Tailored Health Self-Management Interventions for Highly Distressed Family Caregivers
Phase: NA
Conditions: Distress, Caregiver
Sponsor: Case Western Reserve University

 
PROTOCOL TITLE:  
Tailored Self-Management Interventions for Highly Distressed Family Caregivers  
Supplement Title: Caregiving Burden and Heart Rate Variability: differences by race and gender  
 
Identifiers: NCT03023332   Unique Protocol ID: 1R01NR016817-01 
 
 
PRINCIPAL INVESTIGATOR  
Jaclene Zauszniewski  
Nursing Science  
216-368-3612  
jaz@case.edu 
 
Document Date: March 11, 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
Page 1 of 29  
  
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WITH NO BIOMEDICAL/CLINICAL COMPONENTS]  

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PROTOCOL TITLE:  
Tailored Self-Management Interventions for Highly Distressed Family Caregivers  
Supplement Title: Caregiving Burden and Heart Rate Variability: differences by race and gender  
PRINCIPAL INVESTIGATOR  
Jaclene Zauszniewski  
Nursing Science  
216-368-3612  
jaz@case.edu  
UH FACULTY ADVISOR:  
If the principal investigator’s primary role at UH is resident, fellow or student, identify a faculty advisor.  
N/A  
OTHER DEPARTMENTS INVOLVED IN THIS STUDY (IF APPLICABLE):  
VERSION NUMBER:  
6.2  
DATE:  
6/30/2020  
10/30/2020 (p. 13)  
3/11/2021  

   
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Indicate the origin of this protocol (who conceived of and leads the development of the protocol regardless 
of funding):  
☒ Investigator initiated (Investigator(s) developed protocol, regardless of funding)  
☐ Industry (Pharmaceutical, Device, etc.) (Industry developed protocol)  
☐ Federal (NIH, DOD, etc.)  
☐ Cooperative Group (SWOG, GOG, etc.)  
☐ Other - Please specify:  
Funding  
NIH/NINR: RO1NR016817  
NIH/NINR: RO1NR016817-03S1  
Objectives  
The study has two aims: the primary aim (A1) is to examine differences across the four groups (control, usual 
care, SM-need, and SM-preference) on caregiver health (health risks and mental and physical health) over 
time. We hypothesize that the caregivers who receive a self-management intervention based on need (SM-
need) or preference (SM-preference) will have better outcomes than those in the usual care or control groups.  
Secondary aims are to: A2) explore whether caregiver baseline need or preference for intervention (i.e. 
choice) is associated with: a) care recipient’s symptoms; b) caregiver reactions; and c) caregiver 
involvement and A3) build caregiver profiles from demographic/contextual factors that are associated with 
their needs and preferences for the self-management interventions (A3).  
We will also conduct a supplemental analysis to examine relationships among psychological stress responses 
(caregiver reactions and caregiving involvement), physiological stress responses (heart rate variability 
domains), and caregiver characteristics (race and gender) in caregivers of people with bipolar disorder. The 
major aims of the supplemental analysis (SA) are to: SA1) determine whether there are differences by 
caregiver characteristics (race and gender) on measures of psychological stress responses (caregiving 
involvement and caregiver reactions), SA2) determine whether there are differences by caregiver 
characteristics (race and gender) on measures of physiological stress responses (heart rate variability 
domains), SA3) examine associations among indicators of psychological stress responses (caregiver reactions 
and caregiving involvement) and physiological stress responses (heart rate variability domains), and SA4) 
explore relationships among time and frequency domains of heart rate variability.  
Background  
Directions: Describe the relevant prior experience and gaps in current knowledge describing how it will 
add to existing knowledge. Include any relevant preliminary data.  
Family caregivers provide care and support for over 10 million Americans who have bipolar disorder, which 
is characterized by intensity and fluctuations in mood ranging from depression to mania.1 With an early onset 
and chronicity across the lifespan, bipolar disorder  

   
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accounts for more disability-adjusted life years than all forms of cancer and major neurologic conditions.2 It 
is the most expensive behavioral health care diagnosis,3 costing more than twice as much as depression per 
affected person.4,5 Yet, this does not reflect the adverse effects on the health of the caregivers of persons with 
bipolar disorder who are highly distressed6 and experience greater stress due to the unpredictability and 
severity of bipolar episodes.7 They have more mental and physical health problems than the general 
population8-10 and are less likely to practice adequate self-care to minimize health risks that compromise their 
health.7 Chronic stress endured by these caregivers leads to greater use of mental health and primary care 
services.11 And, greater stress and declining caregiver health can lead to symptom exacerbation, affective 
episodes, and re-hospitalization of the diagnosed family member.12  
Existing psychoeducation7,13-17 and family therapy interventions16,18-20 for caregivers of persons with bipolar 
disorder have shown little effect on caregiver health. Self-management interventions focused on promoting 
caregiver health, including those specifically tailored to address the family caregivers’ needs and preferences 
for bipolar education, stress-reduction, or self-help and help-seeking strategies (i.e. resourcefulness skills) for 
maintaining caregiver health, have not been examined. This randomized controlled trial will evaluate how 
varying levels of participation by family caregivers in selecting self-management interventions (ranging from 
no input into the selection to selection based on need or preference) affect their health risks and physical and 
mental health over time.  
The findings from this study will generate new scientific knowledge about the effectiveness of novel, easy to 
use, independently performed interventions that can be individualized and self-tailored to promote family 
caregiver health through education, biofeedback, or resourcefulness. The study will reveal demographic, 
contextual, and illness-related factors that are associated with caregiver need and preference for self-
management intervention(s) to elucidate for whom and under which circumstances an intervention may be 
most beneficial. This study is clinically significant in testing self-management interventions in a vulnerable, 
understudied, highly distressed population of caregivers, for whom interventions to promote their own health 
are critical for their continued service in the caregiving role Once established, these health self-management 
interventions can be tailored to match the needs and preferences of other equally distressed family caregivers 
of persons with other chronic mental or physical conditions.  
Bipolar disorder affects men and women equally and rates are not significantly different by race21. However, 
the caregiving experience can differ by gender and race. Female caregivers contribute more time to 
caregiving and experience greater amounts of role conflict and role strain than male caregivers22. Due to 
caregiving responsibilities, female caregivers are more likely to lose income, lose job benefits, and reduce 
work hours compared to males23.  
In studies comparing White and African American caregivers, African Americans generally provide more 
caregiving hours and perform more caregiver tasks than White caregivers24-26. However, African American 
caregivers report lower levels of burden and depression than White caregivers25-29. Furthermore, African 
American caregivers tend to appraise caregiving as less stressful, but are more cognitively impaired and in 
worse physical health than White caregivers25, 30. The supplemental analysis will examine relationships 
among psychological stress responses, physiological stress responses, and caregiver characteristics in 
caregivers of people with bipolar disorder. The findings will generate new scientific knowledge about the 
stress experienced by White and African-American, male and female caregivers of adults with bipolar 
disorder, using previously untapped measures of heart rate variability to  

   
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capture physiological stress. Most importantly, the supplemental analysis holds the potential to significantly 
advance the sciences of caregiving, self-management, and biobehavioral health by uncovering unknown 
associations between race and gender and indicators of heart rate variability from which health disparities 
related to stress and health may be identified and may inform the future tailoring of health self-management 
interventions.  
 
Inclusion and Exclusion Criteria  
 
Number of Research Participants  
Directions: Indicate the target number of research participants to be accrued locally, and, if this is a 
multi-site study, indicate the total number of research participants to be accrued across all sites.  
Based on previous research by the PI and Co-Is, we conservatively estimate that 1 in 5 caregivers may not 
meet eligibility criteria. Thus, we will screen 750 participants to obtain the desired sample of size of 360.  
Special/Vulnerable Populations  
1. Indicate specifically if you will include each of the following special populations by checking the 
appropriate box:  
 
☐ Adults unable to consent  
☐ Minors (infants, children, teenagers)  
☐ Wards of the state 
 
 
 
 
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☐ Foster Children  
☐ Pregnant Women  
☐ Neonates  
☐ Neonates of Uncertain Viability  
☒ Employees of CWRU or UHHS  
☐ Prisoners  

☒ Illiterate Individuals  
☒ Non-English Speaking  
☒ University Students  
☐ None  
 
 
2. If the research involves individuals that are included in a special/vulnerable population, describe the 
additional safeguards included to protect the rights and welfare of the individuals for each population 
indicated. If family caregivers who do not speak/understand the English language come forward with interest 
in participating and if they meet all other study criteria, we will make accommodations for translating the 
study measures and intervention materials or for having and interpreter provide appropriate explanations. If 
an illiterate individual comes forward with interest in participating and if they meet all other study criteria, 
we will make accommodations to dictate the consent form and all study questions. If a caregiver is an 
employee or student of CWRU, the consent form identifies participation in this research study is voluntary 
and if they choose not to participate, it will not affect their current or future relations with the university.  
 
3. If excluding pregnant women, illiterate or non-English speaking individuals, provide a scientific rationale 
for the exclusion. Inconvenience or cost is not an acceptable rationale.  
Pregnant women are excluded due to the measure of heart rate variability (HRV). The inclusion of pregnant 
women has the potential to alter the analyses that involve HRV measurement.  
Recruitment Methods  
Note: Attach all applicable recruitment materials to the last section of the Smart form under “Recruitment 
Materials.”  
1. Which of the following methods will be used to recruit research participants. – Select all that apply  
 
☐ Email  
☐ Phone call  
☐ Letter  
☒ Advertisement (e.g., poster, flyer, etc.)  
☒ Social media  
☐ Other. Please specify: 
 
 
2. Describe when, where, and how potential research participants will be recruited . 
 
 
 
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Study participants (who meet the study criteria) will be recruited through both public and private mental 
health agencies, counseling centers, support groups, community health centers, health fairs and other 
community events, print and e-newsletters (e.g. CASE Daily), local magazines and newspapers, the registry of 
bipolar persons used by CI Sajatovic and other research registries of people with mental illness and/or their 
family caregivers approved for use from the investigators in the Department of Psychiatry, and private 
physician offices in Cuyahoga and 6 adjacent counties in Northeastern Ohio. We will post/distribute flyers 
describing the study and contact information in public venues; caregivers will contact the study office for 
further information and enrollment. In addition, agency personnel/health care professionals may nominate a 
caregiver for the study. If additional caregivers are needed, we will use snowball recruitment by asking study 
participants to refer others like them to the study. We will also recruit via the internet using social media sites 
(e.g. Twitter, Facebook, Instagram, and other online sources).  
3. Describe the source (e.g., from what department, EMR, etc.) of the research participants.  
 
Study participants will be recruited through both public and private mental health agencies, counseling 
centers, support groups, community health centers, health fairs and other community events, print and e-

newsletters (e.g. CASE Daily), local magazines and newspapers, the registry of bipolar persons used by CI 
Sajatovic and other research registries of people with mental illness and/or their family caregivers approved 
for use from the investigators in the Department of Psychiatry, and private physician offices in Cuyahoga and 
6 adjacent counties in Northeastern Ohio.  
4. Describe the methods that will be used to identify potential research participants.  
 
When a person contacts the study to be screened, they will receive a screening ID in the screening log. 
Contact information will then be collected including name, telephone number(s) and/or email address(es) on 
all individuals screened will collected for our screening log; this information will be stored in a password-
protected computer file.  
The project manager or other trained research staff will screen by phone to ensure that caregivers are at 
least 18 years old, have a family member with bipolar disorder who is at least 18 years old, and have 
cared/supported them for at least 6 months, but not necessarily in the same household, live in the study area, 
and have the physical capability to perform the interventions (i.e. does not have a pacemaker, is not currently 
pregnant). We will also be collecting demographic information (gender, race, ethnicity). All screening 
documentation will be kept in a screening for on REDCap. 
 
We will also ask study participants if they would like to be contacted for future research; we let them know 
there is no penalty to them if they do not wish to be contacted. Furthermore, we inform them that agreeing to 
be contacted does not obligate them to participate in future research, this only permits us to contact them. We 
will maintain a password-protected list on Box.com of individuals that have consented to be contacted for 
future research, along with their contact information and contact preferences. This list will be maintained by 
the Project Manager and may be shared with research team case-by-case basis.  
 
 
 
 
 
 
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After eligibility is verified during phone screening by team member, the consent form will be reviewed 
verbally, questions about the study will be answered, and the study enrollment/first data collection 
appointment will be made.  
5. Describe the feasibility of recruiting the required number of suitable research participants within the agreed 
recruitment period. For example, how many potential research participants do you have access to?  
 
Based on previous research by the PI and Co-Is, we conservatively estimate that 1 in 5 caregivers may not 
meet eligibility criteria. Thus, we will screen 450 potential participants to obtain the desired sample size of 
360. 
 
Setting  
Directions: Make sure to describe: 1) sites and locations where your research team will conduct the 
research; 2) where your research team will identify and recruit potential research participants; and 3) 
include the physical location where research procedures will be performed.  
Study participants will be recruited through both public and private mental health agencies, counseling 
centers, support groups, community health centers, health fairs and other community events, print and e-
newsletters (e.g. CASE Daily), local magazines and newspapers, the registry of bipolar persons used by CI 
Sajatovic and other research registries of people with mental illness and/or their family caregivers approved 
for use from the investigators in the Department of Psychiatry, and private physician offices in Cuyahoga and 
6 adjacent counties in Northeastern Ohio.  
The project manager or other research team member will screen by phone to determine eligibility and 
schedule first data collection meeting. All data will be collected either in the community (e.g. participants 
home or other private venue of their choice, including mental health center/physician’s office, private/ closed 

room in local library, etc.), on the campus of Case Western Reserve University (e.g. the School of Nursing), 
or Department of Psychiatry Walker Building.  
 
Consent Process  
Indicate whether you will be obtaining consent:  
☒ Yes ☐ No  
If yes, answer the following questions:  
1. Describe where the consent process will take place:  
 
After eligibility is verified during phone screening by a team member, the consent form will be reviewed 
verbally and questions about the study will be answered. During the first appointment with the data collector, 
the consent form will be reviewed again and signed by both the study participant and data collector before 
beginning the data collection interview. 
 
 
 
 
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The time that will be devoted to the consent discussion:  
There are no time constraints to the consent discussion. The consent discussion will take place during the 
screening phone call and again at the enrollment meeting, prior to data collection.  
3. Any waiting period available between informing the prospective subject and obtaining the consent:  
 
Yes. After verifying eligibility and reviewing the consent form during the screening phone call, there is a 
period of time between the phone call and the enrollment meeting. The length of time between the two varies 
depending on the meeting time selected by the research participant and team member.  
4. Steps that will be taken to ensure the research participants’ understanding:  
 
Study participants will have time to ask questions about the study and review the consent form before signing 
it.  
5. Any process to ensure ongoing consent:  
 
Within approximately one month of the first data collection session, the participants will be made aware of 
which of the four groups (control, usual care, SM-need, or SM-preference) that they have been randomly 
assigned to. Those who are randomly assigned to usual care, SM-need, or SM-preference will need a second-
level consent, obtained at the beginning of the training session for that particular intervention. The second-
level consent process is needed in order to keep the control group and usual care groups blinded to the 
content of the interventions being tested. Knowledge of the other interventions could motivate them to seek out 
similar strategies on their own and confound the study.  
6. Steps that will be taken to minimize the possibility of coercion or undue influence to the subjects:  
 
The study participants will be informed that his or her participation in the research study is completely 
voluntary. If he or she chooses not to participate, it will not affect their current or future relations with the 
University or with physicians, mental health centers, or community venues from whom they may have 
obtained information about the study. Study participants will also be informed that there is no penalty of loss 
of benefits for not participating of for discontinuing participation in the study.  
For Adult Participants  

Indicate if you will be asking for a waiver or alteration of consent process or documentation (consent 
will not be obtained, written consent will not be documented)  
☐ Yes ☒ No  
If yes, indicate which part of the consent process you are requesting be waived or altered and the 
rationale for requesting the waiver or alteration:  
☐ I will obtain consent, but not participant’s signature  
☐ I will obtain consent, but request a waiver for pre-screening purposes 
 
 
 
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☐ I will obtain consent, but request a waiver of some of the elements of consent (e.g. use of deception)  
☐ I will not obtain consent, and I am requesting a full waiver of consent  
1. Give the rationale for the request of a waiver or alteration of the consent process or documentation.  
 
N/A  
2. Explain how the research involves no more than minimal risk.  
 
N/A  
3. Explain why the waiver or alteration of consent will not adversely affect the rights and welfare of the 
participants.  
 
N/A  
4. Explain why the research could not practicably be carried out without the waiver or alteration of consent.  
 
N/A  
5. Indicate if the subjects will be provided with additional information about the study after participation.  
 
N/A  
6. If you will obtain consent, but not document consent in writing (e.g. over the phone, verbally, electronic 
survey, etc.), please describe and provide a rationale.  
 
☒ N/A  
7. Describe how you will be documenting that a research participant has consented.  
 
N/A  
Additional Considerations for Consent Process with Adults  
Non English Speakers (Please select one)  
☐ I am not enrolling non-English speaking individuals in this research study. The following is justification 
for why non-English speaking individuals cannot be enrolled:  
☐ I will be targeting non-English speaking adults  
1. Describe the process to ensure that the oral and written information provided to those research participants 
will be in that language during initial consent as well as throughout the study.  
 
2. List the language(s) other than English that will be targeted:  
 

☒ I am not targeting non-English speaking individuals. If a non-English speaking individual is eligible for 
the study, we will use the following procedures to enroll:  
1. Describe the process to ensure that the oral and written information provided to those research participants 
will be in that language during initial consent as well as throughout the study.  
 
If family caregivers who do not speak/understand the English language come forward with interest in 
participating and if they meet all other study criteria, we will make 
Page 9 of 29 
 
 
accommodations for translating the study measures and intervention materials or for having an interpreter 
provide appropriate explanations.  
2. List the language(s) other than English that will be targeted:  
 
Adults Unable to Consent  
☒ I am not enrolling adults unable to consent in this research study – please leave the rest of this section 
blank.  
☐ There is an anticipated direct benefit to the subject. Explain:  
☐ There is NOT an anticipated direct benefit to the subject. Explain:  
1. Describe the process to determine whether an individual is capable of consent.  
 
2. List the individuals from whom permission will be obtained in order of priority (e.g. durable power of 
attorney for health care, court appointed guardian for health care decisions, spouse, and adult child).  
 
3. For research conducted outside of the state, provide information that describes which individuals are 
authorized under applicable law to consent on behalf of a prospective subject to their participation in the 
procedure(s) involved in the research.  
 
☒ N/A  
4. Describe the process for assent of the research participants. Indicate:  
1. Which subjects that are unable to consent will be required to give assent? If not all, explain why.  
 
2. Describe whether assent of the research participants will be documented and the process to document 
assent.  
 
☐ The subject will be informed about the research to the extent compatible with the subject’s understanding.  
☐ Subjects will be closely monitored.  
☐ The subject will be withdrawn if they appear unduly distressed.  
Research Participants Who Are Not Yet Adults (infants, children, teenagers)  
☒ I am not enrolling participants who are not yet adults in this research study. – please leave the rest of this 
section blank  
1. Will parental permission be obtained from:  
Page 10 of 29 
 
 
 
 
 
 
 
 
 
 

 
 
 
One parent even if the other parent is alive, known, competent, reasonably available, and shares legal 
responsibility for the care and custody of the child  
☐ Both parents unless one parent is deceased, unknown, incompetent, or not reasonably available, or when 
only one parent has legal responsibility for the care and custody of the child  
☐ Requesting a waiver of parental permission  
If you are getting parental/guardian permission:  
1. Indicate how you will be documenting the permission:  
 
☐ Signed consent form  
☐ Requesting a waiver of documentation of parental permission  
2. Describe whether permission will be obtained from individuals other than parents, and if so, who will be 
allowed to provide permission. Describe the process used to determine these individuals’ authority to consent 
to each child’s participation in research.  
 
If a waiver of parental permission is being requested:  
1. Describe how the study is designed for a subject population for which parental/guardian permission is not a 
reasonable requirement to protect the subjects, if applicable.  
 
2. Describe how the research could not practicably be carried out without the waiver of parental permission.  
 
a. Indicate if the subjects will be provided with additional information about the study after participation.  
 
3. Will assent be obtained from:  
 
☐ all of the children  
☐ some of the children  
☐ none of the children  
If assent will be obtained from some children, indicate which children will be required to assent.  
When assent of children is obtained, describe how it will be documented.  
4. For children who are pregnant, describe how assent and permission are obtained.  
 
☐ N/A  
Sharing of Results with Research Participants  
Results will be shared with research participants:  
☒ Yes ☐ No 
Page 11 of 29 
 
 
 
 
 
 
 
 
 
If yes, describe how the results will be shared.  
Study participants will receive a one-page summary of the results by mail or email based on contact 
preference.  
Results will be shared with others:  

☒ Yes ☐ No  
If yes, describe with whom and how the results will be shared.  
Results of the study will be shared with others through manuscripts and presentations.  
Study Design/Procedures  
Directions: 1) Describe the overall study design. 2) Provide a description of all study-related research 
procedures being performed, including the length of time involved. 3) Include procedures being 
performed to monitor research participants for safety or minimize risks. 4) Describe the source records 
including medical or educational records, which will be used to collect data about subjects.  
The study is a four-year randomized controlled trial in Northeastern Ohio and includes a convenience sample 
of family caregivers of adults with bipolar disorder. After eligibility is verified during phone screening by 
team member, the consent forms will be reviewed verbally, questions about the study will be answered, and 
the study enrollment/first data collection appointment will be made.  
There are three structured data collection time points (T1/enrollment, T2/ 6months after initiation of 
intervention, T3/ 12 months after initiation of intervention); these will be face-to-face with a research 
assistant, using a desktop, laptop, or iPad with secure REDCap software. During the enrollment and first 
data collection meeting, we will obtain informed consent from the caregiver. Caregivers will have time to ask 
questions about the study and review the consent form before signing it.  
COVID-19 Modifications: Some T2 and T3 data collection will take place remotely, as a response to the 
COVID-19 pandemic (beginning in April 2020). We will use phone (Google voice) or Zoom (computer video) to 
complete the data collection. An email will be sent, if possible, to participants with the answer response 
choices for each survey. If we are using phone for data collection, the Research Assistant (RA) will ask the 
participant each question and record the responses in our REDCap Surveys project. If collecting data using 
Zoom video, the RA will share the screen of the REDCap Surveys project, and record the answers for the 
participant as they review each survey question. If neither of those two options are available for the 
participant (e.g., limited phone minutes, inability to use Zoom), the study may email the REDCap surveys to 
study participants for them to complete on their own at an agreed upon date / time (similar to in-person 
appointment); in this instance, the RA can be available to answer questions or clarify information as needed, 
by phone or email. It may be that none of these options will work for a study participant, in which case we 
will consider that data “missed” if we cannot wait to collect the data in person at a later date (when we 
resume normal study activities). The precise method(s) will depend on the ability and resources of the study 
participant. For these data collection sessions, HRV data (collected by placing electrodes on the wrists) may 
not be collected and will be considered missing data (see following page for more detail regarding remote 
HRV data collection). We will contact active participants with Zoom/ phone instructions, by phone/text 
and/or email, as needed, and we will record the methods used 
 
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for each data collection done remotely. A COVID-19 questionnaire will be asked at remaining T2 and T3 
data collections; script to obtain consent for these questions is included in the questionnaire.  
Individuals will be assigned a study ID using our enrollment log. In addition, at enrollment we will collect 
demographic information including age, gender, race, ethnicity, marital status, education, income, 
occupation, hours of work/week, if the participant is an employee or student at CWRU, health conditions, 
current medications, relation to person with bipolar, age of family member with bipolar, how many years ago 
was family member diagnosed with bipolar disorder, specific diagnosis of family member, predominant 
behavior style of family member with bipolar, whether or not caregiver lives with this family member, 
whether or not caregiver provides care/assists with basic needs (and how many hrs/day), how many years 
caregiver has been providing care, if other adults help provide care for family member with bipolar disorder. 
Some, but not all of the demographic and other questions asked at baseline will also be asked at T2 and T3.  
We will then proceed with data collection, consisting of surveys to measure bipolar symptoms, caregiver 
reactions, caregiving involvement, bipolar knowledge, resourcefulness, health risks, and health outcomes. 
They will also have their heart rate variability (HRV) measured using a non-invasive device on the wrists; it 

will take approximately 10 minutes to collect the data. The entire first meeting will take approximately 60-90 
minutes. The second and third data collection meeting will be approximately 60 minutes. In the event there is 
an equipment malfunction or a poor reading is obtained by a research team member, we may need to re-
collect the HRV and/or survey data again after a data collection meeting. COVID-19 modification: HRV 
data will may not be collected when data collection is done remotely (T2 or T3 only) and will be considered 
missing data. When we are able to collect HRV data, we will do so by bringing an HRV device to the study 
participant at a set date and time, providing instructions on how to use the HRV device, safety information on 
the HRV device, and also providing support via phone or video. HRV data collected this way will be collected 
for 15-20 minutes instead of 10 minutes, to ensure reliable data is collected. A study team member will collect 
the HRV device the same day or within 28 hours, at a mutually convenient time. Each HRV device will be 
sanitized before and after each study participants’ use.  
Following the T1 data collection, the project manager will randomize each caregiver into one of four groups 
using Qminim, a secure online minimization program. Research assistants will be blinded as to which 
intervention arm caregivers are assigned to. The four groups are: 1) control group- no intervention; 2) usual 
care group- will receive bipolar education; 3) Self-management (SM)- need based, determined by baseline cut 
scores from T1- either bipolar education (ED), biofeedback (BF), resourcefulness training (RT), or no need; 
4) SM-preference-based, caregiver selects intervention (ED, BF, RT, or no intervention). For SM-need, for 
example, caregivers scoring <70% on bipolar knowledge would be assigned to ED, < 97 on the 
resourcefulness scale to RT, and low HRV as determined by SDNN parameter for age and gender to BF.  
Those in the SM-need and SM-preference groups will perform one SM intervention (as listed above). Those in 
the usual care group will receive the same bipolar educational intervention as others in the SM-need or SM-
preference groups. All interventions will take 4 weeks and these 4 weeks will occur between the T1 and T2 
data collections; the T2 data collection is planned to occur 6 months after the initiation of the intervention. 
The T3 data 
 
 
Page 13 of 29 
 
 
 
 
we are excluding pregnant women from joining the study (due to the variance in HRV data which would affect 
scoring for minimization), if someone becomes pregnant while they are enrolled in the study, we will not 
exclude them from the remainder of the study.  
Caregivers in the control group will receive a phone call (or email/text depending on their preferred method 
of contact) letting them know of their assignment; they will also have access to three interventions at the end 
of the study. Caregivers in the usual care, SM-need and SM-preference groups will receive training by a 
trained interventionist, which consists of a single face-to-face session in the caregiver’s home/private venue. 
The session includes training/education via a voice-over PowerPoint presentation on iPad or laptop, and 
print materials to keep/review regarding the intervention. Other commonalities during the single session for 
ED, RT and BF are: 1) all caregivers will keep a structured journal, though the content will differ by 
intervention; journals will be collected after 4 weeks/ 28 days; 2) all will be taught to indicate day and time of 
the journal entry with the suggestion to do it at the same time each day; and 3) all will have the opportunity to 
complete a journal entry during the training session. During the 28-days after the initial session, all 
caregivers will: 1)perform the assigned intervention independently; 2) have print access to intervention 
content for review as they wish; 3) receive weekly follow-up from interventionists (3-5 minute phone call or 
email).  
The ED and RT interventions involve providing educational information about bipolar disorder or teaching 
self-help (stress management, problem-solving) and help-seeking skills, respectively. BF training consists of 
the use of a hand-held device that shows the participant their changes in heart rate based on changes in their 
breathing patterns (as they relax); caregivers who need or prefer the biofeedback will be given a device to 
use for the study (for 28 days). Caregivers may use their intervention whenever and as often as they wish (i.e. 
self-tailoring). Dosing (number of times intervention is performed) and fidelity (using checklists) will be 
monitored. After 28 days, we will collect the BF hand-held devices and journals from all three interventions. 

Individuals will be encouraged to continue with the interventions if they found them helpful (for BF, 
caregivers will have been given information on deep-breathing techniques without using a device).  
Caregivers who cannot be reached by phone or email for follow-up (either intervention or data collection) 
will have a letter sent to them if they have consented to having a letter sent to their home. Occasionally, calls 
will need to be made to study participants outside of the office (e.g., evenings/ weekends; when a research 
team member is working remotely/ in the field) or participants will request to be contacted by text. In these 
instances, the research team will use Google Voice, which allows users (research team) to set up a phone 
number through their CWRU email and is connected to their personal mobile phones. Calls and texts can be 
made to/ from the mobile phones while masking the actual phone number. When the research team is not 
working, calls will be directed to voicemail.  
From Modification #8 (approved 03/06/2019)-- At the end of the T3 data collection, study participants will 
receive a brochure from each of the three interventions being researched, as well as an answer sheet for 
Caregiver Knowledge of Bipolar Disorder Questionnaire. Study participants who received an intervention will 
be asked a series of questions (up to 16) about their experience with, and opinion of, the intervention they 
received. Study participants who have already completed all three data collection sessions and have already 
agreed to be contacted for any questionnaire follow-up will be called and asked questions over the phone. 
 
 
Page 14 of 29 
 
 
The supplemental analysis will use baseline data (T1) to explore relationships among caregiver 
characteristics (race and gender), psychological stress (caregiver reactions and caregiving involvement), and 
physiological stress (heart rate variability time and frequency domains). De-identified baseline data from the 
demographic measures, psychosocial measures (caregiver reactions, caregiver involvement) and the HRV 
measurements will be used for this analysis.  
Study Timeline (optional)  
ClinicalTrials.gov Information  
Directions: If this study has been registered on ClinicalTrials.gov, provide the ClinicalTrials.gov 
identifier and the investigator/sponsor responsible for registering. If this study has not been registered 
on ClinicalTrials.gov, provide the rationale as to why and if/when it will be. If it does not meet the 
requirement for being registered on ClinicalTrials.gov, please state that.  
NCT03023332  
List of Data to be Collected  
• Indicate what identifiers you will collect  
 
☒ Name  
☒ Address (e.g., Zip code, other geographical designation, etc.)  
☐ Dates related to an individual (e.g., Date of admission, birth, surgery, etc.)  
☒ Telephone number  
☐ Fax number  
☒ Email address  
☐ Social security number  
☐ Medical record number  
☐ Health plan beneficiary number  
☐ Account number  
☐ Certificate/license number  
☐ Any vehicle or other device serial 
 
 
Page 15 of 29 

☐ Device identifiers or serial numbers  
☐ Web URL  
☐ Internet protocol (IP) address  
☐ Finger or voice prints (includes audio recordings)  
☐ Photographic images (includes video recordings)  
☒ Other: Any characteristic that would uniquely identify the individual  
If other, please explain:  
Heart rate variability requires non-invasive electrocardiography  
1. List all other data to be collected for the research study. Attach all data collection tools on the Local Site 
Documents page of the SpartaIRB smart form (Other Attachments).  
• Questionnaires to measure bipolar symptoms, caregiver reactions, caregiving involvement, bipolar 
knowledge, resourcefulness, health risks, and health outcomes. (Listed under site related documents as 
‘questionnaires.pdf’)  
• Intervention evaluation questionnaire  
 
(Listed under site related documents as ‘script intervention eval questionnaire.pdf’)  
• Intervention journals  
 
(Listed under site related documents as ‘resourcefulness sample journal page.pdf’, ‘biofeedback sample 
journal page.pdf’, ‘bipolar education sample journal page.pdf’)  
• COVID-19 questions at remaining data collection sessions (consent included with questionnaire)  
 
Data Analysis Plan  
Directions: Describe the data analysis plan, including any statistical procedures. If applicable, provide 
a power analysis, and study/safety endpoints.  
The primary aim (A1) is to examine differences across four groups of family caregivers on caregiver health 
over time. The underlying analyses for A1 are built around the repeated measures analysis of variance 
(RMANOVA). The primary analysis will be a set of 4 group X 3 time waves RMANOVA. These analyses will 
compare the four groups: 1) a control group (no intervention); 2) education (usual care); 3) SM-need; or 4) 
SM-preference across three time waves of health risks and physical and mental health outcomes. When using 
RMANOVA, one not only assesses mean differences across time, but also assesses group differences and the 
interaction of time X group, which allow us to test the trend of the means over time across the four groups. 
The RMANOVA, not only can be used to determine if there are mean differences across the three time 
periods, it can utilize orthogonal polynomial contrasts to determine if there are mean and quadratic trends of 
the means across time. Orthogonal polynomials are weights assigned to each time period that model a linear 
or quadratic non-linear trend. RMANOVA can determine if these trends in the mean are significant. A linear 
trend is indicated if there is a change in direction based on scores across the tome waves. The major 
assumption to be tested with RMANOVA is sphericity. Sphericity is a form of compound symmetry and refers 
to the equality of variances of the differences between time waves. If the assumption of sphericity is violated 
based on the Mauchly’s test, SPSS provides and adjusted F, df, and P-value in RMANOVA to account for the 
violation.  
Secondary aims are to: A2) explore whether caregiver need or their preference for interventions associated 
with: a) care recipient’s symptoms; b) caregiver reactions; and c) 
 
 
 
 
 
 
 
 
Page 16 of 29 

caregiving involvement; and A3) build caregiver profiles from demographic/contextual factors that are 
associated with their needs and preferences for the self-management interventions. Accordingly, A2 will be 
tested with a series of bivariate analyses including correlations, one way analyses of variance (ANOVA) and 
independent samples t-tests. We will run correlations when both variables are continuous. If the independent 
predictor variable is categorical and the dependent outcome is continuous, we will run an ANOVA. When the 
independent variable is dichotomous and the outcome is continuous, an independent samples t-test will be 
run. A3 will build profiles 8 groups from two of the study arms: 1) SM-need and 2) SM-preference. To identify 
the unique characteristics of each group. Univariate descriptive statistics will be run on the contextual 
variables within the caregiver, care recipient, and caregiving situation. We will also examine cut points from 
measures of the self-management processes (knowledge, resourcefulness, and heart rate variability). These 
analyses will build profiles to show which caregivers may benefit most from a specific self-management 
intervention. We will prescreen for potential violations of assumptions for correlations. Scatter plots between 
two variables will identify influential cases, patterns of nonlinearity and constant-error variance that may 
reduce Parson’s r. To address potential violation of the assumptions, influential cases can be removed. Data 
transformations can be used to remedy issues such as non-linearity, non-constant error variance, and non-
normal error variance. For ANOVAs and t-tests, assumptions of normality and homogeneity of variance will 
be tested. Non-parametric equivalence tests will be used if assumptions are violated.  
For the supplemental analysis, VivoSense software will be used to perform automatic cleaning and 
computation of heart rate variability measures (SDNN, RMSSD, TP, VLF, LF, HF, LF/HF). Data analysis 
will consist of descriptive and inferential statistics using SPSS. Description of the sample will include age, 
gender, race/ethnicity, marital status, education level, annual income, and caregiver relationship. 
Additionally, descriptive statistics will be calculated for the study measures.  
The aims for the supplemental analysis are to: SA1) determine whether there are differences by caregiver 
characteristics (race and gender) on measures of psychological stress responses (caregiving involvement and 
caregiver reactions), SA2) determine whether there are differences by caregiver characteristics (race and 
gender) on measures of physiological stress responses (heart rate variability domains), SA3) examine 
associations among indicators of psychological stress responses (caregiver reactions and caregiving 
involvement) and physiological stress responses (heart rate variability domains, and SA4) explore 
relationships among time and frequency domains of heart rate variability. SA1 and SA2 will be tested with a 
series of independent samples t-tests. SA3 and SA4 will be tested with a series of bivariate correlations. 
Potential violations of assumptions for correlations and t-test will be assessed. To address violations of the 
assumptions for correlation, influential cases may be removed. Data transformations may be used to remedy 
issues such as non-linearity, non-constant error variance, and non-normal error variance. To address 
violations of the assumptions for t-test, non-parametric equivalence tests will be used if assumptions are 
violated.  
Confidentiality of Data  
1. To maintain the confidentiality of the data: ☒ I will use a unique study identifier to code individuals’ 
identifiable data and will store the master list separate from the study data..  
 
Page 17 of 29 
 
 
 
 
 
 
 
 
 
 

HRP-  
☐ Other (please explain)  
Provide a plan to destroy identifiers including how and when.  
2. How are you storing your electronic data? ☐ UH Redcap ☒ 
CWRU Redcap ☐ Secure Research Environment (SRE) ☒ 
CWRU Box ☐ OnCore ☐ UH Secure Network Drive ☒ 
CWRU Secure Network Drive ☐ Other - List storage method 
and provide justification:  
3. Storage location of the paper research data and documents, if 
applicable:  
 
☒ Paper research data and documents will be stored in a 
double-locked secure environment in the following location:  
France Payne Bolton School of Nursing study office  
4. Will data be shared?  
 
☐ Yes  
1. List the exact data elements that will be shared:  
2. Describe how data will be sent:  
 
☒ No  
☐ N/A  
(Please note: if sharing data, please contact the UH Grants and 
Contracts Specialist or CWRU Tech Transfer Office to ensure 
the proper contracts/agreements are in place.)  
 
HIPAA Authorization  
Does this study collect, access, use, or distribute any Protected 
Health Information (PHI)?  
☒ Yes ☐ No  
If yes, indicate how HIPAA authorization will be obtained 
(check all that apply):  
☒ HIPAA authorization is in the consent form  
☐ Requesting a full or partial waiver of HIPAA for prescreening  
☐ I will complete the Request for Waiver of HIPAA 
Authorization form. See SpartaIRB Library  
☐ Requesting a full or partial waiver of HIPAA  
☐ I will complete the Request for Waiver of HIPAA 
Authorization form. See SpartaIRB Library  
Devices 
 
 
 
 
 
 
Page 18 of 29 
 
 
 
 
 
 
 
 

☒ This is not device study. The protocol is considered non-therapeutic (non-therapeutic is defined 
as research not intended to diagnose, prevent, cure, mitigate, treat, etc. a disease or condition) by the 
FDA. – You may delete the rest of this section.  
OR  
☐ This is a device study. The protocol is considered therapeutic (research intended to diagnose, 
prevent, cure, mitigate, treat a disease or condition) by the FDA.  
1. Is there an IDE (Investigational Device Exemption) for the proposed study?  
 
☐ Yes, provide an official letter of support or proof of approval which identifies the IDE holder and 
IDE number.  
☐ No  
2. Is the device (and its use) a non-significant risk device for the proposed study design?  
 
☐ Yes  
☐ No  
☒ N/A  
3. If the research involves device(s), describe your plans to use, store, handle, administer and track 
those device(s) to ensure that they will be used only on research participants and be used only by 
authorized investigators.  
 
Risks to Research Participants  
1. List the reasonably foreseeable risks such as breach of confidentiality, discomforts, hazards, or 
inconveniences to the research participants related to their participation in the research. Include a 
description of the probability, magnitude, duration, and reversibility of the risks. Include the physical 
psychological, social, legal, and economic risks.  
 
No physical, psychological, social, legal, or economic risks other than associated with daily living, 
are expected for the caregiver who participates in this study. Thus, the risks for emotional/physical 
distress should be minimal. Several measures will be taken to minimize the potential risk for distress 
while completing study questionnaires, HRV measurement, or during the interventions that involve 
journaling about the use of education, resourcefulness skills or breathing techniques, or use of the 
biofeedback device. If a caregiver becomes upset during a data collection interview or intervention 
meeting or phone call/email/text, the team member will offer to end it immediately, provide 
emotional support and/or make a referral to a mental health professional as needed. It is possible 
that discussion of stresses related to having a family member with bipolar disorder may stimulate 
emotional responses in the caregiver during the 4 week interventions. All weekly phone 
call/email/text field notes will be stored in REDCap. In addition, there will be ongoing supervision by 
the intervention supervisor (Suresky), who is an experienced, doctorally-prepared, advanced practice 
psychiatric nurse. The data collectors and interventionists will report adverse effects to Dr. Suresky 
and PI Zauszniewski as soon as discovered. 
 
 
 
Page 19 of 29 
 
 
 
 

In regard to the use of the HRV measuring instrument, there have been no reported safety risk with 
the use of this instrument thought participants may fear it. It has passed electromagnetic interference 
and compatibility tests. Thus, there is no danger of electric shock from use of the device. We let the 
individual know that the device is for research purposes only and not meant to be diagnostic, the 
data obtained from the device will record heart rhythm but will not give information about 
treatments needed for heart health. If the individual would like more information about heart health 
or risk, they will be encouraged to talk to their doctor.  
2. If applicable, indicate which experimental procedures may have risks to the research participants 
that are currently unforeseeable.  
 
☒ N/A  
3. If applicable, describe the risks to others who are not research participants.  
 
☒ N/A  
4. Describe the availability of medical or psychological resources that research participants might 
need.  
 
☒ N/A  
Provisions to Protect the Privacy Interests of Research Participants  
Directions: Describe the steps that will be taken to protect research participants’ privacy 
interests. (consider issues such as physical space, proximity to other, and participant 
preferences)  
After eligibility is verified during phone screening by a team member, we will confirm with all study 
participants whether or not we can leave a voicemail message on their phone(s), and whether or not 
we can send mail to their home (in the event we cannot reach them by phone, and/or if they are 
randomized to the control group). We will ask if there are any disclosure concerns and make note if 
applicable in REDCap contact form. We will also ask study participants if they would like to be 
contacted for future research; we let them know there is no penalty to them if they do not wish to be 
contacted. Furthermore, we inform them that agreeing to be contacted does not obligate them to 
participate in future research, this only permits us to contact them. We will maintain a password-
protected list on Box.com of individuals that have consented to be contacted for future research, 
along with their contact information and contact preferences. This list will be maintained by the 
Project Manager and may be shared with research team members, Co-Investigators, and/or other 
CWRU CREC-certified administrators on a case-by-case basis.  
Privacy language is included in the informed consent form. Participants have the option of 
withdrawing from the study at any time and can request that no further information be shared about 
them from that point on. Participant names will not be shared in any report of the finding or with 
other study participants. Data collection interviews and intervention sessions will be conducted in a 
private setting (i.e. participant’s home or other venue where others, including the persons with 
bipolar disorder, will not be present).  
Confidentiality will be assured during all phases of the project by the following procedures. 
Screening and Study ID numbers will be used for all caregivers. A list of screening and study ID 
numbers with identifying names, phone numbers, and addresses will be kept locked in password-
protected files in Box.com and REDCap. The survey data will be kept in a separate 
 
 
Page 20 of 29 
 

file from the data collected during the study and will only be accessible to the PI and research staff 
that need access to assure accurate follow-up in this longitudinal study. This identifiable information 
will be destroyed after all data have been collected.  
Confidentiality issues will be addressed during training of research staff that will do the data 
collection and the interventionists. All data collected throughout the study, including signed consent 
forms, quantitative data using the REDCap system, HRV parameters, journals, emails, and field 
notes maintained by research assistants and interventionists will be stored in locked files and 
password protected computer databases only accessible to the PI, Co-I's, project manager, and 
research staff. These data will not include any identifiable information that may have been obtained 
during recruitment and screening. These measures have been used successfully to protect the rights 
of human subjects in our previous studies. In addition, we will implement the following specific 
strategies to protect data obtained from the journals or emails used by the caregivers.  
1) Structured journal – caregivers receiving an intervention will be provided with a structured 
journal for their use during the four weeks between the first (T1) and second (T2) data collection 
interviews. They will be instructed to store the journal in a private place (known only to them) in 
their home during the four weeks. They will be directed to not use real names of friends, relatives, 
etc. within the journal entries; they may use alternative names if they wish. Interventionists will 
review the journals immediately upon retrieval (after the 28 day period) and if names are found, they 
will be blackened out and not appear within the transcribed text data files. The journals will be 
stored in a locked cabinet in the research office and the text files will be stored in a password 
protected computer database. Both the journal and text files will be kept for a period not to exceed 3 
years. 2) Email - Individuals may use email to get more information about the study, and/or to 
contact staff once enrolled in the study. Email contacts and outcomes will be recorded generally on 
our contact forms, which use Study ID number and not names. If an email needs to be printed or 
otherwise saved, it will be securely downloaded to a PDF file, with names and other contact 
information redacted, and delete the original email message. The PDF file will be stored in the 
password protected computer file for a period not to exceed 3 years.  
Potential Benefit to Research Participants  
☐ There is potential benefit to research participants.  
Describe the potential benefits that individual research participants may experience from taking part 
in the research. Include the probability, magnitude, and duration of the potential benefits.  
☒ There is no direct benefit to research participants.  
If no direct benefit, state the potential benefit to society or others. Do not list compensation.  
Withdrawal of Research Participants 
 
Page 21 of 29 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Directions: Describe the anticipated circumstances under which research participants will be 
withdrawn from the research without their consent. Also include the procedures that will be 
followed when a research participant withdraws or are withdrawn from the research, including 
partial withdrawal from procedures with continued data collection.  
☐ N/A  
Participants have the option of withdrawing from the study at any time and can request that no 
further information be shared about them from that point on. If a study participant withdraws 
consent to participate in the study, a research team member will notify the project manager to 
complete end of study documentation.  
The project manager will review cases regularly with research staff to determine which study 
participants should be withdrawn from the study. Research participants will be withdrawn from the 
research without their consent if they are non-responsive to phone calls, emails, texts, or letters and 
considered lost to follow up.  
Data that were collected prior to a study participant’s withdrawal will be de-identified and still be 
used in the data analysis for the study. After withdrawal, no further data will be collected for that 
participant.  
Alternatives to Participation  
Directions: List other options to participation. If subjects will be compensated with extra 
course credit, the course instructor offering extra course credit must provide alternatives to 
earn extra course credit. The alternative assignment must require equal or less time and effort 
for the same amount of earned extra credit that you can earn through participation in 
research. If there are other available clinical treatments, what would be included if a subject 
continued on standard of care therapy. If there is a viable alternative you must list it in the 
consent.  
☒ The alternative is for research subjects not to participate.  
Costs to Research Participants  
☒ There are no costs to research participants or their insurance companies (there are no clinical visits 
or billable procedures.) – You may delete the rest of the section.  
1. Describe what costs research participants will be responsible for as a result of their participation in 
the research, including but not limited to: clinical services required by the protocol deemed billable 
to insurance, transportation to study visits, parking, costs of drugs, cost of therapy, lost broken or 
stolen devices, etc.  
2. Explain who will be responsible for payment of provided services in the event of insurance 
denials.  
3. List what procedures, drugs, devices, supplies will be paid by the study sponsor or covered by 
other funding. List the other funding source.  
Research Participant Compensation  
☐ There is no compensation for research participants – please leave rest of this section blank  
☒ There is compensation for research participants. 
 
 
 
Page 22 of 29 
 
 

Describe the schedule, payment method, and payment total of any incentives or compensation that 
research participants will receive for participation in the research (e.g., gift cards or cash with 
amount, t-shirts, devices, bags, swag, etc.)  
Incentive will be provided as follows: completion of entire data collection at T1 (enrollment): $20; 
T2 (6 months post intervention or from the date of enrollment if randomized to the control group): 
$25; and T3 (6 months after second data collection): $30 for a maximum total of $75.  
COVID-19 modification: For T2 and T3 data collected remotely, study participants will receive a 
gift card mailed to them. The study will have 1-3 gift card vendor options to choose from/ the amount 
of the gift card will be $25 for T2 and $30 for T3.  
☒ There will be reimbursement for research participants.  
Describe the schedule, payment method, and payment total of any reimbursement that research 
participants will receive for participation in the research (e.g., gift cards or cash with amount, etc.)  
If someone takes a bus or drives to CWRU or other community location to meet a research team 
member for T1, T2, T3, or an intervention meeting, we will reimburse that individual a 2-trip bus 
pass or parking voucher as appropriate.  
Compensation for Research Related Injury  
Describe who will pay for the costs of medical treatment and/or compensation in the event of a 
research related injury:  
☐ Funding agency is providing some/all payment for injury  
☐ Funding agency is providing no payment for injury  
☒ N/A  
Provisions to Monitor the Data to Ensure the Safety of Research Participants  
1. Describe how often the data will be monitored for completeness, accuracy and adherence to the 
protocol.  
 
2. Indicate if there will be a Data and Safety Monitoring Board or Committee:  
 
☐ There will not be a formal Data and Safety Monitoring Board/Committee.  
☒ There will be a formal Data and Safety Monitoring Board/Committee.  
Provide information about the DSMB/C including the contact information of the committee 
member(s) (as applicable); whether it is independent from the study sponsor; how often it meets; the 
type of data that will be used; written reports, etc.  
A Safety Monitoring Committee (SMC) has been formed as the monitoring entity for this grant. The 
SMC is independent from the study sponsor and consists of:  
• Dr. Ronald Hickman , SMC chair, who serves as the Associate Dean for Research and is Associate 
Professor, Frances Payne Bolton School of Nursing, CWRU  
 
Rlh4@case.edu 
 
 
 
 
 
 
 
Page 23 of 29 
 

 
Dr. Sara Douglas, Assistant Dean for Research, and Professor, Frances Payne Bolton School of 
Nursing, CWRU  
Sld4@case.edu  
• Dr. Joseph Calabrese, Professor of Psychiatry from the CWRU School of Medicine, who has 
studied persons with bipolar disorder for more than three decades  
 
Joseph.calabrese@UHhospitals.org  
• Study team members will include Dr. Jaclene A. Zauszniewski, PI, and Dr. Christopher J. Burant, 
statistician cxb43@case.edu  
 
1. Monitoring Study Safety  
a) Monitoring schedule - Twice per year throughout the project, the SMC will review data on the 
study regarding study safety. For example, the SMC will review any occurrences of caregiver 
emotional distress that required intervention by data collector or interventionist as well as those 
requiring referral and follow-up and instances where caregivers withdrew from the study.  
b) Audits for compliance with IRB requirements – Random internal audits of 10% of the files will be 
done twice annually to insure the approved IRB protocol is being followed. The SMC will review 
recruitment procedures, compliance with meeting the inclusion/exclusion criteria, consistency with 
random assignment process to the treatment conditions, provision of interventions within timeframe 
defined within the protocol, and scheduling of data collection sessions as outlined within the 
protocol.  
c) Conformance with informed consent requirements – Random internal audits will be conducted 
twice per year to verify that informed consent requirements are being met. For example, the SMC 
will review 10% of the consent forms for signatures and dates, make sure all consent forms are 
accounted for and stored in locked files and that the correct form is being used. Data collectors will 
be asked to describe the consent process quarterly to re-assess their knowledge of this process 
quarterly and review / retraining will be done as needed.  
d) Verification of source documents – This study does not involve printed or written documents; data 
will be collected through electronic data capture using REDcap software and then downloaded 
directly into SPSSPC files. Heart rate variability data will be downloaded from the assessment 
device and transcribed into the SPSSPC files. These sources will not include any data that would be 
personally identifiable.  
The SMC will review 1) all causes of mortality (e.g., caregiver death); 2) issues with participation 
(e.g., numbers and reasons for withdrawing from the study or refusing interventions, etc.) as well as 
recruitment refusal (percent and reasons) and subject attrition (percent and reasons); 3) missing 
data (including whether there are systematic patterns or whether data are missing at random); and 
4) errors in data entry (which are expected to be minimal given the use of software for data 
collection with direct download into SPSS). In addition, differential attrition from the intervention 
groups (including the control and usual care groups, and the groups assigned to intervention based 
on need or personal preferences) will be monitored. 
 
Page 24 of 29 
 
 
 
 
 
 

 
Page 25 of 29  
If concerns or problems are identified by the SMC, they will be reported to the IRB and NINR/NIH 
via email by Dr. Zauszniewski and Dr. Hickman, respectively, within 3 business days after they are 
identified. If there are recommendations made by the SMC, the action plan for response or notice of 
any actions taken by the IRB regarding the research and any responses to those actions will be 
provided to NINR Officials within 2 weeks.  
e) Investigator compliance – Compliance of the investigators and all research team members who 
will have access to the data will be monitored annually. All research team members will be CREC 
certified; the CWRU intranet hosts a website where verification of compliance with continuing 
education for all investigators and team members can be evaluated.  
2.) Reviewing and Reporting Adverse Events/unanticipated problems  
a) Event identification- At the onset and for the duration of the study, all research staff and 
investigators will have instructional review of the nature and types of unanticipated and adverse 
events as described by the CWRU IRB. Potential risks for this study may include caregiver distress 
and breach of confidentiality (as described above). Caregiver distress may be identified by the data 
collector (during data collection) or the interventionist (during the interventions or phone follow-up). 
Breach of confidentiality may be identified by any research team member.  
b) Reviewing and reporting- As they occur, all unanticipated events and adverse events will 
immediately be reported to Dr. Zauszniewski (PI) who will report them to the IRB according the 
CWRU IRB protocol reporting procedures for both serious and non-serious adverse events and 
unanticipated problem reporting. These will be summarized in the semi-annual reports to the SMC. 
Annual progress reports to the CWRU IRB and NINR/NIH will include a summary of the SMC’s 
activities and findings as well as any adverse events regarding human subjects. Program Officials at 
NINR will be informed in a timely manner (3 business days) of unanticipated problems (e.g., a data 
breach) or unexpected serious adverse events that may be related to the study protocol or IRB-
approved revisions to the study protocol that indicate a change in risk for participants. All adverse 
events and protocol deviations will be reviewed with the staff involved within 3 business days. 
Factors leading up to the event or deviation will be discussed and strategies for preventing 
recurrence will be developed and implemented immediately.  
Community-Based Participatory Research  
☒ This is not a community-based participatory research project – please leave the rest of this section 
blank  
☐ This is a community-based participatory research project  
Describe the involvement of the community in the design and conduct of the research. 
 
 
 
 
 
 
 
 
 
Page 25 of 29 
 
 
 

Note: Community based research is research that is conducted as an equal partnership between 
academic investigators and members of a community. In Community Based Participatory Research 
(CBPR) projects, the community participates fully in all aspects of the research process.  
MULTI-SITE RESEARCH (when UH or CWRU is the IRB of Record)  
Does this project have multiple sites?  
☐ Yes  
☒ No – please leave the rest of this section blank  
Non-Local Site Information for Multi-Site Studies  
If this is a multi-site study where you are the lead investigator, list the following information for each 
relying site:  
1. Name of site:  
2. PI of relying site:  
3. Name of IRB contact:  
4. Phone number of IRB contact:  
5. Email address of IRB contact:  
 
Non-Local Recruitment Methods for Multi-Site Studies  
If this is a multi-site study and research participants will be recruited by methods not under the 
control of the local site (e.g. call centers, national advertisements) describe those methods. Local 
recruitment methods are described above.  
1. Describe when, where, and how potential research participants will be recruited.  
 
2. Describe the methods that will be used to identify potential research participants.  
 
3. Describe the materials that will be used to recruit research participants.  
 
Multi-Site Research Communication Plan (when you are the lead investigator)  
If this is a multi-site study where you are the lead investigator, describe the processes to ensure 
communication among sites including:  
☐ All sites will have the most current version of the protocol, consent document, and HIPAA 
authorization  
☐ All required approvals (initial, continuing review and modifications) have been obtained at each 
site (including approval by the site’s IRB of record)  
☐ All modifications have been communicated to sites, and approved (including approval of the site’s 
IRB of record) before the modification is implemented  
☐ All engaged participating sites will safeguard data, including secure transmission of data, as 
required by local information security policies  
☐ All engaged participating sites will safeguard data, including secure transmission of data, as 
required by local information security policies  
☐ All local site investigators conduct the study in accordance with applicable federal regulations 
and local laws 
 
 
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☐ All non-compliance with the study protocol or applicable requirements will be reported in 
accordance with local policy  
If this is a multi-site study where you are the lead investigator, describe the method for 
communicating to engaged participant sites the following:  
1. Problems:  
2. Interim results:  
3. The closure of the study:  
Additional Information  
If you have any additional information regarding your study not covered in the template, please 
include it here.  
References  
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