A Clinician-Focused Nudging Intervention to Optimize Post-Surgical Prescribing
Phase: NA
Conditions: Opioid Prescribing, Surgical Procedure, Unspecified
Sponsor: Vanderbilt University Medical Center

 
 
 
A Clinician-Focused Nudging Intervention to Optimize Post-Surgical 
Prescribing 
 
Principal Investigator: 
Daniel B. Larach, M.D., M.S.T.R., M.A. 
Assistant Professor of Anesthesiology, Vanderbilt University Medical Center 
Sponsor: 
The National Institute on Aging 
P30 Grant #5P30AG024968 
NCT05299528 
 
 
 
Version 1.8 
April 27, 2023 
 

 
Protocol Version 1.8 
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Table of Contents 
A Clinician-Focused Nudging Intervention to Optimize Post-Surgical Prescribing.......................   
1 
PRÉCIS ........................................................................................................................... 3 
1.1 
Study Title .........................................................................................................................3 
1.2 
Objectives..........................................................................................................................3 
1.3 
Design and Outcomes ........................................................................................................3 
1.4 
Interventions and Duration ................................................................................................3 
1.5 
Sample Size and Population ...............................................................................................4 
2 
STUDY TEAM ROSTER ..................................................................................................... 5 
3 
STUDY OBJECTIVES ......................................................................................................... 7 
3.1 
Primary Objective ..............................................................................................................7 
3.2 
Exploratory Objectives .......................................................................................................7 
4 
BACKGROUND AND RATIONALE ..................................................................................... 7 
4.1 
Background on Condition, Disease, or Other Primary Study Focus .......................................7 
4.2 
Study Rationale .................................................................................................................7 
5 
STUDY DESIGN ............................................................................................................... 8 
6 
SELECTION AND ENROLLMENT OF PARTICIPANTS ........................................................... 8 
6.1 
Inclusion Criteria ................................................................................................................9 
6.2 
Exclusion Criteria ...............................................................................................................9 
6.3 
Study Enrollment Procedures ........................................................................................... 10 
7 
STUDY INTERVENTIONS ................................................................................................ 11 
7.1 
Interventions, Administration, and Duration..................................................................... 11 
7.2 
Handling of Study Interventions ....................................................................................... 12 
7.3 
Concomitant Interventions ............................................................................................... 12 
7.3.1 
Allowed Interventions.......................................................................................................................... 12 
7.3.2 
Required Interventions ........................................................................................................................ 12 
7.3.3 
Prohibited Interventions ...................................................................................................................... 12 
7.4 
Adherence Assessment .................................................................................................... 12 
8 
STUDY PROCEDURES .................................................................................................... 12 
8.1 
Schedule of Evaluations ................................................................................................... 12 
8.2 
Description of Evaluations ................................................................................................ 15 
8.2.1 
Preliminary Evaluations (Days -30 to 0) ............................................................................................... 17 
8.2.2 
Initial Patient Group Contacts and Surgeon Pre-Intervention Prescribing Evaluation (Days 1-74) ..... 18 

 
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8.2.3 
Nudging Intervention (Day 97) ............................................................................................................ 20 
8.2.4 
Follow-Up Patient Group Contacts and Surgeon Post-Intervention Prescribing Evaluation (Days 105-
178) 
20 
9 
SAFETY ASSESSMENTS .................................................................................................. 22 
9.1 
Risk/Benefit Profile and Risk Mitigation ........................................................................... 22 
9.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters............... 23 
9.3 
Adverse Events and Serious Adverse Events ...................................................................... 23 
9.3.1 
Reporting Procedures .......................................................................................................................... 25 
9.3.2 
Follow-up for Adverse Events .............................................................................................................. 28 
9.4 
Safety Monitoring ............................................................................................................ 28 
10 
INTERVENTION DISCONTINUATION........................................................................... 28 
11 
STATISTICAL CONSIDERATIONS ................................................................................. 29 
11.1 
General Design Issues ...................................................................................................... 29 
11.2 
Sample Size and Randomization ....................................................................................... 29 
11.2.1 
Treatment Assignment Procedures ..................................................................................................... 29 
11.3 
Interim analyses and Stopping Rules ................................................................................ 29 
11.4 
Outcomes ........................................................................................................................ 30 
11.4.1 
Primary outcomes ................................................................................................................................ 30 
11.4.2 
Exploratory outcomes .......................................................................................................................... 30 
11.5 
Data Analyses .................................................................................................................. 30 
12 
DATA COLLECTION AND QUALITY ASSURANCE .......................................................... 31 
12.1 
Data Collection Forms and Data Management .................................................................. 31 
12.2 
Quality Assurance ............................................................................................................ 31 
12.2.1 
Training ................................................................................................................................................ 31 
12.2.2 
Metrics ................................................................................................................................................. 31 
12.2.3 
Protocol Deviations and Monitoring .................................................................................................... 32 
13 
PARTICIPANT RIGHTS AND CONFIDENTIALITY ........................................................... 32 
13.1 
Institutional Review Board (IRB) Review ........................................................................... 32 
13.2 
Informed Consent Forms .................................................................................................. 32 
13.3 
Participant Confidentiality ............................................................................................... 33 
13.4 
Study Discontinuation ...................................................................................................... 33 
14 
ETHICAL CONSIDERATIONS ....................................................................................... 33 
15 
COMMITTEES ........................................................................................................... 34 
16 
PUBLICATION OF RESEARCH FINDINGS AND DATA SHARING ..................................... 34 
17 
REFERENCES ............................................................................................................. 35 
 
 
 

 
Protocol Version 1.8 
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1 
PRÉCIS 
1.1 
Study Title  
A Clinician-Focused Nudging Intervention to Optimize Post-Surgical Prescribing  
1.2 
Objectives  
Overall goal: Develop pilot data for a new, easily scalable strategy to optimize post-
surgical opioid prescribing. 
 
Specific objective #1: Evaluate feasibility and acceptability of carrying out a novel nudge 
intervention that may reduce excess postoperative opioid prescribing by surgeons. 
 
Exploratory objective #2: Determine whether the nudge intervention leads to changes in 
subsequent postoperative opioid prescribing by surgeons. 
 
Exploratory objective #3: Determine whether this technique affects patient opioid 
consumption, refill requests, medical visits for pain, satisfaction with analgesia, and 
opioid misuse. 
1.3 
Design and Outcomes   
Pilot single site randomized controlled trial to assess the feasibility and acceptability of a 
nudging intervention providing surgeons with procedure-specific feedback regarding 
patients’ postoperative opioid prescription-to-consumption ratio in individuals 18 years 
of age and older. 
 
Primary outcomes:  
Feasibility: 
1. Percentage of surgeons approached who agree to participate in study 
2. Percentage of patients contacted who agree to participate in study 
 
Acceptability: 
1. Surgeon-reported acceptability of intervention 
 
Exploratory outcomes: Mean pre-post percentage change in procedure-specific 
prescription size, mean pre-post change in patient opioid consumption, opioid refills, 
medical visits for pain, satisfaction with analgesia, and opioid misuse, surgeon-reported 
perceived usefulness of intervention.  
1.4 
Interventions and Duration  
In the first phase, patients undergoing specific elective surgeries at the study site 
(Vanderbilt University Medical Center [VUMC], Nashville, TN) during study days 1-60 
will be contacted by telephone or electronically 14 days postoperatively (study days 15-
74) and asked to perform an opioid pill count; they will also be asked about opioid refills, 
satisfaction with analgesia, emergency room visits or hospitalizations for pain, and opioid 
misuse. 

 
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First phase data will then be analyzed and patients’ surgeons randomized in a 1:1 ratio to 
the intervention or control arms. After study day 97, surgeons in the intervention arm will 
be provided procedure-specific direct feedback on opioid prescribing and consumption 
for their patients who had surgery during days 1-60. 
 
After this intervention, we will assess pre-post change in opioid prescription size 
(measured in oral morphine equivalents) from baseline between the two groups for 
surgeries performed during days 108-167 
 
We will also contact patients undergoing post-intervention surgeries (during days 108-
167) 14 days postoperatively (days 122-181) to assess pre-post changes in patient opioid 
consumption, satisfaction with analgesia, medical visits for pain, opioid refills, and 
opioid misuse. 
1.5 
Sample Size and Population  
Patients (initial phase): We anticipate successfully contacting 5 patients per day for a 
total of 300 patients. 
 
Surgeons: We anticipate obtaining mean pre-post prescribing change in up to 60 surgeons 
(30 per group). 
 
Patients (second phase): We anticipate successfully contacting 5 patients per day for a 
total of 300 patients.

 
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2 
STUDY TEAM ROSTER  
Principal Investigator: 
Daniel B. Larach, M.D., M.S.T.R., M.A. 
 
Assistant Professor of Anesthesiology 
 
Vanderbilt University Medical Center 
 
719 Thompson Ln. Ste. 22209 
 
Nashville, TN 37204 
 
 
Telephone (615) 322-6033 
 
Fax (615) 322-9089 
 
Email address daniel.larach@vumc.org 
 
 
Main responsibilities/Key roles: Overall PI 
Co-Investigators/Staff: Stephen P. Bruehl, Ph.D. 
 
Professor of Anesthesiology 
 
Vanderbilt University Medical Center 
 
701 Medical Arts Building 
 
1211 21st Ave. South 
 
Nashville, TN 37212 
 
 
 
Telephone (615) 936-1821 
 
Fax (615) 936-8983 
 
Email address stephen.bruehl@vumc.org 
 
 
Main responsibilities/Key roles: VUMC site co-I 
 
David A. Edwards, M.D., Ph.D. 
Associate Professor of Anesthesiology and Neurological 
Surgery 
 
Vanderbilt University Medical Center 
 
719 Thompson Lane, Ste. 22209 
 
Nashville, TN 37201 
 
 
 
Telephone (615) 322-6033 
 
Fax (615) 322-9089 
 
Email address david.a.edwards@vumc.org 
 
 
Main responsibilities/Key roles: VUMC site co-I 
 
Sarah S. Osmundson, M.D., M.S. 
 
Assistant Professor of Obstetrics and Gynecology 
 
Vanderbilt University Medical Center 
 
719 Thompson Lane, Ste. 27100 
 
Nashville, TN 37201 

 
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Telephone (615) 343-5700 
 
Fax (615) 343-6724 
 
Email address sarah.osmundson@vumc.org 
 
 
Main responsibilities/Key roles: VUMC site co-I 
 
Benjamin C. French, Ph.D. 
 
 
Associate Professor of Biostatistics 
 
Vanderbilt University Medical Center 
 
2525 West End Ave., Ste. 1100, Rm. 1137 
 
Nashville, TN 37203 
 
 
Telephone (615) 322-2001 
 
Fax (615) 343-4924 
 
Email address b.french@vumc.org 
 
 
Main responsibilities/Key roles:  Study biostatistician; will 
provide statistical expertise for the study, including study 
design, protocol development, and analysis of the results. 
 
 
Tracie D. Baker, C.C.R.P. 
 
 
Research Coordinator IV 
 
Vanderbilt University Medical Center 
 
701 Medical Arts Building 
 
1211 21st Ave. South 
 
Nashville, TN 37212 
 
 
 
Telephone (615) 875-1852 
 
Email address tracie.d.baker@vumc.org 
 
 
 
Main responsibilities/Key roles: Study coordinator; will be 
responsible for carrying out study-related procedures including 
recruiting, consenting, and surveying patients as well as 
implementing the personalized feedback to surgeons in the 
Intervention Arm. 
 
 
 
 
 
 
 

 
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3 
STUDY OBJECTIVES 
3.1 
Primary Objective 
Evaluate the feasibility and acceptability of a novel nudge intervention that may reduce 
excess postoperative opioid prescribing by surgeons. 
3.2 
Exploratory Objectives 
Determine whether surgeons randomized to the Intervention Arm will exhibit greater 
mean pre-post percentage change in procedure-specific prescription size compared to the 
Control Arm. Additionally, determine whether the novel nudge intervention affects 
patient opioid consumption, refill requests, medical visits for pain, satisfaction with 
analgesia, and opioid misuse. 
 
4 
BACKGROUND AND RATIONALE  
4.1 
Background on Condition, Disease, or Other Primary Study Focus 
Among those aged 55 and older, opioids caused 8,877 deaths in the U.S. in 2017 (the 
most recent year for which data are available). 4,564 of these deaths were from 
prescription opioids.(1) The total number of U.S. opioid-related deaths in 2017 was 
47,600, 17,029 of which involved prescription opioids. 
Physician prescribing is deeply connected with opioid use disorder: Most Americans 
misusing prescription opioids were either directly prescribed these medications or 
received them from a friend or relative with a prescription,(2) and most current heroin 
users started opioid use with prescribed medication.(3) Surgical prescribing comprises an 
increasing proportion of first-start opioid prescriptions to opioid-naïve patients;(4) 6% of 
such patients develop new persistent opioid use postoperatively.(5) Up to 70% of 
prescribed postoperative opioids go unconsumed and become a reservoir for potential 
diversion or misuse.(6) 
4.2 
Study Rationale 
Evidence-based postoperative prescribing guidelines have been propagated(7-10) in order 
to decrease both the number of surgical patients developing new persistent opioid use and 
the overprescribing of post-surgical opioids. Other nudging techniques like changing 
electronic medical record prescription size defaults have been used in the surgical setting 
to decrease opioid prescribing,(11) although such tactics run the risk of increasing opioid 
prescribing for already-low prescribers.(12) 
Despite these initiatives, evidence remains limited regarding the optimal methods for 
reducing post-surgical opioid prescribing.(13) Our proposed project will test a novel 
nudging technique that has not been studied in the postoperative opioid prescribing space: 
direct feedback to surgeons about their patients’ opioid prescription-to-consumption 
ratios. Direct feedback to opioid prescribers after patients suffered a fatal opioid overdose 
has been shown to reduce subsequent opioid prescribing significantly.(14) We believe 
that providing granular data to a wide population of surgical prescribers (not just those 
whose patients overdose) will prove similarly effective. Should our intervention decrease 

 
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surgical prescribing, we anticipate it playing a significant role in the national strategy to 
combat the opioid crisis. 
 
5 
STUDY DESIGN 
We plan a pilot randomized controlled trial randomizing surgeons to either intervention 
(direct feedback) or control (no direct feedback) arms. Surgeons frequently performing 
specific elective general, gynecologic, orthopedic, and neurological surgeries at VUMC 
will be identified during a 30-day study lead-in period. Then, patients aged at least 18 
years undergoing these surgeries at VUMC during study days 1-60 will be contacted by 
telephone 14 days postoperatively (study days 15-74) and asked to perform an opioid pill 
count; they will also be asked about opioid refills, satisfaction with analgesia, emergency 
room visits or hospitalizations for pain, and opioid misuse. The electronic medical record 
will be also queried for the size of the initial postoperative opioid prescription as well as 
evidence of any refills for each enrolled subject. We anticipate successfully contacting 5 
patients per day for a total of 300 patients in this initial phase. We plan to consent 
patients electronically at the time of the telephone contact as consenting patients 
immediately after surgery may influence their subsequent opioid consumption. 
Surgeons will be consented without overt discussion of the nudge intervention. Following 
the first block of surgeries and associated patient follow-up (study days 1-74), data will 
be analyzed and then surgeons will be randomized in a 1:1 ratio to the intervention or 
control arms. Randomization will be stratified by both surgical specialty and by mean 
opioid prescription size during the initial block of surgeries. After study day 97, surgeons 
in the intervention arm will be provided procedure-specific direct feedback on opioid 
prescribing and consumption for their patients who had surgery during days 1-60. 
After this intervention, we will assess pre-post change in opioid prescription size 
(measured in oral morphine equivalents) from baseline between the two groups for 
surgeries performed during days 108-167. That is, mean size of post-intervention 
prescriptions (from electronic medical record queries) will be compared with mean pre-
intervention prescription size by the same surgeon for the same procedure in order to 
calculate change from baseline. Primary outcomes are measures of study feasibility and 
acceptability given that this is a pilot study. The main exploratory outcome will be mean 
percentage change in procedure-specific prescription size. We will then compare mean 
per-surgeon percentage change in prescription size between the direct feedback and no-
direct-feedback groups. Multiple regression analyses adjusting for case type and surgical 
specialty will also be employed to permit more granular examination of the targeted 
changes. To evaluate other exploratory outcomes, we will contact patients undergoing 
post-intervention surgeries (during days 108-167) 14 days postoperatively (days 122-181) 
to assess pre-post changes in patient opioid consumption, satisfaction with analgesia, 
medical visits for pain, opioid refills, and opioid misuse. We again anticipate contacting 5 
patients per day for a total of 300 patients in this second phase. 
 
6 
SELECTION AND ENROLLMENT OF PARTICIPANTS  
 

 
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6.1 
Inclusion Criteria  
Study surgeon participants must meet all the inclusion criteria below to participate in the 
study: 
• General, gynecologic, orthopedic, or neurological surgeon at VUMC during the 
study period performing any of the surgeries listed below 
Study patient participants must meet all the inclusion criteria below to participate in the 
study: 
• Aged greater or equal to 18 years 
• Undergoing specified elective general, gynecologic, orthopedic, and neurological 
surgeries at VUMC during the specified study periods (days 1-60 for the initial 
patient group; days 108-167 for the follow-up patient group) 
o General: laparoscopic or open cholecystectomy, laparoscopic or open 
appendectomy 
o Gynecologic: abdominal hysterectomy, laparoscopic/robotic 
hysterectomy, vaginal hysterectomy, anterior repair/colporrhaphy, 
posterior repair/colporrhaphy, tension-free vaginal tape procedure, 
sacrospinous ligament suspension, sacrocolpopexy, uterosacral ligament 
suspension, colpocleisis, perineorrhaphy 
o Orthopedic: total knee arthroplasty, total hip arthroplasty, total shoulder 
arthroplasty, 1- or 2-level spinal laminectomy and/or discectomy (without 
fusion) 
o Neurological: 1- or 2-level spinal laminectomy and/or discectomy 
(without fusion) 
• Provided opioid prescription for postoperative pain relief (verified in VUMC 
EMR) 
• Able to understand study procedures and participate in the pill count and 
telephone/electronic interview process in English or Spanish 
• Provide informed consent 
 
6.2 
Exclusion Criteria  
There are no planned exclusion criteria for study surgeon participants, although those 
performing <3 of the specified surgeries during the first 60-day period of surgeries will 
not be eligible for randomization. 
Study patient candidates meeting any of the following exclusion criteria at baseline will 
be excluded from study participation: 
• Opioid prescription filled (per VUMC electronic medical record [EMR] and 
patient self-report) between 3 months and 14 days prior to surgery 
• Primary reason for surgery as assessed by chart review is cancer-related 

 
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• Surgery is a repeat/revision surgery (e.g., revision total knee arthroplasty) 
• Patient has been inpatient for >3 days postoperatively prior to receiving post-
discharge prescription 
• Vulnerable populations: current pregnancy, prisoners 
• Inability or unwillingness of patient to give informed consent 
• (Partial exclusion) Prior participation in this study (e.g., a patient included in the 
initial patient group undergoing a left total knee arthroplasty on study day 15, 
followed by a right total knee arthroplasty on day 115; such a patient would be 
included in the initial patient group but would not be recontacted for the follow-
up patient group) 
 
6.3 
Study Enrollment Procedures 
During the 30-day lead-in period, study surgeon participants will be identified through 
VUMC EMR queries of historical and booked case numbers for the specific procedures 
listed in section 4.1, above. Given the nature of the planned behavioral nudging 
intervention, it is not feasible for full consent to be obtained prospectively from surgeon 
participants as this would very likely affect prescribing behavior in both the Intervention 
and Control Arms due to the Hawthorne effect. Consequently, we plan to request 
permission from the VUMC Institutional Review Board to utilize deception for surgeon 
participants, who will be asked to consent for participation in a study giving them 
information about their patients’ opioid consumption (surgeons will be debriefed fully on 
study purposes upon completion of the study). Surgeon participants will be prospectively 
selected in a participant log kept by study staff. Surgeons will be randomized on a 1:1 
basis to either the Intervention or Control Arms prior to administration of the nudge 
intervention. Enrolled surgeons must complete a minimum 3 listed cases during the initial 
60-day study period (study days #1-60) to be eligible for randomization. 
Study patient candidates will be identified through VUMC EMR queries of performed 
surgical cases for study surgeon participants. All patient candidates including procedures 
by study surgeons will be sent a pre-recruitment letter by the VUMC Department of 
Anesthesiology informing them that may be contacted by telephone postoperatively 
regarding the study. Study team members contacting patients will be blinded to the 
surgeon randomization assignments. All patient candidates undergoing included 
procedures by study surgeons and otherwise meeting inclusion/exclusion criteria will be 
contacted 14 days postoperatively by telephone or electronic messaging and asked to 
complete an opioid pill count and a brief verbal questionnaire relating to postoperative 
opioid use and analgesia. Because preoperative or immediate postoperative consenting 
for the study might affect patient participants’ subsequent opioid consumption, we plan to 
obtain electronic informed consent from patients at the time of contact. Study research 
coordinators will securely document the consent process. Study personnel will also 
maintain a screening log containing records for all evaluated candidates as well as 
reasons for study ineligibility and non-participation of eligible candidates. 
Additionally, at the request of the study Data and Safety Monitoring Board, a third 
participant population will comprise all patients undergoing surgery of any kind by 

 
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surgeons in the nudge intervention group for 60 days following receipt of the nudge 
intervention. This will entail only EHR queries on POD #10 and #30 (on a rolling basis) 
for pain-related medical concerns and healthcare visits. This is to determine whether 
surgeon prescribing practices changed sufficiently following nudge relief to compromise 
postoperative analgesia and potentially harm patients. These patients will not be 
contacted by study staff unless they otherwise meet inclusion criteria for the study as 
listed above. 
 
7 
STUDY INTERVENTIONS  
7.1 
Interventions, Administration, and Duration  
The one-time contact of patient participants will take place on postoperative day 14 (or 
no later than postoperative day 19) for the initial contact group. After verifying eligibility 
and documenting consent, patients will be asked to obtain their prescribed opioid pill 
bottle and conduct a pill count. If the patient consumed the entirety of the prescription 
and disposed of the bottle, this will be documented. If the patient does not have their pill 
bottle readily available, arrangements will be made to follow up with the patient by 
telephone or secure electronic messaging later to complete this aspect of the query. 
Patient participants will also be asked to answer several questions related to our 
exploratory outcomes: 
• Overall satisfaction with postoperative analgesia (numeric rating scale) 
• To select from the following answers: “I received a) too many opioid pills, b) the 
right amount of opioid pills, c) too few opioid pills.” 
• Whether patient required any medical visits primarily due to postoperative pain 
(office visits, emergency department visits, or hospital admissions) 
• Whether additional opioid refills were prescribed after the initial postoperative 
prescription (this will also be evaluated through EMR queries) 
• Evidence of opioid misuse (Current Opioid Misuse Measure-9 [COMM-9]) 
The one-time intervention for surgeon participants in the Intervention Arm will take 
place on approximately study day 97. This will entail procedure-specific direct feedback 
(through electronic communication) on patients’ opioid consumption-to-prescription 
ratio. E.g., “Your abdominal hysterectomy patients were prescribed a mean 60 opioid 
pills last month. These patients consumed a mean 20 pills (33%).” Surgeon participants 
who perform more than one of the specified procedures (see section 4.2, above) will 
receive nudging communications for each individual procedure. Since the data on opioid 
consumption provided to surgeons is based on self-report data from consented patients, 
surgeons will be specifically informed that the data is self-reported through inclusion of 
the following statement: “This is based off self-reported pill counts. The information is 
self-reported and not validated so it could be erroneous.” 
Surgeon participants randomized to the Control Arm will not be contacted directly at any 
time during the study.  

 
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7.2 
Handling of Study Interventions  
The one-time contact of patient candidates will take place as follows: (1) Initial contact 
of patients by research coordinators through telephone or secure electronic message; (2) 
consent process and electronic documentation of consent; (3) pill count and questionnaire 
by telephone or secure electronic message (REDCap Twilio). 
The one-time intervention for surgeon participants in the Intervention Arm will be 
delivered by text message, paging or e-mail on the same day. 
7.3 
Concomitant Interventions 
7.3.1 Allowed Interventions 
All drugs and treatments/interventions are permitted. 
7.3.2 Required Interventions  
There are no required interventions. 
7.3.3  Prohibited Interventions 
There are no prohibited drugs and treatments/interventions. 
7.4 
Adherence Assessment  
No formal adherence assessment is planned. 
 
8 
STUDY PROCEDURES 
8.1 
Schedule of Evaluations 
 

 
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Assessment 
Days -30 to 0 
Days 1-60  
Group #1 
PT Surgeries 
Days 15-74 
Patient 
Phone calls 
Day 75-93 
Surgeon 
prescribing 
practice 
review 
 
Day 97Surgeon  
Nudge Arm 
notification 
Days 108-
167 
Group #2  
PT 
Surgeries 
Days 122-
181 
Patient 
Phone calls 
Days 181+  
Surgeon survey 
Identification of Surgeon 
Participants 
X 
 
 
 
 
 
 
 
Preliminary Screening of 
Patient Candidates 
(EMR/PDMP) – Initial 
Patient Group 
 
X 
X 
 
 
 
 
 
Inclusion/Exclusion 
Criteria – Initial Patient 
Group 
 
 
X 
 
 
 
 
 
Consent of Patient 
Candidates – Initial 
Patient Group 
 
 
X 
 
 
 
 
 
Pill Count – Initial 
Patient Group 
 
 
X 
 
 
 
 
 
Exploratory Outcome 
Questions – Initial 
Patient Group 
 
 
X 
 
 
 
 
 
Assessment of Pre-
Intervention Opioid 
Prescribing by Surgeon 
Participants 
 
 
 
X 
 
 
 
 
Randomization of 
Surgeon Participants 
 
 
 
X 
 
 
 
 

 
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Nudging Intervention 
 
 
 
 
X 
 
 
 
Assessment of Post-
Intervention Opioid 
Prescribing by Surgeon 
Participants 
 
 
 
 
 
X 
X 
 
Screening of Patient 
Candidates 
(EMR/PDMP) – Follow-
Up Patient Group 
 
 
 
 
 
 
X 
 
Inclusion/Exclusion 
Criteria – Follow-Up 
Patient Group 
 
 
 
 
 
 
X 
 
Consent of Patient 
Candidates – Follow-Up 
Patient Group 
 
 
 
 
 
 
X 
 
Pill Count – Follow-Up 
Patient Group 
 
 
 
 
 
 
X 
 
Exploratory Outcome 
Questions – Follow-Up 
Patient Group 
 
 
 
 
 
 
X 
 
Acceptability Questions - 
Surgeons 
 
 
 
 
 
 
 
X 
Adverse Events  
 
 
 
X 
X 
X 
X 
X 

 
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8.2 
Description of Evaluations  
Figure 1: Study Flow Diagram (Days -30 through 0) 
 
 
Figure 2: Study Flow Diagram (Days 1 through 60) 
 
 
 

 
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Figure 3: Study Flow Diagram (Days 15 through 74) 
 
 
 
 
Figure 4: Study Flow Diagram (Days 97 through 167) 
 
 
 
 

 
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Figure 5: Study Flow Diagram (122 through 181) 
  
 
 
8.2.1 Preliminary Evaluations (Days -30 to 0) 
Identification of Surgeon Participants 
•  Up to 60 general, gynecologic, orthopedic, and neurological surgeons at 
VUMC regularly performing the following procedures: 
o General: laparoscopic or open cholecystectomy, laparoscopic or open 
appendectomy 
o Gynecologic: abdominal hysterectomy, laparoscopic/robotic 
hysterectomy, vaginal hysterectomy, anterior repair/colporrhaphy, 
posterior repair/colporrhaphy, tension-free vaginal tape procedure, 
sacrospinous ligament suspension, sacrocolpopexy, uterosacral 
ligament suspension, colpocleisis, perineorrhaphy 
o Orthopedic: total knee arthroplasty, total hip arthroplasty, total 
shoulder arthroplasty, 1- or 2-level spinal laminectomy and/or 
discectomy (without fusion) 
o Neurological: 1- or 2-level spinal laminectomy and/or discectomy 
(without fusion) 
• EMR query will be utilized to identify surgeons most frequently performing 
these surgeries historically at VUMC  

 
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• The date of screening and of enrollment of surgeon participants will be kept in 
the password-protected and encrypted research database. 
 
Preliminary Screening of Patient Candidates (EMR/PDMP) – Initial Patient Group 
• Age ≥18 years 
• Undergoing specified surgeries with surgeon participants between study days 
1-60 
• Provided opioid prescription that was subsequently filled 
• Opioid-naïve (no prior opioid prescriptions between study days -90 to -14) 
• Non-cancer surgery 
• Non-repeat/revision surgery 
• Demographic information, including gender and race/ethnicity, will be 
collected 
• Screening date will be recorded in the password-protected and encrypted 
research database 
 
8.2.2 Initial Patient Group Contacts and Surgeon Pre-Intervention Prescribing Evaluation 
(Days 1-74) 
Inclusion/Exclusion Criteria – Initial Patient Group 
• Confirmation of inclusion/exclusion criteria first assessed during preliminary 
screening 
• Assessment of other inclusion/exclusion criteria: 
o Able to understand study procedures and participate in pill count and 
interview process in English or Spanish 
o Not a member of a vulnerable population (current pregnancy, 
prisoners) 
o Able to give informed consent 
 
Consent of Patient Candidates – Initial Patient Group 
• Identified patient candidates will be contacted by telephone or electronically 
by trained research coordinators. 
• After description of study is provided and risks reviewed, telephone or 
electronic consent will be obtained. 
• Documentation of electronic consent and enrollment of patient participants 
will be made by the research coordinator and stored in the password-

 
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protected, encrypted research database. 
 
Pill Count – Initial Patient Group 
• Consented patients will be asked to physically obtain their prescribed opioid 
pill bottle and conduct a pill count. 
• Patients who report having consumed the entirety of their prescription and 
disposed of the bottle will be considered to have a pill count of 0; absence of 
the empty bottle will be documented in the patient’s study record. 
• For patients who consent to participate but do not have their pill bottle readily 
available, arrangements will be made to follow up with the patient by 
telephone or secure electronic messaging later to complete this aspect of the 
query. 
• All data will be stored in a password-protected and encrypted research 
database. 
  
Exploratory Outcome Questions – Initial Patient Group 
• Patient participants will be asked several questions related to exploratory 
outcomes: 
o Overall satisfaction with post-discharge adequacy of analgesia (Likert 
scale) 
o Whether patients felt they received too many, too few, or the proper 
amount of opioid pills 
o Whether patient required any medical visits primarily due to 
postoperative pain (office visits, emergency department visits, or 
hospital admissions) 
o Whether additional opioid refills were prescribed after the initial 
postoperative prescription (this will also be evaluated through EMR 
queries) 
o Evidence of opioid misuse (Current Opioid Misuse Measure-9 
[COMM-9]) 
 
Assessment of Pre-Intervention Opioid Prescribing by Surgeon Participants 
Baseline pre-intervention opioid prescribing by surgeon participants in both the 
Intervention and Control Arms will be assessed through VUMC EMR queries for all 
patient participants who complete the screening, consent, and pill count processes. 
 
Randomization of Surgeon Participants 
1:1 randomization of surgeon participants between Intervention and Control Arms 

 
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will be completed prior to the study intervention on approximately study day 97  
 
8.2.3 Nudging Intervention (Day 97) 
• On approximately study day 97, surgeon participants randomized to the 
Intervention Arm will receive the one-time nudging intervention. 
• Procedure-specific direct feedback on patients’ opioid consumption-to-
prescription ratio delivered through text message, paging or email message 
• Example: “Your abdominal hysterectomy patients were prescribed a mean 60 
opioid pills last month. These patients consumed a mean 20 pills (33%).” 
 
8.2.4 Follow-Up Patient Group Contacts and Surgeon Post-Intervention Prescribing Evaluation 
(Days 108-181) 
Screening of Patient Candidates (EMR/PDMP) – Follow-Up Patient Group 
• Age ≥18 years 
• Undergoing specified surgeries with surgeon participants between study days 
4108-167 
• Provided opioid prescription that was subsequently filled 
• Opioid-naïve (no prior opioid prescriptions between 14 and 90 days prior to 
the date of surgery) 
• Non-cancer surgery 
• Non-repeat/revision surgery 
• Not a prior participant in the Initial Patient Group of this study 
• Demographic information, including gender and race/ethnicity, will be 
collected 
• Screening date will be recorded in the password-protected and encrypted 
research database 
 
Assessment of Post-Intervention Opioid Prescribing by Surgeon Participants 
Post-intervention opioid prescribing by surgeon participants in both the Intervention 
and Control Arms will be assessed through VUMC EMR queries for all patient 
participants who complete the screening process (primarily to exclude patients who 
are not opioid naïve and who may have participated earlier in the study). 
 
Inclusion/Exclusion Criteria – Follow-Up Patient Group 
• Confirmation of inclusion/exclusion criteria first assessed during preliminary 
screening 

 
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• Assessment of other inclusion/exclusion criteria: 
o Able to understand study procedures and participate in pill count and 
interview process in English or Spanish 
o Not a member of a vulnerable population (current pregnancy, 
prisoners) 
o Able to give informed consent (or for legal guardian/representative to 
do so) 
 
Consent of Patient Candidates – Follow-Up Patient Group 
• Identified patient candidates will be contacted by telephone or electronically 
by trained research coordinators. 
• After description of study is provided and risks reviewed, electronic consent 
will be obtained. 
• Documentation of electronic consent and enrollment of patient participants 
will be made by the research coordinator and stored in the password-
protected, encrypted research database. 
 
Pill Count – Follow-Up Patient Group 
• Consented patients will be asked to physically obtain their prescribed opioid 
pill bottle and conduct a pill count. 
• Patients who report having consumed the entirety of their prescription and 
disposed of the bottle will be considered to have a pill count of 0; absence of 
the empty bottle will be documented in the patient’s study record. 
• For patients who consent to participate but do not have their pill bottle readily 
available, arrangements will be made to follow up with the patient by 
telephone or secure electronic messaging later to complete this aspect of the 
query. 
• All data will be stored in a password-protected and encrypted research 
database. 
 
Exploratory Outcome Questions – Follow-Up Patient Group 
• Patient participants will be asked several questions related to exploratory 
outcomes: 
o Overall satisfaction with postoperative analgesia (Likert scale) 
o Whether patients felt they received too many, too few, or the proper 
amount of opioid pills 
o Whether patient required any medical visits primarily due to 

 
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postoperative pain (office visits, emergency department visits, or 
hospital admissions) 
o Whether additional opioid refills were prescribed after the initial 
postoperative prescription (this will also be evaluated through EMR 
queries) 
o Evidence of opioid misuse (Current Opioid Misuse Measure [COMM-
9]) 
 
Acceptability Questions – Surgeons 
• At the study’s conclusion, surgeon participants will be informed of the nature 
of the nudge intervention and asked several questions related to study 
acceptability: 
o Yes/no response to question involving perceived acceptability of 
receiving feedback on patients’ opioid consumption 
o Surgeon-reported perceived usefulness of intervention 
• All randomized surgeons will be provided with feedback on their patients’ 
opioid use across the entire study at the end of the study.  
 
9 
SAFETY ASSESSMENTS  
9.1 
Risk/Benefit Profile and Risk Mitigation 
Potential risks: We anticipate that this will be a minimal risk study. There is a small 
risk that people who are not connected with this study will learn a participant’s 
identity or their personal information through violation of HIPAA compliance and 
established research protocols. There is also a small risk that physicians may 
experience some discomfort in learning the opioid consumption patterns of their 
patients, or that deception was used in the initial vague description of the purpose of 
the study. Finally, there is a small risk that surgeon participants in the Intervention 
Arm may, following the intervention, prescribe insufficient amounts of postoperative 
opioids and consequently that patients undergoing surgery with these physicians after 
the intervention may be at higher risk of pain-related medical visits. 
 
Potential benefits: There may be no direct benefits to patients participating in this 
study. Providers may benefit from the post-surgical opioid prescribing guidelines 
disseminated during the intervention. Prescribers may also be more likely to exercise 
more careful use of opioids after they have been made aware of discrepancies 
between opioids prescribed and consumed. They may also be more likely to adjust 
their prescribing practices, discuss opioid prescribing with colleagues, and identify 
careful use of opioids with their self-image in the future. 
 
Risk mitigation: Study staff will protect the privacy of study participants. We do not 

 
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anticipate greater than minimal risk to patients or surgeons given that patient contact 
consists only of a pill count and several questions related to postoperative pain and 
the surgeon contact consists only of feedback regarding opioid 
prescription/consumption ratio and published prescribing guidelines. Differences in 
pain-related medical visits will be evaluated as described below. The consent process 
informs a volunteer about the study, indicates the participation is voluntary and 
he/she has the right to stop at any time. Risks are described during the consent 
process.  Surgeons will be fully debriefed on the purpose of the study as soon as 
deception is no longer necessary (upon completion of the study). 
 
Only designated members of the research team will have access to study data. Only 
data from eligible subjects will be analyzed. All data will be stored on password-
protected computers and accessible only accessible to study personnel with 
appropriate password authorization. These measures should be effective in 
minimizing breaches of confidentiality. Prior to study initiation, approval will be 
obtained from the Institutional Review Board at Vanderbilt University Medical 
Center. This approval will be reevaluated each year as part of the Human Subjects 
Committee annual review process, paying particular attention to patient 
confidentiality and the Health Insurance Portability and Accountability Act of 1996 
(HIPAA). 
 
9.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters 
For this single-site minimal risk intervention pilot study, the study staff and principal 
investigator will be responsible for ensuring participants’ safety daily and for 
monitoring and responding to any adverse events or unanticipated problems and for 
reporting them to the IRB, DSMB, and the NIA Program Officer. No formal safety 
parameter analyses are planned, but study staff will monitor for differences in pain-
related medical visits between the Intervention and Control Arms. 
9.3 
Adverse Events and Serious Adverse Events  
We will monitor for specific unanticipated problems during the study period that 
might be related to the study intervention. At any time, clinicians can report an 
adverse event or unanticipated problem potentially related to the study to study staff, 
the Safety Officer, or the DSMB. We do not expect there to be adverse events directly 
influenced by the clinical guidance being delivered in this study. All study 
interventions encourage clinicians to follow well-established national guideline 
recommendations and known best practices. While the expectedness of adverse 
events is very low, we will investigate every numerator case identified in all safety 
measures described above. 
 
As requested by the DSMB, we will perform EHR queries for all patients in the 
follow-up intervention patient groups (that is, patients having surgery after the one-
time study has been delivered to the surgeon intervention and control arms) at 
approximately postoperative day 14. The purpose of these EHR reviews will be to 
assess for evidence of uncontrolled pain through review of hospital admissions, 

 
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emergency department visits, clinic visits, and patient phone calls/electronic portal 
messages. 
 
For cases identified by the safety monitoring measures, we will perform manual 
physician chart review to examine the clinical circumstances and to make a judgment 
(1) the expectedness of the event (unexpected, expected), (2) the likelihood that the 
safety event was study related (not related/possibly related/definitely related) and (3) 
judge the event’s severity (abnormal clinical finding without symptoms/symptoms 
requiring clinical intervention/short term disability or hospitalization/death AND 
separately define the severity as mild, moderate, or severe). 
 
These will be conducted only by authorized study personnel. Study personnel will 
interview patients' treating clinicians when needed to obtain additional information. 
Each case identified will have a case report form with these variables and will be 
signed and dated by study staff completing the form. These forms will be stored in a 
locked office. Each adverse event will be given an identification number. If study 
personnel believe that a patient that experienced an adverse event would benefit from 
seeing or communicating with their prescribing surgeon, the PI will within 2 business 
days reach out to this clinician advising them to contact the patient as soon as 
possible. All study personnel will be trained in HIPAA-compliant procedures. Data 
will be kept on a password protected drive on a secure network, to which study 
personnel will have restricted access. 
 
Adverse events will be defined as: Any untoward or unfavorable medical occurrence 
in a human study participant, including any abnormal sign (e.g., abnormal physical 
exam or laboratory finding), symptom, or disease, temporally associated with the 
participants’ involvement in the research, whether or not considered related to 
participation in the research.  For this study, we will only be collecting adverse events 
involving the study interventions, pain, or opioid use. Other post-surgical 
complications or adverse events will not be captured. 
 
Adverse events will be assessed by a qualified medical professional using the 
following guidelines to describe severity: 
 
• Mild: Events require minimal or no treatment and do not interfere with the 
participant’s daily activities. 
 
• Moderate: Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with 
functioning. 
• Severe: Events interrupt a participant’s usual daily activity and may require 
systemic drug therapy or other treatment. Severe events are usually potentially 
life-threatening or incapacitating.  Of note, the term “severe” does not 
necessarily equate to “serious”. 
Additionally, Serious Adverse Events will be defined as any adverse event that: (1) 

 
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Results in death; (2) Is life threatening, or places the participant at immediate risk of 
death from the event as it occurred; (3) Requires or prolongs hospitalization; (4) 
Causes persistent or significant disability or incapacity; (5) Results in congenital 
anomalies or birth defects; or (6) Is another condition which investigators judge to 
represent significant hazards. 
 
Additionally, all Adverse Events and Serious Adverse Events will be assessed for 
their relationship to study procedures as follows: 
 
• Definitely related: There is clear evidence to suggest a causal relationship, and 
other possible contributing factors can be ruled out. The clinical event, 
including an abnormal laboratory test result, occurs in a plausible time 
relationship to study intervention administration and cannot be explained by 
concurrent disease or other drugs or chemicals. 
 
• Possibly related: There is some evidence to suggest a causal relationship (e.g., 
the event occurred within a reasonable time after the trial intervention or 
patient contact). However, other factors may have contributed to the event 
(e.g., the participant’s clinical condition, other concomitant events). 
 
• Not related: The AE is completely independent of study intervention 
administration/patient contact, and/or evidence exists that the event is 
definitely related to another etiology. There must be an alternative, definitive 
etiology documented by a qualified medical professional. 
9.3.1 Reporting Procedures 
Should a serious, unanticipated, and possibly or definitely related adverse event, 
unanticipated problem or safety analysis occur, we will notify the Safety Officer, 
DSMB Chair, NIA Program Officer, and theVUMC IRB within 48 hours of the study 
team becoming aware of the event. Our report will include appropriate identifying 
information for the study, a detailed description of the unanticipated, 
possibly/definitely related, serious adverse event, and a description of any changes to 
the protocol or other corrective actions that have been taken or are proposed. If an 
unanticipated, possibly/definitely related, serious adverse event occurs, we will 
review relevant clinical decision support and ensure others are not at a greater risk of 
harm than was previously known or recognized. 
 
Patient deaths related to this study are not expected. However, should we identify a 
possibly related or definitely related patient death in safety measures described above 
we will report the death to the Safety Officer, NIA Program Officer, DSMB chair, 
and the VUMC IRB within 48 hours of our knowledge of the death.  
 
The summary of all SAEs (both anticipated and unanticipated) and safety measures 
will be reported and shared with the Safety Officer, NIA Program Officer, DSMB 
chair, and the VUMC IRB quarterly throughout the duration of the project, unless 
otherwise requested. In addition, the summary for reporting all reportable adverse 

 
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events (including a report of all numerator cases to all safety measures identified in 
this report) will be shared with the Safety Officer, NIA Program Officer, DSMB 
chair, and VUMC IRB quarterly, unless more frequent reports are requested by the 
NIA, DSMB, or IRB. 
 

 
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9.3.2 Follow-up for Adverse Events 
The occurrence of a reportable adverse event (AE) or serious adverse event (SAE) 
may come to the attention of study personnel during study visits and interviews of a 
study participant presenting for medical care, or upon review by a study monitor. 
All reportable AEs including local and systemic reactions not meeting the criteria for 
SAEs will be captured on the appropriate case report form (CRF). Information to be 
collected includes event description, time of onset, qualified medical professional’s 
assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the 
event. All reportable AEs occurring while on study must be documented 
appropriately regardless of relationship. All AEs will be followed to adequate 
resolution. 
Changes in the severity of an AE will be documented to allow an assessment of the 
duration of the event at each level of severity to be performed. AEs characterized as 
intermittent require documentation of onset and duration of each episode. 
The study team will record all reportable events on consented patients with start dates 
occurring any time post-discharge until the last day of study participation. Events will 
be followed for outcome information until resolution or stabilization. 
 
 
9.4 
Safety Monitoring 
For this single-site minimal risk intervention pilot study, the study staff and principal 
investigator will be responsible for ensuring participants’ safety daily and for monitoring 
and responding to any adverse events or unanticipated problems and for reporting them to 
the Safety Officer, IRB, DSMB, and the NIA Program Officer. The Data and Safety 
Monitoring Board (DSMB) will act in an advisory capacity to the NIA Director to 
monitor participant safety, evaluate the progress of the study, to review procedures for 
maintaining the confidentiality of data, the quality of data collection, management, and 
analyses. As the NIA has requested the oversight of a DSMB, we will utilize the 
oversight of the standing Roybal Centers DSMB. The study team will prepare safety 
reports quarterly to be reviewed by the NIA and DSMB for recommendations for or 
against the trial's continuation, as well as any modification to the study. The DSMB will 
meet at least biannually either in-person or by teleconference call to review study 
progress, data quality, and participants safety. 
 
10 INTERVENTION DISCONTINUATION  
There are no formal criteria for discontinuing the study, although the discovery of any 
unanticipated adverse event would warrant immediate consideration of this. 
Study participation for patient participants is anticipated to last no longer than a day, and 
in most cases approximately 15-30 minutes. Subjects may withdraw voluntarily from 

 
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participation in the study at any time and for any reason. Subjects who withdraw from the 
study will not be replaced. For any subject who withdraws from the study due to an AE 
or SAE, every effort will be made to collect safety data related to the AE or SAE and 
ensure the study receives appropriate care under medical supervision until the symptoms 
of any AE resolve or the subject’s condition becomes stable. 
11 STATISTICAL CONSIDERATIONS  
11.1 General Design Issues  
This is a pilot randomized controlled trial assessing the effect of a brief behavioral 
nudging intervention on surgeons’ postoperative opioid prescribing. In addition to 
determining feasibility and acceptability, we are chiefly interested in obtaining precise 
estimates of mean and variance to aid in planning a larger, sufficiently powered efficacy 
trial. 
 
Exploratory hypotheses include that (1) surgeons in the Intervention Arm will exhibit a 
larger pre-post percentage change in procedure-specific prescription size (measured by 
oral morphine equivalents [OMEs]) compared with surgeons in the Control Arm who do 
not receive the nudging intervention and (2) there will be no pre-post difference between 
the Intervention and Control Arms in terms of patient opioid consumption, opioid refills, 
medical visits for pain, satisfaction with analgesia, and opioid misuse. 
11.2 Sample Size and Randomization 
We anticipate obtaining mean pre-post prescribing change in  up to 60 surgeons (30 per 
group). This exceeds the suggested rule-of-thumb threshold of 12 per group for an 
adequately precise estimate of the variance of a continuous variable to use in future 
studies.(16) 
11.2.1 Treatment Assignment Procedures 
For randomization, a list of all surgeon participants will be generated. Using 
random.org’s sequence generator, a true random integer sequence derived from 
atmospheric noise will determine order in the list. Randomization will be stratified by 
surgical specialty (e.g., neurological surgery) and by mean opioid prescribing amount 
during the first 60-day surgical period prior to randomization (greater or equal to 
median vs. below median). We will at minimum ensure an even or near-even split 
among the four overall major surgical divisions (general, orthopedic, gynecologic, 
and neurological) across the intervention and control arms. 
11.3 Interim analyses and Stopping Rules 
We will assess study measures and safety measures in the middle of the study. There are 
no interim analyses planned that would trigger early stopping for this pilot study as it 
involves only a single communication with surgeons and a single communication with 
participating patients. As noted in section 8, above, the discovery of any adverse event 
would prompt immediate evaluation by the study team (including study statistician and, if 
necessary, DSMB statistician) to review the events by group to determine whether there 

 
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are statistical and/or clinical concerns. The statistician would report their findings to a 
closed session of the DSMB and/or NIA. Findings would be used to determine what steps 
would be taken. 
11.4 Outcomes  
11.4.1 Primary outcomes   
• Percentage of surgeons approached who agree to participate in study (goal: 
>50%) 
• Percentage of patients contacted who agree to participate in study (goal: 
>50%) 
• Surgeon-reported acceptability of intervention (goal: >75% respond “Yes” to 
question regarding perceived acceptability of nudge intervention) 
11.4.2 Exploratory outcomes   
• Mean pre-post percentage change in procedure-specific prescription size, as 
measured by OMEs. Mean size of post-intervention prescriptions (from 
electronic medical record queries) will be compared with mean pre-
intervention prescription size by the same surgeon for the same procedure in 
order to calculate change from baseline. 
 
• Pre-post change in patient opioid consumption, as measured by OMEs 
 
• Pre-post change in satisfaction with overall postoperative analgesia, as 
measured by patient-reported numeric rating scale 
 
• Pre-post change in patient satisfaction with general amount of opioids 
prescribed 
 
• Pre-post change in incidence of medical visits for pain (office visits, 
emergency department visits, and/or hospital admissions) 
 
• Pre-post change in number of subsequent opioid refills after the initial 
postoperative prescription (from EMR/PDMP data) 
 
• Surgeon-reported perceived usefulness of intervention (goal: median response 
to question “Do you think the nudge intervention would be useful?” ≥4 on 0-5 
scale, where 0 is “not at all” and 5 “extremely.” 
11.5 Data Analyses 
Primary feasibility and acceptability outcomes will be assessed on a descriptive basics 
among both the intervention and control surgeon groups (each group will be given a full 
explanation of the nature of the study following completion). After the intervention, we 
will also assess pre-post change in opioid prescription size (measured in oral morphine 

 
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equivalents) between the two groups. We will compare postoperative prescription size 
from the baseline (surgeries performed during days 1-60) to prescription size for 
surgeries performed during days 108-167. The specific exploratory outcome will be mean 
percentage change in procedure-specific prescription size. That is, mean size of post-
intervention prescriptions (from electronic medical record queries) will be compared with 
mean pre-intervention prescription size by the same surgeon for the same procedure in 
order to calculate change from baseline. We will then compare mean per-surgeon 
percentage change in prescription size between the Intervention and Control Arms. We 
will plan a multiple regression analysis adjusting for case type and surgical specialty to 
further explore the targeted intervention effects. 
To evaluate our other exploratory outcomes, we will assess pre-post changes across 
groups in patient opioid consumption, satisfaction with analgesia, medical visits for pain, 
opioid refills, and opioid misuse. 
Additionally, we will examine differential consent rates between patients in the follow-up 
intervention patient group vs. those in the follow-up control patient group using 
descriptive statistics. This is due to the potential for varying consent rates among patients 
who are more or less satisfied with their postoperative analgesia following delivery of the 
one-time study intervention to surgeons. 
We will not undersample or oversample surgeons who are women and/or members of 
minority racial and ethnic groups, so we expect to enroll them in proportion to their 
population prevalence at VUMC. We will use VUMC EMR data to assess sex/gender and 
race/ethnicity of patient participants, and will conduct analyses to investigate any 
differences between groups (including any sex/gender or race/ethnicity differences in 
willingness to participate in the study).  
12 DATA COLLECTION AND QUALITY ASSURANCE 
12.1 Data Collection Forms and Data Management 
Trained research coordinators with appropriate clearances will contact, consent, and 
interview each patient participant; they will extract pertinent information from VUMC 
EMR data (after obtaining appropriate IRB approval) into Case Report Forms utilizing a 
password-protected, encrypted REDCap database. Study team members, including the 
study biostatistician, will perform outcome assessments as described above. 
12.2 Quality Assurance  
12.2.1 Training 
All project personnel handling study data will be certified by the Collaborative IRB 
Training Initiative (CITI) program, which consists of courses in the Protection of 
Human Research Subjects for Biomedical Research and Quality Control. 
12.2.2 Metrics 
It is the primary responsibility of study staff to record surgeon and patient provider 
data in a secure, password-protected database at VUMC and track surgeon 

 
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participants in regard to intervention status. Consistent delivery of the study 
interventions will be monitored throughout the intervention phase of the study. 
12.2.3 Protocol Deviations and Monitoring 
This protocol defines a protocol deviation as any noncompliance with the clinical trial 
protocol, International Council on Harmonisation Good Clinical Practice (ICH GCP), 
or Manual of Procedures (MOP) requirements. The noncompliance may be either on 
the part of the participant, the investigator, or the study site staff. As a result of 
deviations, corrective actions will be developed by the site and implemented 
promptly.  
It will be the responsibility of the site investigator to use continuous vigilance to 
identify and report deviations within 2 working days of identification of the protocol 
deviation. All deviations will be addressed in study source documents, reported to 
NIA Program Official. Protocol deviations will be sent to the VUMC Institutional 
Review Board (IRB) per their policies. The site investigator will be responsible for 
knowing and adhering to the reviewing IRB requirements. Further details about the 
handling of protocol deviations will be included in the MOP. 
The study team will review protocol deviations on an ongoing basis and will 
implement corrective actions when the quantity or nature of deviations are deemed to 
be at a level of concern.  
Should independent monitoring become necessary, the PI will provide direct access to 
all trial related sites, source data/documents, and reports for the purpose of 
monitoring and auditing by the sponsor/funding agency, and inspection by local and 
regulatory authorities.  
13 PARTICIPANT RIGHTS AND CONFIDENTIALITY  
13.1 Institutional Review Board (IRB) Review 
This protocol and the informed consent document and any subsequent modifications will 
be reviewed and approved by the IRB or ethics committee responsible for oversight of 
the study. 
13.2 Informed Consent Forms 
Electronic patient participant consent procedures and templates will be IRB-approved and 
the participant will be asked to review their content as appropriate. The 
investigator/clinical research staff will explain the research study to the participant and 
answer any questions that may arise. A verbal explanation will be provided in terms 
suited to the participant’s comprehension of the purposes, procedures, and potential risks 
of the study and of their rights as research participants. Live Spanish translation services 
will be provided for Spanish-speaking subjects participating in the consent process that 
do not speak and/or understand English. Participants will be informed that participation is 
voluntary and that they may withdraw from the study at any time, without prejudice, and 
that the quality of their medical care will not be adversely affected if they decline to 
participate in this study. Participants will have the opportunity to ask questions prior to 

 
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giving consent. The informed consent process will be conducted and documented in the 
source document (including the date), and the form signed, before the participant 
undergoes any study-specific procedures. A copy of the signed informed consent 
document will be sent to the participants for their records.  
Permission to engage in deception for surgeon participants will be obtained from the 
VUMC IRB. 
13.3 Participant Confidentiality  
Every effort will be made to avoid the risk of people not connected with the study 
learning participants' identities or personal information. The minimum necessary data 
will be extracted to address our study objectives. Study staff will protect the privacy of 
study participants. Only designated members of the research team will have access to 
study data. Only data from eligible subjects will be analyzed. All data will be stored on 
password-protected computers and accessible only accessible to study personnel with 
appropriate password authorization. All study staff will undergo mandated VUMC 
training on appropriate research conduct, including HIPAA compliance and protection of 
participant information. These measures should be effective in minimizing breaches of 
confidentiality. 
Any data, specimens, forms, reports, video recordings, and other records that leave the 
site will be identified only by a participant identification number (Participant ID, PID) to 
maintain confidentiality.  All records will be kept in a locked file cabinet.  All computer 
entry and networking programs will be done using PIDs only. Information will not be 
released without written permission of the participant, except as necessary for monitoring 
by IRB, the FDA, the NIA, and the OHRP. 
13.4 Study Discontinuation  
The study may be discontinued at any time by the IRB, the NIA, the OHRP, the FDA, or 
other government agencies as part of their duties to ensure that research participants are 
protected. 
14 ETHICAL CONSIDERATIONS 
The study will be conducted in accordance with VUMC’s clinical research standards that 
meet regulations relating to Good Clinical Practice (GCP). These standards adhere to the 
following guidelines: 
 
Good Clinical Practice: ICH Consolidated Guideline (International Conference on 
Harmonization of Technical Requirements for the Registration of Pharmaceuticals for 
Human Use, May 1996). 
 
United States (US) Code of Federal Regulations (21 CFR) dealing with human subject 
protection and conduct of investigational clinical studies (21 CFR parts 50, 54, 56, 312, 
and 314). 
 

 
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Declaration of Helsinki, concerning medical research in humans (“Recommendations 
Guiding Physicians in Biomedical Research Involving Human Subjects,” Helsinki 1964, 
amend Tokyo 1975, Venice 1983, Hong Kong 1989, revised version of Somerset West, 
Republic of South Africa, October, 1996 and Scotland, 2000). 
15 COMMITTEES 
Not applicable 
16 PUBLICATION OF RESEARCH FINDINGS AND DATA SHARING 
We will adhere to the USC Roybal Center Master Dissemination Plan to ensure that our 
study findings and interventions are quickly and widely shared: 
In accordance with recommended practice for clinical trials, we will register this study 
with ClinicalTrials.gov within the recommended timeframe (not later than 21 calendar 
days after the enrollment of the first participant). We will also ensure that results 
information is submitted in adherence with the timeframes (no later than one year 
following study primary completion date) outlined in ClinicalTrials.gov policies to 
facilitate timely dissemination of study findings. Likewise, we will ensure that informed 
consent documents include a specific statement relating to the posting of clinical trial 
information at ClinicalTrials.gov. VUMC also has an internal policy in place to ensure 
that clinical trials registration and results reporting occur in compliance with policy 
requirements. 
This study will be conducted in accordance with the following publication and data 
sharing policies and regulations: National Institutes of Health (NIH) Public Access 
Policy, which ensures that the public has access to the published results of NIH funded 
research. It requires scientists to submit final peer-reviewed journal manuscripts that arise 
from NIH funds to the digital archive PubMed Central upon acceptance for publication. 
This study will comply with the NIH Data Sharing Policy and Policy on the 
Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials 
Registration and Results Information Submission rule. As such, this trial will be 
registered at ClinicalTrials.gov, and results information from this trial will be submitted 
to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-
reviewed journals. Timeframe for data sharing is discussed in the Clinical Trial 
Dissemination Plan, above. All data and resources generated through this study will be 
available for replication on a website or repository hosted on the Vanderbilt research 
cloud. This will include pilot study protocols (with detailed information on recruitment, 
randomization, and workflow specifications), intervention language, and any other study 
specific resources necessary to facilitate replication. The PI will share with the scientific 
community these data in a timely manner, and no later than the online publication date of 
any publications related to the project. It will be available for download from a repository 
hosted on the Vanderbilt research cloud, and will include a “readme” file that explains 
how a researcher can get access to the data and a description of the files and a data 
dictionary that will guide a researcher through potential replication of the study. 
Data will be a HIPAA-compliant, limited data set. Prior to sharing of data, data use 
agreements will be executed and data will only be made accessible to key project staff. 

 
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The data use agreement will include language requiring the user(s) to certify that no 
attempt will be made to reidentify participants from de-identified data. There are 
restrictions with sharing this data. Some data will be extracted from the BioVU electronic 
medical record at Vanderbilt University Medical Center. Data may be made available 
through data use agreements among researchers interested in using the data. Patient and 
physician data will be recorded in a secure, electronic database (REDCap), and 
maintained by study analysts. Data will be entered, tracked, edited, updated and reported 
by pre-approved analysts with the appropriate clearance. Shared data will be fully 
deidentified following HIPAA and VUMC IRB procedures. Study documents will be 
retained for a minimum of 3 years after of study completion. No records will be 
destroyed without the written consent of the sponsor/funding agency, if applicable. 
Any presentation, abstract, or manuscript will be made available for review by the 
sponsor and the NIA prior to submission. 
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