Journal Pre-proof

Spanish Adaptation of the Pediatric Memorial Symptom Assessment Scale for

Children, Teens, and Caregivers

Maria Laura Requena, MSc Social Sciences, Liliana Orellana, PhD, Valeria Cordeiro,
MD, Flavia Luna, RN, Maria S. Bevilacqua, MD, Karina Gomez, MD, Joanne Wolfe,
MD, MPH, Veronica Dussel, MD, MPH
PII: S0885-3924(20)30850-2
DOI: https://doi.org/10.1016/j.jpainsymman.2020.10.022
Reference: JPS 10696

To appear in: Journal of Pain and Symptom Management

Received Date: 29 August 2020

Revised Date: 20 October 2020
Accepted Date: 21 October 2020

Please cite this article as: Requena ML, Orellana L, Cordeiro V, Luna F, Bevilacqua MS, Gomez K,
Wolfe J, Dussel V, Spanish Adaptation of the Pediatric Memorial Symptom Assessment Scale for
Children, Teens, and Caregivers, Journal of Pain and Symptom Management (2020), doi: https://
doi.org/10.1016/j.jpainsymman.2020.10.022.

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© 2020 Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine
Spanish Adaptation of the Pediatric Memorial Symptom Assessment Scale for Children,

Teens, and Caregivers

Maria Laura Requena, MSc Social Sciences,1 Liliana Orellana, PhD,2 Valeria Cordeiro, MD,1 Flavia

Luna, RN, 3 Maria S Bevilacqua, MD,4 Karina Gomez, MD,3 Joanne Wolfe, MD, MPH,5,6,7 Veronica

Dussel, MD, MPH1,8

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Affiliations:

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1
Center for Research and Implementation in Palliative Care, Instituto de Efectividad Clínica y Sanitaria,

Buenos Aires, Argentina; -p

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2
Biostatistics Unit, Deakin University, Geelong, Australia;
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3
Grupo de Trabajo de Cuidados Paliativos, Hospital Pedro de Elizalde, Buenos Aires, Argentina;
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4
Unidad de Cuidados Paliativos, Hospital de Pediatría Juan P Garrahan, Buenos Aires, Argentina;
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5
Department of Pediatrics, Boston Children’s Hospital, Boston, MA;
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6
Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Boston, MA;
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Harvard Medical School, Boston, MA;

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Dana-Farber / Boston Children’s Cancer and Blood Disorders Center, Boston, MA.

Address correspondence to:

Veronica Dussel, MD, MPH

Associate Research Scientist, Pediatric Palliative Care

Dana-Farber Boston Children’s Cancer and Blood Disorders Center

And

Director, Center for Research and Implementation in Palliative Care (CII-CP)

Institute for Clinical Effectiveness and Health Policy (IECS)

450 Brookline Ave

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Boston, MA 02215

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Email: veronica_dussel@dfci.harvard.edu
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Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE for Disclosure
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of Potential Conflicts of Interest and indicated no potential conflicts of interest.
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Author Contributions: Dussel, Requena, and Orellana had full access to the data and take

responsibility for its integrity and accuracy of data analysis.

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Study concept and design: Dussel, Requena, Orellana

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Data acquisition and assembly: Requena, Luna, Cordeiro, Gomez, Bevilacqua

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Data analysis and interpretation: Requena, Dussel, Wolfe, Orellana

Statistical Analysis: Orellana, Requena, Dussel

Drafting of manuscript: all authors

Critical revision of the manuscript for important intellectual content: all authors.

Obtained Funding: Requena, Wolfe, Dussel

Administrative, Technical, or Material Support: Requena, Dussel

Study Supervision: Dussel

Running Head: Validation of Spanish Pediatric-MSAS

Keywords: Memorial Symptom Assessment Scale, pediatrics, cancer, symptom distress, patient

reported outcomes, MSAS, symptom assessment, validity

Abbreviations:

MSAS: Memorial Symptom Assessment Scale

Pediatric-MSAS-Sp: Pediatric MSAS Spanish

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Number of Tables: 5 (five) and 1 (one) box

Number of Figures: 5 (five) -p

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No. References: 28 (twenty-nine)
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Word Count: 247 (abstract), 3,469 (manuscript)

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Abstract
Context. There are no validated Spanish tools to assess symptom burden in pediatric cancer. The

Pediatric Memorial Symptom Assessment Scale (Pediatric-MSAS) is an English valid multidimensional

and comprehensive instrument.

Objectives. To validate Pediatric-MSAS-Spanish (MSAS-Child, MSAS-Teen, and MSAS-Caregiver

versions) in cancer patients treated in two public hospitals in Buenos Aires, Argentina.

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Methods. Cross-sectional study, classical psychometric theory. We recruited a convenience sample of

148 caregivers of children ≥2 years old, 51 young children (7 to 12 years) and 48 adolescents (≥13

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years). We assessed feasibility, comprehensibility, internal consistency, and convergent and known-

groups validity.
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Results. Pediatric-MSAS-Spanish was feasible, acceptable and comprehensible. Reliability of MSAS-
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total and subscale scores was satisfactory (Cronbach alpha: 0.90, 0.89, 0.71 respectively for caregiver,
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teen, and child MSAS-total score). MSAS-total caregiver, teen, and child scores met a priori criteria for

convergent validity correlating with Pediatric Quality of Life Inventory total scores (Spearman correlation
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(rs)=-0.59, -0.66, and -0.32, respectively) and visual-analogue-wellbeing scores (rs=-0.63, -0.46, and -
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0.4, respectively). Caregiver-teen correlation was strong for total (rs=0.78) and physical (rs=0.85)

scores, and moderate for global distress index (GDI) (rs=0.64) and psychological (rs=0.45) scores.

MSAS-total caregiver-child correlation was moderate (rs=0.30) and Kappa analysis showed poor

agreement. All MSAS-Caregiver scores and MSAS-Teen total and physical scores differentiated

inpatients/outpatients and patients on/off-treatment, while MSAS-Teen psychological and GDI

subscales or MSAS-Child scores did not.

Conclusion. Pediatric-MSAS-Spanish is feasible and reliable for assessing symptom burden in

children with cancer. Validity of MSAS-Caregiver and MSAS-Teen was largely supported. Further work

on MSAS-Child is warranted.
Key Message
We report the first validation of a caregiver version of Pediatric-MSAS and the validation of Pediatric-

MSAS in Spanish (MSAS-Child, MSAS-Teen, and MSAS-Caregiver). Results support the concurrent

use of Pediatric-MSAS-Spanish for parents and children and extends the instrument's use to children

as young as 2 years old.

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Introduction
Whenever possible, the assessment of children’s symptoms and quality of life should include both child

and parent perspectives.(1–3) The pediatric Memorial Symptom Assessment Scale (Pediatric-MSAS) is

a self-report, multidimensional instrument,(4,5) the broadest of its kind.(6) Although frequently used in

children with cancer,(7–11) the tool does not have a validated version for parents. This study extends

Pediatric-MSAS’ reach by validating Spanish versions of the child and teen instruments and adding one

for caregivers.

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Pediatric-MSAS was adapted from the adult version(12) and validated in children with cancer rendering

two versions: MSAS 10-18,(4) recommended for 13 to 18 years old, and MSAS 7-12,(5) for 7 to 12
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years old. These instruments evaluate 31 and 8 symptoms respectively. Both versions showed good
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convergent and known-groups validity; reliability (Cronbach α) for all MSAS 10-18 scores was above
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0.80 and for MSAS 7-12 total score, 0.67.(4,5) Several adaptations and translations of Pediatric-MSAS

have been published but not formally validated: a proxy-version for pediatric nurses,(13) including the
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31 symptoms from MSAS 10-18; PediQUEST-MSAS (PQ-MSAS),(11) used in children with advanced
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cancer that includes: PQ-MSAS 7-12 (8 symptoms, switched itch for dyspnea), PQ-MSAS 13-18 (24
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symptoms), and PQ-MSAS-Proxy for parents (26 symptoms, the 24 from PQ-MSAS 13-18 plus

bleeding and seizures); a Swedish version of Pediatric-MSAS for caregivers,(9) (31 symptoms); and,

Spanish versions of Pediatric-MSAS 7-12 and 10-18.(14)

The aim of this study was to validate Pediatric-MSAS in Spanish for Argentina among children and

adolescents with cancer and their caregivers. The Spanish adaptation includes three versions: MSAS-

Child (for children 7 to 12 years old), MSAS-Teen (for children 13 and above), and MSAS-Caregiver

(for parents). For each version, we evaluated conceptual equivalence, feasibility, comprehensibility,

acceptability; and explored whether the timeframe for the questions, past week, was correctly

interpreted. Finally, we examined reliability, and construct (convergent and discriminant) validity testing
the following hypotheses: MSAS scores will: (H1) show inverse correlation with quality of life scores;

(H2) display inverse correlation with general well-being scores; (H3) have moderate to high correlation

between caregiver and patient MSAS scores, higher for the total and physical than for the global

distress index and psychological sub-scores; and, (H4) distinguish patients receiving and not receiving

cancer treatment in the past 10 days, and (H5) discriminate inpatients from outpatients.

Methods

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Design and Setting

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Cross-sectional study conducted at two public pediatric tertiary level hospitals in Buenos Aires city,

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Argentina. Data were collected between April and July 2017.
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Participants

We enrolled children 2 years old and above, with a diagnosis of cancer at any stage, that were on or
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off-treatment, with active disease or in remission, and one of their caregivers. Caregivers and patients
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≥7 years old had to be Spanish native-speakers. We excluded patients with leukemia in maintenance

phase, clinically unstable at the time of recruitment and/or with comorbidities (e.g. asthma, HIV). The
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caregiver (mother, father, or guardian) provided signed informed permission/consent for the patient and
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themselves. Teens (≥13yo) provided written consent and children (7-12yo) gave verbal assent prior to

participation. Institutional review boards at each site approved the study.

Recruitment

We identified candidate patients through clinic rosters and ward rounds and confirmed eligibility using

medical records and informal interviews with treating physicians. Caregiver and patient (if ≥7yo) or

caregiver only (when patients <7yo) were invited to participate. We recruited a purposeful sample to

ensure balance in age groups (<7yo, 7-12yo, and 13yo and above), disease status and treatment

intensity.
Study Instruments

Pediatric-MSAS Spanish (Pediatric-MSAS-Sp)

Spanish MSAS-Child (for 7 to 12 years old) and MSAS-Teen (for adolescents 13 and above) was

adapted in 2001 by an interdisciplinary team that included two authors (VD, MSB) and followed

international standards of cross-cultural adaptation(15) including forward and back translation, team

review and approval by author. The same adaptation team developed MSAS-Caregiver based off

MSAS-10-18. The three versions use neutral Spanish. For the current study, we consulted with

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clinicians from six Latin American countries who confirmed face validity and suggested some symptom

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descriptors to increase understanding across the region.

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MSAS-Child evaluates 9 symptoms, MSAS-Teen 31, and MSAS-Caregiver 33 symptoms. For each
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symptom reported, frequency, severity, and extent of bother are assessed (for some symptoms only the

latter two are asked). The list of symptoms, timeframe, administration style, response options and
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scoring for each version are shown in Box 1. Following Wolfe et al., all scores were coded in a 0 to 100
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scale (100 worst).(16) Individual, subscale and total scores were calculated if at least 50% of the items

were answered.
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Pediatric Quality of Life Inventory (PedsQL 4.0) Generic Core Scale

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This well validated 22-item quality of life instrument evaluates four domains of health related quality of

life (HRQOL), physical, emotional, social and school functioning, in children from 2 to 18 years of

age.(17) We used the Spanish for Argentina age- and respondent- adapted versions, which showed

good internal consistency and discriminant validity.(18) We used “during the past 7 days” as the

timeframe for all participants. Total and subscale scores have a 0-100 range, where 100 indicates best

quality of life.
Visual analogue wellbeing scale (VAS-WB)

A one-item instrument assessed overall wellbeing: “How well did you/your child feel in general.” Time

frame matched MSAS scales: “during the past week” for caregivers and teens and “yesterday or today”

for 7-12yo. VAS-WB anchors were “Not well at all” and “Extremely well”.

Sociodemographic and clinical data form

A 17-item questionnaire gathered patient and caregiver’s information, including date and place of birth,

gender, highest education level, health insurance, and household income and size. Clinical data was

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extracted from medical records: type of cancer, date of diagnosis, disease status (relapse, progression,

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regression, full remission), date of last change in status, and type and dates of any cancer treatments

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Comprehensibility and Acceptability Questionnaire
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To evaluate comprehensibility (degree of difficulty and understanding of questions and printed format),

acceptability (burden), and relevance of Pediatric-MSAS-Sp we developed de novo a semi-structured

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survey. Structured items used a 5-point Likert scale with anchors “not at all” to “very much.” All domains
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included open ended questions.

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Timeframe accuracy

To understand how participants interpreted the timeframe, i.e. “during the past week,” following survey

completion researchers asked caregivers and teens the date/s they/their child experienced each

symptom, whether it was present “yesterday and/or today”, and if so, extent of bother in past two days

(using the corresponding MSAS item).

Study procedures

The study was carried out in two phases. Phase I (Initial linguistic validation): To establish conceptual

equivalence, research staff instructed the first participants to think-aloud as they responded. After this

process, participants completed all Phase II procedures. Phase II (Validation): All instruments were
completed in printed format consecutively on the same day. Research staff administered the socio-

demographic form first and the MSAS timeframe evaluation, when appropriate, at the end. All

caregivers and children ≥7yo completed the corresponding Pediatric-MSAS-Sp, the Comprehensibility

and Acceptability questionnaire, PedsQL 4.0, and VAS-WB. These instruments were self-administered

or read to participants depending on age and request for help, as explained in Box 1 for Pediatric-

MSAS-Sp. If after two rounds of instructions, participants continued to require assistance, the tools

were administered by an investigator. Whenever possible, the study was conducted first with the

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child/teen and separate from the caregiver.

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Data Analysis

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Phase I. For each version of Pediatric-MSAS-Sp, the research team discussed problematic
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questions/wording identified through the think-aloud method(19) and changes, when appropriate, were

decided by consensus. Iterative cycles of think-aloud and instrument refinement continued until no
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further issues were detected. Phase II. a) Feasibility was defined for each Pediatric-MSAS-Sp version
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as ≥90% participants able to answer it and ≥80% administered as intended (i.e. self-administered for

subjects >7yo and research-administered for 7yo); b) Patterns of use. We examined proportion of
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missing items, whether all symptom questions and response options were used, proportion using
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highest and lowest scores, and usage of “other symptoms” items; c) Comprehensibility and

acceptability questionnaire responses were summarized as means, medians, or proportions for

structured items. Open-ended items were coded and grouped into categories. We used the Chi-square

test to explore associations between feasibility, comprehensibility with socioeconomic and demographic

factors (child’s age, educational level and household income level analyzed as above or below poverty

and indigence lines obtained from the National Institute of Statistics and Census);(20) d) Timeframe

accuracy is reported as proportion of participants who reported that symptoms occurred within the prior

week and within the past two days.

We tested internal reliability of the summary (total and subscale) scores using Cronbach alpha and

considered values >0.70 as appropriate.(21) Construct validity hypotheses H1 to H3 are reported as

Spearman correlations (rs) and 95% confidence intervals (CI). For H1 and H2 we anticipated moderate

correlations (0.3-0.49)(22) as quality of life and overall wellbeing are related with symptoms but do not

measure the same constructs. For H3 we anticipated strong correlations (≥0.5)(22) for parent-teens

and moderate for younger children. We further explored the relationship between MSAS and

categorical PedsQL (<60, “Poor”; 60-79, “Fair”; ≥80, “Very good/Excellent”)(23) total scores (H1), using

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Kendall correlation Tau b as a test for ordinal categories. For H3, patient-caregiver agreement, we also

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calculated the Kappa statistics regarding symptom presence. Given patient-caregiver views tend to be

complementary, rather than fully concordant, we considered a Kappa ≥0.4 as acceptable. To analyze
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known-groups validity, we compared MSAS scores for patients who received cancer directed treatment
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in the past 10 days and those that didn’t (H4) and in- and out-patients (H5) using the Wilcoxon ranked
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test.
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Sample size considerations

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We planned to recruit 150 caregivers, including 50 adolescents and 50 children 7-12 years old based
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on feasibility and pragmatic considerations. The target sample sizes would a) produce Spearman’s

correlation 95%CI of width 0.32 for caregivers and 0.56 for teens or children (H1-H3); b) achieve 80%

power to detect moderate differences (Cohen’s D = 0.46) for parent’s scores and large differences

(Cohen’s D = 0.80) for children and teens’ scores between the groups (H4-H5). This last calculation

assumed balanced sample sizes in the groups defined by H4 and H5, α=0.05 and two-sided test.

Results
We recruited 247 participants (148 caregivers, 48 teens, and 51 children 7-12 years old). Through the

think-aloud process we verified that questions were adequately understood confirming conceptual

equivalence. We added synonyms to four symptoms to increase clarity. Since no major changes to the
survey were introduced, all Phase I participants were incorporated into the final sample. Table 1 shows

participants characteristics. As per our sampling strategy, age groups were balanced. More than half of

the children were girls; all children were at the corresponding school level. Half of the children had

active disease, 60% with no changes since diagnosis and 40% had disease progression. Of the 55%

that received cancer-directed treatment in the past ten days, 36 (44%) received ambulatory oral or IV

chemotherapy, 41 (51%) received IV inpatient chemotherapy, and four (5%) had undergone high

intensity treatment (surgery). Of the 45% participants who did not receive treatment, 49 (73%) had

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been off treatment and in remission for over 6 months and the remaining 18 (27%) had active disease

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and were between cycles, or were off treatment because of side effects, just relapsed, or refractory

disease progression.
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Caregivers were mostly mothers and over 50% had completed high school. Most families lived below
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the poverty line (62%), and 50% were uninsured, dependent on public health coverage.
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Feasibility
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Pediatric-MSAS-Sp versions were feasible (see Table 2). All participants were able to complete the

questionnaire independently or with assistance. Over 80% used the tool as expected, i.e. self-
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administered or administered by researcher depending on age, and most needed only one round of
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instructions. Twenty one percent of children and 10% of teens were only able to complete the

instrument with study personnel assistance, about half of them because of clinical reasons. Of the 16%

of caregivers who needed help to respond, 5% said they did not understand the questionnaire (more

details in Table 2). Self-administration was associated with child’s age (91% of children ≥10 years were

able to complete Pediatric-MSAS-Sp on their own compared to 63% of 8 to 9-year-olds, p=0.02) and

caregiver’s educational level (90% completion for caregivers with a high school degree versus 76%

without , p=0.02). Poverty level was not associated with self-administration after controlling for

education (16% data missing). Most participants said that answering Pediatric-MSAS-Sp was not

burdensome at all (70%, 80%, and 99% of children, teens, and caregivers, respectively). About half of
the children (n=26) and teens (n=23), reported that the printed format was somewhat to very difficult to

follow. Only 7% of caregivers reported having at least some difficulty with the printed format.

Use of Pediatrics-MSAS-Sp

Most participants felt that questions were pertinent (70% of children, 80% of teens and 92% of

caregivers said items were very relevant). All symptoms, except for seizures, were reported at least

once. The number of missing responses was 1% for MSAS-Teen, 0.6% for MSAS-Caregiver and

0.25% for MSAS-Child. Table 3 presents the overall prevalence for each symptom, the individual

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symptom score and the prevalence of “high” frequency (a lot/almost always), severity (severe/very

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severe), and extent of bother (quite a bit/very much) responses among those reporting the symptom.

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On average, children, adolescents, and caregivers reported 2.8 (SD 2.2), 9.7 (SD 6.1), and 8 (SD 6)
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symptoms per survey each. MSAS-total median scores were 12, (IQR 4-28), 8 (IQR 5.5-18), and 9

(IQR 3-16) for children, teens and caregivers respectively (Figure 1).
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Participants used all response options, with lowest scores (0 or 25 depending on the item) being more
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frequently used than the highest score (100). Considering all the opportunities where a high or low

score could be used (i.e. 3,248 items for caregivers, 1,284 for teens, and 365 for children), the highest
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score was used 7% (n=224) of the times for MSAS-Caregiver, 7% (n=84) for MSAS-Teens, and 22%
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(n=81) for MSAS-Child. The lowest score was selected by 29% (n=947), 35% (n=446), and 35% (n=

128) of caregivers, teens and children respectively. Thirteen percent of children (n=7) and teens (n=7),

and 1.5% of caregivers (n=22) reported “other symptoms” (44 in total) with an average score of 58 (SD

29.7) for children, 47 (26.3) for teens, and 39 (19) for caregivers. Further details on “other symptoms,”

open-ended coding, and qualitative comments noted during field work, are summarized in Table 4.

Comprehensibility

Whereas most caregivers (86%) considered that Pediatric-MSAS-Sp questions were easily understood,

30% of teens and 37% of younger children said other children would find the questions somewhat to
very difficult. However, when asked to identify questions that were hard to understand, only a few were

able to (Table 4).

Timeframe accuracy

Most of the symptoms reported by teens and caregivers—93% and 95% respectively—were present

during the week prior to completing the survey. In addition, of the 1,203 symptoms reported by

caregivers, 61% were experienced in the two days prior, and of these, 56% bothered the child/teen

quite a bit or very much. Among adolescents, 57% of the 477 symptoms reported were present in the

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past two days, and 59% of them were causing quite a bit or very much bother.

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Reliability and Construct validity
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Results support the tool’s reliability and validity for the three Pediatric-MSAS-Sp versions. Table 5
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displays summary scores and results of internal consistency and testing of hypothesis H1-H3. Internal
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consistency was satisfactory for all Pediatric-MSAS-Sp scores and Cronbach alpha estimates were not

affected by any individual symptom score. We found a strong inverse correlation between MSAS and
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PedsQL total and subscale scores (H1) for caregivers and teens; in children the correlation was
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moderate. Figure 2 shows a different view of the relationship of MSAS and PedsQL scores providing

further support of validity for teens and caregivers but not for young children. Correlation between
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MSAS total/GDI scores and wellbeing-VAS score (H2) was strong for caregivers, and moderate for

teens and children. As expected, correlation between teens and caregivers (H3) was strong for MSAS

total, physical and GDI scores and moderate for MSAS psychological score. Correlation between

parents and children MSAS total score (H3) was moderate. Agreement (Kappa statistics) between

children/teens and caregivers about symptom presence was acceptable to good for 20 of the 31

symptoms in MSAS-Teen whereas it was acceptable for only two out of nine symptoms (itch and

dyspnea) in MSAS-Child (Figure 3).

Known-groups validity (Figures 4 and 5) was supported for MSAS-Caregiver’ and MSAS-Teen total and

physical scores. These scores were significantly higher in patients that received cancer treatment in the
past ten days and in inpatients compared to outpatients. MSAS-Teen’s psychological and GDI scores

and MSAS-Child’s scores did not significantly differ by admission or treatment status.

Discussion
For the first time, this study validates a caregiver’s version of Pediatric-MSAS and a full set of the tool in

Spanish. Pediatric-MSAS-Sp was feasible, well accepted, and comprehensible. Questions were

perceived as relevant. Most symptoms reported had occurred in the past week. Approximately four out

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of ten symptoms had resolved by the time the survey was administered. Internal consistency was

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adequate, and results support the construct validity of MSAS-Caregiver and MSAS-Teen versions, with

Pediatric-MSAS-Sp total and subscale scores showing good convergent and known-groups validity for
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most scores. Results for MSAS-Child were weaker, convergent validity met our a priori criteria but was
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not confirmed through agreement analysis and known-groups validity could not be demonstrated.
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The study uncovered important considerations when using Pediatric-MSAS-Sp. First, some participants

expressed confusion around whether the focus of the instrument was only on illness/treatment or was
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more general. Of note, these participants used a more general approach to report. Unfortunately, we
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don’t know what the remaining participants assumed and if they left out information that was ultimately

relevant to their quality of life. To obtain standardized responses, clarifying the instructions seems

necessary. Second, we identified subgroups that required more assistance during administration, i.e.

younger children and less educated caregivers. However, once help was provided, these participants

were able to respond, suggesting literacy challenges. Our findings are aligned with other studies done

in Argentina and other countries with low-literacy levels: with assistance, most participants answer

reliably.(18,24,25) The use of electronic platforms with audio questions could be an efficient way of

providing such support. In settings like ours, these systems have helped reduce reading-

comprehension barriers and problems with paper surveys.(26,27)

Importantly, Pediatric-MSAS-Sp may help improve symptom communication. In line with what is

reported in the literature,(11,28) participants described that Pediatric-MSAS-Sp helped increase their

awareness about their/ their child’s symptom distress, and helped organize discussions with clinicians.

Further, in knowing that participants accurately report the symptoms that occurred in the past week,

even if not present at the time of the survey, clinicians may be less skeptical about these tools(11,28)

and create more opportunities to address patient’s suffering.

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Our results strongly support the construct validity of MSAS-Caregiver. This first validation of a MSAS-

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Caregiver’s version demonstrated convergent and known-groups validity for the total score and the

three subscales among parents of children with cancer aged 2 and above. In addition, results further
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build on MSAS-Teen’s validity. Using similar methods to those of Collins’,(4) we obtained closely
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related results. Our finding that both MSAS-psychological and MSAS-GDI subscales do not differentiate
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patients based on their treatment or admission status, does not necessarily reflect poor validity of the
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tool. Instead, scores seem to indicate high psychological burden among patients on and off treatment

and across settings, an experience we underestimated when choosing the hypothesis. Finally, the
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validity of MSAS-Child was weak. While MSAS-Child correlated with quality of life and wellbeing scores
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as anticipated, the agreement between parent and young child symptom reports was low, and known-

groups validity was not demonstrated, albeit scores behaved in the expected directions. Differences

between parent and child views are increasingly understood as a reflection of diverse, complementary,

perspectives rather than an intrinsic instrument problem.(29,30) Still, the low level of parent-child

agreement observed for MSAS-Child, warrants additional explanations. Agreement was especially low

for pain, nausea, lack of appetite and emotional items, which may reflect parent’s difficulty to grasp

less-observable symptoms in children who may not be developmentally able to articulate their

experiences.(31) Of note, children’s understanding of the questions, a reported barrier,(31) was

specifically evaluated and not found to be a major problem in this sample. Regarding known-groups

validity of MSAS-Child, the study was probably underpowered to detect small differences due to the
large score variability and the small sample size of the groups under comparison. Further research will

help better understand Pediatric-MSAS-Sp functioning in young children.

This study has some limitations including the lack of a confirmatory factor analysis and analysis of the

instrument’s responsiveness. Budget and logistic constraints precluded the recruitment of a larger

sample and longitudinal follow-up. Another limitation was the low representation of patients with

advanced disease or those receiving highly intense treatments. The few identified were too unstable to

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participate. Nevertheless, the reduced heterogeneity did not largely affect Pediatric-MSAS-Sp’s

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capacity to measure symptom burden.

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In summary, our study extends Pediatric-MSAS by adding a validated Spanish caregiver version and
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makes available a tool that can capture the symptom experience of Spanish speaking children and
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teens, an essential step towards improving symptom management. Results contribute and support the
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validity of MSAS-Caregiver and MSAS-Teen. More research is needed to continue to understand how

to better assess symptoms in young children with cancer.

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Disclosures and Acknowledgments

The study was supported by funding from the Instituto Nacional del Cancer (Argentina) and Hospital

Garrahan (Argentina). We are thankful to participants for their willingness to collaborate. We thank

Luciano Uzal, Anthrop. for his help in setting up the study databases and Rodolfo Verna, MD for his

help in implementing the study at Hospital Garrahan. The content of this article is solely the

responsibility of the authors and does not necessarily represent the official view of neither of these

institutions.

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Box, Tables and Figure Legends

Box 1
Main Characteristics of Pediatric-MSAS Spanish Versions

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 Table 1
Clinical and socio-demographic characteristics of Pediatric-MSAS-Sp
validation study participants
Children/Teens (n=148)
n %
SOCIO-DEMOGRAPHIC CHARACTERISTICS
Site 1 57 39
2 91 61
Gender, Female 82 55
Age in years, median (IQR) 9.1 (6.1-14.2)
Age groups (yo, years old) 2 to 6 yo 49 33
7 to 12 yo 51 34
13 to 20 yo 48 32
Educational level Not attending school 18 12
Pre-school 21 14

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Elementary school 55 37
Middle/High School 50 34

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College/University 4 3
CLINICAL CHARACTERISTICS
Types of cancer Leukemias/Lymphomas -p
Solid tumors
78
55
53
37
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CNS tumors 15 10
Disease status, active 76 51
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Received cancer directed treatment in past 10 days 81 55

Adolescents, n=48 23 48
Children 7-12 yo, n=51 28 55
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Inpatient 53 36
Adolescents, n=48 16 33
Children 7-12 yo, n=51 19 37
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Caregivers/ Households (N=148)

n %
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SOCIO-DEMOGRAPHIC CHARACTERISTICS
Age in years, median (IQR) 36.6 (29.1 - 43.6)
Gender, female 126 85
Highest educational level attained
Elementary school, incomplete 5 3
Elementary school, complete 61 41
High School, complete 53 36
University graduate 27 18
Household size, median (IQR) 4 (3-6)
Poverty Level
Families living below the poverty linea 92 62
a
Families living below the indigence line 36 24
Did not know/answer 24 16
Families with health insurance coverageb 74 50
Pediatric-MSAS-Sp: Pediatric Memorial Symtpom Assessment Scale Spanish; IQR:
a
Interquartile range; Household income was measured with a six-category
ordinal question and then collapsed by 2017 poverty and indigence income
20 b
thresholds for Argentina; Includes private, social security, and public
assistance healthcare plans.
 Table 2
Feasibility of administering the Pediatric MSAS Spanish versions
MSAS-Children MSAS-Teens MSAS-Caregivers
7yo 8-12 yo TOTAL ≥13 yo
(N=148)
(n=13) (n=38) (n=51) (n=48)
Administration details n % n % n % n % n %
PLACE OF ADMINISTRATION
Ward 5 38 14 37 19 37 16 33 53 36
Oncology Clinic 8 61 24 63 32 63 32 67 95 47
ADMINISTRATION
Self-report 30 79 43 90 124 84
One round of instructions 23 61 32 67 74 50
Two rounds of instructions 7 18 11 23 50 34

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With researchers help, reasons 13 100 8 21 8 16 5 10 24 16
As per tool instructions, 7yo 13 100

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a
Clinical reasons 4 11 2 4
"Tired"-"Not up to doing it by myself" 2 5 2 4 8 5
"Not understanding how to do it"
"Not having reading glasses"
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2 5 1 2 7
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"Taking care of the child" 3 2
a
Most frequently because of having an intravenous line which precluded the use of the pencil
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 Table 3.
Prevalence and Characteristics of Symptoms Reported by Pediatric-MSAS Spanish version
MSAS-Caregivers (n=148) MSAS-Teens (n=48) MSAS-Children (n=51)
Individual Prevalence of high… Individual Prevalence of high… Individual Prevalence of high…
Overall Overall Overall
Symptom Freq Sev Bother Symptom Freq Sev Bother Symptom Freq Sev
prevalence prevalence prevalence Bother
Score, A lot- S-VS QB-VM Score, A lot- S-VS QB-VM Score, AA VS
(%) (%) (%) VM (%)
Symptom mean (SD) AA (%) (%) (%) mean (SD) AA (%) (%) (%) mean (SD) (%) (%)
Anorexia 31.7 45.7(18.4) 34.8 15.2 17.4 25.0 52.0(21.3) 41.7 33.3 8.3 41.2 49.1(19.3) 76.2 NA 28.6
Constipation 23.1 48.4(24.2) NA 32.4 38.2 25.0 48.3(21.3) NA 25.0 16.7
Cough 37.8 43.6(15.9) 29.1 7.3 21.8 45.8 32.7(14.8) 9.1 9.1 4.5
Diarrhea 14.9 37.9(14.2) 13.6 4.5 13.6 25.0 40.2(18.1) 25.0 16.7 16.7
Difficulty
23.6 39.5(13.5) 20.0 2.9 11.4 20.8 41.7(16.2) 20.0 0.0 20.0
concentrating
Dizziness 12.9 39.7(14.8) 5.3 0.0 31.6 20.8 40.7(16.0) 20.0 20.0 10.0

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Drowsiness 31.3 42.9(14.3) 41.3 8.7 13.0 54.2 39.1(15.4) 26.9 15.4 0

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Dry mouth 21.6 43.8(22.2) 25.0 12.5 21.9 39.6 39.9(19.4) 31.6 15.8 10.5

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Taste changes 23.0 42.1(25.1) NA 20.6 26.5 18.8 28.0 (12.1) NA 11.1 0.0
Dysphagia 10.1 55.9(24.1) 42.9 35.7 50.0 16.7 46.9(21.7) 37.5 37.5 25.0

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Dyspnea 17.6 39.4(15.5) 7.7 7.7 15.4 16.7 39.4(21.7) 12.5 0.0 12.5 19.6 48.4(19.5) 30.0 50.0 40.0

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Dysuria 6.1 53.8(20.0) 33.3 33.3 22.2 8.3 50.0 (21.4) 50.0 50.0 25.0
Fatigue 41.9 44.3(15.6) 22.6 4.8 22.6 54.2 40.0 (16.5) 11.5 15.4 11.5 39.2 48.7(23.8) 65.0 70.0 15.0

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Hair loss 26.4 41.0(24.0) NA 34.2 23.7 37.5 41.3(25.9) NA 38.9 16.7
Headache 31.1 39.8(19.7) 17.8 11.1 22.2 47.9 35.7(15.3) 8.7 13.0 0.0

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Image issues 21.6 56.5(29.6) NA 37.5 48.4 25.0 49.2(31.3) NA 33.3 33.3
Irritability 48.0 50.2(19.6) 36.6 22.5 31.0 47.9 39.9(18.8) 30.4 17.4 13.0
Itching
Mouth sores
18.9
14.2
41.9(19.8)
44.7(28.4)
17.9
NA
10.7
23.8
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28.6
33.3
22.9
18.8
40.9(17.6)
46.1(35.3)
27.3
NA
9.1
44.4
18.2
22.2
27.5 55.1(19.0) 50.0 78.6 28.6
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Nausea 31.8 45.1(20.2) 19.1 8.5 38.3 29.2 49.4(25.9) 35.7 21.4 35.7 23.5 51.3(25.9) 66.7 NA 33.3
Nervousness 56.8 44.0(18.2) 25.0 14.3 25.0 54.2 43.2(16.9) 23.1 19.2 7.7
Numbness 18.4 45.3(22.0) 22.2 14.8 40.7 35.4 38.4(22.8) 11.8 17.6 11.8
Pain 44.6 48.9(18.5) 24.2 15.2 40.9 50.0 54.9(19.3) 50.0 20.8 29.2 43.1 53.2(25.1) 59.1 77.3 22.7
56.0
Sadness 39.9 47.1(17.3) 20.3 11.9 25.4 56.3 46.6(20.4) 25.9 18.5 22.2 25.5 53.8 61.5 30.8
(23.8)
Skin issues 14.2 43.1(22.6) NA 9.5 33.3 22.9 30.9(12.9) NA 9.1 0.0
Sleep problems 25 45.7(17.3) 16.2 21.6 18.9 18.8 39.8(17.5) 33.3 11.1 11.1 33.3 58.6(36.4) NA NA 52.9
Sweating 29.1 47.1(23.2) 38.1 24.4 21.4 29.2 42.8(19.2) 35.7 21.4 7.1
Swelling 3.4 57.6(30.) NA 20.0 40.0 10.4 30.2(14.2) NA 40.0 0.0
Vomiting 21.6 43.2(19.6) 21.9 6.3 31.3 25.0 36.1(24.6) 16.7 16.7 8.3
Weight loss 20.3 33.5(17.1) NA 6.7 20.0 27.1 20.6(14.9) NA 7.7 0.0
Worrying 35.8 45.9(19.9) 20.8 17.0 30.2 43.8 42.4(14.2) 19.0 14.3 9.5 27.5 54.4(19.2) 42.9 71.4 50.0
a NA NA NA NA
Bleeding 2.7 NA NA NA 75 NA
Abbreviations: AA: almost always, S: severe, VS: very severe, QB: quite a bit VM: very much. NA: not applicable (item not assessed). Seizures not included in table because no caregiver reported it;
a
Caregivers also reported that bleeding bothered them (the caregivers) on average a moderate amount.
 Table 4.
Qualitative comments about MSAS administration and use
• Some teens and caregivers were not sure what type of information was being asked and
wondered whether they should report any type of symptom experienced or only those related to
the illness or its treatment. In general, these participants went on to report any symptom
Underlying
they/their child experienced in the past week. For example, one teen reported “nervousness”
framework
because she sat for a school test; one mother reported her son had “itching” caused by
“mosquito bites;” and another answered her daughter had “bleeding,” which was due to her
period.
• Six young children mentioned at least one (and not more than two) of the following were hard to
understand: shortness of breath, lack of appetite, nausea, or itching.

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Questions that • One teenager didn’t understand the irritability and skin changes items.
were “hard to • One mother said she didn’t understand whether the hair loss item referred to the amount of hair
understand” loss or the emotional aspects of it, another mentioned that the irritability and worry items were

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“vague.”
• One caregiver found all questions were difficult to understand.
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• Less than 15% of participants in each version reported “other symptoms.”
• Caregivers, teens and one young child used this section to provide more details on symptoms
that they had already reported in the main section of the questionnaire (e.g. specify pain
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Use of the
location— headache, muscle, back, or abdominal—or, paraphrased “tiredness,” or “sleep”).
“Other
• Caregivers also used this section to report on other medical problems, such as fever, infections,
symptoms”
or palpitations.
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section
• Young children more frequently reported general thoughts that seemed to reflect emotions, such
as “sadness because I argued with a friend,” “everything,” “the possibility of getting a feeding
tube.”
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• "The questionnaire does not ask if children are happy with their lives" (Boy, 11yo)
• “It would be good to know if the child / teen has difficulties talking about his or her illness” (Girl,
15yo)
• “It was not asked if kids beat you at school” (Boy, 7 yo)
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Things
participants • “How they feel sentimentally” (Girl, 14 yo)
would have • Some caregivers suggested the inclusion of questions about psychosocial aspects such as child
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liked included and caregiver’s mood, feelings, fears, psychological support for the dyad, and schooling
• A few suggested asking whether they had information about the treatment protocol or side
effects
• Some suggested including vital signs, bruises, and mucositis.
• A case of selective mutism in a teen female patient was identified while completing the survey.
Health care team was alerted, and patient successfully treated.
Impact of MSAS • Soon after completing MSAS, a boy (8yo) bursted into tears with his mother. When he calmed
on child and down, he said "Nobody had asked me if I was sad or worried before." He was offered
teen’s voice psychological support.
• Younger patients felt their view was taken into consideration: "The survey is good because I feel
that I am important to someone" (Child,10yo)
• "I would like to fill it out before seeing the doctor, because when I talk to them, I forget things"
(Teen, 14yo)
• "The survey helped me realize that I was worried and that I had been nervous and irritable"
Participants (Teen, 17yo)
views • “The survey is very good because questions are asked that are sometimes forgotten in the
about MSAS consultations and it is also entertaining for the kids because staying at the hospital becomes long
and boring" (Caregiver, patient in treatment)
• “It would have been very helpful to do the survey while on treatment. Surely it will useful for
many kids " (Caregiver, patient in remission)
 Table 5.
Pediatric-MSAS-Sp PedsQL, and wellbeing summary scores
Caregivers (n= 148) Teens (n= 48) Children (n= 51)
Score median (IQR) median (IQR) median (IQR)
MSAS-Total 8.7 (3.4, 15.5) 8.7 (5.5, 17.8) 12.2 (3.7, 27.7)
MSAS-Physical 7.9 (2.8, 17.2) 9.3 (2.6, 19.5) NA
MSAS-Psychological 13.0 (4.0, 25.0) 13.9 (5.5, 29.4) NA
MSAS-GDI 13.9 (5.6, 27.8) 18.1 (6.9, 30.6) NA

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n= 148 n= 48 n= 49
PedsQL-Total 80.0 (60.5, 90.0) 75.0 (60.5, 87.5) 74.0 (61.0, 79.0)

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PedsQL-Physical 78.0 (56.0, 94.0) 78.0 (54.5, 88.0) 72.0 (56.0, 88.0)
PedsQL-Psychological 80.0 (67.5, 90.0) 79.0 (66.0, 88.5) 72.0 (57.0, 80.0)
WB-VAS 71.2 (27.8) -p 66.6 (23.7)
Internal Consistency (Cronbach α)
81.7 (25.8)
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MSAS-Total MSAS-Physical MSAS-Psychological MSAS-GDI
Children 0.72 NA NA NA
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Teens 0.89 0.86 0.78 0.80

Caregivers 0.90 0.83 0.80 0.81
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Testing Construct Validity

Hypothesis 1. Correlation between Pediatric-MSAS-Sp and PedsQL total and subscale scores
MSAS-Total vs. MSAS-Physical vs. MSAS-Psychological vs.
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b b b
PedsQL-Total PedsQL-Physical PedsQL-Psychological
Children -0.32 (-0.55, -0.04) NA NA
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Teens -0.66 (-0.79, -0.46) -0.58 (-0.74, -0.35) -0.64 (-0.78, -0.43)
Caregivers -0.59 (-0.68, -0.47) -0.52 (-0.63, -0.39) -0.57 (-0.67, -0.45)
Hypothesis 2. Correlation between Pediatric-MSAS-Sp and Wellbeing-VAS (WB-VAS) scores
b b
MSAS-total vs. WB-VAS MSAS-GDI vs. WB-VAS
Children -0.48 (-0.67, -0.23) NA
Teens -0.46 (-0.66, -0.20) -0.45 (-0.65, -0.19)
Caregivers -0.63 (-0.72, -0.52) -0.61 (-0.70, -0.49)
Hypothesis 3. Correlation between caregiver and child/teen Pediatric-MSAS-Sp scores
b b b b
MSAS-Total MSAS-Physical MSAS-Psychological MSAS-GDI
Caregivers Children 0.30 (0.03, 0.53) NA NA NA
vs Teens 0.78 (0.64, 0.87) 0.85 (0.74, 0.91) 0.45 (0.19, 0.65) 0.64 (0.44, 0.78)
MSAS: Memorial Symptom Assessment Scale; PedsQL: Pediatric Quality of Life Inventory; WB-VAS: visual
analogue scale. GDI: Global Distress Index score;
a
We considered reliability to be satisactory if Cronbach α values were between 0.70-0.95.
b
Spearman correlation (95%CI); we considered acceptable proof of construct validity r value >0.3 (moderate).
Figure Legends
Figure 1. Pediatric Memorial Symptom Assessment Scale (Pediatric-MSAS-Sp)

Summary Scores and Number of Symptoms.

Legend: Panel A: shows boxplots of Pediatric-MSAS-Sp total, physical (Phys),

psychological (Psych), and global distress index scores (GDI) for MSAS-Caregiver

(n=148), MSAS-Teen (n=48), and MSAS-Child (n=51). Panel B: displays boxplots

of the number of symptoms reported by caregivers, teens and children.

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Figure 2. Convergent Validity of Pediatric-MSAS-Sp: Distribution of scores across

health-related quality of life categories.

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Legend: Relationship between Pediatric-MSAS-Sp scores and number of

symptoms for each MSAS version across three categories of health-related quality
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of life (HRQOL), as measured by Pediatric Quality of Life Inventory (PedsQL) total

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score: >80 (excellent), 60-79 (good) and <60 (fair/poor). Kendall Tau b test. Panel
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A: MSAS-total score; Panel B: Number of symptoms; Panel C: MSAS-physical;

Panel D: MSAS-psychological; Panel E: MSAS-Global Distress Index.

Figure 3. Convergent Validity of Pediatric-MSAS-Sp: Caregiver – Child/Teen

agreement.

Legend: Agreement between caregiver and teens (Panel A) and caregiver and

children (Panel B) regarding symptom presence as reported in MSAS

questionnaire. Agreement indicated by Kappa estimate (solid line) and 95%

confidence limits (dash lines). Kappa ≥0.4 was considered acceptable.

Figure 4. Known-groups validity of Pediatric-MSAS-Sp: Comparison of scores of

patients who received treatment in the past 10 days against those who did not

receive treatment.

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Legend: Relationship between Pediatric-MSAS-Sp scores and number of

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symptoms for each version among patients who received cancer-directed
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treatment in the past ten days (81 caregivers, 25 teens, and 28 children) compared
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to their counterparts (67 caregivers, 23 adolescents, and 23 children). Wilcoxon
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ranked test. Panel A: MSAS-total score; Panel B: Number of symptoms; Panel C:

MSAS-physical; Panel D: MSAS-psychological; Panel E: MSAS-Global Distress

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Index.
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Figure 5. Known-groups Validity of Pediatric-MSAS-Sp: Comparison of outpatient

versus inpatient scores.

Legend: Relationship between Pediatric-MSAS-Sp scores and number of

symptoms among outpatients (95 caregivers, 32 teens, and 32 children) and

inpatients (53 caregivers, 16 adolescents, and 19 children). Wilcoxon ranked test.

Panel A: MSAS-total score; Panel B: Number of symptoms; Panel C: MSAS-

physical; Panel D: MSAS-psychological; Panel E: MSAS-Global Distress Index.

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