Toward Thriving: A Set of Reflective Tools to Empower Chronic Pain Patients and Help Them Envision a Personal Path to Thriving.
Phase: NA
Conditions: Chronic Pain
Sponsor: University of Michigan

 
Toward Thriving Study 
HUM00176302 
 
 
 
 
 
Study Protocol 
V1.6 
April 20, 2023 
 
 
 
 
MPIs 
Afton Hassett, PsyD 
Stephanie Tharp 
Hannah Smotrich 
 
 
 

 
Contents 
1. 
Protocol Summary .......................................................................................................................................................... 4 
1.1. 
Synopsis .................................................................................................................................................................. 4 
1.2. 
Schema ................................................................................................................................................................... 4 
1.3. 
Schedule of Activities (SOA) ................................................................................................................................... 4 
2. 
Introduction .................................................................................................................................................................... 5 
2.1. 
Objective ................................................................................................................................................................. 5 
2.2. 
Specific Aims ........................................................................................................................................................... 5 
2 . 3 .  
Background ......................................................................................................................................................... 5 
2.4. 
Methodology .......................................................................................................................................................... 5 
3. 
Study Population ............................................................................................................................................................ 5 
3.1. 
Inclusion Criteria ..................................................................................................................................................... 5 
3.2. 
Exclusion Criteria .................................................................................................................................................... 5 
3.3. 
Screen Failures........................................................................................................................................................ 5 
3.4. 
Strategies for Recruitment and Retention ............................................................................................................. 6 
4. 
Study Intervention .......................................................................................................................................................... 6 
4.1. 
Overall .................................................................................................................................................................... 6 
4.2. 
Phase 1 and Workshop (T3) .................................................................................................................................... 6 
4.3. 
Phase 2 and Exit Interview (T4) .............................................................................................................................. 6 
5. 
Statistical Design and Analysis ........................................................................................................................................ 6 
5.1. 
Acceptability Study ................................................................................................................................................. 6 
Hypotheses tests are two-sided performed at the 5% significance level. 95% confidence interval will be conducted. ... 7 
5.2. 
Feasibility Study ...................................................................................................................................................... 7 
6. 
Study Intervention Discontinuation and Participant Discontinuation/Withdrawal ....................................................... 7 
6.1. 
Discontinuation of Study Intervention ................................................................................................................... 7 
6.2. 
Participant Discontinuation/Withdrawal from the Study ...................................................................................... 7 
6.3. 
Lost to Follow-Up.................................................................................................................................................... 7 
7. 
Study Assessments and Procedures ............................................................................................................................... 8 
7.1. 
Efficacy Assessments .............................................................................................................................................. 8 
7.2. 
Safety and Other Assessments ............................................................................................................................... 8 
7.3. 
Adverse Events, Serious Adverse Events and Unanticipated Problems ................................................................. 8 
7.3.3.1. 
Severity of Event ............................................................................................................................................. 8 
7.3.3.2. 
Relationship to Study Intervention ................................................................................................................. 8 
7.3.3.3. 
Expectedness .................................................................................................................................................. 9 
7.3.3.4. 
Time Period and Frequency for Event Assessment and Follow-Up................................................................ 9 
7.3.4. 
Adverse Event Reporting .................................................................................................................................... 9 
7.3.5. 
Serious Adverse Event Reporting ....................................................................................................................... 9 

 
7.4. 
Unanticipated Problems (UaP) ............................................................................................................................... 9 
7.5. 
Risk/Benefit Assessment ...................................................................................................................................... 10 
8. 
Supporting Documentation and Operational Considerations .............................................................................. 10 
8.1. 
Regulatory, Ethical, and Study Oversight Considerations .................................................................................... 10 
8.1.1.1. 
Consent/assent and Other Informational Documents Provided to participants ......................................... 10 
8.1.1.2. 
Consent Procedures and Documentation .................................................................................................... 11 
8.1.9.1. 
Data Collection and Management Responsibilities ...................................................................................... 13 
8.1.9.2. 
Study Records Retention .............................................................................................................................. 13 
8.2. 
Additional Considerations .................................................................................................................................... 13 
8.3. 
Abbreviations........................................................................................................................................................ 14 
8.4. 
Protocol Amendment History ............................................................................................................................... 15 
8.5. 
Appendix A: Intervention Documents .................................................................................................................. 16 
8.6. 
References ............................................................................................................................................................ 16 
 
 
 

 
1. Protocol Summary 
1.1. 
Synopsis 
Title: 
Toward Thriving Study 
Grant Number: 
N/A 
Study Description: 
A longitudinal clinical trial in a cohort of chronic pain to assess feasibility of a new 
behavioral intervention based on the principles of positive psychology. The study will 
recruit 20 participants, who will complete 4 timepoints (T1-T4). Participants will be 
consented at T1. T2 will be a kickoff meeting for all participants. After T2, participants 
will complete study intervention phase 1 (cultural probe kit) for three weeks. Next 
participants will participate in a facilitated workshop at T3, complete phase 2 of the 
intervention, followed by an exit interview at T4. Participants will complete a study 
survey at T1 and T4. 
Objectives*: 
 
The purpose of this pilot study is to introduce and test a positive psychology 
intervention meant to empower chronic pain patients and help support their 
resiliency and thriving. 
Endpoints*: 
1. Primary: Feasibility and acceptability of the behavioral intervention (cultural 
probe kit related activities). 
Percent (%) of participants engaging in the intervention between T1 and T4 
2. Secondary:  
Change in PGIC between T1 and T4 
Change in PROMIS Pain Interference between T1 and T4 
3. Exploratory: 
Change in PROMIS 29 depression, anxiety sleep, fatigue between T1 and T4 
Study Population: 
Participants over the age of 18 with chronic pain 
Description of Sites/Facilities 
Enrolling Participants: 
This study will recruit patients at the Michigan Medicine. There will be no sites 
outside of the US. 
Description of Study 
Intervention/Experimental 
Manipulation: 
Participants will complete a cultural probe kit over 3-weeks. This kit is a design 
research tool, to prompt participants to document, map, journal, and reflect on 
various aspects of their daily lives 
Study Duration*: 
12 months 
Participant Duration: 
4 months 
1.2. 
Schema 
 
Figure 1 Study Schema 
1.3. 
Schedule of Activities (SOA) 
Table 1 Study SOA 
  
Screening 
T1 
T2 
T3 
T4 
Screening 
x 
  
  
  
  
Consent 
  
x 
  
  
  
Demographics 
  
x 
  
  
  
PROMIS 29-+ 2 
  
x 
  
  
x 
PGIC 
  
  
  
  
x 

 
Chronic Pain 
Conditions 
 
X 
 
 
 
Facilitated 
Interview 
 
 
x 
 
x 
2. Introduction 
2.1. 
Objective 
The purpose of this pilot study is to introduce and test a positive psychology intervention meant to empower chronic 
pain patients and help support their resiliency and thriving. 
 
2.2. 
Specific Aims 
Testing the efficacy of a custom-designed set of reflective tools (plus interactive workshop) to empower chronic pain 
patients and help them envision a personal path to thriving. 
2 . 3 .  Background 
‘Large studies in Europe, North America, Australasia, and other regions disclose that one in five of the adult population 
suffers from chronic moderate to severe pain 1 ,’ yet there are societal misconceptions about what it means to live with 
chronic pain. Chronic pain sufferers encounter frequent barriers and few supports to help them live meaningful lives. 
This project has the potential to provide support to patients through positive psychology methods. 
2.4. 
Methodology 
Participants will be using a cultural probe kit, a design research tool, to prompt participants to document, map, journal, 
and reflect on various aspects of their daily lives. During an interactive, in-person workshop, participants will review and 
synthesize the contents of their probe kit and set goals for themselves. The workshop, which takes place after 
participants have completed three weeks of at-home activities, will be facilitated in small groups by a designer and 
psychologist team. Participants will end the study with 3-weeks of at-home activities and an exit interview about their 
experience. Specific instructions, as delivered in each week of the probe kit materials, as well as plans for the kickoff 
meeting, workshop and exit interview, follow. 
3. Study Population 
3.1. 
Inclusion Criteria 
 
Persistent or recurrent pain lasting longer than 3 months 
 
Age 18+ 
 
Able to read and write English 
3.2. 
Exclusion Criteria 
 
Cancer  
o History of any bone-related cancer or cancer that metastasized to the bone  
o Currently in treatment for any cancer or plan to start cancer treatment in the next 12 months  
o History of any cancer treatment in the last 24 months 
 
Active substance abuse 
 
Uncontrolled depression or psychosis 
 
Visual or hearing difficulties that would preclude participation 
 
Individuals started receiving disability or compensation within the past year, or currently involved in litigation  
 
Current/planned (in the next 2 years) enrollment in another study of a device or investigational drug that would 
interfere with this study, this may include participation in a blinded trial. 
 
Any other diseases or conditions that would make a patient unsuitable for study participation as determined by 
the site principal investigators. This would include but not be limited to severe psychiatric disorders, active 
suicidal ideations or history of suicide attempts, and an uncontrolled drug and/or alcohol addiction) 
3.3. 
Screen Failures 

 
Screen failures are defined as participants who consent to participate in the clinical trial but are later to found to be 
ineligible. A minimal set of screen failure information is required to ensure transparent reporting of screen failure 
participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any serious adverse event (SAE). 
3.4. 
Strategies for Recruitment and Retention 
3.4.1. Methods of Recruitment 
Participants will be screened and recruited through Michigan Medicine via the following methods: 
1. In-person recruitment through Back and Pain Center (B&PC) 
2. Umhealthresearch.com 
3. Data direct queries 
4. Flyers in clinic across Michigan Medicine 
5. B&PC new patient registry APOLO HUM00041820 
3.4.2. Recruitment and Enrollment 
Participants will be tracked and screened using REDCap, a HIPAA compliant electronic data capture system. Those 
patients who meet eligibility criteria will be consented electronically through REDCap. They will then be asked to 
complete a study survey via REDCap and scheduled for future visits.  
3.4.3. Incentives 
Participants will be paid up to $250. They will receive $150 for completing the workshop (T3) and associated 
intervention phase 1 kit and $100 for completing the exit interview and associated phase 2 activities 
4. Study Intervention 
4.1. 
Overall 
Participants will complete two phases of the study intervention before and after the T3 visit. The interventions are 
made up of self-guided at home activities.  
4.2. 
Phase 1 and Workshop (T3) 
Participants will be using a cultural probe kit, a design research tool, to prompt participants to document, map, journal, 
and reflect on various aspects of their daily lives. During an interactive, in-person workshop (T3), participants will review 
and synthesize the contents of their probe kit and set goals for themselves. The workshop, which takes place after 
participants have completed three weeks of at-home activities, will be facilitated in small groups by a designer and 
psychologist team.  
4.3. 
Phase 2 and Exit Interview (T4) 
Participants will end the study with 3-weeks of at-home activities and an exit interview about their experience. T4 may 
be completed in-person or virtually and maybe recorded. 
5. Statistical Design and Analysis 
5.1. 
Acceptability Study  
We will conduct semi-structured interviews to understand participant perception of the intervention at T4.  We will 
assess the proportion of participants who report that the intervention was relatively easy to understand after 
orientation, low burden (easy to do), and potentially effective. 
5.1.1. Hypothesis 
≥80% of participants will report that the intervention was relatively easy to understand after orientation, low burden, 
and potentially effective. 
5.1.2. Outcome 
The primary outcome is the patient assessment of the cultural probe tool and the overall experience including 
orientation and facilitated workshop. A series of prompts in the semi-structured interview will elicit opinions about the 
intervention, the ease of completion, and the possibility that it could help promote positive emotions and resilience. 
5.1.3. Hypothesis test and power analysis  

 
Hypotheses tests are two-sided performed at the 5% significance level. 95% confidence interval will be conducted.  
5.2. 
Feasibility Study  
We will collect data related to the number of participants approached and consented; the percentage consented who 
attend the facilitated workshop, the number of activities the participants at the workshop have completed, the number 
of participants who take part in the exit interview and the progress made towards goals set at the Sensemaking 
Workshop. We will also explore the intervention’s potential to improve patient-reported outcomes including patient 
global impression of change (PGIC). Patient-reported outcomes will be measured before and after the intervention.  
5.2.1. Hypothesis 
≥80% of participants attending the facilitated workshop will have completed at least 2 of the 3 reflective tools. 
5.2.2. Outcome 
The primary outcome is the proportion of participants who attending the Sensemaking Workshop have completed at 
least 2 of the 3 reflective tools. The secondary outcomes are patient's belief about the efficacy of intervention (PGIC) 
and other symptoms including pain interference, depression, anxiety, and sleep, etc. The rate of patients being lost-to-
follow-up will also be tracked to aid in appropriate design of a future randomized clinical trial. 
5.2.3. Hypothesis test and power analysis  
Frequencies will be calculated related to feasibility data (e.g., number of participants approached, consented, and take 
part in the workshop). Descriptive statistics of patient-reported outcomes will be calculated before and after the 
intervention. Paired t-tests are used on patients’ changes from T1 to T4. Wilcoxon test will be applied if departure from 
the assumption of normality. Hypotheses tests are two-sided performed at the 5% significance level. 95% confidence 
interval will be conducted. Power analysis for efficacy is based on t-tests.  
6. Study Intervention Discontinuation and Participant Discontinuation/Withdrawal 
6.1. 
Discontinuation of Study Intervention 
Discontinuation from the intervention will be considered withdrawal from the study as well. This is further described 
below. 
6.2. 
Participant Discontinuation/Withdrawal from the Study 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 
 
Significant study intervention non-compliance  
 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation occurs such 
that continued participation in the study would not be in the best interest of the participant 
 
Disease progression which requires discontinuation of the study intervention 
 
If the participant meets an exclusion criterion (either newly developed or not previously recognized) that 
precludes further study participation 
The reason for participant discontinuation or withdrawal from the study will be recorded on the off-study Case Report 
Form (CRF). Subjects who sign the informed consent form but do not receive the study intervention may be replaced.  
Subjects who sign the informed consent form, and receive the study intervention, and subsequently withdraw, or are 
withdrawn or discontinued from the study, will not be replaced. 
6.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he or she fails to complete the study visits and scheduled surveys 
and are unable to be contacted by the study site staff after three attempts at any point in the study.  
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
 
The site will attempt to contact the participant and reschedule the missed visit within a 2-week timeframe and 
counsel the participant on the importance of maintaining the assigned visit schedule and ascertain if the 
participant wishes to and/or should continue in the study. 

 
 
Before a participant is deemed lost to follow-up, the investigator or designee will make every effort to regain 
contact with the participant (where possible, 3 telephone calls, text message and, if necessary, a certified letter 
to the participant’s last known mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s study record.  
 
Should the participant continue to be unreachable, he or she will be considered to have withdrawn from the 
study with a primary reason of lost to follow-up. 
7. Study Assessments and Procedures 
7.1. 
Efficacy Assessments  
All study evaluations are listed in section Error! Reference source not found.. Screening will occur the day of the T1 
study visit. The T1 study visit will include consenting and completion of the study survey.  
7.2. 
Safety and Other Assessments 
As this is a minimal risk study, there are very few safety risks anticipated. Study staff will review the study risks with the 
participant during consent and answer any questions. Participants can withdraw at any time if they feel discomfort.  
7.3. 
Adverse Events, Serious Adverse Events and Unanticipated Problems 
7.3.1. Definition of Adverse Events (AE) 
Adverse event means any untoward medical occurrence associated with the use of an intervention in humans, whether 
or not considered intervention-related (21 CFR 312.32 (a)). 
7.3.2. Definition of Serious Adverse Events (SAE)  
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of either the investigator or 
sponsor, it results in any of the following outcomes:  
 
death,  
 
a life-threatening adverse event,  
 
inpatient hospitalization or prolongation of existing hospitalization,  
 
a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions,  
 
a congenital anomaly/birth defect.  
Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered 
serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical 
or surgical intervention to prevent one of the outcomes listed in this definition.  
7.3.3. Classification of an Adverse Event 
7.3.3.1. 
Severity of Event 
For adverse events (AEs) not included in the protocol defined grading system, the following guidelines will be used to 
describe severity.  
 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic measures. Moderate 
events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug therapy or other 
treatment. Severe events are usually potentially life-threatening or incapacitating.  Of note, the term “severe” 
does not necessarily equate to “serious”.] 
7.3.3.2. 
Relationship to Study Intervention 
All adverse events (AEs) must have their relationship to study intervention assessed by the PI who examines and 
evaluates the participant based on temporal relationship and clinical judgment. The degree of certainty about causality 
will be graded using the categories below. 
 
• 
Related – The AE is known to occur with the study intervention, there is a reasonable possibility that the study 
intervention caused the AE, or there is a temporal relationship between the study intervention and event. 

 
Reasonable possibility means that there is evidence to suggest a causal relationship between the study 
intervention and the AE. 
• 
Not Related – There is not a reasonable possibility that the administration of the study intervention caused the 
event, there is no temporal relationship between the study intervention and event onset, or an alternate 
etiology has been established. 
7.3.3.3. 
Expectedness  
Study staff will be responsible for determining whether an adverse event (AE) is expected or unexpected.  An AE will be 
considered unexpected if the nature, severity, or frequency of the event is not consistent with the risk information 
previously described for the study intervention. 
7.3.3.4. 
Time Period and Frequency for Event Assessment and Follow-Up 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of study personnel 
during study visits and interviews of a study participant or upon review by a study monitor. 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on the appropriate case 
report form (CRF). Information to be collected includes event description, time of onset, clinician’s assessment of 
severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and 
time of resolution/stabilization of the event. All AEs occurring while on study must be documented appropriately 
regardless of relationship. All AEs will be followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as baseline and not 
reported as an AE. However, if the study participant’s condition deteriorates at any time during the study, it will be 
recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event at each level of 
severity to be performed. AEs characterized as intermittent require documentation of onset and duration of each 
episode. 
 
Study staff will record all reportable events with start dates occurring any time after informed consent is obtained until 
7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation.  At each study visit, the investigator 
will inquire about the occurrence of AE/SAEs since the last visit.  Events will be followed for outcome information until 
resolution or stabilization. 
7.3.4. Adverse Event Reporting  
Reporting timeline for this study is described in Table 2. Unrelated AEs will not be reported. 
7.3.5. Serious Adverse Event Reporting  
A timeline for reporting AEs, SAEs, UaPs and Protocol deviations to the Institutional Review Board of the University of 
Michigan are described in Table 2. 
Table 2 Timeline for Reporting Study Events to IRB 
Event 
UM IRB 
Non-serious Adverse Events 
Will not be reported 
Serious Adverse Events (Unrelated) 
Will not be reported 
Serious Adverse Event (Related) 
Within 7 days of occurrence notification 
Serious Adverse Event (Anticipated) 
Annual report to IRB prior to scheduled continuing review 
Non-serious adverse events grade 2 or 
higher (moderate or greater) 
Annual report to IRB prior to scheduled continuing review 
Privacy violation or breach of 
confidentiality  
Report to IRB within 7 days 
Within 24 hours to the UMHS Privacy Office 
Protocol deviations 
Annual report to IRB prior to scheduled continuing review 
7.4. 
Unanticipated Problems (UaP) 

 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to participants or 
others to include, in general, any incident, experience, or outcome that meets all of the following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are described in 
the protocol-related documents, such as the Institutional Review Board (IRB)-approved research protocol and 
informed consent document; and (b) the characteristics of the participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a reasonable 
possibility that the incident, experience, or outcome may have been caused by the procedures involved in the 
research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
7.4.1. Unanticipated Problem Reporting (UaP) 
The investigator will report unanticipated problems (UaPs) to the reviewing Institutional Review Board (IRB) and lead 
principal investigator (PI). The UP report will include the following information: 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome represents an UaP;  
• 
A description of any changes to the protocol or other corrective actions that have been taken or are proposed in 
response to the UaP. 
To satisfy the requirement for prompt reporting, UPs will be reported using the timeline described in Error! Reference 
source not found.. 
7.5. 
Risk/Benefit Assessment   
7.5.1. Known Potential Risks  
The known potential risks in this study are no more than mild risk level. The table below describes the specific risks for 
this study.  
Table 3 Potential Study Risks 
Risks 
 
Questionnaires 
Survey questions about pain, emotions, and thinking patterns about pain will 
be administered as part of this study. Some participants may feel minor 
discomfort sharing information about their physical and mental health.  
Breach of 
Confidentiality 
Even with extensive protections in place, there is a very unlikely possibility of 
breaches in confidentiality. This will be considered a severe adverse event and 
will be reported to the IRB within 7 days.  
7.5.2. Known Potential Benefits  
Participants might benefit from being in the study by taking time and having structures to examine their supports and 
barriers, enhance positive emotions, gain health education, and clarify goals and values. They may also benefit from 
interactions with other chronic pain patients. 
7.5.3. Assessment of Potential Risks and Benefits  
The risks associated with this study are minimal. Study team will monitor for any complaints related to survey 
discomfort and breaches in confidentiality. 
 
8. Supporting Documentation and Operational Considerations 
8.1. 
Regulatory, Ethical, and Study Oversight Considerations 
8.1.1. Informed Consent Process 
8.1.1.1. 
Consent/assent and Other Informational Documents Provided to participants 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the participant and 
written documentation of informed consent is required prior to starting study.  

 
8.1.1.2. 
Consent Procedures and Documentation 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study and continues 
throughout the individual’s study participation. Consent forms will be Institutional Review Board (IRB)-approved and the 
participant will be asked to read and review the document. The investigator will explain the research study to the 
participant and answer any questions that may arise. A verbal explanation will be provided in terms suited to the 
participant’s comprehension of the purposes, procedures, and potential risks of the study and of their rights as research 
participants.  Participants will have the opportunity to carefully review the consent form and ask questions prior to 
signing. The participants should have the opportunity to discuss the study with their family or surrogates or think about 
it prior to agreeing to participate.  
 
The participant will electronically sign the informed consent document prior to any procedures being done specifically 
for the study. Participants must be informed that participation is voluntary and that they may withdraw from the study 
at any time, without prejudice. A copy of the informed consent document will be available to the participants. The 
informed consent process will be conducted and documented in the source document (including the date), and the 
form signed, before the participant undergoes any study-specific procedures. The rights and welfare of the participants 
will be protected by emphasizing to them that the quality of their medical care will not be adversely affected if they 
decline to participate in this study. 
8.1.2. Study Discontinuation and Closure 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause.  Written 
notification, documenting the reason for study suspension or termination, will be provided by the suspending or 
terminating party to study participants and investigator.  If the study is prematurely terminated or suspended, the 
Principal Investigator (PI) will promptly inform study participants, the Institutional Review Board (IRB), and sponsor and 
will provide the reason(s) for the termination or suspension.  Study participants will be contacted, as applicable, and be 
informed of changes to study visit schedule. 
  
Circumstances that may warrant termination or suspension include, but are not limited to: 
 
Determination of unexpected, significant, or unacceptable risk to participants 
 
Demonstration of efficacy that would warrant stopping    
 
Insufficient compliance to protocol requirements 
 
Data that are not sufficiently complete and/or evaluable 
 
Determination that the primary endpoint has been met 
 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, and satisfy the 
sponsor and IRB. 
8.1.3. Confidentiality and Privacy  
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their staff, and their 
interventions. Therefore, the study protocol, documentation, data, and all other information generated will be held in 
strict confidence. No information concerning the study or the data will be released to any unauthorized third party 
without prior written approval. 
 
All research activities will be conducted in as private a setting as possible. At the beginning of group sessions, ground 
rules will be shared with the participants. These rules will encourage participants to maintain confidentiality, privacy 
and dignity of the members in the group. 
 
Representatives of the Institutional Review Board (IRB) or regulatory agencies may inspect all documents and records 
required to be maintained by the investigator. 
 

 
The study participant’s contact information will be securely stored at each clinical site for internal use during the study. 
At the end of the study, all records will continue to be kept in a secure location for as long a period as dictated by the 
reviewing IRB, Institutional policies, or sponsor requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be transmitted 
to and stored at the B&PC Research Center. This may include the participant’s contact or identifying information. 
Rather, individual participants and their research data will be identified by a unique study identification number. The 
study data entry and study management systems used by clinical sites and by B&PC Research Center staff will be 
secured and password protected. At the end of the study, all study databases will be de-identified and archived here. 
8.1.4. Future Use of Data  
Data collected for this study will be analyzed and stored at the B&PC Research Center. After the study is completed, the 
de-identified, archived data will be transmitted to and stored at the B&PC Research Center, for use by other researchers 
including those outside of the study.  
 
When the study is completed, access to study data and/or samples will be provided through the B&PC Research Center. 
8.1.5. Key Roles and Study Governance 
Principal Investigator 
Principal Investigator 
Principal Investigator 
Hannah Smotrich 
Stephanie Tharp 
Afton Hassett 
STAMPS Faculty 
STAMPS Faculty 
Back & Pain Center 
734-763-5226 
734-763-5226 
734-763-5226 
smotrich@umich.edu 
smtharp@umich.edu 
afton@med.umich.edu 
8.1.6. Safety Oversight 
Safety oversight will be under the direction of a designated study monitor, designated from the study team. They will be 
responsible for reviewing regulatory compliance and ensuring participant and data safety. The study monitor will review 
the study on an annual basis and complete documentation.  
8.1.7. Clinical Monitoring 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants are protected, that the 
reported trial data are accurate, complete, and verifiable, and that the conduct of the trial is in compliance with the 
currently approved protocol/amendment(s), with International Conference on Harmonization Good Clinical Practice 
(ICH GCP), and with applicable regulatory requirement(s).  
 
A study monitor will conduct an audit on an annual basis by reviewing 10% of the records randomly. Errors and 
discrepancies will be documented and reviewed with the study team.  
8.1.8. Quality Assurance and Quality Control 
Our clinical site will perform internal quality management of study conduct, and data documentation and completion. 
 
Quality control (QC) procedures will be implemented beginning with the data entry system and data QC checks that will 
be run on the database will be generated. Any missing data or data anomalies will be communicated to the site(s) for 
clarification/resolution. 
 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical trial is conducted and 
data are generated and biological specimens are collected, documented (recorded), and reported in compliance with 
the protocol, International Conference on Harmonisation Good Clinical Practice (ICH GCP), and applicable regulatory 
requirements (e.g., Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP)).  
 
The investigational site will provide direct access to all trial related sites, source data/documents, and reports for the 
purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory authorities. 
8.1.9. Data Handling and Record Keeping  

 
8.1.9.1. 
Data Collection and Management Responsibilities  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site investigator. The 
investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data reported. 
 
All data will be recorded in the electronic case report form (eCRF) derived from source documents should be consistent 
with the data recorded on the source documents.  
 
Clinical data (including adverse events (AEs), concomitant medications, and expected adverse events data will be 
entered into REDCap, a 21 CFR Part 11-compliant data capture system provided by the University of Michigan. The data 
system includes password protection and internal quality checks, such as automatic range checks, to identify data that 
appear inconsistent, incomplete, or inaccurate.  
 
8.1.9.2. 
Study Records Retention  
Study documents should be retained for a minimum of 2 years have elapsed since the formal discontinuation of clinical 
development of the study intervention. These documents should be retained for a longer period, however, if required 
by local regulations. It is the responsibility of the sponsor to inform the investigator when these documents no longer 
need to be retained 
8.1.10. Protocol Deviations  
It is the responsibility of the site investigator to use continuous vigilance to identify and report deviations as described 
in Error! Reference source not found..  Protocol deviations must be sent to the reviewing Institutional Review Board 
(IRB) per their policies. The site investigator is responsible for knowing and adhering to the reviewing IRB requirements.  
8.1.11. Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical industry, is 
critical.  Therefore, any actual conflict of interest of persons who have a role in the design, conduct, analysis, 
publication, or any aspect of this trial will be disclosed and managed. Furthermore, persons who have a perceived 
conflict of interest will be required to have such conflicts managed in a way that is appropriate to their participation in 
the design and conduct of this trial.  All study group members will be asked to disclose all conflicts of interest and will 
establish a mechanism for the management of all reported dualities of interest. 
8.2. 
Additional Considerations 
N/A 
 
 

 
8.3. 
Abbreviations 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
B&PC 
Back & Pain Center 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation  
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
LSMEANS 
Least-squares Means 
MedDRA 
Medical Dictionary for Regulatory Activities 
MSDS 
Material Safety Data Sheet 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UaP 
Unanticipated Problem 
 
 

 
8.4. 
Protocol Amendment History 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a description of the 
change and rationale.  
 
Version 
Date 
Description of Change  
Brief Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
8.5. 
Appendix A: Intervention Documents 
8.6. 
References 
 
1.  ‘Unrelieved Pain is a Major Global Healthcare Problem.’ International Association for the Study of Pain. 
Accessed January 4, 2020. http://www.iasp-pain.org/ (pdf, p.1).