Efficacy of Perioperative Opioid Sparing Techniques on Time to Initiation of Chemotherapy: A Randomized Single Blinded Control Study
Phase: NA
Conditions: Perioperative Opioid Sparing Techniques
Sponsor: University of Tennessee Graduate School of Medicine

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Title: Efficacy of Perioperative Opioid Sparing Techniques on Time to Initiation of Chemotherapy: A 
Randomized Single Blinded Control Study
Investigators:
PI: 
Che A. Solla, MD, MBA 
Co-PI:
James McLoughlin, MD, MBA
Co-I:
Ryan Schmocker, MD
Matthew Vance, MD
Gregory Low, MD
Robert Heidel, PhD, Pstat
Ardy Davarifar, MD, PhD
Andrew Russ, MD
Jason Buehler, MD
Jonathan DeLong, MD
Jeffery Staack, MD
Mark Murray, MD
Peyton Murdock, MD
Study Coordinators: 
Trey Henderson, MS
Travis Delk, MA
Data Analyst: 
Gulsah Onar, MPH
Location:
University of Tennessee Graduate School of Medicine
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Contents
1.0 INTRODUCTION .................................................................................................................................7
2.0 RATIONALE ........................................................................................................................................7
3.0 TRIAL OBJECTIVES..............................................................................................................................8
Hypothesis:..............................................................................................................................................8
3.1 Primary objective...............................................................................................................................8
3.2 Secondary objectives.........................................................................................................................8
3.3 Outcomes ..........................................................................................................................................8
4.0 STUDY PLAN.......................................................................................................................................9
4.1 Study Design......................................................................................................................................9
4.2 Study Duration...................................................................................................................................9
4.3 Selection of Study Participants & Informed Consent ........................................................................9
4.4.1 Inclusion Criteria.............................................................................................................................9
4.4.2 Exclusion Criteria ............................................................................................................................9
4.5 Discontinuation of Subjects...............................................................................................................9
5.0 STUDY PROCEDURES........................................................................................................................10
5.1 Screening Assessments....................................................................................................................10
5.2 Enrollment/Baseline Assessments...................................................................................................10
6.0  Randomization................................................................................................................................11
7.0 INTERVENTIONS/GROUPS ...............................................................................................................11
Intervention 1........................................................................................................................................11
Intervention 2:.......................................................................................................................................11
Intervention 3:.......................................................................................................................................11
8.0 Follow Visit/Collection Time Points (90-post discharge).................................................................11
9.0 Study Schematic ..............................................................................................................................12
10.0 RISKS..............................................................................................................................................13
10.1 Physical Risks.................................................................................................................................13
10.2 Intervention Risk............................................................................................................................13
10.3 Psychological Risks: .......................................................................................................................13
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10.4 Research Risk.................................................................................................................................13
10.5 BENEFITS........................................................................................................................................13
11.0 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS.......................................................................14
SAE Reporting........................................................................................................................................15
12.0 STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE..................................................15
13.0 STUDY MANAGEMENT ..................................................................................................................16
14.0 DATA MANAGEMENT ....................................................................................................................17
14.1 Data Protection .............................................................................................................................17
14.2 Data and Safety Monitoring ..........................................................................................................17
14.3 Protocol Deviations .......................................................................................................................18
14.4 Records..........................................................................................................................................18
14.5.1 Source Documents......................................................................................................................18
14.5.2 Direct Access to Source Data and Documents............................................................................18
14.5.3 Storage of Records .....................................................................................................................18
15.0 COMPLETION OF TRIAL..................................................................................................................18
16.0 REFERENCES ..................................................................................................................................18
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1.0 INTRODUCTION
Enhanced recovery after surgery (ERAS) has become the standard of perioperative care for patients 
undergoing oncologic surgery1–4. Multimodal and regional anesthetic techniques to reduce postoperative 
pain and opioid requirements are a key component of ERAS5,6. Epidural analgesia was considered 
standard in early ERAS protocols7,8 however, it is labor-intensive, requires close postoperative follow-up, 
and may exacerbate hemodynamic instability. 
Long-acting intrathecal (IT) opioid use in oncologic surgery has been described as an equianalgesic 
technique to epidural analgesia with an improved safety profile, although both have the potential for 
neurological complications and respiratory depression9–14. Quadratus lumborum (QL) block is an 
alternative opioid sparing technique to neuraxial analgesia for abdominal surgery6,15. QL blocks can 
provide similar pain coverage as an epidural with decreased hemodynamic instability. However, it is 
limited by its relatively short duration of effect, which ranges from 6 to 12 h16. Another method employed 
is the transversus abdominus plane block. One of the advantages of this technique is that it does not 
depend on a separate service to perform like ITM and QL as it is commonly performed by the surgeon 
during surgery. However, unlike the QL block which has been shown to spread to the lumbar plexus and 
even thoracic paravertebral space providing both somatic and visceral analgesia, TAP blocks only provide 
somatic analgesia coverage20. TAP blocks are still frequently performed by oncologic surgeons though the 
long term success compared to QL and ITM blocks is unclear. Most research looking into the efficacy of 
these techniques has been aimed at studying their effects on pain scores, opioid requirements, and opioid 
related adverse drug events.
Time to initiation of adjuvant chemotherapy (AC) following oncologic surgery is an important predictor of 
survivability19 that has not yet been considered in QL vs. IT comparison studies. Two meta-analyses 
demonstrated that postponing the postoperative AC was associated with poor survival in colorectal 
cancer patients. Results from Biagi et al. showed that every 4 weeks delay result in a 14% decrease of 
overall survival (OS)17. Similarly, Guetz’s study indicated that delaying the initiation of AC for > 8 weeks 
after operation significantly decreased OS18. In pancreatic and colorectal cancer, several factors are 
involved in this metric. One of the more common factors in this patient population is gastrointestinal 
complications including ileus. Some of these complications can be affected by perioperative opioid 
consumption.
2.0 RATIONALE
The primary objective is, therefore, to compare time to initiation of chemotherapy between regional 
blocks specifically quadratus lumborum blocks, surgeon administered Transversus Abdominis Plane (TAP) 
block, and IT opioid analgesia in oncologic abdominal surgery and whether there is a significant difference 
between these techniques and standard post operative pain management protocol. Secondary objectives 
are to compare duration of hospital stay, incidence of postoperative ileus and use of intravenous patient-
controlled analgesia. This study aims to establish whether certain opioid sparing techniques are superior 
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in terms of their ability to decrease time to initiation of chemotherapy following oncologic surgery. 
Additional sub-aims include evaluating the efficacy of long acting vs. short acting bupivacaine on pain 
management and time to initiation of chemotherapy. Current clinical practice at UTMC is that some 
surgeons elect to administer long-acting bupivacaine as TAP blocks.  Additionally, the anesthesia team 
exclusively uses short acting bupivacaine for the QL blocks. Though this study is not designed to compare 
various products for injection per procedure (i.e. TAP with short acting vs. long-acting bupivacaine), one 
of the anticipated outcomes is data that will compare pain management between these two techniques.  
Additional studies may need to be designed to further identify superiority of short acting vs. long-acting 
bupivacaine. 
3.0 TRIAL OBJECTIVES
Hypothesis:
Preoperative intrathecal morphine administration will significantly reduce the time to initiation of post-
operative chemotherapy.
3.1 Primary objective
To determine if intrathecal morphine (ITM) administration is superior to quadratus lumborum block or 
surgeon administered TAP blocks result in decreased time to initiation of chemotherapy following 
oncologic surgery.
3.2 Secondary objectives
To determine a difference between interventions in time to return of bowel function in days.
To determine a difference between interventions in incidence of opioid related adverse drug events 
(ORADEs). 
To determine a difference between interventions in cumulative and post-operative total morphine 
milligram equivalents. 
To determine a difference between interventions in quality-of-life assessment tool and patient 
satisfaction (brief pain index short form BPI-sf9).
To determine a difference between interventions in hospital length of stay in days.
To determine the difference between cumulative pain scores between interventions.
To determine the difference between short acting and long-acting bupivacaine in pain management and 
time to chemotherapy
3.3 Outcomes
The primary outcome is time to initiation of chemotherapy (in days) as deemed by a blinded medical 
oncologist.
 
The secondary outcomes are time to return of bowel function, incidence of ORADEs, cumulative and 
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postoperative morphine milligram equivalents, hospital length of stay, pain scores, and quality of life.
4.0 STUDY PLAN
4.1 Study Design
A prospective, parallel group randomized clinical study in patients undergoing oncologic (foregut, 
hepatopancreatobiliary (HPB), and colorectal cancer) surgical procedures. 
4.2 Study Duration
We plan to enroll ~10 patients per month for 20 months. The total study duration will be 
approximately 24 month’s post IRB approval and study initiation.
4.3 Selection of Study Participants & Informed Consent
Patients at the UT Medical Center who meet the predefined inclusion and exclusion criteria will be 
enrolled after they provide consent to participate. Consent will take place during the clinical pre-operative 
visit.  The nature and purpose of the study will be explained to the patient by the study member designee 
and the patient will be given a copy of the informed consent to review. The investigator and/or study 
coordinator will answer any questions which the patient may have prior to their signing the consent. The 
signed informed consent will be kept in the patient’s research chart and a copy will be given to the patient. 
No study related interventions will be performed until after the patient signs the informed consent.
4.4.1 Inclusion Criteria
1. 18-80 years of age
2. Patients undergoing open surgery for foregut, HPB, and colorectal cancer 
3. Able to read and understand study procedures
4. Willing to participate and sign an ICF
5. If female of childbearing potential, subject must have a negative pregnancy test
6. Recommended for adjuvant chemotherapy
7. Patients scheduled for an AM admit procedure
8. English speaking
9. Patients with a midline incision
4.4.2 Exclusion Criteria
1.
Chronic Opioid Use (received an opioid within 90 days preoperatively)
2.
Recreational Drug Use 
3.
Patients with cognitive impairments that can affect their ability to give consent.
4.
Patients that are currently taking anti-coagulants <7 days prior to surgery
5.
Pregnant or breastfeeding  
6.
Does not require adjuvant chemotherapy 
7.
Relative Contradictions for receiving a nerve block*
8.
Patients that have been admitted prior to surgery for chief complaint related to complications from 
malignancy
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9.
Inability to provide consent  
*Absolute Contraindications

Lack of patient consent.

Skin infection at the site of needle insertion.
Relative Contraindications

Coagulopathy.

Systemic infection.

Anatomical distortion.

Neuropathy.
Drugs/Device usage within 7 Days of Randomization if any: 

Anticoagulants
 4.5 Discontinuation of Subjects
An individual patient is to be withdrawn from the trial if any of the following criteria apply:

The patient withdraws consent, without the need to justify the decision

The patient is no longer able to participate for medical reasons (e.g., surgery, AEs, or other diseases)

Decision by the PI to discontinue a specific patient for his/her safety (e.g., in case of SAEs)
Data of patients who discontinue or withdraw prior to enrollment will be entered in the study 
database and will be listed. Data of patients who discontinue or withdraw after enrollment will be 
documented and the reason for withdrawal will be recorded in the study record. The data will be 
included in the study database and will be reported.
5.0 STUDY PROCEDURES
5.1 Screening Assessments
Screening assessments should be completed by delegated study personnel during the patient’s pre-
operative visit in the surgeon’s office. Assessments will be initiated after the Informed Consent Form 
(ICF) Process. The PI and/or study designee will present the study information to the patient. They will 
explain the purpose, risk, and benefits to the subject and present them with an IRB approved ICF. The 
potential participant will be given ample time to read the ICF and all questions and concerns from the 
subject will be addressed by the PI and/or study team member. No procedures will be initiated prior 
to the subject signing and dating the ICF. After the subject signs the ICF, a copy will be given to them 
for their records. Participants will be informed that they can decline participation in the study without 
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any effect on their health care. They can also withdraw their consent, including the consent to do 
various screening tests, at any time.

Informed Consent

Medical History Review for Exclusion Criteria

Concurrent Medication Review

Review of Inclusion / Exclusion Criteria

Confirmation of Subject eligibility by PI and/or study designee representative on eligibility form.
5.2 Enrollment/Baseline Assessments
Enrollment/Baseline assessments will be completed on the scheduled day of surgery. This will be after 
the screening/enrollment visit after the patient has signed the informed consent form if all enrollment 
criteria have been confirmed. 

Concurrent Medication Monitoring (gabapentin, NSAIDs, topicals, muscle relaxers, opioids, and 
SNRIs)

Medical History Review for Eligibility

Confirm Inclusion & Exclusion Criteria

Enrollment

Intervention Assignment

Study Intervention Administration
6.0 Randomization
Randomization will be completed by a selected study team member. When a patient is qualified for entry 
into the randomized interventional period, intervention assignment will be made by means of a 
randomization table prepared by a third-party biostatistician or applicable team member. Randomization 
will be done in a 1-1-1 fashion. Using allocation software, patients will be allocated randomly into 1 of 3 
groups: the intrathecal morphine group (ITM), the quadratus lumborum group (QL), or the TAP block 
group (TAP).
7.0 INTERVENTIONS/GROUPS
Intervention 1: 
The ITM group will receive an intrathecal morphine block performed by the Anesthesiologist. This will be 
accomplished by placing the patient in a preoperative holding room with standard ASA monitors 150 mcg 
of morphine will be administered intrathecally. 
Intervention 2: 
The QL group will receive a bilateral quadratus lumborum block containing 30 mL of 0.25% bupivacaine 
and 4mg of dexamethasone. This will be accomplished by placing the patient in a preoperative holding 
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room with standard ASA monitors where the bilateral quadratus lumborum block will be performed by 
the Anesthesiologist. 
Intervention 3:
In the TAP block group, patients will undergo a bilateral transverse abdominis plane block performed by 
the surgical team using an exparel-based solution mixed with 50mL of saline. This block will be performed 
intraoperatively before the incisions are closed. 
8.0 Follow Visit/Collection Time Points (90-post discharge)
Perioperative data will be extracted from the patient’s chart. The first follow-up visit will take place 
14 days following the baseline visit when intervention was administered. Three additional follow-up 
visit assessments will be completed once per month. The study coordinator and/or investigator will 
review the subject’s concurrent medication and medical history. They will question the subjects for 
any possible adverse events. If adverse events are reported, the PI will assess for causality, severity, 
intervention, and outcomes. The following procedures will be completed:

Concurrent Medication Monitoring (gabapentin, NSAIDs, topicals, muscle relaxers, opioids, and 
SNRIs) (intra-operative, PACU, inpatient, and up-to 90 days post discharge refills and number of 
pills remaining) 

Time to bowel function return documented during first follow-up visit

Time to initiation of first chemotherapy. (Decision made by investigators only)

Visual Analog Scale (post-op 1h, 2h, 6h, 24h, 48h, 7, 30, 60, and 90 days), The Face, Legs, Activity, 
Cry and Consolability (FLACC) scale 30 minutes and 1h, height, weight, BMI, gender, date of surgery, 
duration of operation, estimated blood loss, PACU length of stay, and hospital length of stay. 

Patient satisfaction scores (BPI-sf9) post-op 14, 30, 60, and 90 days.

Adverse Event Monitoring

Record criteria for decision to start chemotherapy off pain medication, return to bowel function, 
no uncontrolled infection, no continued post-operative drains, and nutritional intake. 
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9.0 Study Schematic
Screen 
Visit/ 
Enrollment 
(in clinic)
Baseline 
(at day 
of 
surgery)
Post-op 
to 
discharge 
(See 
times 
above) 
Study 
Day 
14 
(±3 
days)
Day 
30 
(±7 
days)
Day 
60 
(±7 
days)
Day 
90 
(±7 
days)
Informed Consent
x
Demographics
x
Inclusion/Exclusion
x
x
Randomization 
x
Medical History
x
x
x
x
x
x
Study Intervention 
Administration
x
The Face, Legs, 
Activity, Cry and 
Consolability 
(FLACC) scale
x
Visual Analog Scale
x
X
X
X
X
Perioperative 
Details(date of 
surgery, blood 
loss, hospital LOS, 
duration of 
operation)
x
CC Opiate Med
(pre-operative, 
intra-operative, 
PACU, 
inpatient, 
90-
day MMESs)
x
x
x
x
x
x
x
Patient satisfaction 
scores (BPI-sf9)
x
x
x
x
Time to bowel 
function return
x
Time to initiation 
of first 
chemotherapy
x
x
x
Report opioid 
related adverse 
events
x
x
x
x
x
x
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10.0 RISKS
10.1 Physical Risks
Although the intervention being used in this protocol have been well tested for efficacy and safety, 
there may be potential risks associated with participation. Any medical treatment can have temporary 
and permanent side effects and can cause unforeseen adverse reactions, intolerance, or worsening of 
co–morbidities (including, revealing unknown allergies), which could lead to acute adverse event such 
as itching, prolonged length of stay. Any subject with known medical conditions, or on a concurrent 
medication in which the study intervention is not recommended, will be excluded from participation. 
The intervention used in this study are currently in common use and will be administered in 
accordance with current standards. Patients will be carefully screened for contraindications to 
participation prior to study enrollment. We will monitor for adverse events in enrolled patients, refer 
to section 11.0.
 
10.2 Intervention Risk
There is the potential risk of an interventional failure for study participants. The study results may 
not support the primary hypothesis that in patients undergoing a foregut, HPB, or colorectal cancer 
surgery, ITM intervention is a superior analgesic. It is possible that the intervention will prove to be 
less effective than QL or TAP blocks. Patients receiving neuraxial or regional blocks will be 
comprehensively informed of potential risks during the informed consent process, including failed 
block, respiratory depression, post-dural puncture headache, bleeding, infection, neurologic injury, 
allergic reactions, and local anesthetic systemic toxicity). Moreover, they will be made aware of 
potential side effects, such as nausea, pruritis. 
Throughout the regional/block placement procedure, patients will be continuously monitored with 
pulse oximetry, electrocardiography, and blood pressure monitoring.  Additionally, an equipped 
regional cart containing emergency medications (such as lipid emulsion, ACLS medications) and 
airway management supplies will be readily accessible. Postoperatively, anesthesia personnel will 
conduct evaluations to detect any regional/block-related adverse events. All identified adverse 
events will be meticulously monitored, documented, and reported to the Institutional Review Board 
in accordance with regulatory requirements.
 10.3 Psychological Risks:
A potential psychological risk could occur if patients feel a sense of coercion to participate in the study. 
The likelihood is small, because patients will be assured in the informed consent document and face-to-
face discussion that participation is purely voluntary, and they can withdraw their participation at any 
time. 
10.4 Research Risk
No identifiable patient information will be linked to patient assessments during the study. For this 
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specific project, all information related to patients will be identified only by patient initials and study 
number. However, for research purposes, it may be required to collect PHI such as age, DOB, 
Medical Record Number, and dates of diagnoses. Only the study team will have access to this data, 
and it will not be shared with anyone outside of the study team. The greatest research risk, although 
rare, is the loss of confidentiality caused by unauthorized release or misuse of information from 
research records. 
10.5 BENEFITS
Although there may be immediate clinical benefits for some patients in this study who are assigned to 
the study intervention, the anticipated primary benefit is the future potential to decrease the total 
MME utilization and improve the quality of life for patients undergoing oncologic (foregut, 
hepatopancreatobiliary (HPB), and colorectal cancer) surgical procedures.Information obtained from 
this research may help patients in the future achieve better health outcomes and provide clinicians with 
pertinent information about post-operative opioid induced dependency.
11.0 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS
AEs that are considered possibly, probably, or definitely related to the study procedure will be 
recorded in the CRFs. AEs will be assessed starting with onset, and evaluation will continue until 
resolution is noted, or until the investigator determines that the patient’s condition is stable.
All AEs will be characterized by the following:

AE name

Start and Stop dates

Relationship to study procedure

Severity

Action taken

Outcome
Relationship
The investigators will assess the AEs and using their clinical judgment will assign an attribution to the 
AE using the following categories:

Unrelated – The AE is clearly NOT related to the study procedure

Unlikely – The AE is doubtfully related to the intervention

Possibly – The AE may be related to the study procedure

Probably – The AE is likely related to the study procedure

Definitely – The AE is clearly related to the study procedure
Severity
The severity of the AEs should be graded by the investigator as follows:
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
Mild – Transient discomfort; no prescribed medical intervention/therapy required and 
does not interfere with daily activities.

Moderate – Low level of discomfort or concern with mild to moderate limitation in daily 
activities; some assistance may be needed; medical intervention/therapy required.

Severe – Discomfort and limitation in daily activities, assistance required; medical 
intervention/therapy required.
Action Taken
The action taken in response to the AE should be reported using the following categories:

None

Procedure or physical therapy

Withdrawn from study due to AE

Hospitalization

Prescription drug therapy

Non-prescription drug therapy

Other (specify)
Outcome
The clinical outcome of an AE should be characterized as follows:

Resolved without sequelae

Resolved with sequelae (specify)

Ongoing (i.e. continuing at time of study discontinuation)

Death

Unknown/lost to follow-up

Other
SAE Reporting
All SAEs will be documented in the CRFs. SAEs will be reported to the local IRB per the following guidelines:
Adverse event reports will only be submitted to the local IRB if they are determined by the 
principal investigator to be: unanticipated, serious, and possibly, probably or definitely related to 
a research study procedure.
SAEs meeting these criteria (except for deaths) must be reported to the IRB within 5 working days of 
the study team’s notification of occurrence. Deaths that are unanticipated and are possibly, probably 
or definitely related to a research study procedure must be reported to the IRB within 24 hours of 
notification of occurrence. Any relevant follow-up information regarding the SAE should be submitted 
to the IRB as soon as it becomes available and/or upon request. SAE reports to the IRB must include 
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the following: subject identifier, adverse event or problem description, the event relationship to the 
test article or underlying condition, seriousness assessment, whether the event was anticipated or 
unanticipated, type of report (initial or follow-up), date of injury, whether the intervention was 
stopped, and, if so, whether it was re-started, and whether the event provides new risk information 
that alters the risk-benefit assessment and/or should be added to the informed consent disclosure.
12.0 STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE
The researchers hypothesized a moderate effect size of f = 0.25 associated with the treatment. With 1:1:1 
allocation across the three groups (Arm 1: Arm 2: Arm 3), an alpha value of 0.05, a beta value of 0.20, the 
aforementioned moderate effect size of f = 0.25, and an attrition rate of 20%, a total of n = 201 
participants (n = 67 in each active treatment arm and n = 67 in the TAP arm) for adequate statistical 
power. The power analysis was performed G*Power Version 3.1.
Descriptive and frequency statistics will be used to describe the demographic characteristics of the 
sample. The inferential analyses for the trial will be performed in an “intention-to-treat” fashion. MCAR 
(missing completely at random) analysis will be performed to assess missingness of trial data. If the 
missingness is random (as per Little’s chi-square statistic), then imputation of missing data will be 
performed using multiple imputation with expectation-maximization. A “per-protocol” analysis will also 
be performed on the data. The primary outcome of time to chemotherapy (days) will be assessed 
between the three treatment arms using either a one-way ANOVA (if normality and homogeneity of 
variance assumptions are met), or a Kruskal-Wallis test (if either or both assumptions are violated). 
Means, standard deviations, mean differences, and 95% confidence intervals (95% CI) of the mean 
differences for each group will be reported for ANOVA analyses, medians and interquartile ranges for a 
Kruskal-Wallis test. If a significant main effect is detected for either test, post hoc analyses will be 
performed using either Student-Newman-Keuls tests (ANOVA) or Dunn’s test (Kruskal-Wallis). The same 
statistical methods will be performed for the continuous outcomes measured in days (time to return of 
bowel function, MMEs, number of ORADEs, quality of life assessments, and hospital LOS). The incidence 
of AEs and SAEs will be compared amongst the groups using either chi-square or Fisher’s Exact test. All 
analyses will be performed using SPSS Version 29 and statistical significance will be assumed at an 
O’Brien-Fleming adjusted alpha value of 0.0492.
The researchers plan an interim analysis of the primary and secondary outcomes at 50% enrollment for 
the three treatment arms. A decision will be made regarding early termination due to efficacy or futility, 
or the trial will continue to full enrollment. Statistical significance for the interim analysis will be assumed 
at an O’Brien-Fleming adjusted alpha value of 0.0054 for the primary and secondary outcomes, and an 
adjusted alpha value of 0.0492 for the final analysis at full enrollment. Statistical power calculations will 
be performed based on effect sizes yielded from the interim analysis. 
13.0 STUDY MANAGEMENT
The PI and study team has the site resources, time availability, and the patient population needed to 
complete this protocol under GCP guidelines. The PI is ultimately responsible for the conduct of the 
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trial; however, he will delegate authority to appropriate members of the research team. The PI will 
ensure the following:
Study team complies with be GCP and other regulatory requirements.
The study team allows monitoring and auditing of regulating institutions.
Ensures person delegated trial responsibilities are qualified and trained appropriately.
Ensure that study team members have sufficient time to properly conduct and complete the trial.
Ensure that all persons assisting with the trial are adequately informed about the 
protocol, the treatments being administered, and their study-related duties and 
functions.
Ensures compliance with GCP guidelines regulatory requirements.
Will maintain a list of research team members and delegated duties.
Assures protocol compliance.
Reports protocol non-compliance appropriately.
Obtains IRB approval.
Followings regulations and guidelines to protect subject rights, safety, and welfare.
Assures compliance by all research team members of GCP regulations
14.0 DATA MANAGEMENT 
Data will be collected and managed by trained study team members. Data will be backed up with 
OneDrive and access will be limited to study personnel. Data collected during the study will be 
retained in patients’ research records for at least 6 years after the study is completed. At that time, 
the research information not already in the patients’ medical records will be destroyed, per 
institutional guidelines. 
14.1 Data Protection
Throughout the study, measures to ensure the privacy of information on study subjects will be 
maintained. All project investigators and staff have been trained in the use of human subjects in 
research and have received training in the new HIPAA regulations. Subjects and staff will be informed 
of the confidentiality of information and assured that data will be used only for statistical purposes in 
which the individual cannot be identified. Conversely, no identifiable information on any individual will 
be released to anyone other than project personnel without a signed medical release from the subject, 
or where appropriate, the next of kin or a physician in case of a life-threatening emergency to the 
subject. All project personnel will be instructed not to discuss any cases with persons other than project 
personnel.
For this specific project, all information related to patients will be identified only by patient initials 
and study number. However, for research purposes, it may be required to collect PHI such as age, 
DOB, Medical Record Number and dates of diagnoses. Only the study team will have access to this 
data, and it will not be shared with anyone outside of the study team. Data will be collected on 
paper source documents and transcribed into the GSM REDCap system. Only study team members 
will have access to the database. The database will utilize the study number assigned and will not 
include the subjects name or MRN. All subjects will have an assigned number. All completed paper 
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forms will be kept in locked files in locked rooms to which only project personnel have access. 
14.2 Data and Safety Monitoring
Monitoring will be completed by the GSM Office of Research Support and/or The Office of Clinical 
Trials and include a review of original case records. It will include monitoring to assess patient safety, 
the consent process, record-keeping, protocol adherence, and data collection. The Investigator will 
record all protocol deviations. Unexpected clinically significant adverse events will be reported to the 
IRB. In general, the investigators will monitor any adverse reaction to the questionnaires and 
assessments conducted during the study. Any missing data will be omitted from the final statistical 
analysis.
14.3 Protocol Deviations
A protocol deviation is failure to follow procedures specified in the approved research protocol, which 
include (but are not limited to), deviations from study inclusion/exclusion criteria, or failure to follow 
criteria for subject follow-up, withdrawal, or timely monitoring procedures. Protocol deviations will be 
reported per the UTGSM IRB SOPs. 
14.4 Records
14.5.1 Source Documents
Source documents provide evidence for the existence of the patient and substantiate the integrity of 
the data collected. Source documents will be stored and maintained by the study team in a secure 
location. Data entered in the database that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. All electronic data must be derived 
from source documents.
14.5.2 Direct Access to Source Data and Documents
The PI will permit trial-related monitoring, audits, and regulatory inspection, providing direct 
access to source data/documents.
14.5.3 Storage of Records
The PI will retain the source documents and essential documents for a period of at least 6 years after 
the research is completed and the study is closed with the IRB. Records will be kept longer if other 
requirements apply.
15.0 COMPLETION OF TRIAL
When the trial is completed, the PI will inform the IRB and sponsor of the completion in writing.
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16.0 REFERENCES 
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Yang, Y., Lu, Y., Tan, H. et al. The optimal time of starting adjuvant chemotherapy after curative 
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APPENDIX
I.
Opioid related adverse events with ICD-10 codes
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