Abstract
Objective:
The objective was to describe the reliability and validity of the healthcare professional proxy-report version of the Children’s International Mucositis Evaluation Scale (ChIMES).
Methods:
We included pediatric patients who were between 4 and 21 years of age and scheduled to undergo hematopoietic cell transplantation. Mucositis was evaluated by trained healthcare professionals who scored ChIMES, the World Health Organization oral toxicity scale, mouth and throat pain visual analogue scale, National Cancer Institute – Common Terminology Criteria and the Oral Mucositis Daily Questionnaire. Measures were completed daily and evaluated on days 7-17 post stem cell infusion for this analysis. Psychometric properties examined were internal consistency, test re-test reliability (days 13 and 14) and convergent construct validity.
Results:
There were 192 participants included. Cronbach’s alpha were 0.90 for ChIMES Total Score and 0.93 for ChIMES Percentage Score. Test re-test reliability were as follows: intraclass correlation coefficient (ICC) 0.82 (95% confidence interval (CI) 0.77-0.85) for ChIMES Total Score and ICC 0.82 (95% CI 0.77-0.86) for ChIMES Percentage Score. In terms of construct validation, all correlations between measures met or exceeded those hypothesized (all P < 0.05).
Conclusions:
The healthcare professional proxy-report version of ChIMES is reliable and valid for children and adolescents undergoing hematopoietic cell transplantation.
Clinical Trials Registration:
Keywords: child, adolescent, bone marrow transplantation, health personnel, mucositis, proxy, surveys and questionnaires, mucositis
BACKGROUND
Mucositis is an important and potentially debilitating toxicity of some chemotherapy and myeloablative hematopoietic stem cell transplantation (HSCT) regimens.(Sonis, 2004; Sung et al., 2017) In order to determine the most effective preventive and treatment strategies, we need reliable, valid, sensitive and easy to use outcome measures of oral mucositis. While much effort has been invested in developing oral mucositis scales for use in adults, there remains a lack of adequate instruments for use in children with cancer.(Tomlinson, Judd, Hendershot, Maloney, & Sung, 2007) While the standard in many pediatric mucositis trials remains the World Health Organization (WHO) oral toxicity scale, there are limitations to its use in children.(World Health Organization Handbook for Reporting Results of Cancer Treatment, 1979) The WHO scale requires complete visualization of the oral cavity given that the presence or absence of oral ulcers is critical to correct scoring. In addition, as the WHO score is dependent on a patient’s functional capacity to tolerate liquid or solid foods, it is important to determine whether a limited diet is due to oral pain or other factors such as nausea, vomiting or anorexia. This type of delineation may not be possible in young pediatric patients.
The Children’s International Mucositis Evaluation Scale (ChIMES) is a measure of oral mucositis created specifically for use in pediatric patients receiving cancer therapies including HSCT. It was developed through literature reviews and focus groups with experts in childhood mucositis.(Tomlinson, Gibson, Treister, Baggott, Judd, Hendershot, Maloney, Doyle, Feldman, Kwong, et al., 2009; Tomlinson, Gibson, et al., 2008; Tomlinson, Gibson, Treister, Baggott, Judd, Hendershot, Maloney, Doyle, Feldman, & Sung, 2009; Tomlinson, Isitt, et al., 2008; Tomlinson, Judd, Hendershot, Maloney, & Sung, 2008) ChIMES, when used as pediatric patient self-report and parent proxy-report, is acceptable, understandable and has content validity.(Tomlinson, Gibson, Treister, Baggott, Judd, Hendershot, Maloney, Doyle, Feldman, Kwong, et al., 2009; Tomlinson, Isitt, et al., 2008; Tomlinson et al., 2007) In a multi-center trial, it was found to exhibit excellent test-retest reliability and construct validity for both respondent types.(Jacobs et al., 2013) While in general parent proxy-report can be used when pediatric patients cannot self-report, for example, due to immaturity or illness acuity, there may be particular circumstances in which healthcare professional proxy-report is advantageous(Klaassen, Barr, et al., 2010; Varni, Limbers, & Burwinkle, 2007). Examples of such circumstances include where parents are not available or when used for hospital quality assurance purposes. Further, some clinical trials of hospitalized patients may prefer to use healthcare professional proxy-report to ensure high quality training can be consistently accomplished. Thus, there is a need to evaluate a healthcare professional proxy-report version of ChIMES. The objective of this study was to describe the reliability and validity of the healthcare professional proxy-report version of ChIMES.
METHODS
This analysis is a sub-study of a randomized double-blinded controlled trial conducted by the Children’s Oncology Group in which the primary goal was to determine the efficacy of topically administered Caphosol (EUSA Pharma, LTD, Hemel Hempstead, UK) rinsed orally four times daily to decrease the duration of severe oral mucositis in pediatric patients undergoing HSCT (NCT01305200).(Treister et al., 2017) The study was approved by the National Cancer Institute’s Central Institutional Review Board (IRB) and IRBs of all participating HSCT centers. All participants or guardians provided written informed consent or assent as appropriate.
subjects:
The trial included pediatric and adolescent/young adult (AYA) patients who were between 4 and 21 years of age and scheduled to undergo myeloablative autologous or allogeneic HSCT for both malignant and non-malignant conditions. Eligible allogeneic donors were any human leukocyte antigen-matched donor or partially matched family members. Patients who had received palifermin within 30 days of enrollment and those who had previously been treated with Caphosol were excluded. Participating centers were those who performed HSCT procedures for pediatric patients in the United States, Canada, Australia and New Zealand (n=30 centers).
procedures:
In the primary study, participants were randomized to receive either Caphosol oral rinse or placebo (0.9% sodium chloride) in a double blinded fashion. Study drug was topically administered four times per day from the first day of conditioning and continued until Day +20 following stem cell infusion or discharge, whichever occurred first. For this analysis, we focused on the period in which peak mucositis was expected, which was day 7-17 following stem cell infusion.
Oral mucositis was evaluated by trained healthcare professionals who scored ChIMES, WHO, a mouth and throat pain visual analogue scale (VAS), National Cancer Institute – Common Terminology Criteria v. 3.0 (NCI-CTC) and the Oral Mucositis Daily Questionnaire (OMDQ) daily during the observation period. Healthcare professional assessors included physicians, nurses and other clinical staff. Considerable effort was invested in mucositis training, which was conducted in-person during biannual Children’s Oncology Group meetings and via individual webinars hosted for each participating center. The training sessions were conducted by the same three people. Training materials were also provided. A consistent assessor was encouraged wherever possible.
outcome measures:
ChIMES:
ChIMES consists of the following seven components: ChIMES1: Amount of mouth and throat pain; ChIMES2: Effect of mouth and throat pain on swallowing; ChIMES3: Effect of mouth and throat pain on eating; ChIMES4: Effect of mouth and throat pain on drinking; ChIMES5: Receipt of pain medication; ChIMES6: Receipt of pain medication for mouth or throat pain; and ChIMES7: Presence of ulcers. In young children who are not eating or drinking, it may be difficult to determine whether poor oral intake is due to mucositis or due to other causes such as nausea, pain or anorexia. Thus, ChIMES allows respondents to choose “I can’t tell” if the respondent is not certain if the cause of functional impairment is due to oral mucositis.
ChIMES1-4 are scored from 0 to 5 where 5 is the worst symptoms. ChIMES5 is scored as 1 if the child had received pain medications and ChIMES6 is scored as 1 if the child received pain medications because of mucositis. ChIMES7 is scored as 1 if oral ulcers are present. ChIMES 5-7 are scored as 0 if they are absent. The maximum possible score is 23.
There are two summary scores returned by ChIMES. The ChIMES Total Score is the sum of scores where “I can’t tell” responses and missing responses are scored as 0. The ChIMES Percentage Score is the ChIMES Total Score over the total maximum score taking into account “I can’t tell” and missing responses (missing or “I can’t tell” are excluded from the total possible score) and multiplying by 100. Higher scores mean worse mucositis.
The methods for developing the patient and parent reported version of ChIMES have been detailed previously. The modification for healthcare professionals modified “you/your child” to “your patient” throughout the instrument. (Tomlinson et al., 2011; Tomlinson, Gibson, Treister, Baggott, Judd, Hendershot, Maloney, Doyle, Feldman, Kwong, et al., 2009; Tomlinson et al., 2010; Tomlinson, Gibson, Treister, Baggott, Judd, Hendershot, Maloney, Doyle, Feldman, & Sung, 2009).
WHO:
The WHO scale is based upon the ability to eat and drink, erythema and ulceration.(World Health Organization Handbook for Reporting Results of Cancer Treatment, 1979) The presence of oral ulcers defines a WHO mucositis grade of ≥ 2 versus < 2. WHO grade ranges from 0 to 4 where 4 corresponds to the worst mucositis.
Visual Analogue Scale (VAS):
A horizontal 10 cm VAS was used and ranged from 0 = “no mouth or throat pain” to 10 = ”most severe mouth or throat pain”. In this study, we asked the respondent to indicate today’s level of pain.
NCI-CTC:
The NCI-CTC is the standard approach for reporting adverse events for National Cancer Institute sponsored trials.(National Cancer Institute Common Toxicity Criteria V3.0, 2003) The NCI-CTC v3.0 mucositis functional/symptomatic scale was used in this study. The score ranges from 0 to 5 where 5 corresponds to the worst mucositis.
OMDQ:
The OMDQ consists of the following seven components: OMDQ1: Amount of mouth and throat pain; OMDQ2: Effect of pain on sleeping; OMDQ3: Effect on swallowing; OMDQ4: Effect on drinking; OMDQ5: Effect on eating; OMDQ6: Effect on talking; and OMDQ7: Amount of diarrhea. The self-report and parent proxy-report versions of OMDQ have been validated for all items other than for OMDQ7.(Manji et al., 2012; Tomlinson et al., 2011) Thus, OMDQ7 was not included in this analysis. Each component of the OMDQ was scored separately since an aggregate score has not been validated. For each component, the score ranges from 0 to 4 where 4 corresponds to the worst mucositis.
statistical analysis
To evaluate the psychometric properties of the healthcare professional proxy-report version of ChIMES, we used an approach similar to that taken in the original ChIMES validation study.(Jacobs et al., 2013) In terms of reliability, internal consistency was evaluated by Cronbach’s alpha and we anticipated an alpha ≥ 0.8.(Streiner & Norman, 1995) Test re-test reliability was evaluated by calculating the concordance coefficient (Rothery, 1979) defined as the intraclass correlation (ICC) between days 13 and 14, when maximum mucositis was expected. ICCs for total agreement were computed using a non-parametric measure of ICC (Rothery, 1979). We anticipated an ICC ≥ 0.6 to account for the possibility that different healthcare professionals conducted the assessments.
ChIMES was developed to measure oral mucositis, therefore, factor analysis on day 7 was performed to evaluate structural validity of ChIMES. Data were randomly divided into two data sets via a simple random sampling method without replacement to perform exploratory factory analysis (50%) and confirmatory factor analysis (50%). Data were examined for normality, factorability, and multicollinearity assumptions prior to performing exploratory factory analysis. Because ChIMES consists of binary and Likert scale items, a correlation method considering mixture of binary and Likert scale items was used to estimate the inter-item correlation matrix. Confirmatory factor analysis, considering all items as categorical variables, was performed to confirm the number of factors suggested by the exploratory factory analysis. In consideration of the ordinal and nonnormal nature of the data, the robust weighted least squares with mean and variance (WLSMV) method was used to extract the variances from the data. Several fit statistics including the model chi-square (p-value>0.05), Root Mean Square Error of Approximation (RMSEA <0.06), Comparative Fit Index (CFI >=0.95), and Standardized Root Mean Square Residual (SRMR <0.08) were evaluated to assess model fit. Factory analysis was performed using Lavaan and Psych packages in R 4.0.5.
To evaluate convergent construct validity, we hypothesized that the ChIMES score would be positively correlated with the WHO, pain VAS scale and OMDQ1-6. We described the Spearman correlation coefficients and their 95% CI (using Fisher transformation) and anticipated fair correlation (r > 0.25) between the scales.(Colton, 1974) To take into account that the same patient provided multiple assessments, generalized linear mixed models were used to obtain the P values for the Spearman correlation coefficients. We specified the distribution as multinomial to acquire them. Statistical significance level was defined as a P value < 0.05. ICCs were estimated using R 4.0.5 (concordance function, nopaco package). All other statistical analyses were conducted using SAS 9.4.
Floor and ceiling effects were summarized as the proportion of patients who achieved the worst ChIMES Total Score/floor effect (0/0) or best ChIMES Total Score/ceiling effect (23/23). Similarly, floor and ceiling effects were summarized as the proportion of patients who achieved the worst ChIMES percentage/floor effect (0%/0%) or best ChIMES percentage/ceiling effect (100%/100%).
RESULTS
Between April 4, 2011 and February 7, 2014, the parent trial enrolled 226 participants. From these patients, 4 were ineligible (mismatched donor, n = 1; non-myeloablative conditioning, n = 2; and incorrect short form consent signed, n = 1) and 2 were not randomized (sites were unable to reach the coordinating office due to different time zones or holidays). Among the 220 eligible and randomized participants, 23 participants were excluded from this analysis because they were removed from protocol therapy and did not complete mucositis assessments (physician determines it is in the patient’s best interest, n=2; refusal of further protocol therapy by patient/parent/guardian, n=14; and withdrawal of consent for any further data submission, n=7) and 5 were excluded because they did not have mucositis assessments submitted between days 7-17, resulting in 192 participants included in the analysis. Among these participants, the number of missing diary days was a median of 2 (interquartile range (IQR) 2 to 4.5) for a total of 83 missing days.
Table 1 outlines the demographic characteristics of the cohort. The median age (range) was 13.8 years (4.0 to 21.9) and 98 (51%) were male. Almost all (90.1%) underwent HSCT for a malignant condition. The median day of engraftment was 13 (range 8 to 34).
Table 1.
Baseline Characteristics of the Study Cohort (N=192)
| Characteristic | n (%) |
|---|---|
| Age in Years | |
| 4-7 | 31 (16.2) |
| 8-10 | 26 (13.5) |
| 11-14 | 51 (26.6) |
| 15-18 | 53 (27.6) |
| 19-21 | 31 (16.2) |
| Male | 98 (51) |
| Method of Payment | |
| Private insurance | 89 (46.4) |
| Medicare and private insurance | 4 (2.1) |
| Medicaid | 70 (36.5) |
| Medicaid and Medicare | 1 (0.5) |
| Medicare | 6 (3.1) |
| Self-pay | 1 (0.5) |
| No means of payment | 0 (0) |
| Military | 1 (0.5) |
| Other | 11 (5.7) |
| Unknown | 9 (4.69) |
| Diagnosis | |
| Malignant conditions | 173 (90.1) |
| Non-malignant conditions | 19 (9.9) |
| Transplant Type | |
| Autologous | 51 (26.6) |
| Allogeneic | 141 (73.4) |
| Graft Source | |
| Bone marrow | 88 (45.8) |
| Peripheral blood stem cells | 84 (43.8) |
| Umbilical cord blood | 20 (10.4) |
| Conditioning | |
| With TBI and/or Melphalan | 123 (64.1) |
| Without TBI/Melphalan | 69 (35.9) |
| Characteristics in Allogeneic Group | |
| Matched related donor | 6 (32.6) |
| Mismatched related donor | 1 (0.7) |
| Matched unrelated donor | 56 (39.7) |
| Mismatched unrelated donor | 18 (12.8) |
| Matched or partially mismatched cord blood | 20 (14.2) |
| GVHD prophylaxis with methotrexate* | 94 (66.7) |
| Median Day of Engraftment (range) | +13 (8, 34) |
Abbreviations: TBI = total body irradiation; GVHD = graft-versus-host disease.
Patients without data on GVHD prophylaxis data were excluded
Table 2 outlines the distribution of the best (minimum) and the worst (maximum) scores during the observation period between days 7-17 post stem cell infusion. The median worst ChIMES Total Score was 18 (maximum possible score is 23) and the median worst ChIMES Percentage Score was 78.3% (maximum total possible score is 100%).
Table 2.
Characteristics of Outcomes
| Outcomes | Minimum | Maximum |
|---|---|---|
| Symptom Screening in Pediatric Tool* | Median (IQR) | Median (IQR) |
| ChIMES Total Score | 0 (0, 1) | 18 (11, 21) |
| ChIMES Percentage Score | 0% (0%, 4.3%) | 78.3% (47.8%, 91.3%) |
| World Health Organization Mucositis Scale | 0 (0, 0) | 3 (2, 3) |
| Oral Mucositis Daily Questionnaire 1 | 0 (0, 0) | 3 (2, 3) |
| Oral Mucositis Daily Questionnaire 2 | 0 (0, 0) | 2 (0, 3) |
| Oral Mucositis Daily Questionnaire 3 | 0 (0, 0) | 3 (2, 3) |
| Oral Mucositis Daily Questionnaire 4 | 0 (0, 0) | 3 (2, 4) |
| Oral Mucositis Daily Questionnaire 5 | 0 (0, 0) | 4 (2,4) |
| Oral Mucositis Daily Questionnaire 6 | 0 (0, 0) | 2 (1,3) |
| 10 Point Mouth Pain Categorical Rating Scale | 0 (0, 0) | 6 (3.5, 8) |
Minimum is the lowest score and maximum is the highest score between days 7-17 days post stem cell infusion.
Table 3 reports test re-test reliability of ChIMES. The ICC for ChIMES Total Score was 0.87 (95% confidence interval (CI) 0.86 to 1.00) and the ICC for ChIMES Percentage Score was 0.88 (95% CI 0.86 to 1.00); both exceeded the hypothesized ICC of 0.60. In terms of convergent validity, the Spearman correlation coefficients between measures exceeded those hypothesized and were > 0.50 for all measures.
Table 3.
Psychometric Properties of the Children’s International Mucositis Evaluation Scale
| Property | N | Diary Days | Hypothesis | ChIMES Total Score | ChIMES Percentage Score |
|---|---|---|---|---|---|
| Reliability | |||||
| Test re-test reliability | 186** | 370 | ICC ≥ 0.6 | ICC = 0.87 (95% CI 0.86 to 1.00) |
ICC = 0.88 (95% CI 0.86 to 1.00) |
| Convergent Validity | |||||
| Correlation with WHO | 192 | 2019 | r > 0.25 | r = 0.69 (95% CI 0.67 to 0.71) P < 0.0001) |
r = 0.69 (95% CI 0.67 to 0.71) P < 0.0001 |
| Correlation with OMDQ1 | 192 | 2019 | r > 0.25 | r = 0.84 (95% CI 0.83 to 0.85) P<0.0001 |
r = 0.84 (95% CI 0.83 to 0.85) P < 0.0001 |
| Correlation with OMDQ2 | 192 | 2019 | r > 0.25 | r = 0.59 (95% CI 0.57 to 0.62) P<0.0001 |
r = 0.60 (95% CI 0.57 to 0.62) P < 0.0001 |
| Correlation with OMDQ3 | 192 | 2019 | r > 0.25 | r = 0.82 (95% CI 0.81 to 0.84) P<0.0001 |
r = 0.83 (95% CI 0.81 to 0.84) P < 0.0001 |
| Correlation with OMDQ4 | 192 | 2019 | r > 0.25 | r = 0.81 (95% CI 0.80 to 0.83) P<0.0001 |
r = 0.82 (95% CI 0.80 to 0.83) P < 0.0001 |
| Correlation with OMDQ5 | 192 | 2019 | r > 0.25 | r = 0.81 (95% CI 0.80 to 0.82) P<.0001 |
r = 0.81 (95% CI 0.80 to 0.83) P < 0.0001 |
| Correlation with OMDQ6 | 192 | 2019 | r > 0.25 | R = 0.72 (95% CI 0.70 to 0.74) P<0.0001 |
r = 0.72 (95% CI 0.70 to 0.74) P < 0.0001 |
| Correlation with Pain Scale | 192 | 2019 | r > 0.25 | R = 0.79 (95% CI 0.77 to 0.80) P<0.0001 |
r = 0.78 (95% CI 0.77 to 0.80) P < 0.0001 |
Abbreviations: WHO – World Health Organization Mucositis Scale; OMDQ – Oral Mucositis Daily Questionnaire; r – Spearman correlation coefficient; ICC – intraclass correlation coefficient
P-values derived from generalized linear mixed model
Analysis based on 186 patients who reported outcomes on days +13 and +14. Two patients did not report outcomes for day +14.
Table 4 shows that the internal consistency of the ChIMES instrument (Cronbach’s alpha 0.90) exceeded the hypothesized score of 0.80. Cronbach’s alphas of instruments with multiple questions, i.e. OMDQ, were reported for completeness.
Table 4.
Internal consistency of ChIMES and OMDQ.
| N | Diary Days | Instrument | Hypothesis | Raw Cronbach’s alpha | Standardized Cronbach’s alpha |
|---|---|---|---|---|---|
| 192 | 2021 | ChIMES | Cronbach’s alpha > 0.8 | 0.90 | 0.93 |
| 192 | 2027 | OMDQ | 0.95 | 0.95 |
ChIMES = Children’s international mucositis evaluation scale. OMDQ = Oral mucositis daily questionnaire.
Floor and ceiling effects are summarized for Total ChIMES Score and ChIMES Percentage Score in Table 5. Floor scores and percentages ranged from 14.2% to 34.5%, and 14.2% to 34.5%, respectively. Ceiling scores and percentages ranged from 0.55% to 7.72%, and 0.55% to 2.72%, respectively.
Table 5.
Floor and Ceiling Effects using the ChIMES instrument
| Day | N | Total ChIMES score | Total ChIMES score | ChIMES Percentage Score | ChIMES Percentage Score |
|---|---|---|---|---|---|
| Floor (score=0) | Ceiling (score=23) | Floor (score=0%) | Ceiling (score=100%) | ||
| 7 | 192 | 24.5% | 1.6% | 24.5% | 1.6% |
| 8 | 190 | 14.2% | 1.6% | 14.2% | 2.1% |
| 9 | 190 | 15.8% | 2.1% | 15.8% | 2.6% |
| 10 | 189 | 18.0% | 1.1% | 18.0% | 1.6% |
| 11 | 189 | 14.3% | 1.6% | 14.3% | 2.1% |
| 12 | 188 | 16.0% | 1.6% | 16.0% | 2.1% |
| 13 | 186 | 21.5% | 1.6% | 21.5% | 1.1% |
| 14 | 184 | 23.4% | 2.7% | 23.4% | 2.7% |
| 15 | 181 | 24.3% | 0.6% | 24.3% | 0.6% |
| 16 | 172 | 25.0% | 1.2% | 25.0% | 1.2% |
| 17 | 168 | 34.5% | 0.6% | 34.5% | 0.6% |
Ninety-six patients were randomly selected for exploratory factor analysis and the other 95 patients were for the confirmatory factor analysis. One patient who did not provide a response to any items was excluded from this analysis. When examining the assumptions for factor analysis, inter-item correlation matrix showed ChIMES5 (receipt of pain medication) had near perfect correlation with ChIMES6 (receipt of pain medication for mouth or throat pain), therefore, we excluded ChIMES5 from this analysis. Eigenvalues for the first factor and second factor were 5.17 and 0.38 suggesting that one underlying construct is appropriate. This explains 81% of the variance in the data. Results from the one-factor confirmatory factor analysis indicated that the data support the model specified. The chi-square test of model fit was not significant (p = 0.71). Additional model fit indices including SRMR = 0.02, CFI = 1, and RMSEA = 0 also indicated that the data support the model specified.
DISCUSSION
In this study to evaluate the psychometric properties of the healthcare professional proxy-report version of ChIMES, we found that the ChIMES instrument was reliable (internal consistency and test re-test reliability) and valid (construct validity) in children and AYA undergoing autologous and allogeneic HSCT. This supports the use of a healthcare professional proxy-report of the instrument.
Use of parent- and caregiver-proxy response has been demonstrated to be feasible, reliable and valid for assessing a wide range of symptoms and experiences, but there may be situations in which these proxies are not available.(Irwin et al., 2012; Varni et al., 2007) There are fewer reports of instruments that have been validated for proxy-report by healthcare professionals. Nurses have been demonstrated to contribute reliable and valuable information as proxy respondents, possibly in part due to the close and often longitudinal nature of their relationship with the patient.(Klaassen, Barr, et al., 2010) Some caution should be heeded, however, as a study in persons with disabilities found that proxy-respondents, which included healthcare workers, tended to overestimate impairment and underestimate both pain symptoms and health-related quality of life.(Andresen, Vahle, & Lollar, 2001) Similarly, a study in care home residents found that use of staff proxy-respondents, which included nurses, was associated with relatively low levels of agreement with self-reported outcomes.(Usman et al., 2019)
Since its introduction, ChIMES data have been collected and reported in several clinical trials. In a Brazilian study evaluating light-based therapies for management of mucositis in children (10 months to 18 years), ChIMES was collected by healthcare professionals and demonstrated a significant decrease in pain symptoms.(Ribeiro da Silva et al., 2018) An Indian study evaluating vitamin E and pycnogenol for treatment of oral mucositis in children demonstrated a significant reduction in ChIMES scores over the treatment period.(Khurana, Pandey, Saksena, & Kumar, 2013) Despite ChIMES not yet having been validated for use by healthcare professional proxy reporters, these studies demonstrate that there is interest in and need for such an instrument in pediatric oncology.
There are several limitations to this analysis. First, participant age varied widely (4 to 21 years), and our sample size precluded the ability to stratify psychometric evaluation by age group. It is possible that reliability and validity may vary by age.(Varni et al., 2007) Second, the healthcare professionals who assessed oral mucositis were trained by external experts in mucositis evaluation. While instructions are available, it is unclear how the instrument might perform in the absence of training. Another limitation is that the standardized Cronbach’s alpha for ChIMES was 0.93 and a score above 0.9 may suggest redundancy. (Tavakol & Dennick, 2011) While this may be a concern, the brevity of the instrument may make this issue less of a concern. The results from the factor analysis confirm the one-factor construct to measure pain by ChiMES for use by healthcare professional; this suggests that the ChiMES instrument might be shortened by one question. Finally, in this study, healthcare professional raters could be physicians, nurses, or other clinical staff such as physician assistants and dentists. We did not attempt to evaluate the impact of the specific qualifications of the trained healthcare professional on study outcomes.
Children undergoing cancer therapy who are at risk for developing oral mucositis should be routinely assessed so that early intervention can be provided when symptoms develop, and modified accordingly over time.(Klaassen, Krahn, et al., 2010; Tomlinson, Gibson, et al., 2008) ChIMES is a simple to administer measure of oral mucositis, and the results of this study provide support for the use of ChIMES by healthcare professional proxy-report. This implementation could be in the context of routine clinical care or within the design and conduct of clinical trials.(Immonen et al., 2020; Khurana et al., 2013; Ribeiro da Silva et al., 2018; Treister et al., 2017)
Acknowledgements
LS is supported by a Canada Research Chair in Pediatric Oncology Supportive Care.
EUSA Pharma supported the project through FOC Caphosol.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding information
This research was supported by the following grants from the National Cancer Institute, National Institutes of Health: The Children’s Oncology Group Chair’s Grant U10CA98543–08, NCTN Operations Center Grant U10CA180886, NCTN Statistics & Data Center U10CA180899, Statistics & Data Center Grant U10CA098413, and St. Baldrick’s Foundation.
Footnotes
Ethics approval and consent to participate
The study was approved by the National Cancer Institute’s Central Institutional Review Board (cIRB) and IRBs of all participating HSCT centers. All participants or guardians provided written informed consent or assent as appropriate. The study was performed in accordance with the Declaration of Helsinki.
Competing interests
The authors declare no conflict of interest.
Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.