Exploring the Impact of Human-Animal Interactions on Children With Life-Threatening Conditions and Their Parents
Phase: NA
Conditions: Advanced Cancer, Relapsed Cancer, Refractory Cancer
Sponsor: Vanderbilt-Ingram Cancer Center

Gilmer, MJ 
R21 Exploring the Impact of Human-Animal Interactions on Children with Life-
Threatening Conditions and their Parents R21HD097757 
Version approved by IRB 11-18-2019          NCT04310345

R21 Exploring the Impact of Human-Animal Interactions on 
Gilmer, MJ 
Children with Life-Threatening Conditions and their Parents 
R21HD097757 
Version approved by IRB 11-18-2019 
 
 
 
Overview of the study. We will determine the effects of HAI on reducing anxiety, depression, worry, and pain 
and enhancing QoL in children (n=30) (ages 8-17 years) with a LTC and their parent caregivers (n = 30-60). 
Human-animal interactions will involve visits from a registered canine team for 10-15 minutes during each 
child’s potentially anxiety-producing appointments at the clinic or hospital. These appointments occur 
approximately once/week: Children and parent dyads will receive HAI intervention and complete measures of 
anxiety, depression, worry, pain and QoL at baseline, 4 weeks and at the end of the study (8 weeks). 
 
Eligibility Criteria and Recruitment. Our sample target is 30 children diagnosed with advanced cancer and 
their parents/guardians. We will oversample to conservatively accommodate a drop-out of up to 35%, thus 
our accrual target sample is 48 children and parent/guardian pairs. Inclusion criteria for children are: 1)  ages 
of 8-17 years, 2) diagnosed with advanced cancer as defined by any stage of relapsed, recurrent or refractory 
cancer as indicated by healthcare team and 3) able to understand English or Spanish to complete consents 
and surveys. Inclusion criteria for caregivers are: 1) parent or guardian as determined by person who brings 
child to >50% of their clinic  visits, and 2) able to understand English or Spanish to complete consents and 
surveys. Inclusion criteria for animal therapy teams are: 1) registered Pet Partners or other nationally 
recognized agency team, 2) owner able to speak and understand English or Spanish, 3) owner who has 
successfully completed volunteer training at Vanderbilt University Medical Center. 
Exclusion criteria for both  children and caregiver include a self-reported fear of or allergies to canines or 
cognitive impairment as identified by healthcare team or inability to complete consenting process. Recruitment 
and enrollment for this study will occur over 18 months. In collaboration with each child’s nurse  practitioner or 
physician, our team will determine families eligible for the study.  Final decisions regarding  screening and 
inclusion will be determined by the PI. Approximately 200 children 8-17 years are diagnosed with  cancer at 
MCJCHV each year and about 40 have advanced cancer. In our past study with children diagnosed with 
cancer, only 2 families (3.5%) of 58 families approached declined to participate with no attrition.  We anticipate 
refusals and attrition may be higher with this population, so are very conservative in our estimates (Table 1). 
Table 1. Estimates of Children Meeting Inclusion Criteria and Recruitment Rates 
 
Children Ages 8-17 Years with Advanced Cancer at MCJCHV Total Per Year 
Total 18 Months 
Number of eligible participants per year 
32 
48 
T1: Accrual (96% in previous studies, conservative estimate for this 
population is 85%) 
27 
40 
End of Study: Retention (95% in previous studies, but conservative 
estimate for this population is 75%) 
20 
30 
 
Setting. All study activities including procedures and data collection will take place in the treatment room in the 
hematology/oncology clinic or a private room at MCJCHV and will occur approximately weekly.  Sessions will 
coincide with children and families’ scheduled medical appointments or inpatient hospitalizations. 
Procedures. After potential participant families are identified and screened for inclusion/exclusion criteria, the 
PI or project coordinator will meet with the primary caregiver, introduce the study, and review the IRB- 
approved consent. If the parent/guardian agrees, the child will be approached for assent. Participants will  
then be asked to complete baseline measures. Human-Animal Interactions will occur at each clinic visit or 
hospitalization, as long as they are not more frequent than weekly. Data collection will occur at baseline, 4 
weeks, and study end (8 weeks) with children and parents completing surveys in private sections of the room. 
All study data will be stored in REDCap, a secure, web-based application for building and managing 
databases. Tablets will be used  by study participants to enter their responses to study measures into their 
study record in REDCap. Paper forms will be available to participants if there is a problem with network 
connectivity or if the participant prefers that form. Subsequently, data on paper forms will be double-entered 
into the participant’s record in REDCap by trained study staff and verified. 
Human-Animal Interactions (HAI). Every effort will be made to ensure the same dog is used consistently with 
each family, but a back-up team will be available in the event the HAI team is ill or unavailable. The HAI 
consists of the following: 1) Social Interaction: participants will be guided by the canine owner in interfacing with 

R21 Exploring the Impact of Human-Animal Interactions on 
Gilmer, MJ 
Children with Life-Threatening Conditions and their Parents 
R21HD097757 
Version approved by IRB 11-18-2019 
 
the dog and 2) Activities: participant-selected activities from a core group of 22 activities such as petting the dog 
and talking to the dog, chosen by Pet  Partners to constitute the foundation for HAI. Pet Partners is a non-profit 
organization that assists individuals to  maintain their health or regain their full potential through HAI.35 Activities 
used represent integration of interactions into a child’s treatment plan. Implementation fidelity of intervention  
and receipt of intervention will be determined by documentation by the animal handler, a trained research 
assistant, and the PI after reviewing the video recordings of HAI. 
Implementation Fidelity: As recommended by the NIH Behavior Change Consortium, we will use 5 key 
factors to enhance HAI fidelity: study design, provider training, HAI delivery, treatment receipt (patient 
understands or is able to use the new skills), and enactment (patient treatment skills in the intended situations 
and at the appropriate time).36, 37 In addition to following the activity log developed by Pet Partners for the HAI, 
we will maximize fidelity through 1) comprehensive initial training for all canine owners,  2) reviewing videos 
recorded at each session, 3) monthly research team meetings to review recruitment, protocol activities, and 

R21 Exploring the Impact of Human-Animal Interactions on 
Gilmer, MJ 
Children with Life-Threatening Conditions and their Parents 
R21HD097757 
Version approved by IRB 11-18-2019 
 
 
intervention fidelity, 4) content analyses of interviews and 5) re-training as necessary. Safety: Any evidence of 
aggressive behavior by the dogs will be carefully monitored and the interaction will end immediately with the 
removal of the dog from the premises. At the end of a family’s 2-month participation in the study, we will ask 
children and parents separately: “Please describe what it was like to participate in this project.” Results will 
provide a positive transition at study end and offer feedback and potential revisions to be used in the next study. 
Children will received a stuffed dog at the conclusion of the study to provide continued support when they 
transition away from HAI. 
Measures. Measures are described here and in Table 2 according to specific aims. 
Aim 1: Examine feasibility of HAI sessions for children with a LTC and a primary caregiver, specifically  to: 
a) identify and document necessary modifications for a safe and feasible intervention, b) obtain recruitment 
estimates and determine potential recruitment barriers, c) evaluate elements of implementation fidelity 
(design,  training, delivery/receipt of treatment, enactment), and d) verify safety. 
Safe and feasible intervention: Safety verification will be determined by documentation of any evidence of 
potential risk for  injuries encountered during the sessions. Handler and Site Coordinator Self-Report 
Measure/Animal-Assisted Therapy (AAT) Activity Log  is a checklist for recording people present and activities 
conducted during session to be completed  after each session. Recruitment estimates and potential barriers to 
recruitment: Screening Checklist includes  numbers of children meeting inclusion criteria, number recruited, and 
barriers. 
Aim 2: Determine the preliminary efficacy of HAI sessions for 1) children with a LTC for the outcomes of 
QoL, anxiety, depression, worry, and pain, 2) caregivers of children with a LTC for the outcomes of stress and 
anxiety. 
The Family Demographic Form has 14 items including questions about age, race, gender, diagnosis, family 
members and pet ownership. Similar to other studies and as used in our previous studies, anxiety will be 
measured using the 20-item STAI for Children. This questionnaire has been used extensively in school-aged 
children (Cronbach’s alpha=.82-.87).36   Health-related Quality of Life will be measured by the PedsQL Generic 
(Cronbach’s alpha = .88) and Cancer (.72) report forms.  The PedsQL is a 23-item (general) or 27 item (cancer) 
health-related quality of life questionnaire for child self-report. 38, 39   This study will use the Child Self Report and 
Parent Proxy versions for ages 8-12 and 13-17. The multidimensional scales include physical (5 items), 
emotional (4 items), social (3 items), and school functioning (3 items) dimensions with scores of 0-4 for each 
item for the general Peds QoL, and 8 dimensions (pain-2 items, nausea-5 items, procedural anxiety-3 items, 
treatment anxiety-3 items, worry-3 items, cognitive-3 items, perceived physical appearance-3 items, and 
communication-3 items for the cancer Peds QoL. Caregiver: The Pediatric Quality of Life (PedsQL)  Generic 
Parent (Cronbach’s α=.93) and Cancer (.87) inventories have parent report forms that range from 21-27   
items.38  The State-Trait Anxiety Inventory (STAI) Adult Form assesses primary caregivers’ anxiety, has a 
reported Cronbach’s alpha ranging from.78-.82 and includes 20 items in Likert format to assess trait 
characteristics and 20 items for state anxiety.40 A brief new measure of depression from the Patient Reported 
Outcomes Measurement Informastion System (PROMIS) with strong psychometrics has been added for child 
self-report and parent-proxy (Cronbach’s α=.80). 
Exploratory Aim: To explore mechanisms (reduced salivary cortisol and urinary norepinephrine levels) 
associated with 8 weeks of HAI. 
Mechanisms and biomarkers: As part of our exploratory aim we will measure salivary cortisol and 24 hour 
urinary norepinephrine (NE) levels. Studies have shown that increase in salivary cortisol and urinary NE 
correlate to increased levels of acute stress.41, 42 Similar to the methods of Corbett et al.43 salivary swabs will 
be obtained at baseline at 10:00 am and 2:00 pm before HAI and 30 minutes after HAI on week 4 and week 8 
of the study. Attempts will be made to schedule appointments between 10:00 am and 2:00 pm to control for 
circadian variations. Saliva will be obtained and stored (( -80°C) until time of analysis in the Vanderbilt 
Hormone Analytical Services Core. Urinary NE will be measured from 24-hour urine collections obtained at 
baseline, midway, and toward the end of the study. Twenty-four hour (NE24) levels will be used as an indirect 
measure of stress and adrenergic activation. Urinary creatinine levels will confirm compliance with 24-hour 
collections, and variations in volume. NE values will be compared to normative ranges for sex, ethnicity, and 
BMI. NE will be measured by high performance liquid chromatography (Quest diagnostics). Although not 
primary outcomes, we will  measure heart rate/blood pressure, using a calibrated Dynamap monitoring device. 
Evidence from our work with newly diagnosed cancer patients indicates anxiety and worry may begin to 

R21 Exploring the Impact of Human-Animal Interactions on 
Gilmer, MJ 
Children with Life-Threatening Conditions and their Parents 
R21HD097757 
Version approved by IRB 11-18-2019 
 
increase at the time families realize the HAI sessions are ending. Therefore as noted above, we will obtain 
these measures at baseline, mid-way at 4 weeks, and at the end of the 8 week study. Part of Aim 1 is to 
determine the feasibility of the HAI intervention, especially the most reliable time to obtain these measures. 

R21 Exploring the Impact of Human-Animal Interactions on 
Gilmer, MJ 
Children with Life-Threatening Conditions and their Parents 
R21HD097757 
Version approved by IRB 11-18-2019 
 
 
 
Table 2. Measures and Schedule 
 
Variable 
Measure 
# items/Scoring Range 
Clinical Significance 
Time to 
Complete 
Schedule 
AIM 1 
Minutes 
Safety/Feasibility AAT Activity Log 
22 items 
5 
After each HAI 
Feasibility 
Recruitment Rate, Attrition 
Consent/assent. 
After final HAI 
Intervention 
Videotaping of All Sessions 
15 
During each HAI 
AIM 2 
Children 
Anxiety –Trait 
State-Trait Anxiety Inventory 
for Children (STAIC) 
Trait Form 
20 items/20-80; 
Clinical significance 39-40 
5 
Baseline 
Anxiety – State 
QoL 
HR and B/P 
Depression 
STAIC State Form 
PedsQL-General 
Peds QL-Cancer 
Heart Rate and B/P Log 
PROMIS Depressive 
Symptoms 
20 items/20-80; 
Clinical significance 39-40 
23 items/range 0-92 
27 items/range 0-108 
8 items 
5 
15 
2 
2 
Baseline, 4 & 8 wks 
Baseline, 4 & 8 wks 
Baseline, 4 & 8 wks 
Baseline, 4 & 8 wks 
Baseline, 4 & 8 wks 
Acute Stress 
Salivary Cortisol 
3 
Baseline, 4 & 8 wks 
Urinary NE, creatinine 
20 
Baseline 4 & 8 wks 
HAI Perceptions 
Open-Ended Interview 
Semi-Structured 
15 
End of Study 
Parent 
Child QoL 
Family Demographic Form 
14 items 
10 
Baseline 
PedsQL General and Cancer- 
Parent Proxy 
26 items 
5 
Baseline, 4 & 8 wks 
Anxiety – Trait 
STAI – Trait Form (Adult) 
20 items/20-80; 
Clinical significance 39-40 
5 
Baseline 
Anxiety – State 
STAI –State Form (Adult) 
20 items/20-80; 
Clinical significance 39-40 
5 
Baseline, 4 & 8 wks 
Depression 
PROMIS Depressive 
Symptoms 
Parent Proxy 
6 items 
2 
Baseline, 4 & 8 wks 
HAI Perceptions 
Open Ended Interview 
15 
End of Study 
 
Data Management. Dr. Dietrich (Co-I, VUSN biostatistician) will provide support for: (a) 
the development of REDCap database for study measures and materials, (b) data 
management, and (c) statistical analyses. 
Participation status will be tracked for all enrolled child/parent participants, and monthly 
‘Expectation Reports’ indicating outstanding assessments will minimize loss of data. 
Information (e.g., age, reason for non- participation) from eligible participant who do not 
consent will only be used in summary form to describe the recruitment process. Team 
training will include all investigators and staff at the initial team meeting and booster sessions 
as needed to ensure data collection consistency, quality assurance, and intervention fidelity. 
The PI will provide study manuals, including scripts with instructions, and lead bi-weekly 
team meetings to maximize recruitment, fidelity, and safety. Questionnaires will be 

R21 Exploring the Impact of Human-Animal Interactions on 
Gilmer, MJ 
Children with Life-Threatening Conditions and their Parents 
R21HD097757 
Version approved by IRB 11-18-2019 
 
electronically administered in a standard order with written instructions. Study coordinator or 
research assistant help will be available in-person to clarify instructions to participants and 
answer any questions about items. Dr. Dietrich will develop scoring programs and score all 
measures. Item ranges, and missing and unusual values, will be double-checked. 
 
Statistical Analysis. Analysis of the feasibility and preliminary effects of human-animal 
interactions (HAI) on child and parent stress, depression, anxiety, and quality of life will be 
conducted using SPSS and STATA statistical software. Descriptive statistical and graphical 
methods will be used to summarize and visualize patterns in the study outcome data 
distributions at each time of assessment. Simple group comparisons of participation and 
retention (e.g., differences in demographic, clinical characteristics) will be conducted using 
Chi-Square tests of independence and Mann-Whitney tests. Reliable change indices (RCI)44-
46  will provide the critical foundation for summarizing and analyzing overall efficacy, as well 
as characteristics of the participants most likely to benefit from HAI in future work. While 
effect sizes will be more important than statistical significance in this feasibility study, all tests 
of statistical significance will maintain a maximum p < .05. 
 
Table 3. Study Timeline 
 
Study Timeline 
Year 1 
Year 2 
Activity/Quarter 
1 
2 
3 
4 
1 
2 
3 
4 
Hiring/training personnel, IRB approvals, database 
 
 
 
 
 
 
 
 
Enrolling participants 
 
 
 
 
 
 
 
 
Data collection 
 
 
 
 
 
 
 
 
Data analysis 
 
 
 
 
 
 
 
 
Knowledge dissemination and future grant development 
 
 
 
 
 
 
 
 
 
Summary, Limitations, and Future Directions: This pilot/exploratory study will evaluate 
feasibility, safety, and preliminary efficacy using HAI with children diagnosed with a LTC, but is 
not generalizable beyond children with advanced cancer. Clear strengths of this proposal 
include 1) inclusion of children, parents, and canines; 2) qualitative (video recordings, 
interviews) and quantitative (surveys, physiologic measures) data; 3) use of both established 
and innovative measures with this population, and 5) expertise of investigators. Collection of 
physiologic, survey, and observational data will provide a rich view of the experiences of HAI 
from viewpoints of children with cancer, parents, and  animal handlers. This novel design with 
multiple methods will begin to fill a gap in the literature related to HAI with children with 
advanced cancer and will  lead to future larger studies with other LTC. Infrastructure, 
institutional support, physical resources and a collaborative research team with established 
funding history ensure successful completion. 
The proposed sample size in this study reflects the number of  participants that can 
reasonably be recruited and followed in this very vulnerable population. The  focus will be on 
generating reliable estimates of characteristics of children and parents who benefit most from 
this intervention. The subsequent grant will involve multiple sites with English and Spanish-
speaking populations and preliminary conversations with several large children’s hospitals 
are ongoing and yielding positive responses. 
 
Dissemination: Results will be disseminated through at least 3 presentations at professional 
conferences, such as the American Academy of Hospice and Palliative Medicine and 
Hospice Palliative Nurses Association Annual Assembly, International Congress on Palliative 
Care, Society of Pediatric Psychology, National  State of the Science Congress on Nursing 

R21 Exploring the Impact of Human-Animal Interactions on 
Gilmer, MJ 
Children with Life-Threatening Conditions and their Parents 
R21HD097757 
Version approved by IRB 11-18-2019 
 
Research, and Oncology Nursing Society National Conference  on Cancer Nursing 
Research. Our main form of dissemination will be through several peer-reviewed publications 
in multidisciplinary journals and will include manuscripts related to: (1) outcomes of childhood 
anxiety, depression, worry, pain, and QoL (2) parent outcomes of  anxiety, stress, and quality 
of life, and (3) participants’ qualitative reports on their experiences with HAI. 
 
Data Safety and Monitoring Plan: 
 
A. 
Monitoring Entity or Who Will Monitor the Study: The data and safety monitoring 
plan will follow NIH policy guidance. Based on this study being minimal risk and conducted at 
a single site, a Safety Monitoring Committee (SMC) consisting of at least two (2) experts who 
are not co-investigators or consultants on this study will be established at Vanderbilt 
University at the beginning of this research. SMC membership will follow NIH policy. The 
SMC will serve as an independent advisory board to both the PI and to the NICHD Director. 
The SMC will oversee the activities related to implementing the study to ensure patient safety, 
conformance to the study protocol, overall performance of study components, and integrity of 
the data being collected. SMC members will not have close current or recent affiliations with 
the study, will not have been directly involved in protocol development, nor supervise persons 
who are so involved. We will make every effort to include an independent investigator and 
biostatistician. As soon as possible after each SMC meeting, but within 20 days following 
each SMC meeting, the SMC will provide the PI with a copy to provide to the NICHD Director 
or designee, a written recommendation along with justification related to continuing, changing, 
or terminating the study. The PI will be responsible for submitting any necessary reports to 
the NICHD. 
 
B. Procedures for: 
B1 a)  Monitoring study safety to include monitoring schedule: The SMC will meet a 
minimum of once a year to review study progress through informal evaluation of existing 
data. For each SMC meeting, reports will be prepared and provided to SMC members by the 
PI. Data will be provided in a manner to protect the confidentiality of subjects. The SMC will 
prepare an annual safety report, summarizing the efforts and findings of the Committee. 
B1 b)  Auditing selected cases for compliance with IRB requirements: The SMC will 
annually audit selected cases for IRB compliance with study procedures. 
B1 c)  Conformance with informed consent requirements: The SMC will annually 
audit consent and assent documents and study conformance with related requirements. 
B1 d)  Verification of source documents: The SMC will verify that study record-keeping 
includes documenting the existence of the subject to substantiate data collection integrity. 
B1 e)  Investigator compliance: The SMC will annually review all study investigators’ 
compliance with human safety training. 
B2)      Minimizing research-associated risk: The SMC will monitor study data for 
effectiveness and safety to protect participants from exposure to unreasonable or 
unnecessary research risks. SMC members will review interim data in the context of the most 
recent scientific literature, and ensure that the study does not continue beyond the point when 
the study objectives have been met and a clinically meaningful answer of importance to the 
scientific community and the public has been obtained. 
B3)      Protecting the confidentiality of participant data: The SMC will review study plans 
for and establish specific guidelines for data and safety monitoring, including confidentiality of 
participant data (e.g., location of data storage.) 

R21 Exploring the Impact of Human-Animal Interactions on 
Gilmer, MJ 
Children with Life-Threatening Conditions and their Parents 
R21HD097757 
Version approved by IRB 11-18-2019 
 
 
C. 
Procedures for Identifying, Reviewing, and Reporting Adverse Events and 
Unanticipated Problems to the IRB and NINR.  Any adverse events occurring during the 
course of this study will be collected, documented and reported by the PI (Dr. Gilmer) to the 
SMC, along with reporting to the NICHD and institutional review boards as required. As soon 
as possible after each SMC meeting but within 20 business days following each SMC 
meeting, the SMC will provide the PI and the NICHD with a statement, where appropriate, 
concerning the impact of the study of individually observed or cumulative adverse events. 
Although not anticipated, if any 1 event is identified that may have caused any type of harm to 
a participant, study accrual will be immediately halted until the study team and SMC can 
review the event and determine if any study procedures need to be revised. Study accrual 
will only resume after review of study protocol has been completed and any recommended 
revisions made as suggested by the SMC. 
 
D. 
For Multi-Site Studies, Procedures to Ensure Compliance with Monitoring 
Plan and Reporting Requirements across Study Sites. N/A - as this is a single site 
study. 
 
E. 
An Assessment of External Factors or Relevant Information (i.e., Developments in 
Literature, Results of Related Studies) that May jave Impact of Participant Safety or on 
Ethics for Research Study. The SMC will review published reports of related studies 
submitted by the study investigators or SMC members to determine any external factors 
which may impact participant safety or ethics for our study. The SMC will determine whether 
the monitored study needs to be changed or terminated. 
 
F. 
The Advanced Plans for Interim and/or Futility Analysis: Given the low risk of any 
negative impact of the intervention, as well as the considerable variability commonly seen in 
study outcomes, we will not reduce study statistical power by including an interim or futility 
analysis. Subsequent research will be greatly benefited by the proposed analysis that will 
make use of the full sample recruited in this study.