Default Dosing Settings for Opioid Prescriptions to Adolescents and Young Adults After Tonsillectomy
Phase: NA
Conditions: Tonsillectomy
Sponsor: University of Michigan

 
 
 
 
 
Using Default Opioid Prescription Settings to Limit 
Excessive Opioid Prescribing to Adolescents and 
Young Adults 
 
 
 
 
NCT04066829 
 
Date of IRB Approval: August 24, 2021 
Date of Notification of Approval from IRB: September 8, 2021 
 

 ____________________________________________________________________________________________ 
1 
Default Dosing Settings for Opioid Prescriptions to Adolescents and Young 
Adults after Tonsillectomy 
 
Principal Investigator: 
Kao-Ping Chua, M.D., Ph.D. 
Assistant Professor of Pediatrics 
Susan B. Meister Child Health Evaluation and Research Center  
Department of Pediatrics 
University of Michigan Medical School  
 
Funding Mechanism: Career development award to Dr. Chua from National Institute 
on Drug Abuse (grant number 1K08DA048110-01). 
Institution(s): University of Michigan Medical School 
 
Other Identifying Numbers:  AWD012194, HUM00159821 
 
Protocol Amendments: N/A 
 
Draft or Version Number: 1.2 
 
Day Month Year: 3 May 2021 
 

 ____________________________________________________________________________________________ 
2 
 TABLE OF CONTENTS 
Page 
Title Page…………………………………………………………………………………………1 
Table of Contents ............................................................................................................ 2 
Signature Page ............................................................................................................... 3 
List of Abbreviations ........................................................................................................ 4 
1 
Background/Scientific Rationale .............................................................................. 5 
2 
Objectives ............................................................................................................... 5 
3 
Expected Risks/Benefits.......................................................................................... 6 
4 
Eligibility .................................................................................................................. 6 
5 
Subject Enrollment .................................................................................................. 7 
6 
Study Design and Procedures ................................................................................. 7 
7 
Data Collection and Management Procedures ........................................................ 9 
8 
Data Analysis ........................................................................................................ 10 
9 
Quality Control and Quality Assurance.................................................................. 10 
10 
Statistical Considerations ...................................................................................... 11 
11 
Regulatory Requirements ...................................................................................... 11 
11.1 Informed Consent ....................................................................................... 11 
11.2 Subject Confidentiality ................................................................................ 12 
11.3 Unanticipated Problems ............................................................................. 13 
12 
References ............................................................................................................ 16 
 
 
 
 
 

 ____________________________________________________________________________________________ 
3 
SIGNATURE PAGE 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this study will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable US federal 
regulations. 
Site Investigator:* 
 
Signed: 
 
Date: 
 
August 21, 2019 
 
Name: Kao-Ping Chua 
Title: Assistant Professor of Pediatrics, University 
of Michigan Medical School 
 
 
 
* The protocol should be signed by the clinical site investigator who is responsible for 
the day to day study implementation at his/her specific clinical site.

 ____________________________________________________________________________________________ 
4 
LIST OF ABBREVIATIONS  
EHR   
Electronic health record 
NIDA 
National Institute on Drug Abuse 
AE 
Adverse events 
SAE 
Serious adverse events 
UM 
University of Michigan 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 ____________________________________________________________________________________________ 
5 
1 
BACKGROUND/SCIENTIFIC RATIONALE 
 
• Prescription opioid use by adolescents and young adults aged 12-25 years 
increases their risk of prescription opioid misuse.1,2  Leftover opioids from 
prior prescriptions for acute pain are a key driver of this misuse. As such, it is 
crucial to ensure that quantities in opioid prescriptions match the needs of 
adolescents and young adults.3 
 
• Several prior studies have utilized default dosing settings to reduce the size of 
opioid prescriptions written to adults. In a study in the University of 
Pennsylvania adult emergency department, the default quantity of 
oxycodone-acetaminophen tablets in the electronic health record (EHR), was 
set to 10 tablet; providers could override the settings and prescribe other 
quantities at their discretion. After this intervention was implemented, the 
percentage of Percocet prescriptions written for 10 tablets increased from 
20.6% to 43.3%, demonstrating that EHR default settings can affect opioid 
prescribing.4  
 
• However, no study has utilized default dosing settings to promote appropriate 
opioid prescribing to adolescents and young adults. Furthermore, no study of 
default dosing settings to date has chosen the level of these settings based 
on evidence on patient need.   
 
• In this study, we will collect data on patient-reported post-surgical opioid 
consumption among adolescents and young adults undergoing tonsillectomy 
at the University of Michigan. These data will inform the design of a default 
dosing setting intervention. We will assess whether implementation of the 
intervention is associated with changes in opioid prescribing and 
consumption. Additionally, we will assess for potential unintended 
consequences, including worsened patient satisfaction, pain control, sleep, 
anxiety, depression, and functioning; or increased requests for refills or return 
visits for uncontrolled pain. 
 
• The research team has significant experience with collecting data on patient-
reported opioid consumption and patient-reported outcomes such as pain 
control, as well as with developing evidence-based opioid prescribing 
guidelines.  
 
2 
OBJECTIVES 
 
• To evaluate changes in opioid prescribing, consumption, patient-reported 
outcomes, and health care utilization after implementation of a behavioral 
intervention using evidence-based default dosing settings for opioid 
prescriptions to adolescents and young adults undergoing tonsillectomy 

 ____________________________________________________________________________________________ 
6 
3 
EXPECTED RISKS/BENEFITS 
 
• There are no expected direct benefits to subjects. The expected risks for 
subjects are no more than minimal.  
o The most likely risk to study subjects is the time burden associated 
with completing the surveys. 
o There is a possible risk of breach of confidentiality, although the study 
team will take measures to prevent such breaches.   
o There is a possible risk of worsened pain control, although literature 
suggests this is unlikely. For example, an evidence-based opioid 
prescribing guideline was instituted for University of Michigan patients 
undergoing gallbladder removal in 2015 and 2016. Prior to institution of 
this guideline, patients received an average of 50 pills of 
hydrocodone/acetaminophen but only consumed 6. Institution of the 
guideline was associated with a 63% reduction in prescription size 
without increasing the need for opioid prescription refills.5 
o There is a possible risk that the intervention could cause depression or 
suicidal ideation, or that increased opioid misuse could occur. Prior 
studies evaluating interventions to reduce opioid prescribing for acute 
pain have not evaluated these outcomes, so these risks remain 
theoretical. However, the primary mechanism of these unintended 
consequences would be worsened pain control, which is unlikely given 
the reasons above. 
 
• Future patients and society may benefit from the research results. The default 
setting intervention could be broadly applicable to other procedures and 
conditions, and could also be readily scalable to other institutions due to its 
low cost of implementation. If this intervention is successful in limiting 
excessive opioid prescribing to adolescents and young adults, widespread 
adoption could reduce the number of unused opioids available for misuse and 
diversion in adolescents and young adults.  
 
4 
ELIGIBILITY 
 
• Subject population: Adolescents and young adults undergoing tonsillectomy  
 
• Inclusion criteria 
o Adolescents and young adults aged 12-25 years will be eligible to be 
recruited if they undergo palatine tonsillectomy with or without 
adenoidectomy on the pediatric or general otolaryngology service of 
the University of Michigan Medical School, and if they are not: 
 Patients in foster care or patients with a legal guardian 
 Patients with developmental delays, such as autism 
 Patients who are non-English speaking  
 Patients with recent suicidal ideation 
 Patients undergoing emergent tonsillectomy  

 ____________________________________________________________________________________________ 
7 
 
 
• Exclusion criteria for primary analysis analyzing prescribing 
o Patients who were approached for consent but declined   
o Patients with prescription opioid use prior to surgery 
o Patients undergoing additional major procedures at the same time as 
tonsillectomy  
o Patients enrolled in another study 
o Patients who are not prescribed opioids post-operatively 
o Patients who are enrolled in the “M-POP” pathway, which includes 
education about pain management and a small initial opioid 
prescription (10 doses) 
o Patients with hospitalization with length of stay > 1 day after surgery 
 
• Additional exclusion criteria for secondary analysis examining patient-
reported outcomes through surveys 
o Patients who were not reached for consent  
o Patients who do not complete the baseline and post-operative day 14 
surveys 
 
• Inclusion of vulnerable populations: The purpose of this study is to evaluate 
an intervention on opioid prescribing to adolescents and young adults. As 
such, minors must be included in the study.  
 
5  
SUBJECT ENROLLMENT 
 
• Screening 
o Patients scheduled to undergo tonsillectomy during the study period 
will be identified using the surgical scheduling system and screened to 
against age criteria. 
 
• Enrollment 
o The study team will recruit all eligible patients. Recruitment will occur 
over the phone or in-person during the 14-day period before the day of 
surgery for patients undergoing tonsillectomy at C.S. Mott Hospital or 
University Hospital. A study team member will e-mail patients who 
enroll with a PDF version of the consent and a pain journal they can 
print to record the number of opioid doses consumed. For those 
patients who cannot be contacted, in-patient recruitment will occur pre-
operatively on the day of surgery. A study team member will provide 
patients who enroll with a paper pain journal they can use to record the 
number of opioid doses consumed. 
o Recruitment will occur over the phone during the 14-day period before 
the day of surgery for patients undergoing tonsillectomy at the Brighton 
Center for Specialty Care or Livonia Center for Specialty Care. A study 
team member will e-mail patients who enroll with a PDF version of the 

 ____________________________________________________________________________________________ 
8 
consent and a pain journal they can print to record the number of 
opioid doses consumed. 
 
• Incentives 
o Subjects will be compensated $10 for completing the baseline survey, 
$10 for completing all 13 daily post-operative surveys, and $10 for 
completing the final survey on post-operative day 14. Subjects will be 
compensated based on the number of sets of surveys completed (e.g., 
if they complete the baseline and post-operative surveys, they will 
receive $20). Compensation will be mailed after post-operative day 14. 
 
6 
STUDY DESIGN AND PROCEDURES 
 
• Study design  
o The study will use a difference-in-differences design in which changes 
before and after the intervention will be compared between a treatment 
group and a control group. 
o The treatment group will include all patients undergoing tonsillectomy 
at C.S. Mott Hospital by a pediatric otolaryngology faculty member at 
the University of Michigan. 
o The control group will include all patients undergoing tonsillectomy at 
University Hospital, Brighton Center for Specialty Care, or Livonia 
Center for Specialty Care by a general otolaryngology faculty member 
at the University of Michigan. 
 
• Data collection procedures throughout the study 
o There will be three sets of surveys: a baseline survey, daily surveys on 
post-operative days 1-13, and a final survey on post-operative day 14. 
Post-operative surveys will be sent to all patients who enroll, including 
those who are not prescribed opioids post-operatively. These patients 
will not be included in the primary or secondary analysis but will be 
analyzed in a separate study examining pain recovery without opioids.  
o Baseline survey: Patients will be asked to complete a 10-15 minute 
survey assessing demographics, reason for tonsillectomy, current 
pain, chronic pain, history of opioid use, history of opioid misuse, 
family chronic opioid use, depression, substance use disorders, 
anxiety, sleep, and global health. Patients will be e-mailed a link to the 
baseline survey upon enrollment; for patients who cannot receive e-
mail links, the survey will be administered over the phone. For patients 
at Mott or University Hospital recruited in-person, the baseline survey 
will be administered by a study team member in-person through 
Qualtrics on a tablet. Patients sent the baseline survey who do not 
complete it before surgery will be contacted via e-mail or by phone to 
remind them or approached in-person to complete it through Qualtrics 
on a tablet. If patients are contacted by phone, they will be given the 
option to complete the survey over the phone. 

 ____________________________________________________________________________________________ 
9 
o Daily surveys: At 12:01 am on post-operative days 1 through 13, 
patients will be e-mailed a daily link to complete a 1-minute online 
Qualtrics survey in which pain and opioid consumption over the prior 
24 hours will be assessed. The post-operative day 7 survey will be 
similar except that it will include additional questions assessing pain 
over the prior 7 days. Patients who cannot receive e-mail links will not 
be sent daily surveys. E-mail or telephone follow-up will not occur for 
the daily surveys on post-operative days 1-13. 
o Final survey: on post-operative day 14, patients will be e-mailed a link 
to complete a 10-15-minute online Qualtrics survey assessing pain 
control, opioid use, opioid disposal, opioid misuse, 
acetaminophen/ibuprofen use, depression, anxiety, sleep, and health 
care utilization during the 14 days after surgery, including refills and 
visits to the emergency department or primary care for pain. Patients 
who cannot receive e-mail links will be called and the survey will be 
administered over the phone. Patients may be contacted via e-mail or 
by phone to remind them to complete surveys. If patients are 
contacted by phone, they will be given the option to complete the 
survey over the phone.  
o DataDirect and MiChart will be queried to determine opioid use prior to 
the day of surgery based on the admission history and physical. 
patient demographics, the dosing parameters of post-operative opioid 
prescriptions, the number of return visits for pain at the University of 
Michigan in the 14 days after surgery, and the number of opioid refills 
in the 14 days after surgery.  
 
• Timeline 
o The pre-intervention period will start on October 1, 2019 and end 
September 30, 2020; the months of April and May 2020 will be 
excluded as elective surgeries were scaled down owing to the COVID-
19 pandemic. The intervention will be implemented on October 1, 
2020. The post-intervention period will start October 1, 2020 and end 
on July 31, 2021. 
 
 
• Nature of intervention 
o Currently, pediatric otolaryngology attendings and their residents use a 
MiChart tonsillectomy orderset with three options: patients < 12 years, 
patients ≥12 years, and M-POP. Under the orderset for patients ≥12 
years, the default is currently 30 doses, consistent with the current 
departmental prescribing standard (see MiChart screenshot below). 
o During the pre-intervention period, no changes will be made to the 
default number of doses or any other dosing parameter. 
o During the month of September 2020, opioid consumption data will be 
reviewed by the chief of pediatric otolaryngology. A new default 

 ____________________________________________________________________________________________ 
10 
number of doses lower than 30 will be chosen based on the level and 
distribution of opioid consumption.  
o On October 1, 2020, the tonsillectomy orderset will be changed. The 
new orderset will have three options for patients ≥12 years: one for 
oxycodone solution among patients < 50 kg, one for oxycodone 
solution among patients ≥50 kg, and one for oxycodone tablets. Each 
of these options will auto-populate the default doses field using the 
new setting.  
o The new orderset will display for patients at C.S. Mott Hospital only. 
Thus, all patients in the treatment group (patients undergoing 
tonsillectomy at Mott by pediatric otolaryngology attendings) will have 
clinicians who are exposed to the new default settings. The 
tonsillectomy orderset will not be changed at University Hospital, 
Brighton, or Livonia. Thus, all patients in the control group (patients 
undergoing tonsillectomy in these locations by general otolaryngology 
attendings) will have clinicians who will not be exposed to the new 
default settings, even if they use the pediatric otolaryngology 
tonsillectomy orderset. 
  
 
7 DATA COLLECTION AND MANAGEMENT PROCEDURES 
 
• As noted above, the baseline survey will be administered via an online 
Qualtrics survey for patients recruited over the phone, and via Qualtrics on a 
tablet in-person for patients at Mott or University Hospital. Daily surveys on 
post-operative days 1-13 will be administered via an online Qualtrics survey, 
as will the final post-operative day 14 survey (with the exception of patients 
who cannot receive e-mail links, who will be administered the final survey 
over the phone, or patients who prefer to complete the survey over the 
phone). 
 
• Data entry  
o Survey data obtained through Qualtrics will automatically be uploaded 
into a secure database.  
o All data extracted from DataDirect and MiChart will be manually 
entered into this secure database. 
 
• Data management and security 
o Only study team members trained in human subjects protection will 
have access to study data 
o Only coded patient identifiers will be associated with study data. Only 
the PI will have the crosswalk between these identifiers and identifiable 
information such as patient name.   
o Electronic data files will be password-protected and stored on a secure 
server with restricted access.  
o Data will be destroyed within 90 days of completion of the study.  

 ____________________________________________________________________________________________ 
11 
 
8 
DATA ANALYSIS 
 
• The primary analysis will examine changes in opioid prescribing and health 
care utilization.  
 
• The secondary analysis will additionally examine changes in patient-reported 
outcomes..   
 
9 
QUALITY CONTROL AND QUALITY ASSURANCE 
 
• Data on patient-reported outcomes will be collected using standardized 
measures that have been validated in other samples.  
 
• On a monthly basis, the project coordinator will print frequency data from 
surveys and examine for unexpected results or patterns of missingness. Any 
issues will be resolved with the PI. 
 
• If there are any discrepant results in a participant’s record, they may be 
contacted by phone for further clarification. 
 
• The PI and the project coordinator will ensure all survey data are backed-up 
on UM’s secure network, and will also ensure that data are password-
protected and only accessible to the research team. 
 
• The project coordinator will ensure that all participants are accounted for in 
tracking database. 
 
• 
Each month, participant IDs will randomly be selected to ensure that consents 
have been obtained.  
 
10  STATISTICAL CONSIDERATIONS 
 
• Outcomes in primary analysis 
o Number of doses in the discharge opioid prescription  
o Proportion of patients in which the number of doses in the discharge 
opioid prescription equals the number of doses in the new default 
settings 
o Proportion of patients prescribed opioids at discharge 
o Proportion of patients prescribed opioids at discharge who had at least 
one opioid prescription refill from UM during the two weeks after 
surgery 
o Proportion of patients who saw a UM provider in an office due to pain 
during the two weeks after surgery 

 ____________________________________________________________________________________________ 
12 
o Proportion of patients with at least one emergency department visit or 
hospitalization at UM for pain during the two weeks after surgery 
 
• Additional outcomes in secondary analysis (based on data from the final post-
operative day 14 survey) 
o Overall satisfaction with pain control during the two weeks after 
surgery (scale of 1-10) 
o Proportion of patients who reported that their pain was well-controlled 
o Proportion of patients whose overall pain control was rated as much 
worse or worse than expected 
o Proportion of patients whose pain has resolved by day 14 after surgery 
o Pain score over the past 7 days at its worst (scale of 0-10) 
o Pain score over the past 7 days on average (scale of 0-10) 
o Number of opioid doses taken during the two weeks after surgery  
o Proportion of patients with leftover doses of opioids  
o Proportion of patients with leftover doses who disposed of them 
o Proportion of patients who misused opioids belonging to others at least 
once during the two weeks after surgery 
o Proportion of patients who misused their own opioids at least once 
during the two weeks after surgery  
o PHQ-8 score (depression) 
o Score on PROMIS Pediatric Anxiety – Short Form 8a 
o Score on PROMIS Sleep Disturbance – Short Form 8a 
o Proportion of patients who saw their primary care provider (or a 
colleague) in the office due to poorly controlled pain at least once 
during the two weeks after surgery 
o Proportion of patients who visited an urgent care center due to poorly 
controlled pain at least once during the two weeks after surgery 
o Proportion of patients who visited a retail clinic due to poorly controlled 
pain at least once during the two weeks after surgery 
o Proportion of patients who went to an emergency department and/or 
were hospitalized due to poorly controlled pain at least once during the 
two weeks after surgery 
 
• Data from the daily surveys will be used to assess whether daily opioid 
consumption reports matches the consumption reported on the final post-
operative day 14, and will also be analyzed in a separate study assessing the 
trajectory of pain and opioid use after tonsillectomy. 
 
• We will fit linear or logistic regression models assessing outcomes as a 
function of an indicator of post-intervention status, an indicator of treatment 
group status, and its interaction, controlling for covariates such as 
demographics (e.g., age, sex) and baseline co-morbidities (e.g., depression, 
anxiety). We will graphically and statistically assess the comparability of pre-
intervention monthly trends in outcomes between the treatment and control 
groups. 

 ____________________________________________________________________________________________ 
13 
 
• We hypothesize that there will be no change in outcomes in the control group 
(i.e., that the post-intervention trend in outcomes in the control group will be 
an extension of the pre-intervention trend in outcomes). In contrast, we 
hypothesize that the number of doses and opioid consumption will drop in the 
treatment group after the intervention; that the proportion of patients with 
prescriptions concordant with the new defaults will increase after the 
intervention; and that there will be no change in balancing measures such as 
pain control or depression. 
 
• 
Sensitivity analyses 
o Statistical modeling: we will explore whether results change when 
replacing the indicator of treatment group status with a vector of fixed 
effects for the prescribing clinician, and will explore the feasibility of 
using an interrupted time series approach instead of a difference-in-
differences approach.  
o We will determine whether any otolaryngology residents wrote opioid 
prescriptions for both a pediatric otolaryngology and general 
otolaryngology patients in the post-intervention period, and exclude 
data from any such residents from the analysis 
o We will exclude opioid prescriptions written for patients of the chief of 
pediatric otolaryngology, who will be involved in setting the new 
defaults 
 
• 
Subgroup analysis will occur by age group (ages 12-17 years vs 18 and 
older), gender, payer type (private/public), and baseline co-morbidities (e.g., 
depression and anxiety). 
 
• 
We will separately analyze data from pediatric otolaryngology patients 
undergoing surgery outside of Mott and general otolaryngology patients 
undergoing surgery at Mott to assess for any spillover effects. 
 
• Sample size: Based on historical UM data, we estimate that there will be 113 
patients in the treatment group and 85 in the control group for the primary 
analysis (total 198). If 65% consent to complete the surveys, then there will 
be 74 and 55 patients in the treatment and control groups for the secondary 
analysis, respectively (total 129). 
 
11 
REGULATORY REQUIREMENTS 
 
11.1 Informed Consent  
 
• For patients recruited in-person, a study team member will obtain written 
consent from young adults aged ≥18 years. For minors, written consent 

 ____________________________________________________________________________________________ 
14 
will be obtained from a parent and verbal assent will be obtained from the 
minor.  
 
• For patients recruited over the phone, a study team member will obtain 
verbal consent from young adults. For minors, the study team member will 
obtain verbal consent from a parent and verbal assent from the minor. 
Patients who give verbal consent will receive a copy of the consent via 
email for their records. 
 
• Consent will be obtained via a document approved by IRBMED, the 
University of Michigan Medical School Institutional Review Board. The 
document will include an explanation of the study, including the purpose, 
testing procedures, time commitment, inclusion/exclusion criteria, risks 
and benefits, confidentiality, compensation, study personnel contacts, and 
required regulatory information. All individuals will be given the opportunity 
to ask questions and participant understanding will be assessed.   
 
• Minors will be assured that their responses will not be shared with anyone 
else except in limited circumstances (e.g., imminent self-harm). 
 
11.2 Subject Confidentiality  
 
• Measures to ensure confidentiality 
o Following informed consent, the study participant will be assigned a 
coded study identification number. From this point forward, the 
coded participant identification number will be the primary means of 
identifying the participant.  
o All study staff will be trained, and physical security measures for 
data capture and storage will be used. A minimum of identifiable 
information will be collected. Records will be kept confidential to the 
extent provided by Federal, State, and local law.  
o Subjects will be informed that the sponsor and the Institutional 
Review Board may inspect the records of this investigation.  
o All participants will have direct access to the phone numbers and 
pagers of the study coordinator and responsible investigators, as 
well as a 24-hour contact number.  
o Participants will not be identified in any reports on this study. 
 
• Justification for use of personally identifiable data or private health 
information (PHI)  
o Personally identifiable data (e.g., patient name) is necessary to 
extract information from DataDirect and MiChart. 
 
• Certificate of Confidentiality 
o Because this is an NIH-funded study, a Certificate of Confidentiality 
will automatically be issued.  

 ____________________________________________________________________________________________ 
15 
 
• Exceptions to Confidentiality 
o In the consent document, the following statement will be included: 
“If you disclose to us that you are having feelings of hurting 
yourself, a mental health professional on our team will contact you. 
If we learn that you are at immediate risk of hurting yourself and 
you’re a minor, we may contact your parent or guardian. Otherwise, 
if you are bothered by mood problems or having thought about 
hurting yourself during the study, it’s better to talk to your doctor or 
mental health professional.  We suggest you make an appointment 
with your regular doctor as soon as possible. You can also call the 
University of Michigan Depression Center (734-764-0231 or 1-800-
525-5188) to ask for counseling and other supportive services.  For 
Urgent Care, please call Psychiatric Emergency Services at the 
University of Michigan Hospital at 734-936-5900 or dial 9-1-1.  
 
o Furthermore, in the consent document, it will be stated that “This 
research is covered by a Certificate of Confidentiality from the 
National Institutes of Health. The researchers with this Certificate 
may not disclose or use information, documents, or biospecimens 
that may identify you in any federal, state, or local civil, criminal, 
administrative, legislative, or other action, suit, or proceeding, or be 
used as evidence, for example, if there is a court subpoena, unless 
you have consented for this use. Information, documents, or 
biospecimens protected by this Certificate cannot be disclosed to 
anyone else who is not connected with the research except if there 
is a federal, state, or local law that requires disclosure (such as to 
report child abuse or communicable diseases but not for federal, 
state, or local civil, criminal, administrative, legislative, or other 
proceedings); or you have consented to the disclosure, including for 
your medical treatment; or it is used for other scientific research, as 
allowed by federal regulations protecting research subjects. The 
Certificate cannot be used to refuse a request for information from 
personnel of the United States federal or state government agency 
sponsoring the project that is needed for auditing or program 
evaluation by the National Institute on Drug Abuse, which is funding 
this project, or for information that must be disclosed in order to 
meet the requirements of the federal Food and Drug Administration 
(FDA). You should understand that a Certificate of Confidentiality 
does not prevent you from voluntarily releasing information about 
yourself or your involvement in this research. If you want your 
research information released to an insurer, medical care provider, 
or any other person not connected with the research, you must 
provide consent to allow the researchers to release it. The 
Certificate of Confidentiality will not be used to prevent disclosure 
as required by federal, state, or local law of suspected or known 

 ____________________________________________________________________________________________ 
16 
sexual, physical, or other abuse of a child or older person, or 
threats of violence to self or others. The Certificate of 
Confidentiality will not be used to prevent disclosure for any 
purpose you have consented to in this informed consent 
document.” 
  
11.3 Unanticipated Problems 
 
• According to IRBMED, reportable adverse events (AEs) are “any 
experience or abnormal finding that has taken place during the course of a 
research project and was harmful to the subject participating in the 
research, or increased the risks of harm in the research, or had an 
unfavorable impact on the risk/benefit ratio.” In this context of this study, 
AEs include violation of confidentiality and significantly worsened pain 
control. Serious adverse events (SAEs) include suicidal ideation or opioid 
misuse resulting in overdose. 
 
• Procedures for Reporting Adverse Events  
o IRBMED. AEs and SAEs related to study intervention will be 
reported to IRBMED. The timing of the reporting will be dependent 
on the severity of the event, and whether such adverse events were 
expected (i.e., included in the informed consent). The study team 
will adhere to the IRBMED Reporting Plan regarding the timing of 
report. For SAEs, the initial SAE report will be submitted within 24 
hours. The completed SAE report will be submitted in writing within 
7 days. Non-life threatening AEs that are causally related to the 
research (e.g., breach in confidentiality) will be reported in writing 
within 14 days. For incidents at the level of AE or SAEs, Dr. Chua 
will be notified by study staff as soon possible, and Dr. Chua will be 
responsible for reporting the event to IRBMED on the timeline 
described above.  
o NIDA. All significant actions by IRBMED (including any 
correspondence related to SAEs) will be communicated directly to 
the NIDA program officer within 24 hours of learning of their 
occurrence. Additionally, all yearly reports to NIDA will include a 
summary of all relevant correspondences with IRBMED during the 
past year. AEs will be reported to the NIDA program officer at least 
once per year during an annual progress report. This report will 
describe the AE event, when it occurred, and the 
outcome/resolution. If there were no AEs, the study team will 
submit a statement to the program officer in writing that no AEs 
occurred.  In the event of an SAE, an initial report including a brief 
explanation of the event and when it occurred will be given to the 
NIDA program officer via email within 24 hours of learning of the 
event. Within 72 hours, the study team will provide a written follow-
up including the following details: date of the event, what occurred, 

 ____________________________________________________________________________________________ 
17 
actions taken by the project staff, planned follow up, whether the 
event appears related to the intervention, and whether the 
participant will continue in the study.  
 
• Managing Participant Distress 
o Participants will be made aware of their right to refuse to answer 
any questions that make them uncomfortable or that they do not 
wish to answer, and they will be informed of their right to withdraw 
from the study at any time without penalty. This message will be 
conveyed during the informed consent process. All participants will 
have direct access to the phone number and e-mails of the study 
coordinator and PI. 
 
• Managing Participant Safety 
o We will monitor pain control after surgery through the post-
operative surveys described in the proposal. Of note, most post-
tonsillectomy pain resolves within two weeks. We plan to conduct 
the post-operative surveys two weeks after surgery, so we do not 
anticipate that patients will still be in pain at the time the surveys 
are administered. However, if patients do report poor pain control, 
we will contact the patient’s surgical team, who will follow up with 
the patient and prescribe opioids or bring the patient in for 
evaluation, as appropriate. Electronic prescribing is currently 
available at the University of Michigan, so patients will not 
necessarily have to come back in for a visit to obtain refills. In short, 
we do not anticipate that our intervention will worsen pain control, 
and have a specific plan for addressing this contingency were it to 
occur. 
o In the baseline and post-operative day 14 surveys, we will 
administer the PHQ-8, a depression screen that does not contain 
any questions regarding self-harm. These surveys will 
predominantly be administered via a tablet or online Qualtrics 
survey. A small number of patients may be administered the 
surveys on the phone (e.g., if they cannot receive e-mail links to 
online surveys). If, in the course of these phone surveys, a patient 
discloses thoughts of self-harm to the study coordinator, the study 
coordinator will contact a mental health professional on the team, 
who will contact patients and screen for suicide risk using a suicidal 
ideation protocol developed by the University of Michigan Back and 
Pain Center. Patients without an imminent threat of self-harm will 
be referred to mental health services. For patients with an imminent 
threat of self-harm, we will follow the protocol by trying to keep 
them on the phone while paging an emergency University of 
Michigan-based pager. Details of the protocol are included in the 
data and safety monitoring plan. If the patient with imminent threat 

 ____________________________________________________________________________________________ 
18 
of self-harm is a minor, we will additionally inform their parents or 
guardians. 
 
• Trial Stopping Rules 
o The trial will be stopped if it is discovered that the intervention has 
resulted in substantially higher rates of uncontrolled pain, 
depression, or opioid misuse. This is felt to be unlikely for the 
reasons articulated in Section 3.   
    

 ____________________________________________________________________________________________ 
19 
12 
REFERENCES  
1. 
Miech R, Johnston L, O'Malley PM, Keyes KM, Heard K. Prescription Opioids in 
Adolescence and Future Opioid Misuse. Pediatrics. 2015;136(5):e1169-1177. 
2. 
McCabe SE, West BT, Boyd CJ. Medical use, medical misuse, and nonmedical 
use of prescription opioids: results from a longitudinal study. Pain. 
2013;154(5):708-713. 
3. 
McCabe SE, West BT, Boyd CJ. Leftover prescription opioids and nonmedical 
use among high school seniors: a multi-cohort national study. J Adolesc Health. 
2013;52(4):480-485. 
4. 
Delgado MK, Shofer FS, Patel MS, et al. Association between Electronic Medical 
Record Implementation of Default Opioid Prescription Quantities and Prescribing 
Behavior in Two Emergency Departments. J Gen Intern Med. 2018. 
5. 
Howard R, Waljee J, Brummett C, Englesbe M, Lee J. Reduction in Opioid 
Prescribing Through Evidence-Based Prescribing Guidelines. JAMA Surg. 
2018;3(153):286-287.