqi Freedom: an epidemiological study conducted at two military pain 
management centers. Anesth Analg. 2005; 101(4): 1098-103, table of contents. 
2. Office of The Army Surgeon General, P.M.T.F. Providing a Standardized DoD and VHA 
Vision and Approach to Pain Management to Optimize the Care for Warriors and their Families. 
Final Report. 2010. 
3. Joint Commission Improving the quality of pain management through measurement and 
action. 2003. 
4. Oderda GM, Said Q, Evans RS et al. Opioid-related adverse drug events in surgical 
hospitalizations: impact on costs and length of stay. Ann Pharmacother. 2007;41(3):400-406.  
5. Eichelbaum, M., M. Ingelman-Sundberg, and W.E. Evans. Pharmacogenomics and 
individualized drug therapy. Annu Rev Med. 2006; 57: 119-37. 
6. Diatchenko L, Nackley AG, Slade GD, Bhalang K, Belfer I, Max MB, Goldman D, Maixner 
W. Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-
evoking stimuli. Pain. 2006; 125:216-224  
 
7. Lee Y, Kim H, Wu T, Wang X, Dionne R. Genetically mediated inter-individual variation in 
analgesic responses to COX inhibitory drugs. Clin Pharmacol Ther. 2006; 79:407-418 
 
8. Mogil J, Ritchie J, Strasburg K, Kaplan L, Wallace MR, Romberg R, Bijl H, Sarton E, 
Fillingim R. Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice 
and humans. J Med Genetics. 2005; 42:583-587  
 
9. Tegeder I, Costigan M, Griffin RS, Abele A, Belfer I, Schmidt H, Ehnert C, Nejim J, Marian 
C, Scholz J, Wu T, Allchorne A, Diatchenko L, Binshtok AM, Goldman D, Adolph J, Sama S, 
Atlas SJ, Carlezon WA, Parsegian A, Lotsch J, Fillingim RB, Maixner W, Geisslinger G, Max 
MB, Woolf CJ. GTPcyclohydrolaseandtetrahydrobiopterinregulate pain sensitivity and 
persistence. NatMed. 2006; 12:1269-1277  

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 10 of 34 
 
 
10. Zubieta JK, Heitzeg MM, Smith YR, Bueller JA, Xu K, Xu Y, Koeppe RA, Stohler CS, 
Goldman D. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain 
stressor. Science. 2003; 299:1240-1243  
 
11. Turabi A, Plunkett AR. The application of genomic and molecular data in the treatment of 
chronic cancer pain. J Sur Onco. 2012; 105:494-501 
12. US. Food and Drug Administration website. 
http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm. 
Accessed April 10, 2014. 
13. Solus, J.F., et al., Genetic variation in eleven phase I drug metabolism genes in an ethnically 
diverse population. Pharmacogenomics. 2004; 5(7): 895-931. 
14. Hiratsuka, M., In vitro assessment of the allelic variants of cytochrome P450. Drug Metab 
Pharmacokinet. 2012; 27(1): 68-84. 
15. Yue, Q.Y., et al., Pharmacokinetics of codeine and its metabolites in Caucasian healthy 
volunteers: comparisons between extensive and poor hydroxylators of debrisoquine. Br J Clin 
Pharmacol. 1991; 31(6): 635-42. 
16. Eckhardt, K., et al., Same incidence of adverse drug events after codeine administration  
irrespective of the genetically determined differences in morphine formation. Pain. 1998; 76(1-
2): 27-33. 
17. Sindrup, S.H., et al., Codeine increases pain thresholds to copper vapor laser stimuli in 
extensive but not poor metabolizers of sparteine. Clin Pharmacol The., 1990; 48(6): 686-93. 
18. Kirchheiner, J., et al., Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid 
metabolizers due to CYP2D6 duplication. Pharmacogenomics J. 2007; 7(4): 257-65 
19. Brooks PM. The burden of musculoskeletal disease- a global perspective. Clin Rheumatol 
2006; 25: 778-81. 
20. Cohen SP, Brown C, Kurihara C, Plunkett A, Nguyen C, Strassels SA. Diagnoses and factors 
associated with medical evacuation and return to duty for service members participating in 
Operation Iraqi Freedom or Operation Enduring Freedom.  A prospective cohort study. Lancet. 
2010; 375: 301-9. 
 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 11 of 34 
 
21. Cohen SP, Plunkett AR, Wilkinson I, Nguyen C, Kurihara C, Flagg A 2nd, et al. Headaches 
during war: Analysis of presentation, treatment, and factors associated with outcome.  
Cephalalgia. 2012; 32: 94-108. 
22. Cohen SP, Nguyen C, Kapoor SG, Anderson-Barnes V, Foster L, Shields C, McLean B, 
Wichman T, Plunkett A. Back pain during war: An analysis of factors affecting outcome.  Arch 
Intern Med. 2009; 169: 1916-23  
 
23. Cohen SP, Kapoor SG, Nguyen C, Anderson-Barnes V, Brown C, Schiffer D, et al. Neck 
pain during combat operations: an epidemiological study analyzing clinical and prognostic 
factors.  Spine. 2010; 35: 758-63.  
 
24. Cohen SP, Kapoor S, Anderson-Barnes VC, Turabi A, Nguyen C, Plunkett A. Non-cardiac 
chest pain during war. Clin J Pain. 2011; 27: 19-26.   
25. Deyo RA, Mirza SK, Turner JA, Martin BI. Overtreating chronic back pain: time to back 
off? J Am Board Fam Med. 2009; 22: 62-8. 
26. Saxon AJ. Returning veterans with addictions.  Psychiatric Times. July 14, 2011.  Available at: 
http://www.psychiatrictimes.com/military-mental-health/content/article/10168/1906035 
 
27. Sehgal N, Manchikanti L, Smith HS. Prescription opioid abuse in chronic pain: a review of 
opioid abuse predictors and strategies to curb opioid abuse. Pain Physician. 2012; 15(3 Suppl): 
ES67- 
 
28. Certainty Item: Bennette CS, Trinidad SB, Fullerton SM, Patrick D, Amendola L, Burke W, 
Hisama FM, Jarvik GP, Regier DA, Veenstra DL. Return of incidental findings in genomic 
medicine: measuring what patients value--development of an instrument to measure preferences 
for information from next-generation testing (IMPRINT). Genet Med. 2013 Nov;15(11):873-81. 
 
29. Confidence Scale: Estes R, Hosseini J The gender gap on Wall Street an empirical analysis of 
confidence in investment decision making J Psychol. 1988,12.577. 
 
30. Satisfaction Items: Holmes-Rovner M, Kroll J, Schmitt N, Rovner DR, Breer ML, Rothert 
ML, Padonu G, Talarczyk G. Patient satisfaction with health care decisions: the satisfaction with 
decision scale. Med Decis Making. 1996 Jan-Mar;16(1):58-64. PubMed PMID: 
8717600. 
 
31. Decision regret items: Brehaut JC, O'Connor AM, Wood TJ, Hack TF, Siminoff L, Gordon 
E, Feldman-Stewart D. Validation of a decision regret scale. Med Decis Making. 2003  Jul-
Aug;23(4):281-92. PubMed PMID: 12926578. 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 12 of 34 
 
 
32. Kreft, I. & De Leeuw, J. (1998).  Introducing multilevel modeling.  London: Sage. 
 
33. Singer, J. D., & Willet, J. B. (2003).  Applied longitudinal data analysis. Oxford: Oxford 
University Press. 
 
34. Nesselroade, J. R.  (1991).  Interindividual differences in intraindividual change. In L. M. 
Collins & J. L. Horn (Eds). Best methods for the analysis of change (pp.92-105). Washington, DC: 
American Psychological Association. 
 
35. Maas, C. J. M., & Hox, J., J. (2004).  Robustness issues in multilevel regression analysis.  
Statistica Neerlandica, 58, 127-137. 
 
36. Roberts, J. K., Monaco, J. P, Stovall, H., & Foster, V.  (2011).  Explained variance in multilevel 
models. In J J. Hox & J. K Roberts (Eds). Handbook of advanced multilevel analysis (pp.219-230). 
NY: Taylor and Francis. 
 
37. Raferty, A. E. (1993).  Bayesian model selection in structural equation models. In K. A. Bollen 
& J. S. Long (Eds). Testing structural equation models (pp. 163-180). Newbury Park: Sage. 
 
38. Raudenbush, S., Bryk, A., Cheong, Y. F., Congdon, R., & du Toit, M.  (2011).  HLM 7: 
Hierarchical linear and nonlinear modeling.  Lincolnwood, IL: Scientific Software International. 
 
7.0 PURPOSE:  To determine the confidence and satisfaction with clinical utility of the Pain 
Medication and Mental Health DNA InsightTM  tests in optimizing analgesic regimens. 
 
7.1 HYPOTHESES/RESEARCH QUESTIONS:  
 
This is a pilot study and thus our goal is to explore the feasibility of an appropriately powered 
clinical study, which would investigate the utility of the Pain Medication and Mental Health 
DNA Insight ™ test to improve pain management of patients with chronic pain. Our goal is to 
explore how providers and patients will respond to this test and we intend to use our findings to 
generate hypotheses and preliminary data for a robust, fully powered clinical trial in the future. 
 
Our research questions are: 
 
How does the use of the Pain Medication and Mental Health DNA Insight ™ test affect provider 
satisfaction, certainty and confidence in dosing of opioid and non-opioid analgesics? 
 
How does the use of the Pain Medication and Mental Health DNA Insight ™ affect patient 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 13 of 34 
 
satisfaction, certainty and confidence in pain management plan? 
 
How does the use of the Pain Medication and Mental Health DNA Insight ™ test affect pain 
related patient-reported outcomes, including DVPRS, PROMIS and BPI scores? 
 
7.2 SPECIFIC AIMS/SIGNIFICANCE:   
Specific Aims 
 
1. 
Examine trends in provider decisions in prescribing analgesics and modifying analgesic 
treatment plans and provider outcomes for satisfaction, certainty and confidence in dosing of 
analgesics with and without access to Pain Medication and Mental Health DNA Insight ™ 
genetic testing results.  
 
2. 
Examine trends in patients’ satisfaction, certainty and confidence in dosing of analgesics 
between patient groups whose providers had access to Pain Medication and Mental Health DNA 
Insight ™ genetic testing results and those whose providers did not have access to the genetic 
information.   
 
3. 
Compare patient-reported pain and mental health outcomes between patient groups whose 
providers had early access to Pain Medication and Mental Health DNA Insight ™ genetic testing 
results to those who had delayed access in the control period and subsequently following later 
access to the results.  
 
The general aim of this pilot study is to assess the utility of a test that analyzes the DNA of 
chronic pain patients to determine their metabolic response to common analgesics, anti-
depression and anxiolytic medications, to improve provider and patient confidence and 
satisfaction with the pain treatment plan.  The results of the DNA analysis will help guide 
providers to change or continue the current analgesic regimen. This concept is known as 
“personalized” or “precision” medicine - the ability to treat patients based on their genetic profile 
in order to maximize therapeutic effect and minimize or eliminate unwanted side effects.   
 
7.3 DESIGN 
7.3.1 Design type:  
 
This is a prospective, randomized, controlled, observational pilot study analyzing both providers’ 
and patients’ perceptions and responses to the DNA Insight test. For this study there will need to 
be a total of twelve provider groups to be enrolled and 4-8 of each provider’s patients will be 
enrolled in the study. Enrollment will continue of providers until up to 12 providers and 48 
patients have been enrolled in the study.  Therefore twelve to sixteen military health system 
primary care providers will need to be consented due to withdrawal of providers prior to 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 14 of 34 
 
referring patients.  A total of 48 patients will be enrolled, 4-8 patients for each of the actively 
enrolled providers (12- 16 providers and 48 patients total). Each provider’s patients will be 
randomized into delayed treatment (Group A) or immediate treatment (Group B) at a 1:1 ratio. 
Each participating provider will agree to order and interpret a Pain Medication and Mental 
Health DNA InsightTM test. Results for patients in Group A will be given to the provider with a 3 
month delay. Those in the 3 month delay will serve as a comparison group for the period prior to 
receiving intervention.  Results for patients in Group B will be given to the provider without 
delay, 2-3 weeks after saliva sample collection. The provider will use the results of the Pain 
Medication and Mental Health DNA InsightTM test to evaluate whether changes of medications 
are indicated based on the individual patient’s genetic profile. A measure of the provider’s 
certainty, confidence, satisfaction, perception of care and global impression of change will be 
assessed at baseline, prior to obtaining the test results, and after obtaining the test results, as 
outlined in the data collection section.  Patients’ pain related self-reported outcomes, certainty, 
confidence and satisfaction will be assessed at baseline, prior to obtaining the DNA InsightTM 
test results, and after receipt and implementation of the test results, as described in the data 
collection section of the protocol. 
 
At the baseline visit (Visit 0) each enrolled patient will provide a saliva sample for the Pain 
Medication DNA InsightTM test that identifies genetic variation in CYP metabolism. The 
providers and patients will be recruited from any of the Womack Army Medical Center’s 
Primary Care Medical Homes and family practice clinics. 
 
Provider Inclusion: 
● Licensed provider serving as a primary care manager in the Womack Army Medical Center 
Health Care System to include physicians, physician assistants and nurse practitioners.  
 
Provider Exclusion 
● Resident 
 
Patient Inclusion: 
 
● Military healthcare system beneficiary enrolled in the Womack Army Medical Center 
Health Care System  
● Age 18 or older 
● Patient of the enrolled provider for at least 3 months. 
● Persisting pain for at least 3 months, with average daily pain score of 4 or higher that is not 
expected to improve without directed therapy. 
● No history of chronic liver or kidney disease  
 
Patient Exclusion: 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 15 of 34 
 
 
● Known pregnancy or breast feeding 
● Planned deployment, permanent change of station, or military separation within upcoming 
6 months 
 
7.3.3 Number of Participants:  12-16 Primary Care Managers and 48 patients enrolled in any of 
the Womack Army Medical Center’s Primary Medical Homes or clinics with corresponding 
credentialed primary care managers 
 
7.3.4 Explanation of the process from consenting to data collection:  
 
♦ The Primary and Associate investigators  along with Ms Dennison will recruit the 12- 
16 primary care providers from the Womack MHS. Dr. Agnello, Ms Dennison or Mr. 
Phillips will present a short PowerPoint presentation at the provider monthly meeting, the 
OIC will be ask to leave the room and be presented with the study separately. Interested 
providers will be asked to sign a consent form that explains there role in the study.   They 
also will be shown a sample of what the reports will look like.  
 
♦ A month after presenting to a clinic, providers that attended the meeting will be sent a 
reminder email from the research coordinator. The OIC or HSS for that clinic or Dr. 
Agnello will be ask to distribute a provider ad to all providers (Appendix 1). This ad will 
ask for volunteers and give the research team contact information.  
 
♦ The provider ad will be posted in the WAMC bulletin along with a small description of 
the study.  
 
 
♦ The enrolled providers will identify potential candidates within their panel based on 
inclusion/exclusion criteria and refer the interested patients to the study coordinator for 
potential inclusion in the study.  They will be provided a script (Appendix A) on what to 
say to potential candidates. That script will refer the potential subjects to contact the 
study coordinator. They will be given a sheet with the study coordinator’s contact 
information on it (Appendix B), a patient ad (Appendix 2) will also be attached that gives 
a small amount of information about the study and states that If the patient does not 
contact the coordinator after 5 business days, they will be called to ask about their interest 
in the study (Appendix 3). The provider will email or call the coordinator with the 
patients name and phone number. The providers will provide basic contact information 
that will include name, clinic, phone and email (Appendix C1) This appendix will also 
list their patient volunteers by study ID number that they will be treating.  
 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 16 of 34 
 
♦ AIs will suggest potential candidates to enrolled providers if they deem expectable 
through normal clinic exposure and consults.  
 
♦ The head nurses/nursing staff of each enrolled provider will be briefed on the study, 
inclusion/ exclusion criteria and their role in recruitment. The nurses will be ask to give 
potential candidates they think may qualify for the study a patient ad (Appendix 2).  
 
♦ A poster that looks similar to Appendix 2 will be placed in each recruiting clinic’s lobby 
to expose potential candidates to the idea of the study.  Contact information is provided 
for the potential candidate to contact the research team. The poster asks for interested 
patients to fill out an information card with their name, phone number, and provider 
name. The cards can be placed in a solid box. The research coordinator will pick up all 
cards once a week. All patients will be called. Patients with providers not enrolled in the 
study will be thanked for their interest and told they cannot participate.  
 
♦ The research coordinator will have access to consented providers’ patient list through 
AHLTA. Pain patients will be identified daily through the “reason for visit” column. The 
patient will be sent a recruitment letter stating information about the study. A member of 
the research team will then call the potential patient about 4 days after sending the letter 
to see if the subject is interested and qualifies for the study. If the provider already has 4 
patients participating or feels that patient would not be a good candidate the patient will 
be informed they do not qualify and they will be thanked for their time.  
 
♦ Consented providers will be sent an email to inform them that their pain patients will be 
sent letters to see if they are interested in the study. Providers will be informed if their 
patient is interested in the study.   
 
♦ A screen excel will be kept on a password protected computer. The spreadsheet will be 
used to keep track of patients who have been sent letters. There will be no PHI in the 
spreadsheet. Patient initials, date of sent letter, date of call and if they agreed to 
participate will be recorded.  
 
 
♦ The study coordinator will meet with potential subjects prior to one of their scheduled 
appointments, explain risks/benefits of study, and obtain informed consent for inclusion 
in the study. These potential subjects will have the opportunity to review the consent via 
email prior to their meeting with the study coordinator if they choose.  
 
♦ Once consented; subject will be allocated into one of the two study groups based on a 
table of randomized numbers. Subjects’ demographic information such as age, gender, 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 17 of 34 
 
race, email and phone numbers will be collected. (Appendix C2). This will also list their 
provider study ID number as well. Prior to the first study-related visit with the provider 
(Visit 0) the subject will be asked to complete the Defense and Veterans Pain Rating 
Scale (DVPRS) with Supplemental Items (Appendix D), the Brief Pain Inventory Short 
Form (BPI-SF) Perception of Relief Item over past week (Appendix E), Patient Reported 
Outcome Measurement Information System (PROMIS) short forms for pain interference 
(Appendix F), depression (Appendix G) and anxiety (Appendix H), the Patient 
Perceptions of Care (Appendix I), and Patient Global Impression of Change (Appendix 
J). The subject will be provided with a list of common opioids and NSAIDs (Appendix 
K) and be asked their current medications both prescription and OTC/ alternative 
treatments. (Appendix L). 
 
♦ At Visit 0 a saliva sample will be collected by the study coordinator and labeled with a 
study ID number assigned specifically to that subject and all the samples for that day will 
be shipped to Pathway genomics following IATA (international air transport association) 
shipping regulations. Saliva is collected on all patient volunteers regardless of which 
group they are in. The DNA/ saliva sample will be destroyed 60 days after collection by 
the Pathway Genomics lab.  
 
♦ After the first study-related visit with the provider (Visit 0) the subject will be asked to 
complete the patient certainty, confidence and satisfaction surveys (Appendix M). This 
survey will be provided by email.  
 
♦ After Visit 0 with the subject the provider will be asked to complete the Provider 
Perception of Care (Appendix N), the Provider Global Impression of Change (Appendix 
O), and Provider Certainty, Confidence and Satisfaction surveys (Appendix P).  These 
surveys can be hand-delivered to provider or provided over email. 
 
♦ A member of the research team will query AHLTA to confirm the subject’s current 
analgesic medication regiment at the time of enrollment.  All analgesics will be 
documented as a total daily dose and all opioids will be converted to daily oral morphine 
equivalents using the Hopkins Opioid Program (www.hopweb.org). These data will be 
entered into the CRF [(Case Report Form) (Appendix L).  A medication will be classified 
as an analgesic according to (Appendix Q).  
 
♦ If the subject is randomized to Group A, there will be a 3-month wait period before the 
provider will receive the subject’s DNA test result. During this time the patient will be 
scheduled for monthly visits (Visit 1, 2, and 3) with the provider. Each visit will be at 
least 1 month in advance or as the clinic allows. During these visits the medications may 
be changed or adjusted according to routine care. Before each visit the subject will be 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 18 of 34 
 
asked to complete surveys of Appendix D, E, F, G, H, I, and J. After each visit the 
subject will be asked to complete survey of Appendix M. 
After each visit the provider will be asked to complete surveys of Appendix N, O, and P. 
 
♦ A report for the subjects study ID number will be returned to the provider within 1-3 
weeks of saliva sample collection for subjects in the Group B, and after the 3-month wait 
period for Group A. The test report has only the subject’s study ID on it, so the study 
coordinator will match the name of the subject with the subject study ID once it returns, 
so the provider is aware of the name of the subject. The report will be hand-delivered to 
the Primary Care Manager (PCM) by the study coordinator for use by the PCM at his/her 
discretion  The provider will keep a copy of the results in a research folder for their use at 
other study visits. The provider will be informed in the ICF and when results are handed 
to them that the test results are not to be placed in the patient’s medical record or shared 
with another provider.  
 
♦ The Pain Medication and Mental Health DNA report identifies genetic variations that 
affect how individuals respond to commonly prescribed opioids, pain medications, 
antidepressants and anxiolytics. A sample report of the mental health component is 
shown in (Appendix R). In addition to the medications in the sample report, the Pain 
Medication and Mental Health DNA Insight will also test for genetic variations affecting 
response to carisoprodol, celecoxib, codeine, fentanyl, hydrocodone, methadone, 
methotrexate toxicity, oxycodone and tramadol. 
 
♦ The provider will use his/her professional knowledge and judgment to interpret the test 
results and apply those results to the care of his/her patient.  The consent form signed by 
the primary care managers will emphasize the option to consult with a pain specialist, if 
deemed necessary by the PCM. 
 
♦ The subject will be scheduled for a follow-up appointment upon receipt of the Pain 
Medication and Mental Health DNA Insight Test. Prior to this visit (Visit 1(Group B) or 
Visit 3(Group A)) the subject will be asked to complete Appendices D, E, F, G, H, I, and 
J. At this visit the provider will discuss the test results with the subject and adjust or 
change the subject’s medication as he sees necessary based on the genomic information. 
It is possible the medications will remain unchanged.  
 
♦ After Visit 1 the subject will be asked to complete Appendix M, and the provider will 
be asked to complete Appendix N, O, and P. 
 
♦ After implementation of the test results the subject will be scheduled to see the provider 
monthly for 6 months (Visit 2, 3, 4, 5, 6) and before each visit the patient subject will be 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 19 of 34 
 
asked to complete Appendix D, E, F, G, H, I, and J. At each visit, the subjects’ 
medications may be adjusted or changed as deemed necessary by the provider. After the 
visits the subject will be asked to complete Appendix M, and the provider will be asked 
to complete Appendix N, O, and P. At the last visit the provider will be ask to complete a 
question about provider usage (Appendix S). 
 
♦ After the last visit (Visit 6), a member of the research team will query AHLTA to 
determine the patient’s current analgesic medication regiment at the end of the study. The 
subject will asked at that visit what they are taking as well.  All analgesics will be 
documented as a total daily dose and all opioids will be converted to daily oral morphine 
equivalents using the Hopkins Opioid Program (www.hopweb.org).  These data will be 
entered onto the CRF. 
 
 
 
 
 
 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 20 of 34 
 
Provider Diagram 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Power point presented at 
each FM clinic provider 
monthly meeting  
Interested providers meet with 
AI or study coordinator to 
review and sign consent form 
(5-10 minutes)  
Patient subject will be seen by same 
provider at 7 total visits after each visit the 
provider will complete 3 surveys (can be 
hand delivered by coordinator or emailed) 
4 surveys will be complete at the last visit 
(5 mintues of time)  
Consented provider will be given script 
to go by, patient inclusion/ exclusion 
and a coordinator information sheet to 
hand to patient so patient can contact 
the coordinator 
 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 21 of 34 
 
Patient Diagram 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See below for visit breakdown and chart 
 
 
 
 
 
 
 
Patient will be given 
coordinator 
information sheet if 
determined interested 
by the provider  
Patient will contact study 
coordinator. The consent form 
will be emailed to the patient 
for review. The coordinator 
will setup a time to meet with 
the patient. (Probably 15-20 
minutes before their next 
appointment with the provider)  
Patient will be 
consented and ask the 
baseline survey 
questions and a saliva 
sample will be collected 
Before each visit 
the patient will 
complete 3 surveys  
After each visit the 
patient will be sent a 
survey to complete 
by email  

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 22 of 34 
 
 
7.3.5 Data Collection Instruments:  
Appendix 1: Provider Ad 
Appendix 2: Patient Ad 
Appendix 3: Coordinator Script  
Appendix A: Provider Script  
Appendix B: Coordinator Contact Information 
Appendix C1: Provider Contact information 
Appendix C2: Subject demographics and contact information 
Appendix D: DVPRS side A and B 
Appendix E: BPI-SF Perception of Relief Item 
Appendix F: PROMIS SF v1.0 – Pain Interference-SF8a 
Appendix G: PROMIS SF v1.0 – ED-Depression-SF8a 
Appendix H: PROMIS SF v1.0 – ED-Anxiety-SF8a 
Appendix I: Patient Perceptions of Care 
Appendix J: Patient Global Impression of Change 
Appendix K: Patient Medication Example List 
Appendix L: Case Report Form 
Appendix M: Patient Certainty, Confidence and Satisfaction 
Appendix N: Provider Perception of Pain Care 
Appendix O: Provider Global Impression of Change 
Appendix P: Provider Certainty, Confidence and Satisfaction 
Appendix Q: Medication list of acceptable analgesics 
Appendix R: Sample genomics report for both 
Appendix S: Provider Usage  
 
References: See Section 6.1 
 
 
7.3.6 Variables/Data Points:  
 
Baseline (Visit 0): 
 
All subjects, regardless of group assignment  
 
Before visit with the provider 
– Demographics (Appendix C), DVPRS (Appendix D), BPI perception of pain relief 
item (Appendix E), PROMIS short forms for pain interference (Appendix F), 
depression (Appendix G), anxiety (Appendix H) 
– patient perception of care (Appendix I) 
– patient global impression of change (Appendix J) 
 
At the visit saliva sample is taken and sent for analysis 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 23 of 34 
 
 
After visit with the provider 
– certainty, confidence, satisfaction (Appendix M) 
 
 
Provider 
 
After visit with the subject 
– certainty, confidence, satisfaction (Appendix P) 
– provider perception of care (Appendix N) 
– provider global impression of change (Appendix O) 
 
Visits 1-6    (Group A receives test results at visit 3, Group B receives test results at visit 1) 
 
Subjects 
 
Before visit with the provider 
– DVPRS, PROMIS short forms for pain interference, depression, anxiety, BPI 
perception of pain relief item 
– patient perception of care 
– patient global impression of change 
 
After visit with the provider 
– certainty, confidence, satisfaction 
 
 
Provider 
 
After visit with the subject 
– certainty, confidence, satisfaction 
– provider perception of care 
– provider global impression of change 
– provider usage (visit 6 only)  
 
Table 1: Visit Chart  
 
Group A (Delayed) 
Group B 
Visit 0 
Consent, saliva sample  
Consent, saliva sample  
Visit 1 
 
Receive results  
Visit 2 
 
 
Visit 3 
Receive results 
 
Visit 4 
 
 
Visit 5 
 
 
Visit 6 
Last visit 
Last visit 
 
 
At the end of the study patients’ medications will be extracted from records and changes will be 
documented and analyzed. All opioids will be converted to oral morphine equivalents. 
 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 24 of 34 
 
7.4 RISKS TO SUBJECTS:  
 
There is little direct risk associated with the analysis of the patient’s DNA.  A patient will submit 
a saliva sample only, no invasive procedure is required.  The sample will then be shipped to the 
testing site and results will be forwarded to the medical provider.   
 
The only risk of data collection during the study is potential loss of privacy/confidentiality of 
enrollment in the study.  The consent forms with the subject’s name will be stored in a locked 
file cabinet in the research coordinator’s office at WAMC.  The master link between subject 
name and ID will be stored in a password protected excel file on the V drive at WAMC, with 
access limited to only the study team.  This file will be separate from the file containing the 
collected data. 
 
Analysis of personal genetic information potentially carries risk of future health insurance 
discrimination.  The results of the DNA Insight Test will not become part of the patient’s 
medical record and  not be visible to potential future health insurers.  While price discrimination 
based on genetic make-up is a theoretical risk, the nature of the information in the DNA Insight 
does not lend itself to discrimination by insurers.   
As with any laboratory test, patients are exposed to the potential risk of results misinterpretation.  
In this case, misinterpretation could result in adverse medication effects up to and including 
death of the patient.  When a clinician obtains test results, that clinician is expected to possess 
the appropriate knowledge and clinical judgment to accurately interpret the test and prudently act 
on those results. All primary care providers are trained on basic drug pharmacokinetics and 
pharmacodynamics during medical training.  Primary care providers are expected to have 
knowledge of the CYP system and its genetic heterogeneities.  Furthermore, primary care 
providers are expected to possess clinical judgment in deciding the appropriateness of specialty 
consultation.  For this study, to address the potential risk of results misinterpretation, primary 
care providers will be provided with an information sheet reminding them of the availability of 
pain specialty consult.  All analgesic dosing changes should be done with appropriate clinical 
judgment and prudence in accordance with standard of care for the practice of primary care 
medicine.  Providers credentialed by Womack Army Medical Center are subject to this 
organization’s strict and thorough credentialing process. 
 
 
8.0 DATA ANALYSIS:   
 
For this two-group design, a variety of self-report measures (confidence, certainty, etc.) will be 
taken up to a maximum of 8 repeated measures, including a baseline measure prior to the 
intervention. Given this variability where time is not a fixed factor insofar there may be variation 
for number of measures by individual and/or group a mixed linear modeling (or sometimes referred 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 25 of 34 
 
to by the umbrella term: multilevel modeling-MLM) analysis will be conducted.32 The advantage 
of a MLM approach is that it is sufficiently flexible insofar inter-individual variability on (1) time 
and (2) number of measures can be readily accommodated.33 Moreover, in the context of a 
longitudinal design interindividual differences in intraindividual trajectories can be captured.34 
 
When conducting a MLM analysis, the assumption is that there is a nested structure, and 
particularly for event-based studies, time (level 1-microlevel) will be nested within the patient 
(level 2- individual). For this study there are 12 provider groups with 4 patients nested within the 
groups, hence this could be cast as a 3-level model (time nested within patient nested within 
provider).  However, one caveat is this is a very small sample size for MLM, and power may be a 
significant issue.35  The viability of increasing the sample size or aggregating levels (if deemed 
appropriate insofar it does not compromise the integrity of the design) will be explored.  A 
sequence of models will be examined, with the unconditional means model (no predictors) as the 
starting point, serving to compute the unconditional intraclass correlation coefficient (ICC), and 
hence capturing the extent of between-patient variability.  Subsequent models will entail adding a 
variable that captures time, and then at the macro-level introducing the grouping (experimental vs. 
control) variable.  If deemed appropriate, all time-invariant and time-varying predictors will be 
testing for significance (α = .05) and moreover, the stochastic parameters (i.e., variance 
components) will also be examined: u0 and possibly u1 where u0 is the random coefficient for the 
intercept (i.e. initial basis) and u1 is the random coefficient for the slope.  For the single-item 
ordinal-level outcomes the cumulative logit link function will be employed using residual 
maximum likelihood (REML) as the default estimator (otherwise the identity link function will be 
used for continuously measured outcomes). 
 
 
Selection of the best fitting model will be guided not only by the change in magnitude of the 
variance components, represented in part by the pseudo r2 statistic36, but also information-theoretic 
indices such as the Akaike Information Criterion (AIC) or Bayesian Information Criteiron (BIC), 
of which the model with the lower value evinces better fit37. All MLM analysis will be conducted 
using the HLM7.01 software.38  Data cleaning, testing of assumptions and descriptive analysis will 
be performed in SPSS v. 22 or Stata v. 11.0.  Moreover, as a basis of comparison (again keeping 
in mind small sample size) generalized estimating equations (GEE) will also be considered, with 
an unstructured working correlation matrix stipulated as the error variance/covariance matrix 
(though alternatives such as autoregressive with lag 1 (AR1) may be considered).   
 
As for testing concordance of patients and caretakers, correlations will be computed as well as 
intraclass correlation coefficients (ICC) so as to assess the level of relationship between the 
patients and providers on like-items.   
 
 
Commented [1]: Can Peter address this sentence? 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 26 of 34 
 
References: See Section 6.1 
 
A database will be created in REDCap (Research Electronic Data Capture) after IRB approval. 
REDCap is a secure, web-based application for building and managing online surveys and 
databases. The data will be housed and secured on Defense and Veteran Center for Integrative 
Pain Management (DVCIPM) servers.  Each patient will be allocated a study ID number, 01-48 
and providers will be assigned study ID numbers 101-112, when they sign a consent form, and 
thereafter will be referred to by that number in the database. Investigators and research staff will 
have secure password protected access to RedCap in order to enter data.  
The REDCap data will be extracted and sent to an outside DVCIPM statistician,      for analysis. 
PHI will be removed before sending to the statistician.   
 
 
9.0 MILITARY RELEVANCE:   
 
Modern war fighters suffering from acute and chronic pain are often healing from multiple physical 
and psychological traumas. The National Defense Authorization Act of Fiscal Year 2010 (NDAA) 
mandated pain related research, including that attributable to injuries of modern warfare. The 
PMTF, convened by the OTSG of the Army stated in its Final Report that alternative therapeutics 
should be evaluated and incorporated into pain management practices across the DoD and VA 
health care continuum.2 Prompt, effective and safe treatment of pain in the military population is 
a major healthcare goal.  The treatment of both acute and chronic pain has received national 
attention.19 Several media outlets have reported on the complex problem of adequately treating 
pain, while trying to minimize or eliminate the misuse potential of narcotic analgesics.20-22  
Furthermore, in an environment where downsizing and costs savings are required, the potential to 
save money on medical management and reduced adverse side effect related problems will become 
a major part of military healthcare in the coming years.   
 
Chronic pain is the leading cause of medical boards across all services, and a major cause of unit 
attrition.20-24 Treatment with invasive (i.e., surgery or radiofrequency) procedures is expensive 
and often impractical in theater, and has not been shown to reduce disability rates.  By virtue of 
their younger age and high incidence of psychopathology (in veterans), service members are at 
higher risk than the general population for addiction and overdose from opioids.26, 27   Adjuvants 
such as gabapentin and tricyclic antidepressants do not carry the same risks as opioids, but can 
affect cognition, cause psychomotor impairment, and are associated with other adverse effects 
(e.g. Weight gain) that may adversely impact service members. It is likely in the near future as 
genomic information becomes more easily obtained and interpreted that we would no more 
consider deploying a soldier without understanding their phenotypic response to common 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 27 of 34 
 
medications used on the battlefield than we would allow them to deploy without knowing their 
blood type.  
 
 
 
10.0 MEDICAL APPLICATION:   
 
Personalized medicine is the ability to tailor therapy based on a patient’s individual genotype.  It 
helps eliminate the long and expensive process of trial and error, especially in the chronic pain 
population.  This approach to medicine is being researched and utilized in the pharmaceutical 
industry across the globe.  Genetic susceptibility has led to breakthroughs in treatment for 
numerous auto-immune and cancer related disease processes.  Determining which patients will 
respond best to which class of opioids, with minimal side effects, will drastically improve the 
way pain medicine is practiced.  Of significant importance, is the ability to reduce the risk of 
opioid addiction and overdose in our military beneficiary population.   
 
11.0 BUDGET:  
Will any outside organization provide funding or other resources?  
☒  Yes The Company Pathway Genomics is funding the study and funds will be managed by the 
Henry M. Jackson foundation. A Statement of Work will be submitted.  
☐  No          
 
 
Item 
Cost 
Personnel 
$90065 
Supplies 
$750 
Other 
1250 
Travel 
$6300 
Publication costs 
$2500 
IRB fees 
$2500 
 
 
Total 
$103365 
 
12.0 HIPAA AUTHORIZATION:   
 
i. Are you intending to collect subject’s Protected Health Information (PHI) and any of the following 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 28 of 34 
 
18 personal identifiers?  
☐No – HIPAA does not apply – go to question #iv 
☒Yes – please check which ones:  
☒  1. Names 
☐  2. Street address, city, county, 5-digit zip code 
☒  3. Months and dates (years are OK) and ages >89 (unless all persons over 89 years are 
aggregated into a single category) 
☒  4. Telephone numbers 
☐  5. Fax numbers 
☒  6. E-mail addresses 
☒  7. Social security number 
☐  8. Medical record number 
☐  9. Health plan beneficiary number 
☐10. Account number 
☐11. Certificate/license number 
☐12. Vehicle identification number (VIN) and/or license plate number 
☐13. Device identifiers and serial numbers 
☐14. URLs (Uniform Resource Locators) 
☐15. Internet protocol address number 
☐16. Biometric identifiers, such as finger and voice prints 
☐17. Full face photographic images or any comparable images 
☐18. Any other unique identifying number, characteristic, or code such as patient initials 
 
ii. Can you limit your collection of personal identifiers to just #2, 3 or 18 above?   
☐Yes – then your dataset may qualify as a Limited Data Set – please contact 
usarmy.bragg.medcom-wamc.list.wamc-irb-admin@mail.mil.  for further instructions before 
completing HIPAA authorizations or waivers thereof. Then go to question #iv. 
☒No – Go to question #iii. 
 
iii. Is obtaining patient Authorization “impracticable”?  
☐Yes – Authorization may qualify to be waived by the IRB. Please contact 
usarmy.bragg.medcom.wamc-list.wamc-irb-admin@mail.mil.  for instructions.  
☒No – Research subjects will need to sign a HIPAA Authorization.  
 
3. What precautions will you take to protect the confidentiality of research source documents 
(Case Report Forms, questionnaires, etc.), the research data file, and the master code (if any 
 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 29 of 34 
 
Paper documents will be kept in a locked cabinet in a locked office area. Forms with names on them 
will be kept separate from data collection forms. Electronic files will be password protected and the 
master list will be kept in file separate from the data points. The master list will be destroyed 6 years 
after the end of the study. Only the study investigators and collaborators will have access to the 
research data 
 
4. When will you destroy the research source documents, data file, and the master code?  
 
6 years after the end of the study. All electronic data will be deleted from the computer system.  
 
 
 
vi. Will research data including identifiable Protected Health Information be sent outside of 
WAMC? 
☐Yes  
 
☒No 
 
5. Linkage of extracted data to other databases:   
 
N/A 
 
 
12.1 BENEFITS 
 
The ability to identify how a patient will react to a medication based on their genetic make-up is 
a major advance for pain medicine.  All too often, patients must endure months and years of 
adjustments in their medication regimen, many times resulting in inadequate pain control and/or 
intolerable side effects.  Having the knowledge of how a patient will respond and metabolize a 
certain opioid or other pain medication before treatment is started, will lead to more effective 
medical care and higher patient satisfaction.  This is the epitome of personalized medicine.   
 
 
12.2 RISKS 
 
There are little associated with the analysis of the patient’s DNA.  A patient will submit a saliva 
sample only, no invasive procedure is required.  The sample will then be shipped to the testing 
site and results will be forwarded to the medical provider.   
 
The only risk of data collection during the study is potential loss of privacy/confidentiality of 
enrollment in the study.  The consent forms with the subject’s name will be stored in a locked 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 30 of 34 
 
file cabinet in the research coordinator’s office at WAMC.  The master link between subject 
name and ID will be stored in a password protected excel file on the V drive at WAMC, with 
access limited to only the study team.  This file will be separate from the file containing the 
collected data.   
 
 
12.3 HIPAA AUTHORIZATION WAIVER 
 
If you wish to obtain and use identifiable protected health information for a study without obtaining 
written approval (“HIPAA Authorization”) from the subject, please complete a HIPAA 
Authorization Waiver Form to provide justification for IRB review and approval. Contact 
usarmy.bragg.medcom-wamc.list.wamc-irb-admin@mail.mil.  for assistance. 
 
 
13.0 WAIVER OF THE REQUIREMENT TO OBTAIN INFORMED CONSENT:  Note 
this section pertains to obtaining informed consent. Section 12.3(b) relates to documenting 
informed consent. All 3 of the following must be sufficiently satisfied in order for the IRB to 
waive this requirement. Double left click the box that applies and mark appropriately.   
 
☐  The research involves no more than minimal risk to the subjects (For example, it is 
medical records research, risk is primarily psychosocial in nature, or attendant on breaches 
of privacy and confidentiality) and,  
  
The waiver will not adversely affect the rights and welfare of the subjects  (Explain 
how or why the waiver will not adversely affect the rights and welfare of the subjects, e.g. 
the subjects are no longer living) and, 
 
The research could not practicably be carried out without the waiver. (Explain why 
the research could not be carried out without the waiver of informed consent. For example, 
it is impossible to contact the subjects or some of the subjects may no longer be alive.)  
 
☒  Not applicable  
 
13.1 WAIVER OF THE REQUIREMENT TO DOCUMENT INFORMED CONSENT: 
Note this section pertains to the documentation  of informed consent. Documentation of 
informed consent can be waived by the IRB if it meets one of two criteria below. Double click 
the appropriate box and mark.   
 
☐  1. The only record linking the subject and the research would be the consent document 
and the principal risk would be potential harm resulting from a breach of confidentiality. 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 31 of 34 
 
Each subject will be asked whether the subject wants documentation linking the subject 
with the research, and the subject's wishes will govern; or 
 
☐  2. The research presents no more than minimal risk of harm to subjects and involves no 
procedures for which written consent is normally required outside of the research context. 
In cases in which the documentation requirement is waived, the IRB may require the 
investigator to provide subjects with a written statement regarding the research. 
 
☒  3. Not applicable. 
 
 
 
14.0 IMPACT STATEMENTS:   
Department/ 
Service 
Necessary for Which Proposals? 
Indicate if this is required 
for your study.  If 
answered “yes”, an impact 
statement from the 
Department or Service 
must accompany the 
protocol 
Information 
Management 
Directorate 
(IMD)  
Study involves use of the Internet and/or E-mail for 
patient recruitment and/or data collection; use of Web 
page design, data collection, or other Web-based 
applications 
☐ Yes     ☒No 
Laboratory  
Study involves laboratory staff or resources 
☐ Yes     ☒No 
Nursing 
Study requires any involvement of Nursing personnel 
paid by WAMC 
☐ Yes     ☒No  
If yes, complete the detailed 
Nursing Impact Statement 
found on the IRB Web site 
Pharmacy 
Study uses any drugs, IND or otherwise 
☐ Yes     ☒No 
PAD/Medical 
Records 
Study involves review of medical records 
☐ Yes     ☒No 
Radiology 
Study requires any radiological services 
☐ Yes     ☒No 
Other 
For example, a specific clinic, service or department 
All family practice clinics including the WTU.   
☒ Yes     ☐No 
We will get impact statements prior to any provider recruiting at the individual clinics.   
 
15.0 SIGNATURE: 
 
I verify that the contents of this proposal are accurate and that I have read and agree to 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 32 of 34 
 
comply with the statements above which outline my responsibilities as a Principal Investigator 
or Associate Investigator.  
 
 
 
 
 
Principal Investigator Signature 
Name and Date:  
 
15.1 OTHER SIGNATURES FOR APPROVAL:   
 
I concur with the submission of this proposal to the Clinical Investigation Service for 
review and approval.   
 
 
 
 
 
 
 
 
Service Chief Signature 
       
 
 
Name and Date:                       
 
 
 
              
                                           
 
 
 
Department Chief Signature                
                                                 
Name and Date:  
 
 
 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 33 of 34 
 
Checklist of Support Documents that Must Accompany Protocol 
 
☐ 1.  Protocol Application  Submit the entire protocol as a word document without signatures in 
order to allow track changes. Section 15 is the signature page(s). After it is completed, scan in as a pdf 
file and submit these pages as a “signature” file. Alternatively, you can submit a digitally signed word 
document.    
 
☐ 2.  Investigator Letter of Support Required for Principal Investigators, signed by the 
Department Chief or Directorate if PI is the Department Chief. 
 
☐ 3.  Complete Impact Statement as applicable:  
a.  Information Management Directorate (IMD)   
b.  Laboratory Impact Statement 
c.  Nursing Impact Statement 
d.  Pharmacy Impact Statement (required if study uses any drugs, IND or otherwise) 
e.  Pathology Impact Statement 
d.  Radiology Impact Statement 
e.  Examples may include specific clinic or service. 
 
☐ 4.  Informed Consent Document if applicable See section 13.0-13.1 above. Contact  
usarmy.bragg.medcom-wamc.list.wamc-irb.admin@mail.mil.  for assistance.  
 
☐ 5.  HIPAA Waiver Form, if applicable 
 
☐ 6.  Figures / Graphs / Appendices 
 
☐ 7.  Data Collection Sheets / Questionnaire 
 
☐ 8.  Cooperative Authorization and Development Agreement (CRADA) If receiving 
outside funding, contact usarmy.bragg.medcom-wamc.list.wamc-irb-admin@mail.mil.  for assistance. 
The Clinical Investigations Regulatory Office has final approval of this study.  
 
☐ 9. Conflict of Interest Statement Must be completed for ALL Investigators 
 
☐ 10. Advertisement Materials, if applicable 
 
☐ 11. Responsibilities of Principal Investigator and Associate Investigator Section 3 and 16-
18 must be signed. 
 
☐ 12.  Copy of Curriculum Vitae (CV)  From Principal Investigator and all Associate 
Investigator(s).  The IRB may request CVs from Collaborators depending on their role in the 
study. 

 
IRBnet Number: 409729-12 
PI: MAJ Michael W. Bartoszek 
Protocol Title: Patient and provider confidence and satisfaction with the clinical use of CYP genetic 
variability analysis to guide analgesic treatment: A randomized, controlled pilot study using the Pain 
Medication and Mental Health DNA Insight™  test. 
Initial Date Submitted: 02/10/2015 
Revision Date: 31 August 2016 
 
WAMC Protocol Template Revised 3 January 2014 
 
Page 34 of 34 
 
 
☐ 13.  Certificate on Human Participant Protections Course for all Investigators   
Access at http://www.citiprogram.org/.  Select New Users or login using previous username/password.   
Select Womack Army Medical Center as the Participating Institution. Training is good for 3 years.