Canines andChildhood Cancer

Pilot Study Report

American Humane Associationand Zoetis wish to dedicate this report to the memory of Dr. John C. New, Jr. of the College of Veterinary Medicineat the University of Tennesseein Knoxville. Dr. New was instrumental in helping us implement the CCC Study, and was a constant source of knowledge, collaboration, kindness, and inspiration. He will be dearly missed.

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Since December 2010, the Pfizer Foundationand Zoetis have sponsored AmericanHumane Association (AHA) in developingand executing an innovative research study –the Canines and Childhood Cancer (CCC)Study – to investigate the impact of animal-assisted therapy (AAT) on pediatric oncologypatients, their families, and the therapy dogswho visit them. The goals of thiscollaboration are to promote innovation,evidence-based research, practiceimprovements and knowledge advancementto further the field of research on human-animal interactions and the treatment ofcancer in children. Ultimately, a betterunderstanding of the effects of AAT onpediatric oncology patients will enhancetreatment for children with cancer and their families.

In collaboration with both children’s hospitalsand universities across the country, AHA andZoetis have completed a comprehensive needsassessment and have piloted a research studyto inform the design and implementation of afull clinical trial scheduled to begin in late2013. This report outlines the findings andlessons learned from the pilot study thatconcluded in June 2013.

Before beginning the pilot study, acomprehensive literature review was conducted(www.canines andchildhoodcancer.org), as well as focus groups and interviews withpediatric oncology patients, parents ofchildren with cancer, hospital staff, andanimal-handlers who visit with their therapydogs in pediatric healthcare settings. A summary of literature review, focus group,and interview findings is presented here toprovide the background and rationale for the study.

At any given time in the United States, morethan 40,000 children are undergoing cancertreatment, with nearly 13,500 new diagnosesmade each year (Children’s Oncology Group,2013). According to the National CancerInstitute (NCI) at the National Institutes ofHealth (2013), cancer is the leading cause ofdeath by disease among children aged 1 to 14years. Encouragingly, while the incidence of

childhood cancer has increased slightly overthe past 20 years, mortality rates havedrastically decreased with 5-year survival ratescurrently near 83 percent – a 25 percentjump since 1975 (NCI, 2013).

Still, quality of life for childhood cancerpatients, survivors, and their families remainsa concern. As childhood cancer is a “familydisease,” it often affects patients, parents/guardians, siblings, and extended relatives inprofound ways. Findings from the CCCStudy’s literature review, as well as focusgroups and interviews with hospitals, showthat children with cancer and their familiesnot only cope with physical concerns, but arealso prone to psychosocial and behavioralissues including stress and anxiety, trauma,depression, loneliness, and strain in theirsignificant relationships (Fotiadou, Barlow,Powell, & Langton, 2008; Norberg &Boman, 2008).

While the physical effects associated with thedisease and its treatment may greatly improvefor these children with time, psychosocialeffects often linger and negatively impactcancer survivors and their families for thelong-term (Michel, Rebholz, von der Weid,

Background and Rationale

At any given time

in the United States,

more than 40,000

children are undergoing

cancer treatment.

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Bergstraesser, & Kuehni, 2010). Yet fewevidence-based studies have either criticallyexamined or recommended adjunctiveinterventions to help the entire family copewith these issues during the childhoodcancer experience.

AAT, defined as a goal-directed interventionthat involves a trained animal to aid in aperson’s healing process, is an adjunctiveintervention that has promise for childrenwith cancer and their families. Not only isAAT accessible and affordable, but researchalso suggests that animals can providenumerous benefits for people from all agesand walks of life (Endenburg & van Lith,2011; Nimer & Lundahl, 2007). Reportedbenefits of AAT include reduced stress andanxiety; decreased blood pressure and heartrate; distraction from worry or pain;

unconditional support and acceptance;increased opportunities for physical touch;improved social skills that lead to healthyrelationships; enhanced self-esteem; andincreased motivation to actively participatein treatment (Fine, 2010; Friedmann, Son,& Tsai, 2010; McCardle, McCune, Griffin,Esposito & Freund, 2011).

While many studies have documented thebenefits of AAT, the majority of thesefindings have largely been anecdotal and thefield has consistently struggled withdeveloping and conducting rigorousresearch (Johnson, Odendaal & Meadows,2002; Kazdin, 2010). Many argue that thislack of evidence-based research has hinderedthe ability of AAT to be recognized as aviable treatment option for people in need,particularly by those in the research,funding, and healthcare fields (Palley,O’Rourke, & Niemi, 2010). Althoughtherapy dog programs are common inchildren’s hospitals throughout the UnitedStates, existing evidence concerning theeffectiveness of AAT in pediatric oncologysettings is very limited. In addition, there isa general lack of scientific research on howAAT may impact the therapy animals.

Overall, there are crucial gaps that must befilled if animal-assisted interactions are to beconsidered effective, safe and ethical modesof adjunctive treatment. Thus, the CCCStudy has the potential of not onlyadvancing knowledge in both the pediatriconcology and AAT fields through rigorousand groundbreaking research, but moreimportantly, may greatly improve childhoodcancer treatment by lending credibility to anadjunctive treatment modality aimed atproviding the comfort of a therapy dog tochildren and families who need it now.

... but more importantly,

may greatly improve

childhood cancer treatment

by lending credibility to an

adjunctive treatment

modality aimed at

providing the comfort of a

therapy dog to children and

families who need it now.

Due to the complicated and exceptionalnature of conducting rigorous AAT researchacross multiple pediatric healthcare settings,it was necessary to first pilot the study inorder to fully prepare for a clinical trial.

The goals of the pilot study were to:• Address the feasibility of conducting arandomized control trial utilizing AATwithin multiple pediatric healthcaresettings

• Determine how to address issues ofscientific integrity and protocol fidelity

• Determine the appropriateness andfeasibility of the instruments chosen tomeasure distress across the threepopulations (patients, parents/guardians, and therapy dogs)

• Develop recommendations foroptimization of the protocol leading up to a final research protocol for a fullclinical trial

The hypotheses that were developed basedon the findings of the comprehensive needsassessment are as follows:

• H1: Pediatric cancer patients with AcuteLymphoblastic Leukemia (ALL) whoreceive AAT will experience less distress

throughout the course of their treatmentsessions than patients who do not receive AAT.

• H2: Parent(s)/guardians of pediatriccancer patients with ALL who receiveAAT will experience less distressthroughout the course of their child’streatment sessions than parent(s)/guardians of patients who do notreceive AAT.

• H3: Participating therapy dogs willexhibit minimal distress over the courseof the CCC Study.

Pilot Aims

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The pilot study was conducted for sixmonths – between January and June of2013, with data collection lasting betweenthree and four months, depending upon the hospital site. It was designed andimplemented as a multi-site, randomizedcontrolled study with the control cohortreceiving the standard-of-care for ALL andthe study cohort receiving standard-of-careplus AAT visits.

Prior to the study implementation at eachsite, the study design and protocolunderwent Institutional Review Board(IRB) and Institutional Animal Care andUse Committee (IACUC) review atAmerican Humane Association and eachsite, as appropriate. Once approval wasobtained from each site, the studycoordinators began their recruitment efforts.Once a child and family were determined tobe eligible for the study, the coordinatorapproached them with the appropriateconsent/assent forms to determine theirinterest in the study.

Sites

Two sites participated in the pilot study:East Tennessee Children’s Hospital, inconjunction with the University ofTennessee’s College of Veterinary Medicine,in Knoxville, TN and St. Joseph’s Children’sHospital in Tampa, FL.

Population

The patient population for the pilot wasdefined as children ages 3 through 11 yearswho were newly diagnosed with ALL orwho had been in treatment for ALL for nolonger than 12 months and whoseparent/guardian gave their consent toparticipate in the study and, if appropriatedepending upon age, gave their assent toparticipate in the study. Based on admissionsdata from each of the two pilot sites, theresearch team anticipated that up to sixpatients (or three patients per site) wouldparticipate in the six month pilot trial.

The patient population was selected for thefollowing reasons:

• ALL is the most common form ofchildhood cancer

• ALL patients typically experience acommon treatment protocol under theChildren’s Oncology Group (COG) thatis consistently used at both sites enrolledin the pilot study

• Aside from consistently utilizedmedication, ALL treatment does notinvolve procedures that may directlyimpact neural function or development

• Age 3 is within the peak age range fordiagnosis of ALL

Methods

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The parent/guardian population for thisstudy consisted of parents/guardians of eligible child patients, as determined by the above criteria and who consented to participate.

The therapy dog population for this studyconsisted of registered therapy dogs ofanimal-handlers who regularly visited one ofthe pilot sites, attended a training regardingthe pilot study protocol, and consented to participate.

Randomization

Consent and assent forms completed byfamilies agreeing to participate in the studywere uploaded to AHA’s secure File TransferProtocol (FTP) site. Once the AHA researchteam received the form, the child and familywere randomized into either the controlgroup (standard-of-care for ALL) or the treatment group (standard-of-care plus AAT).

Study Protocol

A variety of physiological and psychologicalmeasures were used to compare the levels ofdistress experienced by the patients and theirparents/guardians in the control and studycohorts. Those children and parents/guardians assigned to the control cohortcompleted measures and/or were videotapedat designated time points, described later inthis document, during their regularly

scheduled treatment sessions at the hospital.The children and parents/guardians in thestudy cohort completed the same measuresas those in the control cohort and/or werevideotaped at designated time points duringtheir regularly scheduled treatment sessionsat the hospital.

Animal-handlers were asked to collect theirdog’s saliva at five different points in time atthe beginning of the study to establish abaseline measurement, and then again aftereach 20 minute session with the child andfamily. Saliva was collected to measurecortisol, a biomarker for stress in dogs.Likewise, handlers completed a self-reportform on their dog’s behavior and activitiesthat occurred during the session after eachvisit with the child and family. Finally, thedog’s behavior during the session wasvideotaped at designated time pointsthroughout the pilot study for comparisonwith their salivary cortisol levels andhandler-documented behavior.

Intervention

Those children and parents/guardiansassigned to the study cohort were pairedwith one animal-handler team and receivedAAT visits approximately once a week overthe course of the pilot study. A back-uphandler was assigned to fill in if the primaryhandler was not available. Visits with thetherapy dog and handler lastedapproximately 20 minutes and the handlerwas trained to end the session earlier if theyfelt their dog was becoming stressed. Inorder to achieve the goal of measuring AATas it is implemented every day in children’shospitals across the country, the activitiesperformed during the intervention werechosen at the discretion of the handler,based on the dog’s abilities and interests.Common activities during AAT sessions arepetting, giving the dog a treat and askingthe dog to do his/her obedience cues such as‘sit’ or ‘down.’ Handlers were asked to logthe activities that were conducted during thestudy session. All of the AAT visits and datacollection throughout the pilot studyoccurred in the outpatient or infusion clinic settings.

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Common activities

during AAT sessions

are petting, giving the

dog a treat and asking

the dog to do his/her

obedience cues such as

‘sit’ or ‘down.’

Measures and Instrumentation

The following measures were utilized forchildren who participated in the pilot study:

• Observational Scale of BehavioralDistress (OSBD): a scale developed tomeasure children’s responses to painfulmedical procedures. Video cameras wereused to record sessions so that the AHAresearch team could document thechild’s behavior utilizing the OSBD.

• Polar RS800CX training watch withPolar WearLink W.I.N.D. transmitter:to measure heart rate variabilitythroughout a study session.

• Blood pressure cuff: to measure systolicand diastolic blood pressure at thebeginning and end of a study session.

The following measures were utilized forparents/guardians:

• State Trait Anxiety Inventory (STAI): aquestionnaire that differentiates betweencurrent state anxiety and more inherenttrait or character anxiety.

• Pediatric Inventory for Parents (PIP): aquestionnaire to specifically measurestress in parents/guardians who aredealing with a critically ill child,particularly a child with cancer.

• Polar RS800CX training watch withPolar WearLink W.I.N.D. transmitter:to measure heart rate variabilitythroughout a study session.

The following measures were utilized fortherapy dogs:

• Handler self-reports: regarding the dog’sbehavior, the dogs’ and family’s reactionto the session, activities that took placeduring the session, session participants,and other pertinent notes. Most of the questions are posed with Likertscale-type answers.

• Salivary cortisol: handlers collected theirdog’s saliva at five different points intime to develop a baseline measurementafter they consented to participate in thestudy. They then collected their dog’ssaliva after each study session and thosecortisol levels were compared to theirdog’s baseline measurement. Saliva wascollected by having the dog chew on asix inch cotton swab for up to fiveminutes. The saturated swab was thenstored in a vial in a designated freezeruntil shipped to an offsite lab foranalysis.

• AAT ethogram: video cameras were usedto record sessions so that the AHAresearch team could document the dog’s behavioral cues utilizing the AAT ethogram.

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Demographics

Patients: a total of six children were enrolledin the pilot study, which was consistent withthe predicted number based on admissionrate. Three children were enrolled at eachsite. At St. Joseph’s Children’s Hospital, twowere enrolled in the treatment group andone in the control group. At East TennesseeChildren’s Hospital, two were enrolled inthe control group and one in the treatmentgroup.

Parent(s)/Guardian(s): a total of six parentswere enrolled in the study, one per childwho participated.

Animal-Handler Teams: a total of nineanimal-handlers consented to participate inthe study and collected their dog’s saliva forthe baseline measurement. Based on thenumber of eligible children, four animal-handlers and their therapy dogs participatedin the study sessions.

Findings

ChildrenHeart rate variability was collected fromchildren once every two months; once attheir first study session and then again twomonths later for a total of two collections.Throughout the course of the pilot, thisequipment was viewed as intrusive forpatients and onsite study coordinators haddifficulty obtaining the data due to a varietyof factors, including the chest straps beingtoo large for many of the children.

Blood pressure was collected from childrenat the beginning and end of the studysession, once every two months. Like theheart rate variability, it was collected at theirfirst study session and then again twomonths later. Some children did refuse tohave their blood pressure measured at times;however, this procedure is common for the children and study coordinators and was not seen to be as intrusive as the heartrate variability.

The Observational Scale of BehavioralDistress (OSBD) was utilized once everytwo months via video recordings of thestudy sessions; once at their first studysession and then again two months later.This scale is intended for use during stressfulmedical treatment procedures. After goingthrough IRB reviews at the pilot sites,hospital sites determined that the therapydogs would not be allowed to visit duringthese types of procedures due to sterilityconcerns. However, it was still necessary topilot this instrument to determine if it couldbe used to detect any potentially distressfulchild behaviors during times when the dogswere allowed to visit. After viewing thevideos while utilizing the OSBD, theresearch team determined that the scale wasnot useful for the study given that each childdid not display any of the distressfulbehaviors included in the OSBD in any ofthe videos, regardless of their cohort(treatment or control).

Parents/GuardiansThe State Trait Anxiety Inventory (STAI)was collected from the parents/guardiansonce every two months; once at their firststudy session and then again two monthslater. A total of five out of the six parents/guardians completed the STAI at the firstsession and two parents/guardianscompleted the STAI two months later.

It was found that the state anxiety scores forthe treatment group were slightly higher attime 1 than they were for the control group.Also, there was a very small drop in thescores for the two parents in the treatmentgroup at time 2 compared to time 1.However, given the small sample size andlack of time 2 measurements for parents inthe control group, no definitive conclusionscan be drawn at this point.

Results

Average Tx Group Time 1 36

Average Tx Group Time 2 35.5

Average Ctrl Group Time 1 30.5

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The Pediatric Inventory for Parents (PIP)was collected from the parents/guardiansonce every two months; once at their firststudy session and then again two monthslater. Like the STAI, a total of five out of thesix parents/guardians completed the PIP atthe first session and two parents/guardianscompleted the PIP two months later.

There are a total of 10 scales on the PIP,including Communication, Medical Care,Emotional Distress, Role Function, andoverall Frequency and Difficulty. Each ofthese PIP scales has two components: 1) the frequency in which a difficult eventoccurred and 2) the level of difficulty that

Emotional Distress Emotional DistressFrequency Difficulty

Average Tx Group Time 1 53.7 52.7

Average Tx Group Time 2 59.5 55

Average Ctrl Group Time 1 42.5 43.5

event presented. For the purposes ofaddressing the hypothesis regardingparents/guardians, the research team wasmost interested in the Emotional Distressscale. Two sample questions/events from theEmotional Distress scale are as follows:“Seeing my child sad or scared” and“Thinking about my child being isolatedfrom others.” Parents were asked to circlefirst how frequently the event had occurredfor them in the past seven days (How Often:1=Never, 2=Rarely, 3=Sometimes, 4=Often,5=Very often) and then were asked to circlehow difficult that event was for them(1=Not at all, 2=A little, 3=Somewhat,4=Very much, 5=Extremely).

It was found that the scores for thetreatment group were slightly higher at time1 than they were for the control group. Also,there was a very small increase in the scoresfor the two parents in the treatment groupat time 2 compared to time 1. However,given the small sample size and lack of time2 measurements for parents in the controlgroup, no definitive conclusions can bedrawn at this point.

Heart rate variability was collected from theparents/guardians once every two months;once at their first study session and thenagain two months later. Throughout thecourse of the pilot, this equipment wasviewed as intrusive for parents (i.e., they hadto tell the onsite coordinator their height/weight/age and affix the strap around theirchest) and onsite coordinators had difficultyobtaining the data due to a variety offactors. Like with the patient population,this instrument was not found to be feasibleover the course of the pilot study.

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Animal-Handler TeamsTo obtain a canine’s baseline salivary cortisolmeasurement for comparison to post-sessioncortisol levels, handlers collected theircanine’s saliva on a non-working day at thefollowing time points:

i. Upon waking (“morning”)ii. Mid-Day (“noon”)iii. Evening, prior to typical bedtime

(“night”)iv. Approximately 20 minutes after the

introduction of a known “trigger,” such as the canine seeing his/her therapy vest/bandanna or visit bag (“trigger”)

v. Approximately 20 minutes after arriving at the hospital around the time of day that they would typically visit (“hospital”)

Preliminary data from nine canines showsthat there is a considerable amount ofvariation at the five time points. The average“morning” cortisol level tended to be thehighest, with the “hospital” samples elicitingthe second highest levels and the “trigger”time-point producing the lowest levels.

Data from three canines showed that there is also a considerable amount of variation between dogs in their post-session cortisol levels. Forexample, it was found that two of the three canines had lower levels of post-session cortisol, on average, than their baseline averages.Conversely, one canine had a slightly higher post-session average (0.21 µg/dL) than their baseline average (0.12 µg/dL). In general, mostpost-session levels tended to fall within the range of the baseline samples.

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A total of 14 handler-self reports werecompleted after study sessions. Anadditional nine sessions were scheduledacross patients, however, due to childillnesses, refusals to visit/interact, absencesand/or scheduling difficulties for the patientor handler, these visits did not take place.There was very good compliance by thehandlers in completing the self-reportmeasure after each study session. Theaverage session duration was exactly 20minutes. Some sessions were slightly shorterwith a minimum of 11 minutes, whilesome sessions were slightly longer with amaximum of 24 minutes.

In answering the Likert scale-type questionsin the post-session surveys, handlersindicated that their dogs were very eager tointeract with the patient during the therapysessions, with an average rating of 4.29 outof 5. However, the handlers indicated thatthe parents (3.54) and children (3.07) werenot as eager to interact with the dogthroughout the entirety of the session.

When handlers were asked to assess howdistressed the children and parents werewhen they arrived to the treatment session,as well as after the interaction with the dog,the handlers indicated that there was veryminimal distress from all participants (1.60for children at arrival and 1.60 for childrenafter interaction out of a possible 5; 1.70 forparents at arrival and 1.80 for parents afterinteraction out of a possible 5).

Most handlers indicated that their dog wasnot tired after the study session, with anaverage rating of 2.2 out of 5. Handlersindicated that the sessions were slightlymore beneficial for the children than for theparents, with average ratings of 3.8 (forchildren) and 3.43 (for parents) out of 5.The following table shows the items, ratingscales and the average ratings of each itemdiscussed above.

Question Scale Ratings Average(1-5) Handler Rating

How eagerly did your dog want to interact 1=clearly did not want to interact;with the patient during this therapy session? 5=extremely eager to interact 4.3

How much did the patient interact with your 1=did not interact at all;dog during this therapy session? 5=did not stop interacting 3.5

How much did the parent/caregiver interact with 1=did not interact at all;your dog during this therapy session? 5=did not stop interacting 3.1

How distressed did the child seem upon your 1=not distressed at all;arrival with your therapy dog? 5=extremely distressed 1.6

How distressed did the parent/caregiver seem 1=not distressed at all;upon your arrival with your therapy dog? 5=extremely distressed 1.7

How distressed did the child seem AFTER 1=not distressed at all;interacting with your therapy dog? 5=extremely distressed 1.6

How distressed did the parent/caregiver seem 1=not distressed at all;AFTER interacting with your therapy dog? 5=extremely distressed 1.8

How tired do you think your therapy dog was 1=not tired at all;immediately following this visitation session? 5=extremely tired 2.2

Overall, how beneficial do you feel your 1=not beneficial at all;dog’s visit was for the child today? 5=extremely beneficial 3.8

Overall, how beneficial do you feel your dog’s 1=not beneficial at all;visit was for the parent/caregiver today? 5=extremely beneficial 3.4

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In just more than half of the sessions (8),handlers indicated that they noticed signs ofstress in their dogs at some point during thesession. Most often, a lack of the studyparticipants interacting with the therapydog was noted as being a stressful event fortheir dog.

The most frequently noted participants inthe therapy session included the child andthe parent/guardian. Often, the child lifespecialist or a nurse would be present butdid not necessarily “participate” in thesession every time.

Talking to the dog and petting the dog werethe most common activities cataloged by thehandlers. Playing with one of the dog’s toys,taking photos of the dog, and gettingstickers of the dog were the other mostfrequently cataloged activities that tookplace during the study sessions.

A total of four study sessions with twochildren (time 1: first study session and time2: two months after the first study session)were recorded for purposes of using theAAT ethogram to examine canine behaviors.A total of three frequency scales were usedin the ethogram: distance seeking behaviors,contact seeking behaviors, and aggression.There are also four duration scales used:active, sitting, laying and passive.

There were some observed behaviors in thevideos that were indicative of canine stress,such as panting, restlessness, lip licking, andlooking to the handler for guidance ordirection. Encouragingly, the handler self-reports from those sessions indicated thatthe handlers were also aware of these typesof behaviors and their probable connectionto stress in their dogs. It became apparentthroughout the video coding process that 20minutes may be too long for the AATsessions, as the number, nature andfrequency of distance seeking behaviorsamong dogs tended to intensify with sessionlength (i.e., in sessions lasting longer than~15 minutes).

Twenty minutes also seemed particularlylong for younger children; this may be dueto their limited attention spans and/or theirstages of development. Across all videos,there were no aggressive behaviors (e.g.,growling) observed. There were a number ofpositive, affiliative behaviors (e.g., tail

wagging) that were observed which were noton the existing AAT ethogram that theresearchers felt were important to capturegoing forward. Therefore, an updated AATethogram was developed for the full trialbased upon the observations and findingsfrom the pilot.

DiscussionBy examining the progress made and lessonslearned in the CCC pilot study, it is clearthat each of the goals of the pilot (outlinedon page 5 of this document) were met.There are several important findings relatedto each pilot goal that will inform theoptimization of the full trial study design, aswell as ensure that the full trial isimplemented in a successful and rigorousmanner.

Goal 1: Address the feasibility ofconducting a randomized control trialutilizing AAT within multiple pediatrichealthcare settings

The research team found that it was feasibleto conduct a randomized control trialutilizing AAT at both of the pilot sites.Integral to the implementation andfeasibility of the pilot study were:

• Support of the study’s goals from thehospital and pediatric oncologydepartment;

• An established AAT visitation programwith committed animal-handler teams;

• A dedicated staff member who was ableto coordinate schedules, as well ascollect, upload, store and ship thedata/specimens on a regular basis;

• Back-up handlers and staff memberswho were willing to fill in whennecessary;

• Protocol-specific training of staff andhandlers prior to the start of the pilot;

• Regular communication on studyprogress between the site participantsand AHA research team;

• Consultation from sites, Zoetis, andother partners on addressing anychallenges that arose.

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Goal 2: Determine how to address issuesof scientific integrity and protocol fidelity

Scientific integrity was ensured throughoutthe course of the pilot study due to theinvolvement of, and approval from, fourseparate Institutional Review Boards (IRBs)and two separate Institutional Animal Careand Use Committees (IACUCs). Theseapprovals and subsequent oversight ensuredthat both the humans and animals involvedin the research study were treated humanelyand ethically throughout the duration of thestudy. All AAT standards, as well as programand hospital requirements, were upheld bythe animal-handler teams and theircertifying organizations at all times. At nopoint were there any adverse events thatrequired action on the part of any site foreither the human or animal participants.

There were a few challenges related toprotocol fidelity that were uncovered duringthe pilot study. These were resolved on acase-by-case basis, as appropriate, and wereincorporated into protocol and trainingmodifications for the full trial design asnecessary. For example, one issue related toprotocol fidelity concerned the length ofAAT sessions. While handlers adheredstrongly to the 20 minute suggestedtimeframe for their sessions, it was notedthat 20 minutes was often too long foreither the dog or the child participant. Thisis an important finding because it will benecessary to adjust the timeframe for thefull trial to ensure the well-being of both the therapy animals and the human participants.

Additionally, procedures related to properdata collection methods (i.e., ensuring thecompletion of all forms by participants,recording all designated sessions via propercamera use, and arranging for a back-upstaff member to collect data when necessary)were not always consistently followed.Therefore, modified training materials willbe developed for the full trial to ensure thatproject staff members are fully informed andcomfortable with all of the data collectionprocedures.

Goal 3: Determine the appropriateness and feasibility of the instrumentation chosen to measure distress across the threepopulations (patients, parents/guardians,and therapy dogs)

In addressing this goal, it was found thatsome of the selected instruments workedwell, while others were not feasible or usefulbased upon the populations and designelements of the pilot study.

In examining the patient measures, theOSBD was not found to be a usefulmeasure due to the timing of the AAT visits.The OSBD is intended to rate childbehaviors observed during stressful and/orpainful treatment procedures. However,upon implementation of the pilot study, theresearch team was informed that AAT visitswould not be allowed to occur duringstressful procedures. Similarly, the patientsin the control group had their study sessionsscheduled at times when they were notundergoing stressful procedures. Therefore,behaviors included on the OSBD were notexhibited by any of the participatingchildren in the pilot study, and theinstrument was not determined to be usefulfor examining distress in the patientsparticipating in the CCC Study.

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The Polar RS800CX training watch andPolar WearLink W.I.N.D. transmitters forevaluating heart rate variability were foundto be infeasible due to the intrusiveness ofthe devices, as well as the difficulties staffencountered in utilizing the devices.Conversely, blood pressure was found to bean appropriate and feasible way ofmeasuring physiological distress in thechildren. Previous studies, conducted in avariety of other settings, have measuredlower blood pressure in subjects when a dogis present versus without a dog (Barker &Wolen, 2008; Friedmann, 1995; Tsai,Friedmann, & Thomas, 2010).

In examining the parent/guardianinstruments, the STAI and the PIP wereboth found to be appropriate and feasiblemeasures for evaluating distress; complianceon both measures was quite high and noreported problems were reported. As withthe patient population, the heart ratevariability monitors were found to beinfeasible due to their intrusive and difficult nature.

In investigating the therapy dog measures, it was found that the salivary cortisolinstrumentation and processes were bothappropriate and feasible in evaluating stressin the participating dogs, both in the designof the baseline collection as well as the post-session collection times. With training andpractice, most handlers became accustomedand/or comfortable with collecting salivafrom their dogs. In some cases, handlersthought the process was stressful for their

dogs, and made adjustments to theircollection routines accordingly. For example,one handler determined that the clinic roomwhere she collected the saliva was stressfulfor her dog and decided to change thislocation to the AAT volunteer office. Shefound that her dog was much more calmand comfortable during the saliva collectionprocess in the new location. Regular andopen communication with handlers will beimportant to continue during the fullclinical trial.

The animal-handler self-reports were foundto be feasible, but in need of modification.Asking handlers to rate the “success” of thesessions was determined to be inappropriatesince their primary focus and role is toensure the safety and well-being of theirtherapy dog. For example, asking them torate the level of distress that the humanparticipants experienced is not appropriatesince handlers are not trained humanservices professionals. Other sections of thehandler self-report, including a listing of theparticipants and activities that took placeduring the session, were found to be bothappropriate and feasible.

Finally, the AAT ethogram was found to befeasible, but in need of modification. TheAHA research team was able to properlycode the videos using the ethogram,however there were some positive andaffiliative behaviors that were observed butwere not included on the existinginstrument. Additionally, depending uponthe behavior, it was difficult to know how toconsistently note each behavior (in terms ofduration and/or frequency) and to interpretbehavior scores using the pilot ethogram.

It was therefore determined that thisethogram needed to be modified for thepurposes of the CCC Study, as it wasdifficult to utilize reliably and tended toprimarily focus on negative or aggressivebehaviors that are rarely seen from highlytrained therapy dogs. An ethogram with abalanced roster of behaviors has beendeveloped for use in the full clinical trial. Asbehavior ethograms specifically for therapydogs do not currently exist, the researchteam collaborated with animal behaviorexperts on the creation of this cutting-edgeresearch tool.

The full trial will last

for approximately

12 months, with each

enrolled patient and

family participating

in weekly sessions for

four months.

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Goal 4: Develop recommendations forrevisions to the protocol leading up to a final research protocol for a full clinical trial

After careful consideration of the pilotfindings, the research team has developed anupdated and optimized protocol for the fullclinical trial to address lessons learnedduring the pilot study. The followingmodifications were incorporated into thefull clinical trial design:

The patient population was updated toexpand the diagnosis criteria beyond ALL.Rather than designating specific diagnoses,participants will be children with cancerwho have been recently diagnosed (withinthe past 30 days) and are undergoing aregular schedule of outpatient chemotherapyas the primary eligibility criteria, with aslightly expanded age range of 3-12 years.The full trial will last for approximately 12 months, with each enrolled patient andfamily participating in weekly sessions forfour months. These expanded eligibilitycriteria and four month data collectionperiods will aid the research team inreaching the enrollment target of 132patients across all sites and in havingadequate statistical power to ensure study rigor.

Due to the lack of distress indicated andexhibited by the pilot population, thehypotheses have been modified slightly tofocus on stress/anxiety for patients andparents/guardians and health-related qualityof life for patients. The updated hypothesesfor the full clinical trial are as follows:

H1: Pediatric cancer patients undergoinga consistent, regular chemotherapytreatment regime who receive AAT willexperience less stress/anxiety and will havean improved health-related quality of life(HRQOL) throughout the course of theirtreatment sessions than patients who donot receive AAT.

H2: Parents/guardians of pediatric cancerpatients undergoing a consistent, regularchemotherapy treatment regime whoreceive AAT will experience less stress/anxiety throughout the course of theirchild’s treatment sessions than parents/guardians of patients who do not receive AAT.

H3: Participating therapy dogs will exhibitminimal distress over the course of theCCC Study.

The AAT protocol has been shortened to 15minutes (+/-5 minutes) to address the issuesrelated to dogs and/or the patientsbecoming stressed, tired or disinterested inAAT sessions lasting 20 minutes.

The most significant changes to the full trialstudy design concern the measures andinstrumentation schedule that will beutilized. For the patients, the OSBD and theheart rate variability monitors will no longerbe used. Instead, the State Trait AnxietyInventory – Children (STAI-C), thePediatric Quality of Life InventoryTM(PedsQL), and pulse will be added to theinstrumentation. Blood pressure willcontinue to be measured. The frequency ofthe data collection will also be increased.The STAI-C, pulse and blood pressuremeasures will be used on a weekly basis. The

PedsQL will be used at the time ofenrollment into the study and on their finalsession (four months after enrollment).

For the parents/guardians, the heart ratevariability monitors will no longer be used,but the STAI and PIP will continue. As isthe case with the patients, the frequency ofthe measures will be increased. The STAIwill be used on a weekly basis and the PIPwill be used on a monthly basis. The

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parents/guardians will also be completing aparent proxy of the STAI-C weekly, as wellas a parent report form for the PedsQL atthe time of enrollment and then again attheir final study session (four months afterenrollment).

For the animal-handlers/therapy dogs, thehandler self-report, salivary cortisol andethogram will again be utilized. While thesalivary cortisol collection will remain thesame as the pilot (5 baseline samples andweekly post-session samples), the handlerself-report and the AAT ethogram will bemodified. The handler self-report has beenmodified to focus on the participants (i.e.,who was present) and the activities thatoccurred during the AAT sessions; theirratings of the amount of interest, stress anddistress among human participants havebeen removed to help ensure that their focusis on their therapy dog and not the othersession participants.

The AAT ethogram has been modified toinclude additional positive and affiliativebehaviors. Finally, an additional instrumentwill be utilized for animal-handlers at thetime of enrollment into the study. TheCanine Behavioral Assessment and ResearchQuestionnaire (C-BARQ) will be used togain a better understanding of each dog’sindividual temperament as rated by theirhandler. This additional instrument willincrease the understanding of the completedethograms and salivary cortisol data as they

relate to the amount of stress that aparticular dog may be experiencingthroughout the duration of the study.

Overall, piloting the research design was asuccessful venture for the CCC Study. Eachgoal established by the research team wasmet, and several important lessons werelearned throughout the process. Further, thefindings gleaned from the pilot study willinform the research team in successfullypreparing and implementing a rigorousclinical trial in five pediatric healthcaresettings across the U.S. – a true trailblazer in the field of AAT practice and research.The participating sites are:

• St. Joseph’s Children’s Hospital inTampa, FL

• Monroe Carrell Jr. Children’s Hospital atVanderbilt in Nashville, TN

• Randall Children’s Hospital at LegacyEmanuel in Portland, OR

• UC Davis Children’s Hospital inSacramento, CA

• UMass Memorial Children’s MedicalCenter in Worcester, MA, in partnershipwith Cummings School of VeterinaryMedicine at Tufts in North Grafton, MA

Upon the conclusion of the CCC Study’s fulltrial, it is predicted that our findings willhelp the practice of AAT gain the respectand recognition it deserves – as a credible,viable, and effective treatment option forchildren with cancer and their families.Likewise, by completing the pilot study ofthis groundbreaking research, AHA andZoetis are now one step closer to providingevidence on the healing power of human-animal relationships and the important rolethese bonds can play for children andfamilies in need of support.

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... AHA and Zoetis are

now one step closer to

providing evidence on

the healing power of

human-animal

relationships and the

important role these

bonds can play for

children and families in

need of support.

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Children’s Oncology Group. (2013). What is cancer? Retrieved fromhttp://www.curesearch.org/ArticleView2.aspx?id=8507&l=8634

Endenburg, N., & van Lith, H. A. (2011). The influence of animalson the development of children. The Veterinary Journal, 190 (2),208-214.

Fine, A. H. (Ed.) (2010). Handbook on animal-assisted therapy:Theoretical foundations and guidelines for practice (3rd ed.). SanDiego, CA: Elsevier Inc.

Fotiadou, M., Barlow, J.H., Powell, L.A., & Langton, H. (2008).Optimism and psychological well-being among parents of childrenwith cancer: an exploratory study. Psycho-Oncology, 17, 401-409.

Friedmann, E. (1995). The role of pets in enhancing human well-being: physiological effects. In I. Robinson (Ed.), The Waltham Bookof Human-Animal Interaction: Benefits and Responsibilities Of PetOwnership (pp. 33-53, 39). Oxford: Pergamon.

Friedmann, E., Son, Heesook, & Tsai C. (2010). The animal/humanbond: health and wellness. In A.H. Fine (Ed.), Handbook on Animal-Assisted Therapy: Theoretical Foundations and Guidelines forPractice (3rd ed., pp. 85-107). San Diego, CA: Elsevier Inc.

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Kazdin, A.E. (2010). Methodological standards and strategies forestablishing the evidence base of animal-assisted therapies. In A.H.Fine (Ed.), Handbook on animal-assisted therapy: theoreticalfoundations and guidelines for practice (3rd ed., pp. 519-546). SanDiego, CA: Elsevier Inc.

McCardle, P., McCune, S., Griffin, J.A., Esposito, L. & Freund, L.S.(Eds.). (2011). Animals in Our Lives: Human-Animal Interaction inFamily, Community, and Therapeutic Settings. Baltimore, MD: PaulH. Brookes Publishing Co.

Michel, G., Rebholz, C. E., von der Weid, N. X., Bergstraesser, E., &Kuehni, C. E. (2010). Psychological distress in adult survivors ofchildhood cancer: the Swiss Childhood Cancer Survivor study.Journal of Clinical Oncology, 28(10), 1740-1748.

National Cancer Institute at the National Institutes of Health (2013).Childhood cancers. Retrieved fromhttp://www.cancer.gov/cancertopics/factsheet/Sites-Types/childhood

Nimer, J. & Lundahl, B. (2007). Animal-assisted therapy: A meta-analysis. Anthrozoös, 20, 225-238.

Norberg, A.L., & Boman K.K. (2008). Parent distress in childhoodcancer: A comparative evaluation of posttraumatic stresssymptoms, depression and anxiety. Acta Oncologica, 47, 267-274.

Palley, L.S., O’Rourke, P.P., & Niemi, S.M. (2010). Mainstreaminganimal-assisted therapy. Institute for Laboratory Animal ResearchJournal, 51(3), 199-207.

Tsai, C-C., Friedmann, E., & Thomas, S.A. (2010). The effect ofanimal-assisted therapy on stress responses in hospitalizedchildren. Anthrozoös, 23(3), 245-258.

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Nov 2013