Non-Pharmacological Options in Postoperative Hospital-based and Rehabilitation Pain Management: The NOHARM Trial
Phase: NA
Conditions: Surgical Procedure, Unspecified
Sponsor: Mayo Clinic

 
 
Non-Pharmacological Options in Postoperative 
Hospital-based and Rehabilitation Pain 
Management: The NOHARM Trial 
 
NCT04570371 
 
21September2023 

NON-PHARMACOLOGICAL OPTIONS IN POSTOPERATIVE 
HOSPITAL-BASED AND REHABILITATION PAIN MANAGEMENT: 
THE “NOHARM” TRIAL  
Principal Investigators: 
Andrea Cheville, MD, MSCE 
Jon Tilburt, MD 
Mayo Clinic, Scottsdale, AZ 
Supported by: 
The National Institute on Aging  
UH3AG067593 
 
 
 
 
IRBe # 20-004839 
Protocol Version 6 
September 21, 2023 
 
 

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TABLE OF CONTENTS 
1 
PRÉCIS ............................................................................................................................... iv 
1.1 Study Title ................................................................................................................................ iv 
1.2 Objectives ................................................................................................................................. iv 
1.3 Design and Outcomes ............................................................................................................... iv 
1.4 Interventions and Duration ....................................................................................................... iv 
1.5 Sample Size and Population ..................................................................................................... iv 
2 
STUDY TEAM ROSTER ................................................................................................... 5 
2.1 Principal Investigators ............................................................................................................... 5 
3 
PARTICIPATING STUDY SITES .................................................................................... 6 
4 
STUDY OBJECTIVES ....................................................................................................... 7 
4.1 Primary Objective...................................................................................................................... 7 
4.2 Secondary Objectives ................................................................................................................ 7 
5 
BACKGROUND AND RATIONALE ............................................................................... 8 
5.1 Background on Condition, Disease, or Other Primary Study Focus ......................................... 8 
5.2 Study Rationale ......................................................................................................................... 8 
6 
STUDY DESIGN ................................................................................................................. 9 
7 
SELECTION AND ENROLLMENT OF PARTICIPANTS ........................................ 11 
7.1 Inclusion Criteria ..................................................................................................................... 11 
7.2 Exclusion Criteria .................................................................................................................... 11 
7.3 Study Enrollment Procedures .................................................................................................. 11 
8 
STUDY INTERVENTIONS ............................................................................................. 12 
8.1 Interventions, Administration, and Duration ........................................................................... 12 
8.2 Handling of Study Interventions ............................................................................................. 14 
8.3 Concomitant Interventions ...................................................................................................... 14 
8.4 Adherence Assessment ............................................................................................................ 15 
9 
STUDY PROCEDURES ................................................................................................... 16 
9.1 Perioperative Care Pathway/NOHARM Touchpoints ............................................................. 16 
9.2 Description of Evaluations ...................................................................................................... 16 
10 
SAFETY ASSESSMENTS ............................................................................................... 18 
10.1 Specification of Safety Parameters .......................................................................................... 18 
10.2 Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters ............... 18 
10.3 Adverse Events and Serious Adverse Events .......................................................................... 18 

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10.4 Safety Monitoring.................................................................................................................... 21 
11 
INTERVENTION DISCONTINUATION ...................................................................... 22 
12 
STATISTICAL CONSIDERATIONS ............................................................................. 23 
12.1 General Design Issues ............................................................................................................. 23 
12.2 Interim analyses and Stopping Rules ...................................................................................... 24 
12.3 Outcomes ................................................................................................................................. 24 
12.4 Data Analyses .......................................................................................................................... 26 
12.5 Subgroup analyses ................................................................................................................... 28 
12.6 Supplementary Analyses ......................................................................................................... 29 
13 
DATA COLLECTION AND QUALITY ASSURANCE ............................................... 30 
13.1 Data Collection Forms ............................................................................................................. 30 
13.2 Data Management.................................................................................................................... 31 
13.3 Quality Assurance ................................................................................................................... 31 
14 
PARTICIPANT RIGHTS AND CONFIDENTIALITY ................................................ 34 
14.1 Institutional Review Board (IRB) Review .............................................................................. 34 
14.2 Informed Consent Forms & Authorization Considerations ..................................................... 34 
14.3 Participant Confidentiality ...................................................................................................... 34 
14.4 Study Discontinuation ............................................................................................................. 34 
15 
ETHICAL CONSIDERATIONS ..................................................................................... 35 
16 
COMMITTEES ................................................................................................................. 36 
16.1 Project Workgroups/Responsibilities ...................................................................................... 36 
17 
PUBLICATION OF RESEARCH FINDINGS .............................................................. 39 
18 
REFERENCES .................................................................................................................. 40 
19 
DESCRIPTION OF SUPPLEMENTS/APPENDICES ................................................. 42 
19.1 Appendix A: Clinician Participants ......................................................................................... 42 
19.2 Appendix B: Resource List ..................................................... Error! Bookmark not defined. 
 
 
 
 

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1 
PRÉCIS 
1.1 
Study Title  
Non-pharmacological Options in postoperative Hospital-based And Rehabilitation 
pain Management: the NOHARM trial  
1.2 
Objectives 
The study objectives are 1) to test the impact of the NOHARM intervention on pain 
and function 3 months following surgery, 2) test the impact of the NOHARM 
intervention on anxiety and opioid use during the 3 months following surgery. 
1.3 
Design and Outcomes 
This is a pragmatic clinical trial using a cluster randomized stepped wedge design. 
Clusters are defined at the level of care teams and qualifying surgical procedures, 
and have been randomized to one of five different tranches to implement the 
intervention at staggered intervals. (See diagram in section 6 “Study Design”). 
1.4 
Interventions and Duration  
The intervention being tested (i.e. compared to usual care/no intervention) is a 
bundled Healing after Surgery Guide + clinical decision support intervention 
embedded within the electronic health record. Participants undergoing qualifying 
surgeries at participating sites will be “on-study” beginning with their decision to 
have a surgical procedure and continuing until final outcomes are collected at 3 
months post-surgery. 
1.5 
Sample Size and Population  
All Mayo Clinic patients receiving one of the surgical procedures included in the 
NOHARM study will be enrolled in the NOHARM trial.  Based on surgical 
volumes from 2018 and the number of patients required for sufficient statistical 
power, we plan to enroll 114,000 patients into the NOHARM trial.

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2 
STUDY TEAM ROSTER  
2.1 
Principal Investigators 
Andrea Cheville, MD 
Mayo Clinic 
200 First Street SW, Rochester, MN 55905 
cheville.andrea@mayo.edu  
Principal Investigator  
 
Jon Tilburt, MD 
Mayo Clinic 
200 First Street SW, Rochester, MN 55905 
tilburt.jon@mayo.edu  
Co-Principal Investigator 
 

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3 
PARTICIPATING STUDY SITES  
Mayo Clinic Rochester, Rochester, MN 
Site Principal Investigator: Andrea Cheville, MD 
 
Mayo Clinic Arizona, Phoenix, AZ 
Site Principal Investigator: Jon Tilburt, MD 
 
Mayo Clinic Florida, Jacksonville, FL 
Site Principal Investigator: Cindy Tofthagen, PhD 
 
Mayo Clinic Health System - Mankato, Mankato, MN 
 
Mayo Clinic Health System – Eau Claire, Eau Claire, WI 
 
Mayo Clinic Health System –La Crosse, WI 
 
* For the purposes of the initial IRB approval, the study has received institutional 
approval from Dr. Amy Williams, Executive Dean of the Practice and Chair of the 
enterprise Mayo Clinic Clinical Practice Committee. This approval assumes that 
all Mayo Clinic surgical practices will participate in the study as an institutional 
priority, but provides that practice-level approvals will be formally solicited. To 
obtain these practice-level approvals, the principal investigators have been 
conducting metings with practice chairs, specialty councils, and allied health 
leadership. All IBR approvals have been obtained for clusters within tranche 1, and 
meetings have begun for subsequent tranches. Obtaining these approvals in 
advance will ensure that cascading communications can occur in a timely manner. 
Practice administration for specific surgical practices, providers, and allied health 
staff implicated in each wave of study implementation will be engaged generally no 
sooner than 3 months prior to the anticipated start date of the implementation wave 
they have been randomized to. Engagement earlier than 3 months before study 
implementation will most likely be counterproductive. 

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4 
STUDY OBJECTIVES 
4.1 
Primary Objective  
To test the impact of a bundled NOHARM Healing after Surgery Guide + clinical 
decision support intervention embedded within an EHR on pain and function 3 
months following surgery.   
4.2 
Secondary Objectives 
To test the impact of a bundled NOHARM Healing after Surgery Guide + clinical 
decision support intervention embedded within an EHR on anxiety and opioid use 
during the 3 months following surgery.   

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5 
BACKGROUND AND RATIONALE  
5.1 
Background on Condition, Disease, or Other Primary Study Focus 
Prescriptions for narcotic pain relief after surgery result in unintended prolonged 
opioid use for hundreds of thousands of Americans.1,2 That trend fuels an excess 
supply of opioids that can lead to dependence, addiction, diversion, and overdoses 
on a national scale.3-10 Non-pharmacological pain care (NPPC) is effective and 
recommended by guidelines for perioperative pain while offering a more favorable 
risk-to-benefit ratio.11-14Additionally, patient and clinician decision support 
interventions are effective in encouraging patient-centered and guideline-
concordant care in many other areas of medicine and hold great promise for 
promoting and facilitating post-operative non-pharmacologic pain management.15,16  
5.2 
Study Rationale 
Nonpharmacological pain care is rarely used as first or second-line therapy after 
surgery, despite guidelines to the contrary. 17,18  NPPC offers a more favorable risk-
to-benefit ratio than opioid medications which may play a critical role in acute 
post-operative management but should be tapered in favor of safer and more 
sustainable analgesic options as patients transition home and gradually resume their 
life roles. Additionally, patient and clinician support interventions have not been 
tested pragmatically as a bundle in everyday postoperative care as a means of 
facilitating the uptake of non-pharmacological pain management strategies in the 
perioperative setting and in the post-acute recovery timeframe. This study will 
address this knowledge gap and test the impact of utilizing patient and clinician 
decision support tools to inform patients and facilitate their preference for non-
pharmacological pain management modalities. 

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6 
STUDY DESIGN 
This study will utilize a cluster randomized stepped wedge design. Clusters are defined at 
the level of care teams and qualifying surgical procedures, and have been randomized to 
one of five different tranches to implement the intervention at staggered intervals (one new 
cluster each wave, see diagram below).  
 
 
The primary outcome of the study is a composite of patient reported pain and function at 
three months post-surgery. This will enable us to determine the effectiveness of a bundled 
NOHARM Healing after Surgery Guide + clinical decision support for promoting non-
pharmacological pain management strategies to patients undergoing qualifying surgeries, 
which may also ultimately curb overall patient demand for opioid prescriptions in post-
acute post-surgical rehab while optimizing functional recovery.  Thus, our secondary 
outcome(s) is opioid use at the 3 month point post-operatively. This will enable us to 
understand the impact of our EHR-embedded decision support intervention in an era where 
opioid prescribing is already being constrained. 
All patients receiving common, pre-defined procedures within 7 surgical practice areas at 6 
Mayo Clinic locations will receive the study intervention if their surgery date coincides 
with the stepped wedge implementation schedule. Study locations include Mayo Clinic 
Rochester, Mayo Clinic Florida, and Mayo Clinic Arizona, as well as three Mayo Clinic 
Health System sites (Mankato, MN; La Crosse, WI; and Eau Claire, WI).  Surgical practice 
areas will include orthopedic surgery, colorectal surgery, gyn surgery, obstetrics, 
pulmonary/thoracic surgery, liver and kidney transplant, and cardiac surgery.  Due to 
variable combining of post-op unit care areas, practice size, and related considerations we 
have formed 22 clusters that will be randomized across 5 tranches.   
Enrollment in the intervention arm of the trial will extend from March 2021 to 
approximately August 2023. Participating practices will be enrolled in the study from the 
point in time the intervention is implemented in their practice and continuing through the 
end of the study. 

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The intervention consists of enhanced electronic medical record functionality that 
interfaces with a patient-facing Healing after Surgery Guide in Epic MyChart patient 
portal. The Healing after Surgery Guide encourages patients to make a plan for post-
operative pain management and to utilize NPPC techniques that appeal to them. The 
intervention also uses EHR tools that remind and prompt clinicians to encourage patients 
to use their selected NPPC techniques throughout the perioperative period. All study 
assessments will be extracted from the electronic health record. Patient reported outcome 
measures will include those collected in routine peri-operative care, as well as a limited 
number specific to the NOHARM trial; self-reported opioid consumption and NPPC 
modality use after surgery. 

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7 
SELECTION AND ENROLLMENT OF PARTICIPANTS  
7.1 
Inclusion Criteria  
All patients 18 years of age and older undergoing qualifying surgeries at 
participating sites will be eligible.  
7.2 
Exclusion Criteria  
None. 
7.3 
Study Enrollment Procedures  
All eligible patients at participating sites will be enrolled in this minimal risk, 
population-based study. An automated EHR-based algorithm will identify patients 
meeting inclusion criteria for the NOHARM study based on age, surgical 
procedure, clinical department, and location.  
Eligible patients in not-yet activated clusters will receive usual care; data collected 
from this group will serve as “control” data in this stepped wedge study.  Control 
state data will be collected prior to cluster activation.  
All patients scheduled for surgery; as well as their care surgical teams, physical and 
occupational therapists, and unit nurses, in activated practice clusters will be 
exposed to the intervention per the randomization scheme. Because the intervention 
is embedded in the EHR, patients who are unable to interact with the portal-based 
Healing After Surgery Guide will not provide the data needed to populate and drive 
the EHR-based algorithms and clinical decision support tools. Therefore, these 
individuals will be less exposed to the intervention. However, the patients who do 
not interact with the Healing after Surgery Guide via the EHR patient portal prior 
to their hospital admission` will have the opportunity to select NPPC modalities 
during their hospitalization, both pre- and post-operatively. By communicating 
their NPPC selections to their unit nurses, their preferences will be entered into the 
EHR via flowsheets.  Subsequently, all EHR clinical decision support 
functionalities to encourage NPPC use will be operational for these patients.  
Cognitive limitations, lack of English fluency, or psychiatric illness may result in 
an inability to use the Healing After Surgery Guide which may also result in 
reduced exposure to the intervention. 

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8 
STUDY INTERVENTIONS  
8.1 
Interventions, Administration, and Duration  
Once the NOHARM intervention is activated at a given participating site, patients 
undergoing qualifying surgical procedures will be exposed to the NOHARM 
intervention.  
The intervention includes: 
Healing after Surgery Guide: 
The Healing after Surgery Guide  is an interactive module in the Mayo Clinic 
patient portal (MyChart). Entry of an order for their surgery will trigger an EHR 
algorithm will automatically send a message to patients’ portals describing the need 
for an “individualized pain management plan to promote healing after surgery.” 
The portal message will provide a link allowing patients to access and engage with 
the HAS Guide before their surgery. The HAS Guide will encourage realistic 
expectations about post-surgical pain, will educate patients on several evidence-
based, non-pharmacological pain management strategies (which are robustly 
validated and endorsed in clinical guidelines), and will encourage patients to select 
the NPPC modalities that appeal to them in managing post-acute pain during the 
months following their discharge. Patient selections elicited via the Healing After 
Surgery Guide will prompt a follow-up portal message, acknowledging the 
patient’s NPPC selections and extending the opportunity for them to receive a 
printed Healing After Surgery workbook if they request that such resources be 
mailed to them. Patients will have the opportunity to receive portal messages based 
on their responses to the Healing After Surgery Guide and PROMIS CAT (standard 
of care) as well as based on the length of time from surgery. These messages will 
include direction on how they can access the website, join Zoom support calls if 
desired or contact the NOHARM team. Section 8.1.1 gives a break down of the 
possible portal messages. The Zoom support calls referenced in the portal messages 
are to assist patients with their selected modalities if they so wish. Patients will log 
into these calls anonymously and PHI will not be discussed. There will be calls that 
center around specific modalities as well as open Q&A style.  
 
EHR-based Clinical Decision Support: 
The NPPC selections  will be stored in the EHR and used to prompt perioperative 
clinician interactions, direct education delivered by unit nurses, inform modality 
choices during physical and occupational therapy sessions, and populate patients’ 
pain management plans for controlling pain following hospital discharge. 
Additionally, patients’ NPPC selection will be visible to clinical providers on the 
Epic inpatient Summary view. These components are considered standard of care.   
Mayo Education Material: 
A suite of self-management educational materials will be available to support 
patients’ use of NPPC modalities and to help them trouble shoot and refine the use 
of their selected modalities.  These print materials and videos provide information 

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and instruction on the safe and appropriate use of NPPC strategies for addressing 
post-surgical, post-acute pain. The materials additionally clarify how patients may 
adapt NPPC modalities to derive optimal benefit given their unique requirements 
and post-surgical precautions. All education materials have been developed, vetted 
and approved through Mayo Clinic’s Office of Patient Education processes and 
reflect existing standard of care for patient education.These materials will be 
available to patients via the Healing After Surgery website 
(healingaftersurgery.mayoclinic.org)and on Mayo Clinic Television.   Brief video 
descriptions of the NPPC modalities are imbedded in the Healing After Surgery 
Guide. The materials include video and print resources, with the latter being 
available in both electronic and paper formats.  The materials offer informational, 
instructional, and guided experiencial content for all NOHARM NPPC modalities, 
as appropriate.   A Healing After Surgery Workbook is also available.  The 
workbook offers patients a location to record their experiences, concerns, and 
successes, as well as providing motivational messages. 
Patients may view the self-management educational materials during their hospital 
stays on Mayo Clinic television.  Based on patients’ NPPC modality selections, 
inpatient nurses will be prompted to  show patients how to navigate to the materials 
on Mayo Television, familiarize them with the Healing After Surgery website, and 
provide them with print materials if desired.   Nurses will also use the educational 
materials to discuss pain management planning with patients to refine their 
management plans following hospital dismissal.   
The materials will be available on a website, DVD, and Mayo Clinic TV.  Unit 
nurses will be able to give patients printed PDFs, as required. Additionally, patients 
will receive a copy of the Healing After Surgery workbook via mail after they are 
enrolled onto the study . They will also have the ability to request from their portal 
messages that a print copy of the workbook be mailed to them.  
See Section 8.1.1 NOHARM Resource List for a brief description of the 
NOHARM materials 
Perioperative live NPPC Support Resources 
Patients have the opportunity to engage with Mayo Clinic specialists in NPPC 
modalities perioperatively to support their selection, troubleshooting, and use of the 
modalities.  Patient are notified of live support resources through their patient 
portal upon completion of the Healing After Surgery guide and are given a RACK 
card distributed at the pre-operative consultation. This support is restricted to 
NPPC modalities and patients are clearly informed that any questions relating to 
medications and other analgesic approaches should be directed to their surgical care 
teams. This support is set up to maximize the patient’s successful self-management 
of the NPPC both pre and post operatively.NOHARM NPPC live  support will take 
to forms: 
 
1.  Toll free call for 1-on-1 discussion of individualized needs.1-833-919-1432  
2. Presentations and group discussions via a virtual platform (Zoom technology).  

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See Appendix B NOHARM Resource List for a brief description of the NOHARM 
materials  
Clinical team decision support: 
Patient NPPC modality selections elicited from the Healing After Surgery Guide 
will be converted to discrete data elements that will prompt clinician decision 
support (CDS) after surgery. CDS tools that promote preference-sensitive, 
guideline-concordant NPPCs at defined touchpoints on the perioperative care 
trajectory will encourage clinicians, nurses, and physical/occupational therapists to 
discuss NPPC modalities with patients and pre-populate fields and functionalities 
within Epic such as the “After Visit Summary”. 
See Section 8.1.1 NOHARM Resource List for a brief description of the 
NOHARM materials 
8.1.1 NOHARM Resource List – Found in Appendix B 
 
 
8.2 
Handling of Study Interventions  
The NOHARM interventionHealing after Surgery will be assigned to patients using 
an EHR Boolean logic-based algorithm that includes age, surgical procedure, 
clinical department, and location. The intervention will be delivered to patients and 
their care teams via the patient portal and EHR, respectively. For some patients, we 
may send paper versions of the pain and physical function PROs to the patients at 
the 1, 2, and 3 month post-op points. If the patient receives and comletes duplicate 
versions, the one time stamped earlier will be used for analysis.  
8.3 
Concomitant Interventions 
This is a pragmatic, population-based clinical trial.  All eligible patients undergoing 
qualifying surgical procedures who receive care at the 6 participating sites will be 
enrolled, regardless of medications, treatment, supplements or other interventions 
they may be taking/receiving.   
8.3.1 Allowed Interventions 
The interventions in this study are a patient-facing “Healing after Surgery 
Guide” and a clinical team-facing clinical decision support augmented by 
existing, vetted patient education materials already consistent with the 
scope of work for perioperative care.  These interventions could prompt 
utilization of NPPC modalities prior to, during, and after the hospital stay.   
8.3.2 Required Interventions  
Among collaborating practices, Healing after Surgery Guide functionality 
and clinical decision support components of the intervention bundle will be 
turned on according to the pre-specified randomization scheme.  How or 

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whether patients and care teams choose to interact with the various  
intervention components and resources will be at their discretion.  The 
NOHARM intervention is conceptually distinct from the index surgical 
procedures for which patients are scheduled, which, though temporally 
associated, are not considered part of the research intervention.   
8.3.3 Prohibited Interventions 
None. We do not have the ability to individually turn off the intervention 
for individual patients, though records of patients who have previously 
indicated they do not want their medical record used for research purposes 
will have data associated with their care redacted from final analytic 
datasets.   
8.4 
Adherence Assessment  
Patients will be encouraged, but not required, to interact with the NOHARM 
Healing after Surgery Guide  and to utilize suggested NPPC modalities.  
Additionally, patients who are unable or unwilling to interact with the portal-based 
Healing After Surgery will not provide the NPPC selection data needed to populate 
and drive the EHR-based algorithms and clinical decision support tools. Therefore, 
these individuals will be more limitedly exposed to the intervention. They will be 
encouraged to use the Healing After Surgery Guide during day-of-surgery intake 
and post-operative care processes, but this may not occur due to many competing 
demands, or patient preferences.  
Cognitive limitations, lack of English fluency, or psychiatric illness may result in 
inability to use the HAS Guide or complete the electronic patient reported outcome 
measures (ePROMs). 
Interaction with the NOHARM HAS Guide, completion of ePROMs and utilization 
of NPPC modalities will be assessed by time-stamped links associated with the 
Healing after Surgery Guide while ePROMs and NPPC modality use will be 
extracted from the medical record.   

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9 
STUDY PROCEDURES 
9.1 
Perioperative Care Pathway/NOHARM Touchpoints  
The figure below briefly summarizes the perioperative care pathway along which 
our bundled, EHR-based intervention will be implemented.   
 
 
9.2 
Description of Evaluations  
9.2.1 Choosing Surgery and Pre-Operative Planning Touchpoints  
Touchpoint 1- Choosing Surgery 
Ambulatory care team members prepare patients to engage with the 
NOHARM intervention (portal-based Healing after Surgery Guide) at the 
time surgery is scheduled.   
Touchpoint 2 – Pre-operative Planning 
Patients interact with the Healing after Surgery Guide via their Epic EHR 
MyChart portals.  The Healing after Surgery Guide will allow patients to 
select NPPC techniques that appeal to them and develop an individualized 
NPPC plan.  Patients will be encouraged to familiarize themselves with and 
practice NPPC modalities prior to their hospital admissions.  Additionally, 
they will be encouraged to obtain needed supplies, engage their caregivers, 
and even schedule appointments with NPPC practitioners prior to their 
hospitalizations so that their individualized pain management plans may be 
seamlessly transitioned from the hospital to the home or post-acute care 
setting. 
9.2.2 Inpatient Stay Touchpoints  
Touchpoint 3 – Acute Hospital Care 
Nursing and physical/occupational therapy staff will offer patients the 
opportunity to receive preference-concordant NPPC modalities during their 

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hospital stay. For self-administered practices, staff will validate patients’ 
preferences and ensure the availability of needed supplies, instruction and 
ambient conditions (e.g. privacy).  
If patients are not experiencing adequate pain relief, they will be prompted 
by nurses to try alternative NPPC modalities in order to raise awareness of 
opioid harms, and enhance clinician support for patients’ NPPC use.  
Additionally, NPPC nurse and physician specialists will be “on call” to 
assist unit nurses, therapists, and members of the surgical care team in how 
to optimize the safety and effectiveness of NPPC modalities for specific 
patients.   
Touchpoint 4 – Hospital Discharge  
During the discharge process, patients will be asked to revise their NPPC 
plan, as needed based on their preferences and responses to specific NPPC 
modalities, and provided with support and resources. Discharge planning 
will include facilitation of continuation of patients’ NPPC use in their post-
acute care settings (e.g. home, rehabilitation facility, etc.). Patients will be 
given prescriptions to receive local NPPC, if available and/or appropriate. 
Patients’ discharge summaries will be auto-populated with selection-
concordant NPPC instructions and resources to find local NPPC providers.   
9.2.3 Post-Hospital Discharge Recovery Touchpoints 
Touchpoint 5 – Remote Healing After Surgery Guide Use and Post 
Operative Follow-up 
Patients will be encouraged to use the Healing After Surgery and follow 
their individualized pain management plans during their post-surgical 
recovery. They will be asked to report on their pain intensity, anxiety, and 
limitations in physical function using PROMIS ePROs via the Epic 
MyChart patient portal.  Patients will, at the same time points, be asked 
which, if any, of the NPPC techniques they have used and at what 
frequency.  These measures will be collected at 1 month, 2 month and 3 
months post surgery.  In addition, at the 3 month timepoint the patient will 
be asked to self-report opioid use measures.     
Include here which responses will trigger which messages.   
Additional Triggered Touchpoints 
Opioid Refill Requests  
Opioid refill requests during the 3-month postoperative interval will trigger 
messaging via the patient’s portal with  information regarding how to access 
resources to support their NPPC use.  Patients will be encouraged to utilize 
the live support resources, particularly the 1-on-1 calls in order to select and 
adapt use of modalities for optimal benfit. 

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10 SAFETY ASSESSMENTS  
This is a minimal risk study. Participants are considered “enrolled” as soon as they meet 
study inclusion criteria and are automatically assigned to receive study interventions and/or 
measurements.   
10.1 Specification of Safety Parameters 
There are no pre-specified safety parameters, as they are not-applicable to the 
intervention being studied. This study engages patients in strategies for post-
surgery pain management that conform to guideline-based care, all of which have 
far lower risk profiles (almost zero risk) and greater benefit-to-risk ratio compared 
to usual post-surgical pain management that involves opioid medications. Patients 
whose pain cannot be sufficiently managed with non-pharmacological pain 
management strategies will be supported by their surgical team (with assistance 
from pain management clinicians, as needed) using conventional pain management 
strategies. 
10.2 Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters 
Our interventions are informational and logistical and designed to enhance safe, 
patient-centered approaches to patient care.  If they were to prompt, for instance, 
less opioid use, in theory, that could lead to worse function or increase pain.  That 
is why we chose the composite outcome measure of pain and physical function.  
Whether it is accurate to associate that “risk” to our intervention itself, versus the 
treatments prompted by our intervention is a topic of debate.  Nevertheless, this is a 
minimal risk study. If we conservatively assume that downstream prescribing 
practices are attributable to our interventions, usual care (using opioid medications 
as a first line approach to pain management in the acute and post-acute recovery 
periods following a surgical procedures) introduces greater risk of dependency, 
addiction, and overdose, than those posed by the intervention we are providing in 
the NOHARM trial which is guideline concordant. 
10.3 Adverse Events and Serious Adverse Events  
Adverse Event (AE): Any untoward or unfavorable medical occurrence resulting 
unambiguously from the misuse or overuse of non-pharmacological pain 
management strategies facilitated by the intervention. All untoward or unfavorable 
medical occurrences will be first assumed to be associated with the patient’s 
surgery. Untoward or unfavorable medical occurrences will be deemed an adverse 
event only if they can be clearly associated with use of non-pharmacological pain 
management strategies recommended and/or facilitated by the intervention and 
could not, under any circumstances, have otherwise happened. 
Serious Adverse Event (SAE): Any adverse event unambiguously associated with 
the intervention that: 
• Results in death 

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• Is life threatening, or places the participant at immediate risk of death from 
the event as it occurred 
• Requires or prolongs hospitalization 
• Causes persistent or significant disability or incapacity 
• Results in congenital anomalies or birth defects 
• Is another condition which investigators judge to represent significant 
hazards 
There are no laboratory or other clinical values which may be used to assess safety 
concerns related to the intervention. Patient reported pain, requests for assistance 
with pain management, and other health outcomes, while measurable, are 
associated with the patient’s surgical procedure and will be gather as part of the 
ultimate outcome data.  If patients were to experience a paradoxical response to a 
modality –massage, for example – those effects would likely be transient and they 
would have access to all the usual care resources of Mayo Clinic as any other 
patient should those symptoms persist. 
Adverse events that may be anticipated in the study involve any patient misuse or 
overuse of non-pharmacological pain management strategies. Patients who elect to 
incorporate non-pharmacological pain management strategies in their recovery 
from surgery will be instructed in the use of those strategies, including whether 
(and when) the use of those strategies is appropriate in their situation. 
Because non-pharmacological pain management modalities recommended by the 
intervention are guideline concordant approaches to pain management under 
normal circumstances, they will be monitored by the patient’s surgical team as a 
part of usual post-acute care. Therefore, we will not actively review for potential 
events with scheduled promptings. 
Unprompted adverse events are possible, but not expected. Surgical teams will 
inform the study team if they are made aware of any untoward medical occurrence 
that could reasonably be attributed to a patient’s misuse or overuse of non-
pharmacological pain strategies as a direct result of the facilitation provided by the 
NOHARM intervention.  Such events are highly unlikely, and the risks of such 
events leading to unfavorable outcomes is almost non-existent. The risks of 
participant cooperation in the NOHARM intervention is far less than the risks of 
usual care which often involve opioid medications alone in the acute and post-acute 
recovery periods. 
10.3.1 Reporting Procedures 
An AE or SAE will be suspected if a member of the patient’s surgical team 
or any member of the study team who interfaces with the patient for any 
reasons suspects that a patient is experiencing a medical issue that is 
unambiguously related to the patient’s interaction with the NOHARM 
intervention. 

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The principal investigator, relevant study team members, and any relevant 
members of the surgical team will adjudicate the relevance of the patient’s 
experience to the NOHARM intervention (versus an anticipated result of 
the patient’s surgical procedure). 
If a patient experience or outcome is determined to be an AE or SAE by 
protocol definition, then that patient’s experience will be documented and 
reported per institutional procedures. The surgical team and/or members of 
the study team with expertise in post-surgical pain management will follow 
up with that patient to ensure that appropriate steps are taken to mitigate any 
negative outcomes and ensure that the patient is properly informed and 
educated about safe use of non-pharmacological pain management 
strategies for the remainder of their surgical recovery. 
Severity of the Event 
All AEs will be assessed by a qualified medical professional using a 
protocol defined grading system.   
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”.  
Relationship to the Study Intervention 
Because this is a minimal risk study and the intervention may be construed 
as less risky than usual care, it would be inappropriate to regard the study 
intervention as suspect, by default, for all medical occurrences in the 
perioperative period. For this reason, the principal investigator, clinical 
experts on the study team, and the patient’s surgical team will adjudicate the 
relevance of patient events outcomes in a binary fashion: 
• Not related to the NOHARM intervention. This will be the 
presumption, unless proven otherwise. Patients may be expected to 
have many challenges to overcome following a surgical procedure. 
These challenges are unrelated to the intervention. 
• Related to the NOHARM intervention. The study team will evaluate 
all occurrences suspected of being associated unambiguously with the 
NOHARM intervention and adjudicate their relevance. We do not 
expect any AEs or SAEs to result from the NOHARM intervention. 

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10.3.2 Follow-up for Adverse Events 
Patient events suspected of being AEs or SAEs will be addressed 
immediately by the Principal Investigator, relevant experts on the study 
team, and/or the patient’s surgical team. Upon determination that an event is 
indeed an AE or SAE, appropriate actions will be taken, including 
contacting the patient and providing instructions. 
All events suspected of being AE will be documented, and documentation 
for recorded events subsequently determined to be an AE or SAE will be 
updated. All AEs and SAEs will be followed to adequate resolution. 
The study coordinator will record all events reportable by the definitions 
above occurring any time following patient enrollment and limited to the 
last data collection point in the study. All events are expected to occur in the 
acute or early post-acute periods of recovery. 
10.4 Safety Monitoring 
The Data and Safety Monitoring Board and/or Safety Officer appointed by the NIA 
will monitor the conduct of the study. 

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11 INTERVENTION DISCONTINUATION  
This study is a pragmatic clinical trial, and as such, patients will not be individually 
consented. However, voluntariness is preserved as patients and surgical teams are not 
required to engage with any component of the intervention they are not interested in or 
deem irrelevant to their care.  Additionally, as a pragmatic clinical trial, “the intervention” 
will be systematically implemented at the surgical practice level, per the stepped-wedge 
schedule, as an element of usual care. 
Therefore, discontinuation of the study, whether for an individual participant                                                
or for all participants at once is defined as the cessation of study measurement prespecified 
by the study timeline.  The discontinuation of the study intervention components, if 
merited, will be at the discretion of the surgical specialties in conjunction with the DSMB; 
discontinuation is not anticipated. 
Removal individual patients from the trial will be functionally achieved in the following 
situations: 
• The patient actively requests to have their records withdrawn from the NOHARM 
study dataset. This is unlikely, as patients will only know of NOHARM as a 
practice-based care initiative per the pragmatic design of the trial. 
• Patients previously indicating their unwillingness to have medical record data used 
for research purposes will have their records redacted from final study datasets prior 
to analysis.   
Cessation of study measurement will happen for the entire trial in the event that: 
• Institutional needs / priorities preclude our ability to conduct study procedures (e.g. 
in the case of institutional response to COVID-19).  
• The study funder requests that study activities cease. 
In the event that an individual patient withdraws from the study or the entire study ceases, 
patients will still be monitored by their surgical team per usual care practices for the 
duration of their post-acute recovery period. Cessation of study procedures will not impact 
patients’ access to standard supportive care following surgery. 

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12 STATISTICAL CONSIDERATIONS  
12.1 General Design Issues  
This study will address the primary objective using a cluster randomized stepped 
wedge design. Surgical practices, or clusters, will be randomized in 5 tranches to 
receive the NOHARM intervention; outcomes of patients treated by these teams 
will be compared by intervention status of the team. The primary statistical 
hypothesis is that pain and function measures will be lower and higher, 
respectively, in the patients treated under the intervention conditions, when 
compared with non-intervention patients in those same practices.  
The cluster randomized stepped-wedge design will allow us to stagger the 
NOHARM implementation while increasing statistical power. The alternative to 
staggering the implementation would be to implement at all sites at the same time, 
which is impractical from a resource perspective. The stepped-wedge design allows 
each site to serve as its own control, reducing the bias due to imbalanced risk 
factors across clusters. Contamination does pose some threat to the internal validity 
of stepped wedge designs when, as here, the intervention rolls out sequentially in 
adjacent clusters.  The 22 NOHARM clusters will minimize potential 
contamination by capitalizing on geographical separations in the built environments 
used to deliver perioperative care including different buildings in some cases, as 
well as subspecialty-designated inpatient wards, office suites, etc.   
The primary hypothesis is that the NOHARM intervention will reduce patient 
reported pain and increase patient reported function following designated surgical 
procedures relative to patients treated under usual care. The primary outcome – a 
composite of patient reported pain and function – 3 months post-operatively will be 
assessed using validated patient reported outcomes.  
12.2 Sample Size and Randomization 
Using pain data for 6,261 patients with these procedures at six sites, we estimated 
the intra-cluster correlation coefficient (ICC) for the pain score to be modest  = 
0.037.  To assess minimal detectable effects, we simulated a large number of 
randomizations and estimated the detectable effect for each. Specifically, for P = 
1,….,5000 permutations, the 22 clusters were randomly assigned to 5 waves. For 
each permutation, the closed form solution of Harrison et al (2019) was used to 
estimate SE(Q) (derived from the formula of Hussey, Hughes (2008)) for true 
effect Q. We used the values 2 = 1 and 2 = 0.488 for the within and between 
variance components so that detectable effects would be in SDs, and assumed ICC 
would be 0.037.  Over the 5,000 permutations, the detectable effect ranged between 
0.048SD and 0.055SD. 
12.2.1 Treatment Assignment Procedures 
In order to balance cluster characteristics, we applied a constrained 
randomization procedure. Constrained randomization allows us to balance a 
larger number of cluster characteristics than is possible through 

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stratification. Here the key cluster characteristics to be balanced were: site 
(6 locations), volume (estimated using 2018 data), procedures (3 groups), 
and number of teams (1-4). Given only 22 sites, it would not be practical to 
stratify or apply minimization, while constrained randomization allows us 
to select an allocation of sites to waves from among a set of allocations that 
has better balance on these factors. 
Specifically, we generated 100,000 allocations of the 22 clusters to 5 waves. 
For each allocation, we then calculated a balance metric B as follows. For 
each characteristic c listed above, let X(c)i be the value of c for each cluster 
i=1,...,22. For categorical factors X is an indicator, for volume and number 
of teams X is a number, rescaled to range from 0-1. Let w=0,...,5 be the 
baseline  (w=0) and 5 intervention waves; and for a given allocation, let Si = 
the first wave at which cluster i is allocated to intervention. Then we 
calculate for each allocation the balance metric  
𝐵=
∑(𝑆𝑖̅ −𝑤) |∑𝑋(𝑐)𝑖(𝑆𝑖≤𝑤)
𝑐
−∑𝑋(𝑐)𝑖(𝑆𝑖> 𝑤)
𝑐
|
𝑤=0.,,5
 
After generating 100,000 allocations, we constrained selection to those with 
values of B in the lowest decile; we then selected one allocation randomly 
from those 10,000 ‘acceptable’ allocations.  This process resulted in a full 
allocation of all 22 sites to waves 1-5 prior to initial intervention.  
12.3 Interim analyses and Stopping Rules 
This is a minimal risk study for which there is no planned interim analysis.  Interim 
analysis may be conducted at the request of the DSMB or if necessitated by 
unforeseen changes in the study plan (e.g. loss of a study site). Similarly, there are 
no pre-specified stopping rules as the probability and magnitude of adverse 
experiences are not greater than those ordinarily encountered in daily life. 
12.4 Outcomes  
Outcomes will be collected via the Epic EHR. PROMs will be collected using 
interfaces available to patients in their MyChart patient portals or the Welcome 
tablet functionality at point of care as available.   Because outcomes will be either 
PROMs or data entered by providers during routine care delivery, requirements for 
adjudication will be minimal.  Health care utilization is an exception in that criteria 
for hospitalizations vary based on designations of observational status.  The 
NOHARM Data Management working group will identify hospitalizations that 
may require adjudication, including ER stays that exceed 24 hours.  A committee 
blinded to a patient’s affiliation with an activated or control cluster will determine 
whether to designate such instances as hospitalizations. 
The cadence and mode of PROM data collection are outlined below.  PROMs 
comprise the NOHARM trial’s co-primary and a majority of its secondary 
outcomes.  PROMs will additionally be collected for use in describing the study 
population and for analytic adjustments. 

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12.4.1 Primary outcome   
Physical function and pain interference, as measured with the Patient 
Reported Outcome Measurement System (PROMIS) computer adaptive 
tests (CATs) are the co-primary outcomes.  The CATs in the Mayo Clinic 
Epic EHR have been parameterized with stopping rules based on number of 
items administered rather than a standard error of measurement-defined 
threshold.  IRT-based instruments have generally better discrimination 
across the entire trait range than legacy PROMs,19,20  and CAT 
administration  enhances measurement efficiency and precision.21,22 The 
PROMIS item banks have been validated in the target populations.23-25   The 
PROMIS physical function and pain interference CATs will be assigned via 
an automated Epic function precisely 3 months following each patient’s 
surgery.  Patients will receive an automated reminder message via their 
patient portals prompting them to complete the PROMs. 
Because post-operative visit requirements and sequences vary across 
surgical practices, administration of the PROMIS CATs will not be linked 
to a specific visit, but rather assigned automatically after 3 months have 
elapsed since surgery.  If this data coincides with a clinic visit, then patients 
will be encouraged to complete the PROMIS CATs via the Epic Welcome 
interface using a tablet in the waiting room prior to their clinic visit.   
12.4.2 Secondary outcomes   
Secondary outcome measures will include opioid consumption, NPPC use, 
healthcare utilization and anxiety.  Anxiety will be measured in a manner 
similar to physical function and pain interference with a PROMIS CAT 
administered via the Epic MyChart portal or the Welcome tablet interface 
prior to a clinic visit that coincides with the 3-month post-surgical time 
point.  
Opioid consumption will be collected using three methods.  First, opioid 
consumption per hospital day, will be extracted from the medication 
administration log in the EHR.  As in previous work, 26-28  parenteral, 
transdermal, and oral opioid consumption will be expressed as oral 
morphine equivalents (OMEs). Second, oral and transdermal opioids 
prescribed by a Mayo Clinic provider at the time of hospital discharge and 
during the interval between hospital dismissal and the 3 month post-surgical 
assessment point will be extracted from the EHR and converted to OMEs. 
Last, because outpatient prescriptions do not accurately capture opioid 
consumption, patients will be queried at the 3 month post-operative time 
point regarding their opioid use using a subscale from a validated opioid 
consumption questionnaire. 28   
NPPC use will be collected using two methods.  First, the frequency with 
which patients use specific NPPCs during their hospital stays will be 

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extracted from Epic flowsheets.  Nurses, as well as occupational and 
physical therapists record delivery of modalities as well as education 
regarding modalities in Epic flowsheets.  This information will be 
electronically extracted and expressed as count data.  Second, patients’ use 
of NPPC modalities will be assessed using self-report.  At the 1-, 2- and 3-
month assessment point patients will be queried regarding which of the 
NOHARM NPPC modalities they have used since hospital discharge.  The 
will be presented with a list of the NOHARM modalities and asked to 
indicate those that they have used.  Epic cascading logic will then present a 
second item for each modality that a patient has used which will ask them 
“How many times per week, on average, do you use modality?” Healthcare 
utilization for NOHARM will consider hospitalizations, post-acute care, ED 
visits, surgery clinic outpatient visits, and calls to the surgery care team and 
post-acute care (PAC).  EHR entries and administrative billing data will be 
aggregated to construct a comprehensive data set of all clinical encounters.  
Data collected for hospitalizations will include procedures and admission 
and discharge diagnoses.  For ED encounters, we will capture diagnoses and 
procedures.  Clinic visits will be captured using billing data which will 
include CPT codes, ICD-10 codes, location, and clinician NPI numbers.   
 
12.5 Data Analyses 
Because patients are randomized in clusters, all statistical methods will account for 
potential correlation of measures within clusters. Such methods include cluster 
adjusted standard errors for t-tests and χ2-tests, and mixed effects models.  Patient 
characteristics will be summarized by intervention status, and tested for difference 
between intervention groups; any factors which are imbalanced will be accounted 
for in the main analyses. Factors assessed for balance and potential inclusion in 
pre-specified analyses are those listed in Section 13.1.1 and all baseline measures 
listed in 13.1.2.  
The primary and secondary outcomes will be compared between intervention 
groups using mixed effects generalized linear models. Each model will include an 
indicator for intervention group; a random intercept for cluster; cluster level factors 
that were used to constrain randomization; calendar time; surgery type; and any 
patient factors that were imbalanced across groups. 
The model details for each outcome are as follows: 
1. PROMIS CATs (anxiety (1°), physical function (1°), pain (1°)). These are 
continuous measures, collected at two time points, pre-operative and 3 months 
post-operative. To assess the impact of the intervention on these we will 
estimate three separate models. If Yijt is the measure at time t =1,2 of the ith 
patient treated by the jth cluster, then we will estimate 
𝑌𝑖𝑗2 = 𝛽0 + 𝛽𝐼𝐼𝑖𝑗+ 𝛽𝐵𝑌𝑖𝑗0 + 𝛽𝑇𝑇+ 𝚩𝑿 𝑿𝒊𝒋+ 𝚩𝒁𝒁𝒋+ 𝑢𝑗+ 𝑒𝑖𝑗  
 
(1) 
 

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where Iij indicates the intervention status, T is calendar time, uj ~ N(0,2) is a 
cluster level random effect, Xij is a vector of patient characteristics, including 
surgery type, Zj is a vector of cluster characteristics used for randomization, and 
eij is a residual error. By testing I = 0 we can assess whether the intervention is 
associated with changes in the corresponding measure.  
 
2. NPPC use. This is collected as a binary value for each of 14 modalities, 
collected at one time point, 3 months post-operative. We will sum these to 
create a score, and use a model similar to (1) but without a baseline value Yij0:  
𝑌𝑖𝑗= 𝛽0 + 𝛽𝐼𝐼𝑖𝑗+ 𝛽𝑇𝑇+ 𝚩𝑿 𝑿𝒊𝒋+ 𝚩𝒁𝒁𝒋+ 𝑢𝑗+ 𝑒𝑖𝑗  
 
(2) 
Again by testing I = 0 we can assess whether the intervention is associated with 
changes in the corresponding measure. 
3. 
 Opioid use will be measured using 4 outcomes:   
a.      Hospital-based consumption, daily oral morphine equivalents (OMEs). 
This is a continuous measure for each day of hospitalization; we will 
assume that this depends in part on the day post surgery, Dij and model 
 
𝑌𝑖𝑗= 𝛽0 + 𝛽𝐼𝐼𝑖𝑗+ 𝛽𝐷𝐷𝑖𝑗+ 𝛽𝑇𝑇+ 𝚩𝑿 𝑿𝒊𝒋+ 𝚩𝒁𝒁𝒋+ 𝑢𝑗+ 𝑒𝑖𝑗  
 
(3) 
 
For this model we will consider Dij as first continuous and then as 
categorical.   
 
b.      Discharge and post-discharge prescriptions, daily oral morphine 
equivalents (OMEs). For this outcome, we will use a model analogous to 
(3), where Dij is replaced by number of days post discharge.  
 
c.      Number of post-discharge prescriptions. These are counts for the 3 month 
period following surgery. The impact of the intervention will be assessed 
using a model similar to (2) but with a Poisson link function: 
 
 
𝑙𝑛(𝐸(𝑌𝑖𝑗)) ~ 𝛽0 + 𝛽𝐼𝐼𝑖𝑗+ 𝛽𝑇𝑇+ 𝚩𝑿 𝑿𝒊𝒋+ 𝚩𝒁𝒁𝒋+ 𝑢𝑗+ 𝑒𝑖𝑗 
 
 
(4) 
𝑌𝑖𝑗~ 𝑃𝑜𝑖𝑠𝑠𝑜𝑛(𝜇) 
 
 
We will assess the distribution first using an empty model, and potentially 
adopt a zero inflated Poisson, negative binomial, or zero inflated negative 
binomial according to the corresponding AIC values.  
 
d.      Daily use of opioids; this is binary outcome collected one time, at 3 
months post-surgery. To assess the impact of the intervention we will use a 
model similar to (4) but with a logit link: 
 

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𝑙𝑜𝑔𝑖𝑡(𝑌𝑖𝑗) ~ 𝛽0 + 𝛽𝐼𝐼𝑖𝑗+ 𝛽𝑇𝑇+ 𝚩𝑿 𝑿𝒊𝒋+ 𝚩𝒁𝒁𝒋+ 𝑢𝑗+ 𝑒𝑖𝑗 
 
 
(5) 
 
For a-d we can again test I = 0 we can assess whether the intervention is 
associated with changes in the corresponding measure. 
4. 
 Healthcare utilization 
a.      Hospitalizations 
b.      ER visits  
c.      Calls to surgical practice 
 
All three of these are count outcomes, and so we will assess the impact of the 
intervention using a model similar to (4) above. As with (4), we will compare 
model specifications using an empty model first to determine the best count 
family (Poisson, negative binomial, zero inflated or not) using AIC, then apply 
that in the final model. 
12.6 Subgroup analyses  
12.6.1 Clinical and Demographic subgroups 
Subgroup analyses will be performed for a) separate procedures b) separate age 
groups c) separate genders and d) separate racial/ethnic groups. Patients will be 
stratified using each classifier and the primary analyses replicated in each 
subgroup.  
12.6.2 Patients at risk of unplanned prolonged opioid use (UPOU).   
Hypothesis: Patients at moderate to high risk for UPOU, defined by score 
on the pain catastrophizing scale, pre-operative opioid use, and/or chronic 
pain will use NPPC modalities significantly less frequently than patients 
who are at low risk of UPOU.   
Self-reported use of NPPC, expressed as a binary (Yes/No) response and 
assessed at 3 month post-surgical time point, will be compared between 
patient subgroups stratified by UPOU risk.  
12.6.3 Patients who are rurally situated. 
Hypothesis. Patients who are rurally situated, as defined by US Census 
Bureau criteria, will use NPPC modalities significantly less frequently than 
patients who are situated in urbanized areas and urban clusters.   
Self-reported use of NPPC, expressed as a binary (Yes/No) response and 
assessed at 3-month post-surgical time point, will be compared across 
patient subgroups defined by US Census Bureau urban/rural criteria. 
 

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12.7 Supplementary Analyses 
12.7.1 Moderators 
In supplementary analyses we will assess whether procedure, age, sex, or 
race/ethnicity moderate the intervention effect. The models (1)-(5) used in the 
primary analysis will be expanded to include indictors for one of these subgroup 
classifiers, as well as the interaction with intervention status. By testing whether the 
interaction effect differs from zero, we can assess whether these factors moderate 
the intervention.  
12.7.2 Mediators 
In related supplementary analyses, we will test whether interim patient measures 
mediate the effect of the intervention on the separate outcomes. We will adapt 
models (1)-(5) to path analysis, a type of structural equation model, which will 
allow us to specify an indirect effect (of the intervention through the potential 
mediator) and test whether it is non-zero.  

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13 DATA COLLECTION AND QUALITY ASSURANCE 
13.1 Data Collection Forms 
All data points for the NOHARM study will be collected via programmatic 
extraction from the electronic health record. In addition to demographic, diagnostic, 
and procedural clinical variables, this includes patient reported outcomes and 
medication information that are captured electronically from patients as part of 
routine (i.e. usual) perioperative care at Mayo Clinic.  
13.1.1 Clinical and Demographic variables 
• Age 
• Sex 
• Race/ethnicity 
• Insurance status 
• Procedure 
• Zip code of residence (for classification as rural or non-rural residence) 
• Comorbidities 
▪ Elixhauser comorbidity index 
13.1.2 Treatment and outcomes variables 
The following items will be captured in addition to clinical and demographic 
variables: 
• Patient Reported Medical Information System (PROMIS) computer adaptive 
test (CAT)  
o Pain interference @ baseline and 1, 2 and 3-months post-surgery  
o Physical functioning @ baseline and 1, 2 and 3-months post-surgery  
o Anxiety @ baseline 3 months post surgery 
o Numerical rating scale pain scores reported q shift during hospitalization 
• Pain catastrophizing scale 
• TAPS prescription medication use item 
• PHQ-4 (four item patient health questionnaire for anxiety (GAD 2) and 
depression (PHQ 2)) 
• Opioid prescribing survey 
• History of opioids prescribed in one year prior to surgical procedure 
• In-hospital administration of medications including oral morphine 
equivalents and opioid alternatives (i.g., acetaminophen) consumed during 

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hospitalization 
• “Discharge” opioid prescriptions, which may be prescribed prior to the 
procedure due to clinic workflow 
• Opioid prescription orders up to 1 year post-discharge (“refills”) 
Data will be programmatically extracted and curated by study team members, 
including data managers, analysts, and/or statisticians. All data will exist prior to 
the time of access, and no further patient contact is needed for the above data 
points. 
Once extracted from the EHR, data will be maintained on secure, encrypted, 
password protected research servers at Mayo Clinic. Access to data files will be 
restricted to individuals listed in the protocol approved by the Mayo Clinic IRB. 
13.2 Data Management  
Individual sites in the NOHARM project (specifically MC Rochester, MC Arizona, 
MC Jacksonville, MC La Crosse, MC Mankato, and MC Eau Claire) will not be 
required to conduct any site- or study-specific, manual data collection. All study 
sites use a unified electronic medical record (Epic) and programmatic data 
extraction can be conducted by study team personnel at the coordinating center 
(MC Rochester). 
The coordinating center (MC Rochester) will extract data from the electronic 
medical record as needed to assess the fidelity of routine data collection activities, 
evaluate the completeness of data collection, and to conduct comprehensive data 
pulls for the final analysis. 
Data collection forms are not applicable to our study design as all data will be 
recorded as part of usual care and electronically retrieved from the medical record 
by study staff. 
13.3 Quality Assurance  
13.3.1 Training 
Data will be extracted, compiled and analyzed by personnel on the study 
team who have expertise in data management, informatics and statistical 
methods.  
13.3.2 Quality Control Committee  
Data will be electronically extracted from the EHR and validated against the 
clinical record. Chart-audit will occur at 3-month intervals, on 2-5%, 
depending on capacity, of patients for each of the most recently activated 
clusters. These audits are intended to insure that data extraction procedures 
are functioning as expected for each cluster.    

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13.3.3 Metrics 
The study team will validate electronic data pulls against the EHR as 
needed. 
13.3.4 Protocol Deviations 
Protocol deviations will be reported promptly to the Mayo Clinic IRB upon 
the study team being made aware of the deviations. The main opportunity 
for protocol deviations is the mis-routing of patients to wrong study arm 
(intervention or control). Care will be taken to make sure the EHR 
assignment algorithms are functioning properly. Protocol modifications will 
be made as new tranches are brought into the intervention arm of the study. 
The following are examples of potential protocol deviations which will be 
carefully avoided, but reported if they occur: 
1. Implementing the intervention without practice approvals.  
As indicated in the protocol and elsewhere, we will be engaging with 
practice leadership in advance of implementing the NOHARM intervention. 
Failure to duly engage practice leadership and obtain documented approval 
prior to implementing the intervention in specific surgical practices would 
violate expectations set in the protocol. 
2. Incorrect routing of patients to intervention/control arms.  
Patient assignment to either the treatment or control arm of the study within 
the EHR will be done via pre-specified algorithms. Rigorous testing and 
validation will be done to ensure the algorithms are functioning as expected. 
Should the algorithms fail to properly assign patients to the treatment or 
control arm of the study, appropriate action will be taken to refine the 
algorithms to prevent further mis-assignment and the affected patients will 
be accounted for, as appropriate, in the study analyses. 
3. Failure to monitor trial for data quality and patient safety.  
Per the protocol, we will monitor study implementation—particularly 
within the surgical practices in which the NOHARM intervention has been 
implemented—to ensure that the intervention is functioning as 
designed/intended and that critical data points are being captured. Further, 
the protocol assumes that data essential for monitoring patient safety and 
ensuring data quality will be abstracted as needed and made available to the 
data safety and monitoring board for review. 
4. Study staff not included in IRB documentation.  
All personnel on the study who will be involved with the conduct of the 
research must be included in IRB documentation per Mayo Clinic policy. 
This excludes members who are involved with NOHARM as Standard of 

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Care.Failure to disclose personnel actively involved in the study conduct 
will constitute a protocol deviation. 
5. Failure to apprise the IRB of updated patient contact materials or study 
procedures. 
It is possible that some of the patient contact materials, including elements 
of the decision aid, after visit summaries, and resource materials provided to 
patients will be updated with alternate and or additional information 
throughout the course of the study. Failure to apprise the IRB of these 
modifications and/or to document these updates as potentially important 
covariates in analysis will be considered a deviation from protocol. 
13.3.5 Monitoring 
The study will be monitored by the DSMB in a manner and frequency 
prescribed by NIA/NIH. 

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14 PARTICIPANT RIGHTS AND CONFIDENTIALITY  
14.1 Institutional Review Board (IRB) Review 
This protocol and any subsequent modifications will be reviewed and approved by 
the Mayo Clinic IRB.  
14.2 Informed Consent Forms & Authorization Considerations 
A waiver of informed consent is being requested for this study, which presents no 
more than minimal risk of harm to subjects. Because this is a population-based, 
EHR-embedded study, it is not practical to conduct the research without the waiver 
of consent. We do not feel the waiver of informed consent will adversely affect the 
rights or welfare of the subjects.   
In lieu of consent, we have sought out and confirmed Mayo Clinic Practice 
leadership support for the trial.  In the 3-6 months prior to each wave of trial 
implementation we will confirm each individual practices’ willingness to 
participate in the trial.  Because some practices will not be randomized until 2023, 
securing their endorsement now, did not make sense.   
See Section 15 – Ethical Considerations for more information.  
14.3 Participant Confidentiality  
Information about study subjects will be kept confidential.  
Only NOHARM study team members (study investigators, project coordinators, 
research assistants, data managers, biostatisticians, etc.) who are IRB-approved 
study staff will have access to individually identifiable private information 
collected for study purposes, except as necessary for monitoring, audits and/or 
inspections by the IRB, the NIA, and/or government regulatory agencies.  
Data that are transferred outside of the Mayo Clinic firewall will be de-identified, 
stripped of personal health information, and encrypted.  
14.4 Study Discontinuation  
The study may be discontinued at any time by the principal investigators, the IRB, 
the NIA, the DSMB, or other government agencies as part of their duties to ensure 
that research participants are protected.  

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15 ETHICAL CONSIDERATIONS 
This is a population-based study, where all eligible patients undergoing qualifying 
surgeries at participating Mayo Clinic locations will be “enrolled.” Neither current 
regulations, nor the peer-reviewed literature explicitly defines when a formal patient 
consent process is required for pragmatic clinical trials, particularly when testing the 
implementation of proven-effective interventions at scale. This type of research, sometimes 
referred to as “standard of care” research, in which the primary research objective is to 
implement and evaluate a strategy that better satisfies the existing clinical standard of care, 
has been debated in recent high-profile cases.70-72 Opinions from ethicists vary but all 
emphasize the vital importance of IRB engagement and assiduous efforts to foster 
disclosure and transparency across all relevant stakeholders.73-75 We believe, and in 
consultation with our local Research Ethics Consult Service have confirmed, that this study 
meets the criteria for being standard of care research in which the marginal incremental 
risks of the proposed interventions do not foreseeably introduce even incremental net risk 
to individuals in the participating practices being studied. The Mayo Clinic IRB has been 
an active partner in developing the NOHARM application and its involvement will 
continue.  Preliminary discussions with the Mayo Clinic IRB executive committee in 
January 2020 concluded this study is minimal risk and that waiver of consent was 
warranted so long as practice endorsement was secured.  
IRB members and the Mayo Clinic Family Advisory Council contributed to the current 
NOHARM “Transparency Promotion and Patient Preference Protection Plan.” The 
Transparency Promotion and Patient Preference Protection Plan is a multi-pronged 
approach that was in place prior to planning and design of the NOHARM trial, but that has 
further matured as a consequence of these efforts. The Mayo Clinic Enterprise, in an effort 
to proactively anticipate ethics, human subject protections, and institutional oversight 
concerns related to the conduct of quality improvement, pragmatic, and “standard of care” 
trials convened a group of key stakeholders. These stakeholders include members of the 
Mayo Clinic IRB, Mayo Clinic Patient and Family Advisory Council, representatives from 
Enterprise Research Administration, and clinicians representing surgical specialties, pain 
management, pharmacy, rehabilitation medicine, and general internal medicine. This 
stakeholder group is entrusted to provide impartial oversight of trial activities that may 
challenge the goal of complete pan-stakeholder transparency and prioritization of patient 
preference.  

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16 COMMITTEES 
The following schematic illustrates the Mayo Clinic research team workgroup structure. 
 
 
 
16.1 Project Workgroups/Responsibilities 
The NOHARM PIs established six workgroups to develop the intervention, engage 
practice partners, create training material and implement with the surgical practices 
identified for the trial. Team members meet face-to-face and virtually on weekly/bi-
weekly basis and report to the trial coordination team. Meeting notes and progress 
reports are maintained on a project folder share for team members’ reference.    
• Trial Coordination 
o Interfaces with the Duke Center, NIH, NIA, and Mayo Clinic IRB, 
practice leaders and committees.   
o Manages the budget, provides oversight and guidance to the project team. 
o Development and maintenance of study materials including the Manual 
of Procedures and study forms  
o AE and SAE monitoring and reporting  
o Quality control procedures  
o Distribution of all changes, updates and policies of reports and 
documents to all participating study sites, NIA and to the DSMB as 
necessary.  

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• Modalities 
o Identify scalable NPPC approaches that can be broadly delivered at high 
fidelity throughout the Enterprise. 
o Develop supportive education material, develop staff training materials, 
and ensure distribution at target sites. 
o Collaborate with Healing after Surgery Guide and Epic team to develop 
system content. 
• Practice Engagement 
o Characterize peri-operative workflows in the target specialties.  
o Develop and deliver training material.  
o Identify and engage key stakeholders and practice champions. 
o Provide support during implementation 
o Conduct site visits to ensure adherence to the protocol and procedures.  
o Communicates with study sites, responding to and documenting ad hoc 
communications.  
• Hospital / Post-Surgical  
o Develop NPPC discharge plan integration and opioid taper counseling 
o Determine Patient reported outcome assessment and response strategy. 
• Epic 
o Define the EHR technical requirements. The EHR components include 
orders, documentation, best practice alerts, patient questionnaires and 
reports. 
o Identify and engage technical resources to configure, validate and 
advance changes through the EHR environments.   
o Obtain approval for the EHR changes from the appropriate committees. 
o Document all components of the EHR build and identify/implement 
changes required for each tranche implementation. 
• Healing after Surgery Guide 
o Conduct interviews, focus groups, and shadowing to gain insights into the 
user experience from both the healthcare staff and patient perspective to 
inform the design of the Healing after Surgery guide. 
o Develop and refine the Healing after Surgery guide, collaborating with 
Mayo Clinic’s Office of Patient Education, Integrative Medicine & 
Health and Department of Physical Medicine and Rehabilitation to define 
patient educational content. 
o Coordinates the GC build with the Epic MyChart and patient portal 
teams.   

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• Data Management 
o Identify clusters based on surgical procedures and sites.   
o Develop the randomization scheme and procedures. 
o Develop the data flow and data management procedures including data 
entry, error identification and correction.  
o Perform programmatic extraction and curation to support trial analyses as 
described in section 13.  
o Maintain data security and integrity in concordance with section 13.1 of 
the IRB protocol. 
• Mayo Clinic Leadership 
While the NOHARM intervention is designed to seamlessly integrate into 
clinical practice and hospital workflows, meaningful stakeholder engagement 
and collaboration is critical to successful implementation.  The project team 
seeks endorsement from Mayo Clinic leaders and practice partners through 
the established committee structure including: 
o Mayo Clinic Clinical Practice Committee 
o Opioid Stewardship Program 
o Mayo Clinic Nursing Practice Council 
o EHR/RMC Oversight Committee 
o Surgical and Procedural Committee 
o Surgical Specialty Councils 

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17 PUBLICATION OF RESEARCH FINDINGS 
The trial will be registered on ClinicalTrials.gov and the NOHARM investigative team will 
follow the requirements outlined in the NIH Policy on Dissemination of NIH-Funded 
Clinical Trial Information. Mayo Clinic has an established internal policy in place to 
ensure that clinical trials registration and results reporting occur in compliance with the 
policy requirements. 
Mayo Clinic strongly supports investigators to present at relevant regional, national, and 
international meetings. Opportunities such as these are both opportunities to share 
knowledge and also cultivate new ideas among colleagues. Given our expertise, diverse 
collaborators, and distinct focus in the project, we foresee a number of manuscript and 
presentation opportunities. We will publish rigorous visible results in quality journals.  
Mayo Clinic’s office of Scientific Publications also supports investigators in developing 
journal articles, chapters, and complete books for academic publication. Additionally, the 
Mayo Clinic College of Medicine supports the development of educational content 
throughout its five schools, ensuring that new, groundbreaking ideas are quickly spread to 
learners at nearly every level of medical education. Importantly, new education spreads 
beyond our own doors in numerous ways. Especially important is the Mayo School of 
Continuous Professional Development, accredited by the ACCME.  

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18 REFERENCES 
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Health Statistics;2018. 
2. 
Hooten WM, Brummett CM, Sullivan MD, et al. A Conceptual Framework for 
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Clarke H, Soneji N, Ko DT, Yun L, Wijeysundera DN. Rates and risk factors for 
prolonged opioid use after major surgery: population based cohort study. BMJ. 
2014;348:g1251. 
4. 
Brummett CM, Waljee JF, Goesling J, et al. New Persistent Opioid Use After Minor and 
Major Surgical Procedures in US Adults. JAMA Surg. 2017;152(6):e170504. 
5. 
Goesling J, Moser SE, Zaidi B, et al. Trends and predictors of opioid use after total knee 
and total hip arthroplasty. Pain. 2016;157(6):1259-1265. 
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Alam A, Gomes T, Zheng H, Mamdani MM, Juurlink DN, Bell CM. Long-term analgesic 
use after low-risk surgery: a retrospective cohort study. Arch Intern Med. 
2012;172(5):425-430. 
7. 
Johnson SP, Chung KC, Zhong L, et al. Risk of Prolonged Opioid Use Among Opioid-
Naive Patients Following Common Hand Surgery Procedures. J Hand Surg Am. 
2016;41(10):947-957 e943. 
8. 
Holman JE, Stoddard GJ, Higgins TF. Rates of prescription opiate use before and after 
injury in patients with orthopaedic trauma and the risk factors for prolonged opiate use. J 
Bone Joint Surg Am. 2013;95(12):1075-1080. 
9. 
Rosenbloom BN, McCartney CJL, Canzian S, Kreder HJ, Katz J. Predictors of 
Prescription Opioid Use 4 Months After Traumatic Musculoskeletal Injury and 
Corrective Surgery: A Prospective Study. J Pain. 2017;18(8):956-963. 
10. 
Sun EC, Darnall BD, Baker LC, Mackey S. Incidence of and Risk Factors for Chronic 
Opioid Use Among Opioid-Naive Patients in the Postoperative Period. JAMA Intern 
Med. 2016;176(9):1286-1293. 
11. 
Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of Postoperative Pain: A 
Clinical Practice Guideline From the American Pain Society, the American Society of 
Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' 
Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J 
Pain. 2016;17(2):131-157. 
12. 
Wardhan R, Chelly J. Recent advances in acute pain management: understanding the 
mechanisms of acute pain, the prescription of opioids, and the role of multimodal pain 
therapy. F1000Res. 2017;6:2065. 
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American Society of Anesthesiologists Task Force on Acute Pain M. Practice guidelines 
for acute pain management in the perioperative setting: an updated report by the 
American Society of Anesthesiologists Task Force on Acute Pain Management. 
Anesthesiology. 2012;116(2):248-273. 
14. 
Tick H, Nielsen A, Pelletier KR, et al. Evidence-Based Nonpharmacologic Strategies for 
Comprehensive Pain Care: The Consortium Pain Task Force White Paper. Explore (NY). 
2018;14(3):177-211. 
15. 
Chaudhry B, Wang J, Wu S, et al. Systematic review: impact of health information 
technology on quality, efficiency, and costs of medical care. Ann Intern Med. 
2006;144(10):742-752. 

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16. 
Keasberry J, Scott IA, Sullivan C, Staib A, Ashby R. Going digital: a narrative overview 
of the clinical and organisational impacts of eHealth technologies in hospital practice. 
Aust Health Rev. 2017;41(6):646-664. 
17. 
Leppin AL, Fernandez C, Tilburt JC. Missed Opportunities: A Mixed-Methods Analysis 
of CAM Discussions and Practices in the Management of Pain in Oncology. J Pain 
Symptom Manage. 2016;52(5):719-726. 
18. 
Soos SA, Jeszenoi N, Darvas K, Harsanyi L. [Attitudes, knowledge and use of 
complementary and alternative medicine among perioperative healthcare professionals]. 
Orv Hetil. 2017;158(10):368-375. 
19. 
Fries JF, Krishnan E, Rose M, Lingala B, Bruce B. Improved responsiveness and reduced 
sample size requirements of PROMIS physical function scales with item response theory. 
Arthritis Res Ther. 2011;13(5):R147. 
20. 
Fries J, Rose M, Krishnan E. The PROMIS of better outcome assessment: 
responsiveness, floor and ceiling effects, and Internet administration. J Rheumatol. 
2011;38(8):1759-1764. 
21. 
Rose M, Bjorner JB, Gandek B, Bruce B, Fries JF, Ware JE, Jr. The PROMIS Physical 
Function item bank was calibrated to a standardized metric and shown to improve 
measurement efficiency. J Clin Epidemiol. 2014;67(5):516-526. 
22. 
Choi SW, Reise SP, Pilkonis PA, Hays RD, Cella D. Efficiency of static and computer 
adaptive short forms compared to full-length measures of depressive symptoms. Qual 
Life Res. 2010;19(1):125-136. 
23. 
Pilkonis PA, Yu L, Dodds NE, Johnston KL, Maihoefer CC, Lawrence SM. Validation of 
the depression item bank from the Patient-Reported Outcomes Measurement Information 
System (PROMIS) in a three-month observational study. J Psychiatr Res. 2014;56:112-
119. 
24. 
Amtmann D, Kim J, Chung H, et al. Comparing CESD-10, PHQ-9, and PROMIS 
depression instruments in individuals with multiple sclerosis. Rehabil Psychol. 
2014;59(2):220-229. 
25. 
Junghaenel DU, Schneider S, Stone AA, Christodoulou C, Broderick JE. Ecological 
validity and clinical utility of Patient-Reported Outcomes Measurement Information 
System (PROMIS(R)) instruments for detecting premenstrual symptoms of depression, 
anger, and fatigue. J Psychosom Res. 2014;76(4):300-306. 
26. 
Thiels CA, Anderson SS, Ubl DS, et al. Wide Variation and Overprescription of Opioids 
After Elective Surgery. Ann Surg. 2017;266(4):564-573. 
27. 
Thiels CA, Ubl DS, Yost KJ, et al. Results of a Prospective, Multicenter Initiative Aimed 
at Developing Opioid-prescribing Guidelines After Surgery. Ann Surg. 2018;268(3):457-
468. 
28. 
CC W, M H, Trousdale ER, et al. Developing and implementing a novel institutional 
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19  DESCRIPTION OF SUPPLEMENTS/APPENDICES 
19.1 Appendix A: Clinician Participants 
Description of the status of clinicians in the NOHARM pragmatic trial. 
19.2 Appendix B: Resource List 
A brief handout provided to patients before discharge that points them to resources 
to help them further pursue information on non-pharmacological pain management 
strategies. 
 
 

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Appendix A: Clinician Participants 
 
 
Clinician Participants 
The clinical practices of care teams involved in the care of surgery patients targeted by the 
NOHARM intervention—including surgeons, nurses, physical therapists, pain management 
specialists—will be impacted by the bundled NOHARM intervention. In the course of providing 
care to surgical patients in active intervention clusters, clinicians will be alerted to non-
pharmacological pain management strategies (via CDS tools embedded in the EHR) for which 
patients have expressed preference. Within their routine workflows (i.e. interface with patients), 
clinicians will be prompted to engage patients about their preferred post-acute pain 
management strategies. 
 
Because of this practice impact, clinicians will be considered “participants” in the NOHARM 
pragmatic trial (in the same way as they have been construed in the pilot application IRB# 20-
001864). This determination has been affirmed by the Mayo Clinic IRB executive committee 
(January 2020 meeting). 
 
Accrual 
Based on data from 2018 on the 22 surgery types targeted by the NOHARM trial (minus neuro / 
spine surgery which is the focus of the NOHARM pilot trial – IRB# 20-001864) we estimate 
there to be approximately 225 surgeons in the enterprise who are routinely performing surgery. 
We will inflate this number to 300 to account for physicians performing one of the target surgery 
types less frequently. To this figure, we will add 0.5 residents / and 0.5 physician assistants per 
surgeon (+300). Assuming a median hospital stay of 3 days (9 nursing shift changes), we will 
add 9 nurses X 300 surgeons (+2700). Finally, assuming 0.5 physical therapist per surgeon and 
0.2 integrative medicine specialist per surgeon, we will add 210 clinicians. This brings our total 
estimated clinician accrual to 3510 participants. 
 
Consent and Data Collection 
 
1. Given the ubiquity of the intervention and the volume of clinicians touched by the trial it 
will not be practicable to obtain individual consent for participation. 
2. Clinician “consent” will be granted in the form of “whole practice consent” granted by 
individual surgical practice leadership within the institution as a pre-requisite for 
implementation in specific surgical practices. 
3. It would be impracticable to formally track clinicians as we are not documenting 
individual consent nor collecting data from clinicians. Although we could potentially 
identify the number of clinicians who log into Epic to provide care for discreet surgery 
patients, this approach would be imprecise. 
4. No clinician variables—including clinician ordering or prescribing behaviors—are being 
assessed. All study outcomes are patient outcomes, as the intervention is intended to 
guide the patient’s surgical recovery experience. 
 
Risks and Benefits 
The risks to clinicians involved in the NOHARM trial are minimal. Clinicians are already 
motivated to employ clinical guidelines for non-pharmacological pain management, and the 
NOHARM pilot study may enhance their personal success that effort. Clinicians may find, 
perhaps at first, that the EHR-based prompts interfere with the rhythms of their workflow, but 

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great effort has been invested to ensure that the EHR-emedded clinical decision support tools 
integrate seamlessly into existing workflows. Further, the Mayo Clinic Clinical Practice 
Committee has endorsed the intervention as an appropriate element for institutional 
improvement in the management of post-surgical pain. Ongoing care will be taken to minimize 
the workflow burden while making the EHR prompts an effective tool in promoting institutional 
adherence to clinical guidelines. Clinicians will always be able to make professional judgments 
about the appropriateness of engaging patients in specific conversations about pain 
management throughout the patients’ post-surgical recovery. Clinicians may freely disregard 
EHR-prompts as they deem appropriate in their professional judgment. Clinicians will be amply 
supported by the study team by way of education and through access to study team members 
with expertise in non-pharmacological pain management modalities and in the management of 
complex pain management cases. 
 
 
 
 

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Appendix B: Resource List 
 
Patient Support 
• Zoom group support calls will help patients by answering questions about the patients’ 
selected modalities. Answers will be provided by NOHARM trial staff. Resources 
include: 
o Zoom Group Call Instructions 
o Welcome Instructions 
o 
Zoom Group Call Talking Points 
• Toll-free number (1-833-919-1432) will help support patients by answering questions 
about the patients’ selected modalities and the NOHARM trial staff will provide 
answers 
• Healing After Surgery Website (www.healingaftersurgery.mayoclinic.org was 
developed to support patients who are portal users 
• Healing After Surgery Workbook was developed to support patients, who may not be 
portal users, may not have access to a computer or to the internet or may not be 
comfortable with technology 
• 
Workbook Cover Letter 
• Transcutaneous Electrical Nerve Stimulation (TENS) Patient Education Video is a 5-
minute patient education instructional video 
• 13 Modality videos. Each video provides a brief modality overview  
• Modality Flyers Each flyer provides a brief overview of each modality and resource list 
• Rack Card - Healing After Surgery Managing Pain is a quick reference guide (rack 
card) about NOHARM and the NOHARM resources 
• Healing after Surgery DVD includes all patient education video content used in the 
NOHARM intervention. The DVD mirrors what is on MCTV.  
• Mayo TV NOHARM Resource List provides the NOHARM patient education resources 
available on Mayo Clinic Television (MCTV) 
• NOHARM TENS units: the NOHARM trial will purchase TENS units for the surgical 
clusters 
• Portal messages 
o 
Pre-op sending/assignment of Healing after surgery guide: message sent 
when the patient is assigned the Healing after surgery guide 
o 
Pre-op Healing after surgery guide non-response reminder message: if 
the patient hasn’t completed the Healing after surgery guide, this 
reminder is sent. 
o 
Pre-op post-Healing After Surgery Guide follow-up message/Thank you (4 
confidence): 4 messages based on the patient’s response to the 
confidence questions.  
o 
Post-Op Discharge (“Welcome Home”) Message: reminds patients of 
NOHARM resources after they are discharged from the hospital. 
o 
1, 2 and 3 month post-op questionnaire reminder (send 4 days after initial 
questionnaire was sent): Standard Epic reminder message 
o 
PROMIS CATs Questionnaire Followup Message: 3 versions depending 
on the patient’s PROMIS CAT scores; reminds patient of NOHARM 
resources and if their pain and or physical function is severe, then 
suggest actions the patient should take 
o 
Message sent after opioid prescription refill 
 
Epic Components (Standard of Care) 
o  
• 
Healing after Surgery Guide is an Epic questionnaire with additional HTML to help 
patients understand what to expect when recovering from surgery, learn about 
pain management techniques and to make a plan to manage pain after surgery. 
There is a Desktop version and mobile version 

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• 
Pre-op questionnaires: Pre-surgery questionnaires are existing PROMIS CAT 
questionnaires: Pain Interference, Physical Function, Anxiety questionnaires 
• 
1, 2 and 3 month post-op questionnaires: (Identify intervention patients that need 
help/struggling; collect data)  
• 
Physical function, Pain Interference, and NPPC usage -and at 3 months a Opioid 
Usage questionnaire (content complete) along with the PROMIS Anxiety are also 
given 
• 
After Visit summary (AVS) (search the folder for AVS to find all files) 
o 
Patient facing: Provides patients with information specific to their selected 
modalities. 
o 
Discharge to facility AVS: A significant number of NOHARM participants 
will be dismissed to post-acute care (PAC) facilities, e.g., skilled nursing 
facilities. For those patients, the AVS content will be directed to clinicians 
at PAC facilities 
 
Mayo Clinic Care team Support 
• Pager (3-5519): NOHARM staff will provide Epic and workflow support 
• Department of Nursing Healing after Surgery (NOHARM) Intranet page  provides a 
NOHARM overview as well as available NOHARM resources 
• Provider NOHARM Overview and Talking Points (elevator speech) reminds the care 
team of NOHARM 
• MyLearning classes: provide a NOHARM overview, set expectations and teach the 
NOHARM workflow for each role 
o NOHARM: Introduction and Overview (COURSE 502E00NOHM0001) 
o NOHARM: Provider Training(COURSE 502E00NOHM0004) 
o NOHARM Inpatient Nursing Training (COURSE 502E00NOHM005) 
o NOHARM: Outpatient Nursing Training(COURSE 502E00NOHM0002) 
o NOHARM: Physical Therapy Training (COURSE 502E00NOHM0003) 
o NOHARM: Pre/post-op and PACU Nursing Training (COURSE 
502E00NOHM0006) 
 
Epic Components (Standard of Care, support for clinical team) 
• 
NOHARM Just in Time Training: role based training that is linked in the Epic 
NOHARM banner 
o 
Inpatient nursing 
o 
PACU  
o 
PT 
o 
Surgeons APP resident 
• 
RN Education points helps RNs provide NOHARM education to patients 
• 
RN Task/Brain/worklist: NOHARM tasks the RN has to complete 
• 
NOHARM Banner: the NOHARM banner is pink to help with awareness 
• 
RN Orders (search folder for Orders for all the files) 
• 
Best Practice Alerts: alert Mayo Clinic care teams about key steps to take for 
NOHARM. Triggered off of certain Epic event 
o 
PT/OT BPA 
o 
Pain > 1 BPA 
o 
Opioid Rx BPA 
 
 Trial Coordination 
• NOHARM Data and Safety Monitoring Board (DSMB) Charter 
• NOHARM Data and Safety Monitoring Plan (DSMP)  
• Letters of Support 

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