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The Children's International Mucositis Evaluation Scale Is Valid and Reliable for the Assessment of Mucositis Among Brazilian Children With Cancer

Open ArchivePublished:July 24, 2018DOI:https://doi.org/10.1016/j.jpainsymman.2018.07.015

      Abstract

      Background

      The Children's International Mucositis Evaluation Scale (ChIMES) is considered a valid and reliable instrument for the assessment of mucositis in pediatric patients aged 0–18 years.

      Objective

      To perform the translation and cultural adaptation of ChIMES to Brazilian Portuguese and assess its psychometric properties.

      Methods

      Methods for translation and cultural adaptation were used. Other measurements obtained concomitantly for the assessment of psychometric properties included the Oral Mucositis Daily Questionnaire, a visual analog scale, the World Health Organization grading scale for mucositis, and the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale. For test-retest analysis, patients and guardians responded to the self-report and proxy versions of ChIMES within intervals of one to seven days.

      Results

      Regarding internal consistency, Cronbach's alpha (α) values were 0.769 (95% CI = 0.631–0.868) and 0.879 (95% CI = 0.872–0.920) for the self-reported and proxy versions, respectively. The convergent validity criteria were met for the self-reported and proxy versions (Spearman's rho = 0.466–0.751; P < 0.001 and Spearman's rho = 0.410–0.551; P < 0.001, respectively). Test-retest reliability assessment for the total score and Items 1, 2, 3, and 4 in both versions showed an intraclass correlation coefficient of ≥0.7.

      Conclusions

      The Portuguese self-reported and proxy versions of ChIMES were considered to be culturally adapted, valid, and reliable for Brazilian pediatric patients ranging from an age of one month to 18 years and were named ChIMES-BR.

      Key Words

      Introduction

      Pediatric tumors are highly curable and more sensitive to treatment, especially chemotherapy.
      • Grabois M.F.
      • Oliveira E.X.
      • Carvalho M.S.
      Childhood cancer and pediatric oncologic care in Brazil: access and equity.
      A common consequence of chemotherapy and other oncologic therapies, such as hematopoietic stem cell transplantation (HSCT), is oral mucositis,
      • Jacobs S.
      • Baggott C.
      • Agarwal R.
      • et al.
      Validation of the Children's International Mucositis Evaluation Scale (ChIMES) in paediatric cancer and SCT.
      a lesion on the oral mucosa surface that manifests itself as erythema and/or ulceration and might be exacerbated by local factors.
      • Institute North Carolina
      Oral complications of chemotherapy and head/neck radiation (PDQ®).
      The clinical conditions of pediatric patients can deteriorate and trigger multiple debilitating oral symptoms, which undoubtedly impair their quality of life.
      • Cheng K.K.
      • Leung S.F.
      • Liang R.H.
      • et al.
      Severe oral mucositis associated with cancer therapy: impact on oral functional status and quality of life.
      Some factors have been described as determinants of the severity of oral mucositis among pediatric patients. Patients with hematologic diseases have a 2.3-fold greater risk of developing a more severe degree of mucositis.
      • Otmani N.
      • Alami R.
      • Hessissen L.
      • et al.
      Determinants of severe oral mucositis in paediatric cancer patients: a prospective study.
      In addition, the severity of mucositis might be related to the type of chemotherapeutic agent used
      • den Hoed M.A.
      • Lopez-Lopez E.
      • te Winkel M.L.
      • et al.
      Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia.
      • Fadda G.
      • Campus G.
      • Lugliè P.
      Risk factors for oral mucositis in paediatric oncology patients receiving alkylant chemotherapy.
      ; methotrexate, an important drug for the treatment of pediatric cancer, has been associated with poorer mucositis scores
      • Otmani N.
      • Alami R.
      • Hessissen L.
      • et al.
      Determinants of severe oral mucositis in paediatric cancer patients: a prospective study.
      and is frequently used for acute lymphoblastic leukemia, which represents 25% of all malignant tumors in childhood.
      • den Hoed M.A.
      • Lopez-Lopez E.
      • te Winkel M.L.
      • et al.
      Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia.
      The symptoms associated with mucositis among children and adolescents undergoing chemotherapy have a negative impact on quality of life, including problems swallowing and being unable to eat some of the things they would like to, in addition to the increased levels of psychological stress in these patients.
      • Cheng K.K.
      • Leung S.F.
      • Liang R.H.
      • et al.
      Severe oral mucositis associated with cancer therapy: impact on oral functional status and quality of life.
      • Cheng K.K.
      • Lee V.
      • Li C.H.
      • Yuen H.L.
      • Epstein J.B.
      Oral mucositis in pediatric and adolescent patients undergoing chemotherapy: the impact of symptoms on quality of life.
      Therefore, the assessment and detection of this complication within the pediatric cancer care setting are necessary.
      Establishing the degree of mucositis has previously relied on scales including the World Health Organization (WHO) scale,
      • World Health Organization (1979)
      WHO handbook for reporting results of cancer treatment. Geneva: World Health Organization.
      the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE),
      • Trotti A.
      • Colevas A.D.
      • Setser A.
      • et al.
      CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment.
      and the Oral Mucositis Assessment Scale.
      • Sonis S.T.
      • Eilers J.P.
      • Epstein J.B.
      • et al.
      Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy.
      It should be noted that these scales are scored according to the health care providers' perception based on clinical examination and the patient's report; therefore, they do not objectively measure oral mucositis within the pediatric cancer care setting.
      The Children's International Mucositis Evaluation Scale (ChIMES)
      • Jacobs S.
      • Baggott C.
      • Agarwal R.
      • et al.
      Validation of the Children's International Mucositis Evaluation Scale (ChIMES) in paediatric cancer and SCT.
      • Tomlinson D.
      • Gibson F.
      • Treister N.
      • et al.
      Understandability, content validity, and overall acceptability of the Children's International Mucositis Evaluation Scale (ChIMES): child and parent reporting.
      • Tomlinson D.
      • Gibson F.
      • Treister N.
      • et al.
      Refinement of the Children's International Mucositis Evaluation Scale (ChIMES): child and parent perspectives on understandability, content validity and acceptability.
      is a self-reporting scale designed for children with cancer; it is reliable, valid, and easy to apply to the pediatric population.
      Given the scarcity of specific instruments for the assessment of oral mucositis among children with cancer, and as ChIMES is a valid and reliable scale for this population, the present study was aimed at performing its translation and cultural adaptation to Brazilian Portuguese and assessing its psychometric properties.

      Methods

      Study Design

      The present study was descriptive, cross-sectional, and methodological (methodology for assessment instrument validation).

      Participant Selection

      The study included pediatric patients aged 8–18 years diagnosed with cancer who had undergone a chemotherapy cycle of seven days (with/without two days) with methotrexate or doxorubicin before answering the questionnaire and/or patients undergoing head and neck radiotherapy and/or HSCT. In addition, proxy respondents were included, namely, parents or guardians of patients aged one month to seven years who met the aforementioned clinical criteria. Both children who answered the self-reported version and proxies had to be able to understand Portuguese. Patients with neurologic or psychiatric disorders or those under invasive or noninvasive mechanical ventilation or sedation were excluded.
      Patients and proxy respondents were recruited at the inpatient wards, outpatient clinics, and the dentistry outpatient clinic. Interviews were performed in private rooms.

      Procedures

      Children's International Mucositis Evaluation Scale

      The original self-reported and proxy versions of ChIMES were developed and validated in 2009.
      • Tomlinson D.
      • Gibson F.
      • Treister N.
      • et al.
      Understandability, content validity, and overall acceptability of the Children's International Mucositis Evaluation Scale (ChIMES): child and parent reporting.
      ChIMES is a self-reported paper-and-pencil scale that consists of six items assessing oral mucositis. Items 1–4 are scored from 0 (best score) to 5 (worst score). The remainder of the items are answered with a yes or no response and are assigned scores of 1 and 0, respectively. The maximum total score is 23.
      • Jacobs S.
      • Baggott C.
      • Agarwal R.
      • et al.
      Validation of the Children's International Mucositis Evaluation Scale (ChIMES) in paediatric cancer and SCT.

      Translation and Cultural Adaptation

      Translation and cultural adaptation of ChIMES were performed according to the standards formulated by Beaton et al.
      • Beaton D.E.
      • Bombardier C.
      • Guillemin F.
      • Ferraz M.B.
      Guidelines for the process of cross-cultural adaptation of self-report measures.
      (Fig. 1).
      Figure thumbnail gr1
      Fig. 1Methodological stages of the translation and cross-cultural adaptation of the Children's International Mucositis Evaluation Scale (ChIMES).
      The scale was translated from English into Portuguese by two translators who are fluent in English. After that, a synthesis of these two translations was performed. The resulting version was back-translated into English by two native English speakers who are fluent in Portuguese. Then, one of the authors of the original scale assessed the back translation to establish whether the meanings of items and responses had been retained.
      An expert panel analyzed the semantic/idiomatic, conceptual, and cultural equivalence of the prefinal version of the scale. For this purpose, scores from 1 (nonrepresentative item) to 4 (representative item) were assigned, and the content validity index (CVI) was calculated as the sum of the number of items scored 3 and 4, divided by the total number of items; the minimum acceptable value was 0.80.
      • Alexandre N.M.C.
      • Coluci M.Z.O.
      [Content validity in the development and adaptation processes of measurement instruments].
      The main aim of the pretest was to establish whether the translated instrument was understood by respondents, who were also asked to suggest changes to improve their understanding.

      Assessment of Psychometric Properties

      Data Collection Instruments

      All the participants completed the following questionnaires: Chimes, the Oral Mucositis Daily Questionnaire (OMDQ),
      • Stiff P.J.
      • Erder H.
      • Bensinger W.I.
      • et al.
      Reliability and validity of a patient self-administered daily questionnaire to assess impact of oral mucositis (OM) on pain and daily functioning in patients undergoing autologous hematopoietic stem cell transplantation (HSCT).
      a visual analog scale (VAS),
      • Jacobs S.
      • Baggott C.
      • Agarwal R.
      • et al.
      Validation of the Children's International Mucositis Evaluation Scale (ChIMES) in paediatric cancer and SCT.
      the WHO Oral Mucositis Grading Scale,
      • World Health Organization (1979)
      WHO handbook for reporting results of cancer treatment. Geneva: World Health Organization.
      and the CTCAE version 3.0.
      • Trotti A.
      • Colevas A.D.
      • Setser A.
      • et al.
      CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment.
      CTCAE version 3.0
      • Trotti A.
      • Colevas A.D.
      • Setser A.
      • et al.
      CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment.
      and the WHO Oral Mucositis Grading Scale
      • World Health Organization (1979)
      WHO handbook for reporting results of cancer treatment. Geneva: World Health Organization.
      were filled out by an experienced researcher. The questionnaires were applied again on the patients with a scheduled follow-up consultation within a period of one to seven days.

      WHO Oral Mucositis Grading Scale

      The presence of oral mucositis is assessed based on clinical manifestations. The score ranges from 0 (the absence of manifestations and symptoms) to 4 (oral feeding is impossible).
      • World Health Organization (1979)
      WHO handbook for reporting results of cancer treatment. Geneva: World Health Organization.

      Visual Analog Scale

      The VAS consists of a 10 cm horizontal line; the ends represent scores of 0 (no pain in the mouth or throat) and 10 (worst possible pain in the mouth or throat).
      • Jacobs S.
      • Baggott C.
      • Agarwal R.
      • et al.
      Validation of the Children's International Mucositis Evaluation Scale (ChIMES) in paediatric cancer and SCT.

      Common Terminology Criteria for Adverse Events

      CTCAE assesses oral mucositis from the clinical and functional/symptomatic perspectives; the score ranges from 0 to 5.
      • Trotti A.
      • Colevas A.D.
      • Setser A.
      • et al.
      CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment.

      OMDQ—Pediatric Version

      This questionnaire is specific for the assessment of mucositis; it consists of seven items related to pain in the mouth or throat and their functional implications. A Brazilian Portuguese version is available. Validation highlighted adequate internal consistency values; Cronbach's alpha was 0.871 (95% CI = 0.825–0.908), and the intraclass correlation coefficient (ICC) varied from 0.700 to 0.913 for Items 1–6. The score is graded from 0 to 4, where 0 corresponds to an absence of signs and symptoms and 4 corresponds to the worst mucositis.
      • Stiff P.J.
      • Erder H.
      • Bensinger W.I.
      • et al.
      Reliability and validity of a patient self-administered daily questionnaire to assess impact of oral mucositis (OM) on pain and daily functioning in patients undergoing autologous hematopoietic stem cell transplantation (HSCT).
      • Manji A.
      • Tomlinson D.
      • Ethier M.C.
      • et al.
      Psychometric properties of the Oral Mucositis Daily Questionnaire for child self-report and importance of mucositis in children treated with chemotherapy.
      • Tomlinson D.
      • Ethier M.C.
      • Judd P.
      • et al.
      Reliability and construct validity of the oral mucositis daily questionnaire in children with cancer.

      Psychometric Properties

      Reliability

      Internal consistency was assessed by Cronbach's alpha. Values from 0.70 to 0.95 were considered to be adequate.
      • Terwee C.B.
      • Bot S.D.
      • de Boer M.R.
      • et al.
      Quality criteria were proposed for measurement properties of health status questionnaires.
      Reproducibility was assessed by means of the questionnaire being applied for a second time one to seven days after the first interview, which was done on 97 patients; 62 answered the self-reported version and 35 answered the proxy version. Values of more than 0.7 were considered acceptable.
      • Terwee C.B.
      • Bot S.D.
      • de Boer M.R.
      • et al.
      Quality criteria were proposed for measurement properties of health status questionnaires.

      Construct Validity

      For convergent construct validity, correlations between the ChIMES items and the OMDQ, CTCAE, and VAS were hypothesized a priori. Correlations with values above 0.4 were expected.
      • Fayers P.
      • Machin D.
      Quality of life: The assessment, analysis and interpretation of patient-reported outcomes.

      Statistical Analysis

      The data were subjected to descriptive and inferential analyses using SPSS, version 20, software (IBM, Armonk, NY). The significance level was set to 5%. For ChIMES translation and cultural adaptation, the sample size was calculated following Beaton et al.,
      • Beaton D.E.
      • Bombardier C.
      • Guillemin F.
      • Ferraz M.B.
      Guidelines for the process of cross-cultural adaptation of self-report measures.
      according to which 10 individuals should assess the difficulty involved in understanding the items. Spearman's correlation coefficient was used for assessment of convergent validity (r > 0.4). Cronbach's alpha was used to assess internal consistency, considering 0.70–0.95 ideal.
      • Terwee C.B.
      • Bot S.D.
      • de Boer M.R.
      • et al.
      Quality criteria were proposed for measurement properties of health status questionnaires.
      The ICC (ICC ≥ 0.7) was used to assess test-retest reproducibility.

      Results

      Translation and Cultural Adaptation

      The self-reported and proxy versions of ChIMES were translated by an oncologist and an English teacher, neither of whom had previous knowledge of the scale. The translated versions were analyzed and synthesized into a single version by three of the authors (B. S. R. P., C. E. P., and E. M. B.). The synthesized version was back-translated by two native teachers and was then assessed by the original instrument's author, who agreed with the provided version.
      The synthesized version was assessed by an expert panel consisting of a nurse who is a cancer researcher, an oncologist, two dentists, and an English teacher. For Items 2, 3, and 4 of both the self-reported and the proxy versions, the panel suggested replacing the word face—translated as rosto—with little faces (carinhas), as ChIMES targets the pediatric population and includes drawings of small faces to facilitate understanding.
      The CVI scores for items and responses to items were 1 for both the self-reported and proxy versions, except for the item “Have you taken medicine for any kind of pain today?/Você tomou algum tipo de remédio para dor hoje?” in the self-reported version, for which the CVI was 0.8.

      Pretest

      The pretest was performed with nine patients for the self-reported version and 10 parents/guardians for the proxy version.
      The pediatric patients had a mean (SD) age of 14.7 (2.2) years old; most were females (n = 7; 77.7%) and white (n = 6; 66.6%). Regarding their clinical characteristics, the predominant diagnoses were osteosarcoma (n = 2; 22.3%) and leukemia (n = 2; 22.3%); the patients underwent chemotherapy (n = 8; 88.9%) and HSCT (n = 1; 11.0%).
      The mean (SD) age of the parents/guardians was 34.1 (9.3) years old; the average household income was $BR 1638.2 ($BR 720.9); most respondents were females (n = 6; 60%), white (n = 6; 60%), and had a complete high school education (n = 4; 40%).
      For Item 1 in the self-reported version, one participant suggested reducing the number of response options because he did not find much difference between them; another participant did not clearly understand the time frame addressed in the questionnaire. Nevertheless, these factors did not interfere with the understanding of the scale items and responses. The other items were well understood by the respondents, who did not suggest any changes.
      All the items in the proxy version were well understood; one respondent suggested changing the order of items in the functional domain to assess swallowing of saliva first, followed by drinking and eating.
      Despite these suggestions, they were not taken under consideration because they would not interfere with the understanding of the tool, which was very well understood by the vast majority of the population of the study.
      Therefore, the final result of the translation and cultural adaptation was the self-reported and proxy versions of ChIMES in Brazilian Portuguese (Escala Internacional de Avaliação de Mucosite em Crianças—ChIMES-BR) (Appendix).

      Assessment of Psychometric Properties

      One hundred fifty-five patients were invited to participate in the study, of whom three refused, leaving 91 participants for the self-reported version and 64 for the proxy version.

      Sociodemographic and Clinical Characteristics

      Table 1 describes the sociodemographic and clinical characteristics of the participants. Most were males and white in both versions. The mean (SD) age of the participants for the self-reported version was 14.1 (3.1), ranging from 8.1 to 18.5 years old. For the proxy version, it was 4.2 (1.8), ranging from one month to 7.7 years old. The most frequent diagnoses were osteosarcoma for the self-reported version respondents (n = 35; 38.5%) and leukemia among the children of proxy respondents (n = 22; 35.2%). In both groups, most patients were receiving their initial chemotherapy cycle: 60 (67.4%) and 34 (57.6%) for the self-reported and proxy versions, respectively. Most participants completed the questionnaire without any help from the researchers: 76 (83.5%) and 47 (73.4%) for the self-reported and proxy versions, respectively. The mean (SD) total mucositis score on the self-reported version was 2.66 (4.05), ranging from 0.0 to 20.0. On the proxy version, it was 0.89 (2.36), ranging from 0.0 to 16.0.
      Table 1Sociodemographic and Clinical Characteristics of Participants
      VariablesN (%)
      Self-ReportProxy
      Sex
       Female36 (39.6)30 (46.9)
       Male55 (60.4)34 (53.1)
      Ethnicity
       White45 (50.6)38 (59.4)
       Black8 (9.0)3 (4.7)
       Brown34 (38.2)21 (32.8)
       Asian2 (2.2)2 (3.1)
      Educational level
       Illiterate0 (0.0)1 (1.6)
       Unschooled children1 (1.1)54 (85.7)
       Literate3 (3.3)1 (1.6)
       Incomplete elementary school43 (47.3)7 (11.1)
       Complete elementary school0 (0.0)0 (0.0)
       Incomplete secondary school37 (40.7)0 (0.0)
       Complete secondary school5 (5.5)0 (0.0)
       Incomplete higher education2 (2.2)0 (0.0)
      Marital status
       Single88 (97.8)57 (100.0)
       Married/stable union2 (2.2)0 (0.0)
      State of provenance
       Minas Gerais21 (23.6)11 (18.0)
       Roraima10 (11.2)6 (9.8)
       São Paulo14 (15.7)14 (23.0)
       Tocantins8 (9.0)7 (11.5)
       Other36 (40.5)23 (37.6)
      Diagnosis
       Osteosarcoma35 (38.5)3 (4.8)
       Rhabdomyosarcoma14 (15.4)4 (6.4)
       Leukemia16 (16.5)22 (35.2)
       Hodgkin lymphoma6 (6.6)0 (0.0)
       Non-Hodgkin lymphoma6 (6.6)5 (8.0)
       Ovarian tumor3 (3.3)0 (0.0)
       Kidney tumor2 (2.2)15 (24.0)
       Peritoneal and retroperitoneal tumor0 (0.0)4 (6.4)
       Neuroblastoma0 (0.0)4 (6.4)
       Other9 (9.9)
      Colon, testicle, brain, cerebellum, T cell lymphoma, and Ewing sarcoma.
      6 (9.6)
      Kaposi sarcoma, myeloma, retinoblastoma, and malignant tumors of the heart.
      Chemotherapy cycle
       160 (67.4)34 (57.6)
       216 (18.0)9 (15.3)
       36 (6.7)6 (10.2)
       Other
      Cycles 4–8.
      8 (7.7)10 (16.0)
      Head and neck radiotherapy
       No89 (97.8)64 (100.0)
       Yes2 (2.2)0 (0.0)
      HSCT
       No90 (98.9)60 (93.8)
       Yes1 (1.1)4 (6.3)
      Application method
       Self-report76 (83.5)47 (73.4)
       Applied by interviewer15 (16.5)17 (26.6)
      HSCT = hematopoietic stem cell transplantation.
      a Colon, testicle, brain, cerebellum, T cell lymphoma, and Ewing sarcoma.
      b Kaposi sarcoma, myeloma, retinoblastoma, and malignant tumors of the heart.
      c Cycles 4–8.

      Reliability

      The self-reported and proxy versions showed Cronbach's alpha values of 0.879 (95% CI = 0.872–0.920) and 0.769 (95% CI = 0.631–0.868), respectively. Item removal did not considerably change Cronbach's alpha, as shown in Table 2. Reproducibility was assessed with 62 patients and 35 proxy respondents in intervals of one to seven days using the ICC for the final score and Items 1, 2, 3, and 4 of both the self-reported and proxy versions. The ICC values were ≥0.7 for all measurements. The reproducibility levels of Items 5, 6, and 7 were assessed by means of the kappa coefficient; Items 5 (P = 0.656) and 6 (P = 0.862) of the proxy version proved to be reproducible (Table 3).
      Table 2Reliability Analysis of ChIMES Self-Report and Proxy Versions by Means of Cronbach's Alphas
      ChIMES ItemCronbach's Alpha (95% CI)Alpha If Item DeletedCronbach's Alpha (95% CI)Alpha If Item Deleted
      Self-ReportProxy
      0.769 (0.631–0.868)0.879 (0.872–0.920)
      Item 10.6790.900
      Item 20.6780.890
      Item 30.7540.872
      Item 40.6830.870
      Item 50.7810.911
      Item 60.7920.901
      Item 70.7590.911
      ChIMES = Children's International Mucositis Evaluation Scale.
      Table 3Test-Retest Reliability
      ChIMES ItemsSelf-Report (n = 62)Proxy (n = 35)
      ICC95% CIPICC95% CIP
      ChIMES 10.7260.544–0.8350.7260.544–0.835
      ChIMES 20.7360.564–0.8410.7360.564–0.841
      ChIMES 30.7130.524–0.8270.7130.524–0.827
      ChIMES 40.7140.525–0.8280.7140.525–0.828
      ChIMES 5<0.001
      Kappa coefficient, significance level at 5%.
      0.656
      Kappa coefficient, significance level at 5%.
      ChIMES 60.862
      Kappa coefficient, significance level at 5%.
      ChIMES 70.004
      Kappa coefficient, significance level at 5%.
      <0.001
      Kappa coefficient, significance level at 5%.
      Total score0.8160.696–0.8890.8160.696–0.889
      ChIMES = Children's International Mucositis Evaluation Scale; ICC = intraclass correlation coefficient.
      a Kappa coefficient, significance level at 5%.

      Construct Validity

      The correlations between the total scores on the self-reported and proxy versions are summarized in Table 4. Regarding convergent validity, the a priori hypothesized correlations between the proxy version and OMDQ items were confirmed with values of 0.410–0.537. The values of the correlations of the proxy version with CTCAE Parts 1 and 2, the VAS, and the WHO mucositis scale were 0.482, 0.520, 0.551, and 0.526, respectively. The values of the correlations between the self-reported version and OMDQ items varied from 0.466 to 0.740; the values of the correlations between the self-reported version and CTCAE Parts 1 and 2, the VAS, and the WHO mucositis scale were 0.751, 0.673, 0.744, and 0.657, respectively (Table 4).
      Table 4Correlation Coefficient Between ChIMES and VAS, OMDQ, CTCAE, and WHO (Convergent Validity)
      DomainsTotal Score ChIMES
      Proxy (n = 64)Self-Report (n = 91)
      1. OMDQ—Pain0.513
      P < 0.001.
      0.740
      P < 0.001.
      2a. OMDQ—Sleeping0.410
      P < 0.05.
      0.466
      P < 0.001.
      2b. OMDQ—Swallowing0.410
      P < 0.05.
      0.737
      P < 0.001.
      2c. OMDQ—Drinking0.497
      P < 0.001.
      0.664
      P < 0.001.
      2d. OMDQ—Eating0.537
      P < 0.001.
      0.679
      P < 0.001.
      2e. OMDQ—Talking0.496
      P < 0.001.
      3. OMDQ—Diarrhea−0.0800.090
      P < 0.05.
      CTCAE—Part 10.482
      P < 0.001.
      0.751
      P < 0.001.
      CTCAE—Part 20.520
      P < 0.001.
      0.673
      P < 0.001.
      VAS0.551
      P < 0.001.
      0.744
      P < 0.001.
      WHO0.526
      P < 0.001.
      0.657
      P < 0.001.
      ChIMES = Children's International Mucositis Evaluation Scale; VAS = visual analog scale; OMDQ = Oral Mucositis Daily Questionnaire; CTCAE = Common Terminology Criteria for Adverse Events, version 3.0; WHO = World Health Organization.
      Spearman correlation (rho).
      a P < 0.001.
      b P < 0.05.

      Discussion

      The aim of the present study was to perform the translation and cultural adaptation of ChIMES to Brazilian Portuguese and assess its psychometric properties. We applied systematic and previously consolidated methods throughout the process based on internationally accepted standards for translation and cultural adaptation of health assessment instruments.
      The translation and cultural adaptation of an instrument that has its origins in another language and culture is not a simple process, especially with regard to Brazil, where there remains a large number of illiterate children and adolescents, in addition to the difficulty that some parents or guardians have reading and understanding some sentences. However, it must be emphasized that following consolidated international guidelines is essential as well as having an expert panel assessing the instrument after the back translation, which contributes to its refinement and may minimize doubts or any misunderstanding that the pretest population might have.
      • Beaton D.E.
      • Bombardier C.
      • Guillemin F.
      • Ferraz M.B.
      Guidelines for the process of cross-cultural adaptation of self-report measures.
      Content validity is an essential phase both in the development of new measurements and in the linguistic adaptation.
      • Fayers P.
      • Machin D.
      Quality of life: The assessment, analysis and interpretation of patient-reported outcomes.
      To adapt an instrument, it is important that the committee is formed by individuals who are fluent in both languages and know the area for which the tool is designed.
      • Beaton D.E.
      • Bombardier C.
      • Guillemin F.
      • Ferraz M.B.
      Guidelines for the process of cross-cultural adaptation of self-report measures.
      • Guillemin F.
      • Bombardier C.
      • Beaton D.
      Cross-cultural adaptation of health-related quality of life measures: literature review and proposed guidelines.
      The pretest presented very positive results. In the self-reported version, one patient suggested reducing the number of answer choices, whereas another patient did not exactly understand which time frame the scale indicated. Likewise, in the proxy version, only one parent or guardian suggested changing the order of the functional domain. In the content validity process of the original scale, with regard to the items and number of answers in the ChIMES, which contains an ordinal scale ranging from 0 (no pain) to 5 (worst pain), the authors found that patients and proxies considered it very easy or easy to understand. Thus, the composition of the number of answers was considered adequate for the application of the scale.
      • Tomlinson D.
      • Gibson F.
      • Treister N.
      • et al.
      Refinement of the Children's International Mucositis Evaluation Scale (ChIMES): child and parent perspectives on understandability, content validity and acceptability.
      Regarding the assessment of psychometric properties, reliability is used to describe the reproducibility and stability of the measurements,
      • Fayers P.
      • Machin D.
      Quality of life: The assessment, analysis and interpretation of patient-reported outcomes.
      meaning that the instrument reproduces the same results. That is, a reliable measurement is one that can produce the same results if they are measured by the same scale. Reliability was assessed by means of Cronbach's alpha coefficient, considering values higher than 0.7; they were found to be satisfactory both for the self-reported and proxy versions, which corroborated the findings of the original study whose values were 0.93 and 0.95 for the self-reported and proxy versions, respectively.
      • Jacobs S.
      • Baggott C.
      • Agarwal R.
      • et al.
      Validation of the Children's International Mucositis Evaluation Scale (ChIMES) in paediatric cancer and SCT.
      Retest was performed with 62 pediatric patients and 35 proxy respondents; the results were considered to be adequate. In pediatric settings, the clinical conditions, mainly the behavior of the patients, are challenging with regard to answering questionnaires, specifically with regard to their attention spans. Moreover, retest procedures require that the same questions be answered again. The period for it to occur, between one and two weeks, is considered ideal to retest self-reported measurements,
      • Terwee C.B.
      • Bot S.D.
      • de Boer M.R.
      • et al.
      Quality criteria were proposed for measurement properties of health status questionnaires.
      although this interval may be adjusted to instruments of retested symptoms.
      • Paiva C.E.
      • Barroso E.M.
      • Carneseca E.C.
      • et al.
      A critical analysis of test-retest reliability in instrument validation studies of cancer patients under palliative care: a systematic review.
      In the present study after the tests, an interval of one to seven days was taken into consideration because of scheduled consultations. Regarding convergent validity, the a priori hypothesized correlations between the ChIMES proxy version and the items in OMDQ, the WHO oral mucositis grading scale,
      • World Health Organization (1979)
      WHO handbook for reporting results of cancer treatment. Geneva: World Health Organization.
      the VAS,
      • Jacobs S.
      • Baggott C.
      • Agarwal R.
      • et al.
      Validation of the Children's International Mucositis Evaluation Scale (ChIMES) in paediatric cancer and SCT.
      and the CTCAE
      • Trotti A.
      • Colevas A.D.
      • Setser A.
      • et al.
      CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment.
      were confirmed and presented strong correlations agreeing with the results of a previous study.
      • Jacobs S.
      • Baggott C.
      • Agarwal R.
      • et al.
      Validation of the Children's International Mucositis Evaluation Scale (ChIMES) in paediatric cancer and SCT.
      The present study has some limitations, including the fact that responsiveness was not performed to assess whether the instrument is capable of detecting changes within a specific time frame. Further studies are needed to evaluate this. Moreover, the long interval required for the retest may have influenced the results once mucositis is a condition that shows variable clinical evolution. In addition to those limitations, the institution where the research occurred uses a preventive standard laser therapy protocol in patients at risk of developing mucositis, which might have contributed to the low incidence of disease in the studied population.
      Thus, it can be concluded that the Brazilian Portuguese versions of ChIMES, both self-reported and proxy, were considered culturally adapted for Brazilian pediatric patients whose ages range from one month to 18 years. The process of evaluating psychometric properties showed that this is a potentially valid tool to assess oral mucositis in oncologic pediatric patients and may be an adequate alternative in situations where a clinical examination is difficult to perform.

      Disclosures and Acknowledgments

      The authors thank the São Paulo Research Foundation (FAPESP) for its financial support (grant number: 2016/09673-6). The authors declare no conflicts of interest.
      Ethical approval: The present study was approved by the Research Ethics Committee of Barretos Cancer Hospital (no. 824.408/2014). Authorization for the validation of ChIMES was requested from the original authors. Consent was requested from the participants, and their parents signed an informed consent form.

      Appendix

      References

        • Grabois M.F.
        • Oliveira E.X.
        • Carvalho M.S.
        Childhood cancer and pediatric oncologic care in Brazil: access and equity.
        Cad Saude Publica. 2011; 27: 1711-1720
        • Jacobs S.
        • Baggott C.
        • Agarwal R.
        • et al.
        Validation of the Children's International Mucositis Evaluation Scale (ChIMES) in paediatric cancer and SCT.
        Br J Cancer. 2013; 109: 2515-2522
        • Institute North Carolina
        Oral complications of chemotherapy and head/neck radiation (PDQ®).
        (Available from:)
        • Cheng K.K.
        • Leung S.F.
        • Liang R.H.
        • et al.
        Severe oral mucositis associated with cancer therapy: impact on oral functional status and quality of life.
        Support Care Cancer. 2010; 18: 1477-1485
        • Otmani N.
        • Alami R.
        • Hessissen L.
        • et al.
        Determinants of severe oral mucositis in paediatric cancer patients: a prospective study.
        Int J Paediatr Dent. 2011; 21: 210-216
        • den Hoed M.A.
        • Lopez-Lopez E.
        • te Winkel M.L.
        • et al.
        Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia.
        Pharmacogenomics J. 2015; 15: 248-254
        • Fadda G.
        • Campus G.
        • Lugliè P.
        Risk factors for oral mucositis in paediatric oncology patients receiving alkylant chemotherapy.
        BMC Oral Health. 2006; 6: 13
        • Cheng K.K.
        • Lee V.
        • Li C.H.
        • Yuen H.L.
        • Epstein J.B.
        Oral mucositis in pediatric and adolescent patients undergoing chemotherapy: the impact of symptoms on quality of life.
        Support Care Cancer. 2012; 20: 2335-2342
        • World Health Organization (1979)
        WHO handbook for reporting results of cancer treatment. Geneva: World Health Organization.
        (Available from:)
        http://www.who.int/iris/handle/10665/37200
        Date accessed: January 17, 2017
        • Trotti A.
        • Colevas A.D.
        • Setser A.
        • et al.
        CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment.
        Semin Radiat Oncol. 2003; 13: 176-181
        • Sonis S.T.
        • Eilers J.P.
        • Epstein J.B.
        • et al.
        Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy.
        Mucositis Study Group. 1999; 85: 2103-2113
        • Tomlinson D.
        • Gibson F.
        • Treister N.
        • et al.
        Understandability, content validity, and overall acceptability of the Children's International Mucositis Evaluation Scale (ChIMES): child and parent reporting.
        J Pediatr Hematol Oncol. 2009; 31: 416-423
        • Tomlinson D.
        • Gibson F.
        • Treister N.
        • et al.
        Refinement of the Children's International Mucositis Evaluation Scale (ChIMES): child and parent perspectives on understandability, content validity and acceptability.
        Eur J Oncol Nurs. 2010; 14: 29-41
        • Beaton D.E.
        • Bombardier C.
        • Guillemin F.
        • Ferraz M.B.
        Guidelines for the process of cross-cultural adaptation of self-report measures.
        Spine. 2000; 25: 3186-3191
        • Alexandre N.M.C.
        • Coluci M.Z.O.
        [Content validity in the development and adaptation processes of measurement instruments].
        Cien Saude Colet. 2011; 16: 3061-3068
        • Stiff P.J.
        • Erder H.
        • Bensinger W.I.
        • et al.
        Reliability and validity of a patient self-administered daily questionnaire to assess impact of oral mucositis (OM) on pain and daily functioning in patients undergoing autologous hematopoietic stem cell transplantation (HSCT).
        Bone Marrow Transpl. 2006; 37: 393-401
        • Manji A.
        • Tomlinson D.
        • Ethier M.C.
        • et al.
        Psychometric properties of the Oral Mucositis Daily Questionnaire for child self-report and importance of mucositis in children treated with chemotherapy.
        Support Care Cancer. 2012; 20: 1251-1258
        • Tomlinson D.
        • Ethier M.C.
        • Judd P.
        • et al.
        Reliability and construct validity of the oral mucositis daily questionnaire in children with cancer.
        Eur J Cancer. 2011; 47: 383-388
        • Terwee C.B.
        • Bot S.D.
        • de Boer M.R.
        • et al.
        Quality criteria were proposed for measurement properties of health status questionnaires.
        J Clin Epidemiol. 2007; 60: 34-42
        • Fayers P.
        • Machin D.
        Quality of life: The assessment, analysis and interpretation of patient-reported outcomes.
        Wiley Community, Chichester2007
        • Guillemin F.
        • Bombardier C.
        • Beaton D.
        Cross-cultural adaptation of health-related quality of life measures: literature review and proposed guidelines.
        J Clin Epidemiol. 1993; 46: 1417-1432
        • Paiva C.E.
        • Barroso E.M.
        • Carneseca E.C.
        • et al.
        A critical analysis of test-retest reliability in instrument validation studies of cancer patients under palliative care: a systematic review.
        BMC Med Res Methodol. 2014; 14: 8