A Randomized Controlled Trial of Symptom Screening by Children With Cancer and Feedback to Providers
Phase: NA
Conditions: Pediatric Oncology, Quality of Life
Sponsor: The Hospital for Sick Children

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A RANDOMIZED CONTROLLED TRIAL OF SYMPTOM SCREENING BY CHILDREN WITH 
CANCER AND FEEDBACK TO PROVIDERS 
 
BACKGROUND  
 
 
There are approximately 1,500 children and adolescents diagnosed with cancer each year in 
Canada and there are currently over 10,000 children living with cancer nationally.1 Over the last few 
decades, impressive gains in survival have been made and now, more than 82% of children with 
cancer will be cured.2 These survival gains have been, in part, attributable to the provision of intensive 
therapies. However, as a result, most children suffer and experience severe and distressing treatment-
related symptoms such as pain, fatigue and nausea.3 In our recent cross-sectional study of 302 
inpatients 8-18 years of age, 99% of children experienced at least one bothersome symptom and 60% 
experienced at least one severely bothersome symptom, including severe pain in 22% and severe 
fatigue in 33% when asked about yesterday or today.4 Symptoms impact on quality of life (QoL), 
morbidity and future psychosocial functioning.5  
 
We know from studies in adult cancer patients that routine collection of patient-reported outcomes 
(PROs), improves patient-clinician communication,6 reduces distress7 and improves QoL.8,9 
Furthermore, a recent randomized trial showed that routine PRO assessment may improve survival in 
adults with metastatic solid tumors.10 Thus, the routine measurement of PROs is considered essential 
to high quality of care.8 Challenges to the incorporation of PROs into clinical practice include lack of 
integration into clinical care work flow.11 We also know that delivery of care consistent with evidence-
based clinical practice guidelines (CPGs) can improve patient outcomes.12 However, compliance with 
CPGs is generally poor.13,14  
Consequently, in Canadian adult oncology practice, screening and assessment of symptoms and 
improving accessibility of supportive care CPGs are important priorities.15-18 Efforts by Cancer Care 
Ontario have culminated in the wide-spread use of a symptom screening tool based upon the 
Edmonton Symptom Assessment Scale (ESAS).19 The ESAS is a validated tool which asks adult 
patients to rate the severity of nine common symptoms including pain, anxiety and nausea. In a 
satisfaction survey of 2,921 patients, 87% of respondents thought the ESAS was an important tool for 
letting healthcare providers know how they feel.20  Furthermore, through an initiative with Cancer Care 
Ontario and the Canadian Partnership against Cancer, evidence-based guidelines were developed to 
manage severe symptoms identified by the tool.20 These efforts have continued to evolve and led to the 
development and implementation of the Interactive Symptom Assessment and Collection (ISAAC) tool, 
Your Symptoms Matter, which allows patients to assess and monitor their symptoms through an online 
computer program. Your Symptoms Matter is available at kiosks in 14 regional cancer centers and 28 
hospitals across Ontario. More than 27,000 patients are screened every month through the system. 
Implementation of ISAAC in the adult cancer setting improved health outcomes,19 led  to decreased 
emergency room visits and triggered clinical action for those with higher symptom scores.21,22 In 
contrast to these advances in adult cancer care, efforts in children are limited.23 We used the 
Knowledge-to-Action cycle24 as the conceptual framework to guide this research program. 
 
Objectives 
 
 
Among children and adolescents 8-18 years of age with cancer seen in hospital daily for 5 days, to 
determine if daily symptom screening and provision of symptom reports to healthcare providers with 
links to supportive care CPGs is associated with the following when compared to standard of care: 
Aim 1: Better self-reported total SSPedi scores  
Aim 2: Better self-reported individual SSPedi symptom, pain (Faces Pain Scale-Revised) and QoL 
(PedsQL 3.0 Acute Cancer Module) scores 
Aim 3: Improved provider documentation of symptoms and intervention provision for symptom control  
 
We hypothesize that daily symptom screening and feedback with links to CPGs will be associated 
with lower total SSPedi scores (less bothersome symptoms), improvement in specific symptoms, pain 
and QoL and better documentation of symptoms and provision of interventions for symptom 

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management.  
 
Preliminary Data 
 
 
Efforts in children to achieve routine 
symptom screening and enhance CPG 
compliance are limited.23 We conducted a 
systematic review and identified the lack of 
appropriate symptom screening tools for children 
with cancer and that no study altered patient 
management based upon identified symptoms.25 
 
SSPedi: Early in our program, we recognized the 
lack of an appropriate symptom screening tool 
for pediatric cancer patients and thus, developed 
the Symptom Screening in Pediatrics Tool 
(SSPedi) (Figure 1).26,27 It is a 15-item symptom 
screening tool for children receiving cancer 
treatments; recall period is yesterday or today. 
Items were generated using a nominal group 
technique among pediatric cancer clinicians and 
a patient advocate.28 Next, based upon input 
from 50 children receiving cancer treatments and 
20 parents of pediatric oncology patients, we 
refined the paper and electronic versions of 
SSPedi and confirmed content validity, 
understandability and ease of use.28-30 The 
electronic version of SSPedi has an audio 
feature which allows specific questions or the 
entire instrument to be read aloud. A help feature provides synonyms for each symptom; these were 
derived primarily from children themselves during cognitive interviewing. 
 
Next, we conducted a multi-center study to evaluate the psychometric properties of SSPedi. 
Among 502 children 8-18 years of age receiving cancer treatments, all were able to complete SSPedi 
without difficulty. We confirmed that SSPedi is reliable, valid and responsive to change. More 
specifically, the intraclass correlation coefficients were 0.88 (95% confidence interval (CI) 0.82 to 0.92) 
for test re-test reliability, and 0.76 (95% CI 0.71 to 0.80) for inter-rater reliability between children and 
parents. Mean difference in total SSPedi scores between groups hypothesized to be more and less 
symptomatic was 7.8 (95% CI 6.4 to 9.2; P<0.001). Construct validity was demonstrated as all 
hypothesized relationships among measures were observed. SSPedi was responsive to change; those 
who reported they were much better or worse on a global symptom change scale had significantly 
changed from their baseline score (absolute mean difference 5.6, 95% CI 3.8 to 7.5; P<0.001).4  
 
SPARK: Supportive care Prioritization, Assessment and Recommendations for Kids (SPARK) (Figure 
2) is a web-based application which builds upon SSPedi and consists of two components: (1) a 
symptom screening component centered on SSPedi; and (2) a supportive care CPG component. CPGs 
contained within SPARK are those that meet rigorous development criteria established by the National 
Guideline Clearinghouse.31 There are patient, family and healthcare provider portals in SPARK. This 
proposal focuses on the patient and provider portals of SPARK. 
 
SPARK pages and function were developed and iteratively refined by performing cognitive 
Figure 1: SSPedi 

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interviews using the think aloud technique with 90 children receiving cancer 
treatment and 60 healthcare providers until 
the website was considered satisfactory for 
longitudinal evaluation.  
 
Next, in a pilot study conducted in 
preparation for the proposed RCT, we 
evaluated the feasibility of daily completion 
of SSPedi for 5 days among children who 
were either admitted to hospital or seen in 
clinic for 5 consecutive days. We defined 
feasibility as the completion of SSPedi 
within SPARK for at least 60% of on-study 
days in at least 75% of participants. In 3 
months, we enrolled 20 participants of 
whom 18 completed assessments all 5 
days. Two children missed one day each: 
one because of transfer to the intensive 
care unit due to a seizure and the second because she was seen in clinic only for blood work and was 
missed by the research team. Consequently, 100% of children met our a priori defined threshold for 
feasibility. All found completion of SSPedi via SPARK was easy and that SPARK was easy to navigate. 
They all thought daily completion was “about right” and not “too much” or “too little” for this population. 
All completely understood their own SPARK bar and line graphs. 
 
Symptom Documentation and Interventions for Symptom Control: Our previous work included the 
description of symptoms documented in the health record and identification of intervention provision for 
symptoms. We created a standard operating procedure and a list of synonyms which met criteria for 
documentation of symptoms. For example “tired”, “feel weak”, “low energy” and “sluggish” were all both 
considered adequate documentation for fatigue. We also created a list of interventions for each 
symptom. For example, acetaminophen, ibuprofen and opioids were all considered interventions for 
pain. We reviewed the medical records of 100 consecutive children and adolescents who had 
completed symptom screening using SSPedi at The Hospital for Sick Children (SickKids). Symptom 
documentation and interventions were generally low for all symptoms except for pain and nausea and 
vomiting. Among those who reported at least medium bother, the proportion of patients in whom the 
symptom was documented by healthcare providers were: problems thinking or remembering (0%), 
changes in how body or face look (4%), changes in taste (3%), feeling more or less hungry (7%), tingly 
or numb hand or feet (10%) and cranky or angry (10%). Among the 21 children with moderately 
bothersome mouth sores, only 62% had any documentation and only 62% had provision of any 
intervention. Among the 33 with severely bothersome fatigue, only 18% had documentation and none 
were given an intervention. While pain was well documented (94%) and associated with interventions 
(100%), it was not completely controlled as 16% of children experienced severely bothersome pain 
despite intervention.   
 
Factors Associated with Total Symptom Score: In our SSPedi validation study, among the 302 patients 
admitted to hospital and expected to be in hospital or clinic 3 days later, older age (P=0.0003) and stem 
cell transplant (P=0.030) were significantly associated with higher SSPedi scores in multiple 
regression.32 
 
Rationale 
 
 
In order to improve symptom control in pediatric cancer, we need a feasible mechanism by which 
children with cancer can be enabled to report and track symptoms, for this information to be readily 
available to clinicians and to facilitate clinician access to supportive care CPGs for symptom 
management. This application builds upon our expertise in pediatric cancer symptom screening, CPG 
Figure 2: SPARK 

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development and conduct of large multi-center pediatric cancer supportive care trials to improve 
pediatric cancer care and QoL. We anticipate the results to be directly translated into patient care if 
successful. 
 
METHODS 
 
This is a multi-center open label RCT and the study schema is shown as Figure 3. The setting is 8 
Canadian academic institutions which care for children with cancer; all participated in our SSPedi 
validation study.4  
 
Intervention and Control Groups 
 
Intervention Arm: For those randomized to the intervention arm, we will use the procedures that were 
feasible in our longitudinal pilot study. Participants will complete symptom screening using SPARK 
once daily on a study-supplied iPad. For inpatients, daily reminders to complete SSPedi will appear on 
the iPad. Reports will be available to the child at any time. For outpatients, clinical research associates 
will provide the iPad in person daily and reports may be viewed at those encounters. Once daily was 
considered the optimal frequency for this population in our pilot study. The intervention is daily 
symptom screening with provision of reports to the healthcare team. Severe symptoms will result in 
email alerts. More specifically, SSPedi reports will be printed daily and provided in the patient chart or 
electronic health records (Figures 4a and 4b show example reports). On days 1 and 3, an alert will be 
emailed to the physician providing direct medical care if any symptom is “a lot” or “extremely” 
bothersome (score 3 or 4 on 0-4 scale). Reports and alerts will have links to SPARK-housed CPGs. 
The procedures developed for email correspondence have been approved by SickKids privacy 
consultants.  

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Control Arm: Participants randomized to the control arm will not complete daily symptom screening. 
They will complete SSPedi on days 1 and 5 to obtain the primary outcome.  Health care providers will 
not be notified of their SSPedi scores and no symptom reports or symptom alerts will be generated. 
 
For both study groups participant’s guardian will be asked to fill out a household demographic form.  
 
 
Allocating Participants 
 
 
The allocation sequence will be computer generated and will be concealed from all participants, 
healthcare providers and research team members. Consenting participants will be randomized 1:1 to 
intervention vs. control groups using permuted block sizes and stratified by treatment (stem cell 
transplant yes vs. no) and age (8-10, 11-14 and 15-18 years) as our previous data suggested that 
these factors were the most strongly associated with higher total SSPedi scores. Assignment of 
enrolled participants will be communicated by email to the institutional principal investigator and clinical 
research associate following randomization. 
 
Protecting against Bias 
 
 
We hypothesize that the key elements to improving symptom control will be: (1) the systematic 
measurement of bothersome symptoms; (2) providing this information to healthcare providers; and (3) 
improving access to supportive care CPGs for providers. Given that this trial is randomized at the 
individual level and not at the cluster level, clinicians caring for patients in the control group may be 
more aware of supportive care CPGs.  Although this information does represent contamination, we 
hypothesize that without a mechanism for children and adolescents to report symptoms, this level of 
contamination will not substantially influence the effectiveness of the intervention. However, we will 
measure documentation of symptoms and provision of interventions to facilitate interpretation of trial 
Figure 4a: Provider Single Day Report 
Figure 4b: Provider Multi-Day Report 

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results. We are not conducting a cluster randomized trial because there are only 17 centers in Canada 
that treat children with cancer, and site numbers and logistical challenges preclude this study design.  
 
Since the main outcomes are subjective, they will be reported by the participants themselves. They 
will not be blinded to allocation, thus raising concerns of reporter bias. Participants in the intervention 
arm will not know which of the five SSPedi scores they provide for the trial is the outcome; this should 
lessen the concern about reporter bias. The use of a standard of care control arm, in contrast to an 
attention control arm, is consistent with the more pragmatic nature of this randomized trial.   
 
In our control group, we will obtain SSPedi scores at baseline and day 5 as they are required for the 
planned statistical analysis. We will not share these scores with the child, family or providers and thus, 
we do not anticipate bias. Further, in our studies of SSPedi and SPARK, we explicitly asked children 
whether they shared scores with their providers and even when patients can access their reports at any 
time (which will not be the case in our control patients), they almost never tell their providers this 
information. Thus, the risk of contamination is minimal.  
 
Planned Inclusion and Exclusion Criteria 
 
 
We will include pediatric patients with cancer who are 8-18 years of age, who can understand 
English and who are expected to be in hospital or in clinic daily for 5 days. Five days was chosen to 
allow longitudinal daily evaluation but preserve feasibility as few children are admitted or seen daily for 
longer than 5 days. Exclusion criteria will be illness severity, cognitive disability, or visual impairment 
that preclude utilization of SPARK according to the primary healthcare team. 
 
Study Duration 
 
 
The study period is 5 days. The study is complete on day 5 after completion of the intervention and 
ascertainment of outcomes. 
 
Primary and Secondary Outcome Measures 
 
 
For both intervention and control groups, all outcomes will be obtained in an identical fashion. 
Primary and secondary outcomes will be obtained at baseline and day 5; a clinical research associate 
will visit the participant at those two visits to facilitate self-reported outcomes. The primary outcome will 
be the self-reported total SSPedi score on day 5. The total SSPedi score is a validated measure that 
reflects the total burden of bothersome symptoms experienced.4 The total score is the sum of each of 
the 15 items’ Likert scores which range from 0 (not at all bothered) to 4 (extremely bothered) to yield a 
total score that ranges from 0 (no bothersome symptoms) to 60 (worst bothersome symptoms).  
 
Secondary outcomes will be self-reported individual SSPedi symptom, pain (Faces Pain Scale-
Revised) and QoL (PedsQL 3.0 Acute Cancer Module) scores. We will also measure documentation of 
symptoms and intervention provision for symptom control. Self-reported pain will be assessed using the 
Faces Pain Scale-Revised which consists of a series of horizontal faces that depict a neutral facial 
expression of no pain on the left and worst pain on the right. It has 6 faces and may be scored on a 0 to 
10 scale in which higher numbers denote more pain.33 Faces Pain Scale-Revised is psychometrically 
sound and feasible for children 4 to 18 years of age.34 Self-reported QoL will be measured using the 
PedsQL 3.0 Acute Cancer Module. This measure is a multidimensional instrument that is reliable and 
valid in children with cancer.35-38 It assesses pain and hurt, nausea, procedural anxiety, treatment 
anxiety, worry, cognitive problems, perceived physical appearance and communication. The self-report 
7-day recall version will be used.  
 
Documentation of symptoms and intervention provision for symptom control will be abstracted from 
the patients’ health records using the procedures we developed. Interventions for each symptom will be 
categorized as any intervention provided vs. no intervention provided.  Both documentation of 
symptoms and interventions for these symptoms will be described for each specific symptom. These 
outcomes will be obtained on day 5 with a one day window before and after the day 5 assessment. In 
other words, if the participant completed SSPedi on a Tuesday, we would accept documentation of that 

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symptom (or provision of an intervention for that symptom) if it were recorded in the health records on 
Monday, Tuesday or Wednesday. 
 
 
The primary and secondary PROs will be measured by patient self-report while documentation of 
symptoms and intervention provision will be abstracted from the health record. Self-reported PROs and 
QoL measures are essential in this study as the intervention is focused on reducing symptom burden. 
 
Sample Size Justification 
 
 
We used data from our SSPedi validation study for power calculations.4 We recruited 302 children 
who were hospitalized and expected to be in hospital or in clinic 3 days later. Children completed 
SSPedi on days 1 and 4 and a 5-point global symptom change scale on day 4. The average absolute 
change in total SSPedi scores for those who rated they were a little worse or a little better (1-point 
change) was 2.7 which is the minimally clinically important difference. The average standard deviation 
of the two total SSPedi scores (on days 1 and 4) was 8.5. Thus, with 80% power and alpha of 0.05, we 
will require 157 patients per group or 314 patients total. Assuming 10% will be non-evaluable, we will 
recruit 345 total.  
 
Recruitment  
 
 
All 8 participating institutions enrolled patients in our previous SSPedi validation study; all have 
experience with SSPedi, recruited patients in a timely fashion and submitted high quality data. 
Investigator calls twice a month will focus on recruitment status and enrollment issues. Specific 
outreach to each institutional principle investigator and clinical research associate will be made in the 
event of lagging accrual and a specific plan to rectify accrual will be made. If accrual continues to lag, 
the institution may be replaced. 
 
Table 1 shows the number of expected eligible participants at the 8 sites; estimates were based on 
our pilot study. We anticipate 160 eligible patients per year. Thus, assuming that at least 60% of 
patients are identified and consent, we will complete enrollment within 4 years although accrual may 
take longer given the COVID-19 pandemic.  Data analysis and knowledge dissemination will occur in 
year 5.  
 
Based upon our pilot data of 20 children completing longitudinal symptom screening, we do not 
anticipate problems with compliance. The loss to follow-up rate is likely very small given the 5 day 
nature of the study; we anticipate it will be less than 10%. There are 8 Canadian centers participating. 
 
ANALYTIC PLAN 
 
Baseline characteristics: Summary statistics on baseline characteristics will be calculated within each 
study arm and presented in a table – means and standard deviations (SDs) for variables treated as 
continuous, counts and percentages for categorical variables, along with total numbers with missing 
data.   
Table 1: Site (PI): Number new cancer 
patients annually (all ages) 
Year 1 
Enroll 
Year 2 
Enroll 
Year 3 
Enroll 
Year 4 
Enroll 
Year 5 
 
Analyze 
 
Publish 
 
KTE 
Toronto (Sung): 300-350 
80 
80 
80 
80 
Vancouver (Dix): 120-160 
30 
30 
30 
30 
Winnipeg (Vanan): 40-60 
10 
10 
10 
10 
London (Patel): 55-70 
10 
10 
10 
10 
Hamilton (Gibson): 65-80 
10 
10 
10 
10 
Ottawa (Johnston): 55-70 
10 
10 
10 
10 
Halifax (Kulkarni): 55-70 
10 
10 
10 
10 
Edmonton (McKillop) 40-70 
10 
10 
10 
10 
     TOTAL 
170 
170 
170 
170 

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Outcomes: Similar tables will be created for all study outcomes.  Individual SSPedi symptom scores 
(which would require a total of 15 X 4 = 60 percentages for full reporting) will be summarized by the 
percentages of participants with scores of 3 or 4, the two most bothersome categories. 
 
Comparative Analyses: The primary analysis will compare the day 5 total SSPedi scores between 
randomized groups using a linear regression model (analysis of covariance, ANCOVA) adjusting for the 
baseline SSPedi score, the two stratification variables age (8-10, 11-14 and 15-18 years) and treatment 
(hematopoietic cell transplant yes or no), diagnosis group (leukemia/lymphoma, solid tumor or central 
nervous system tumor) and relapse status (yes or no).  The model-based estimated mean difference in 
day 5 scores between groups will be presented with a 95% confidence interval (CI) and a p-value for 
the test of the hypothesis that the difference is zero. If the distribution of residuals in this linear model is 
demonstrably skewed, we will use the non-parametric bootstrap with 2000 replications to estimate the 
standard error of the treatment effect (for hypothesis testing) and to estimate the 95% CI for the 
treatment effect.  
 
Secondary outcomes will be analyzed as follows.  
  
1. Self-reported individual symptoms at day 5 on the SSPedi instrument: For each of the 15 
ordinal outcomes representing symptoms (scored 0-4), a proportional odds model will be fitted 
using the corresponding baseline symptom score, participant age and treatment as covariates.  
As some individual symptoms may be uncommon, to avoid specifying models that may be 
overfitted for those symptoms, these models will use only this minimal set of three covariates. 
The estimated odds ratio for the intervention (representing the odds of having a higher versus 
lower score in the intervention group) will be estimated and presented along with a 95% CI. 
2. Faces Pain Scale-Revised: In keeping with common practice, this 6-point scale (scores of 0, 2, 
4, 6, 8,10) will be treated as a continuous variable and analyzed using ANCOVA in the same 
way as the primary SSPedi outcome.  To check the sensitivity of the substantive finding (i.e., 
whether the conclusion about efficacy is the same) to the analytic method, the analysis will be 
repeated using the same ordinal model used for the individual SSPedi components. 
3. PedsQL 3.0 Acute Cancer Module domain scores:  Each of these 8 scores will be treated as 
continuous variables and analyzed using ANCOVA in the same way as the primary SSPedi 
outcome.   
4. Documentation of symptoms on day 5 (±1 day): Analyses will involve three analyses for 
each symptom class. Each analysis will fit a logistic regression model to estimate the odds ratio 
for documentation (on day 5 ±1 days) comparing intervention groups, adjusting for age and 
treatment. It is possible that there will be too few documentation events to reliably fit this three-
parameter model to a sufficient number of the 15 symptoms. To be consistent across analyses 
of symptoms, if more than 5 of the 15 symptoms have fewer than 30 documentation events for 
any of analyses a, b, or c below, all treatment effects here will be estimated by a simple 
difference in the proportions with documentation, p-values will be computed from the Fisher 
exact test, and 95% confidence intervals will use the Newcombe method. 
a. Each participant will be classed as having the symptom documented or not. All 
participants are included in the analytic sample for each symptom. 
b. The analytic sample will be limited to those participants who self-report the symptom on 
the day 5 SSPedi (symptom score > 0).  
c. The analytic sample will be limited to those participants who have the most bothersome 
self-report of the symptom on the day 5 SSPedi (symptom score ≥ 3). 
5. Interventions for symptoms: Analyses will follow a similar flow to the analyses of 
documentation of symptoms. For each of the 15 symptoms, each participant will be classified as 
having an intervention at day 5 (±1 days).  Also collected is whether interventions were 
administered specifically for the specific symptoms. For example, acetaminophen may be 
administered for fever or pain. As interventions are expected to be more uncommon than 
symptoms, all treatment effects will be estimated by simple differences in the proportions with 
interventions, p-values will be computed from the Fisher exact test, and 95% confidence 

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intervals for differences in proportions will use the Newcombe method. 
a. Each participant will be classed as having an intervention for the symptom or not. All 
participants are included in the analytic sample for each intervention-symptom pair. 
b. The analytic sample will be limited to those participants who self-report the symptom on 
the day 5 SSPedi (symptom score > 0).  
c. The analytic sample will be limited to those participants who have the most bothersome 
self-report of the symptom on the day 5 SSPedi (symptom score ≥ 3). 
 
Missing Data: The PedsQL will be scored according to its scoring guide, which includes rules for 
scoring in the presence of missing elements on each domain modules.  No other deterministic rule-
based method will be used to deal with missing data.   
 
If more than 5% are missing data on data needed to fit any of the analytic models (for the primary 
outcome, individual symptom scores, Faces Pain Scale-Revised, and PedsQL 3.0 Acute Cancer 
Module domain scores) the results for that model will use multiple imputation. A set of 20 complete 
datasets will be generated using separate within-treatment-group imputation models. These models will 
include all the study outcomes listed just above, and the key covariates that appear in our adjustment 
models (age, treatment, diagnosis group and relapse status). The models will be fitted in each imputed 
dataset and the pooled estimate of the treatment effect and its standard error will be computed using 
Rubin’s rules.  
 
Analyses of documentation and interventions will not use any imputation. There can be no missing 
data for these outcomes: if a symptom is not documented in the health record and there is no record of 
an intervention being used, then this constitutes a ‘no’ for the outcome. While it is possible that the 
SSPedi symptom score needed for the identification of the analytic datasets in analyses (4b, 4c, 5b, 
and 5c) is missing for some participants, the more exploratory nature of these analyses led us to the 
decision to use only observed data for these outcomes.  
 
We will conduct one end-of-study analysis. There are no planned subgroup analyses. 
 
Justification for Methodological Choices 
 
 
A lower age limit of 8 years was chosen as this is the youngest age for which SSPedi has been 
validated. However, in parallel work, we have developed a proxy (2-7 years) and self-report (4-7 years) 
version of SSPedi for younger children and we are currently evaluating the reliability and validity of 
these instruments. Future work will expand SPARK using these tools in development. 
 
We plan to conduct this study among English-speaking children because SSPedi is currently only 
available in English. Translation to other languages is in progress and future work will expand SPARK 
to include other languages. 
 
 
INNOVATION, KNOWLEDGE TRANSLATION AND FUTURE PLANS 
 
Innovation and Knowledge Translation and Exchange (KTE) 
 
 
An innovative approach throughout our research program is the engagement with choice 
architecture experts to enhance the design of SPARK. Choice architecture is important as context can 
be created to nudge people into actions.29,39 For instance, the layouts, message framing, visual 
elements and other contextual cues in the SPARK platform have been optimized to maximize the 
likelihood that the platform is used and the material is understood. We will continue to incorporate 
choice architecture input as we execute the trial.  
 
The targets of our KTE efforts are patients, families, healthcare providers and decision makers 
including hospital and governmental administrators. 
 
Integrated KTE: To increase awareness and to engage with a variety of stakeholders, we will create an 
Advisory Panel. The Panel will include two childhood cancer survivors, one parent of a child with 

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cancer, healthcare providers and hospital administrators. We will meet face-to-face or by 
teleconference at least annually to discuss progress and identify opportunities for KTE. 
 
End of Grant KTE: We will publish the results of this study in peer-reviewed journals (minimum of 3 mid 
to high impact journals) and support attendance at national and international conferences. We plan to 
distribute plain language summaries throughout the Children’s Oncology Group (COG), the C17 
Research Network (represents the 17 centers in Canada) and the Pediatric Oncology Group of Ontario 
(represents the 5 centers in Ontario). We also plan to hold regular webinars and podcasts. The 
SickKids Industry, Partnerships and Commercialization office will help promote SPARK as a no cost 
web-portal for hospital use within Canada, offering the license to purchase to use the platform, 
technical support and data management outside of Canada. In order to further enhance KTE, we will 
create an end-of-grant report which summarizes the processes refined to achieve symptom screening 
and symptom feedback to providers. This report will include the steps taken, challenges encountered 
and solutions to those challenges. This report will help other institutions to implement the approach 
expeditiously. 
 
Future Plans 
 
Upon completion of this trial, we will use the information garnered to propose an incrementally more 
complex RCT in which we will achieve electronic health records integration of symptom data and create 
actions in the health records based upon high symptom scores. It is premature to undertake this trial in 
pediatric oncology at present as 3 of our 8 sites do not yet have computerized physician order entry. 
Further, achieving electronic health records integration will require years of preparatory work; we plan 
to conduct this work alongside this trial such that the next RCT will include electronic health record 
integration. This next trial will also include ambulatory patients with remote symptom screening from 
home. 
 
A second future project will be to link the data from this trial with a pediatric cancer national 
database named Cancer in Young People-Canada (CYP-C). CYP-C has been collecting detailed 
demographic, cancer-related, and treatment data on all children with cancer in Canada since 2001 and 
it currently includes > 13,000 patients. The consent form for this application’s RCT will allow future 
linking to CYP-C such that we can identify patient and institutional factors associated with high 
symptom scores and we can evaluate survival outcomes for those with uncontrolled symptoms. 
 
 
 

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References 
 
1. 
Childhood Cancer Canada Foundation. Learn More.  http://www.childhoodcancer.ca/learn-
more/. 
2. 
Canadian Cancer Society's Steering Committee on Cancer Statistics. Canadian Cancer 
Statistics. Toronto, ON: Canadian Cancer Society;2011. 
3. 
Baggott C, Dodd M, Kennedy C, Marina N, Matthay KK, Cooper BA, Miaskowski C. Changes in 
children's reports of symptom occurrence and severity during a course of myelosuppressive 
chemotherapy. J Pediatr Oncol Nurs. Nov-Dec 2010;27(6):307-315. 
4. 
Dupuis LL, Johnston DL, Baggott C, Hyslop S, Tomlinson D, Gibson P, Orsey A, Dix D, Price V, 
Vanan M, Portwine C, Kuczynski S, Spiegler B, Tomlinson GA, Sung L. Validation of the 
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