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New measure of health-related quality of life for patients with oropharyngeal mucositis
Development and preliminary psychometric evaluation
Article first published online: 9 MAY 2007
Copyright © 2007 American Cancer Society
Volume 109, Issue 12, pages 2590–2599, 15 June 2007
How to Cite
Cheng, K. K. F., Leung, S. F., Thompson, D. R., Tai, J. W. M., Liang, R. H. S., Kan, A. S. T., Ying, F. W. O. and Yeung, R. M. W. (2007), New measure of health-related quality of life for patients with oropharyngeal mucositis. Cancer, 109: 2590–2599. doi: 10.1002/cncr.22730
- Issue published online: 4 JUN 2007
- Article first published online: 9 MAY 2007
- Manuscript Accepted: 20 FEB 2007
- Manuscript Revised: 16 FEB 2007
- Manuscript Received: 30 NOV 2006
- Health and Health Services Research Fund of the Health, Welfare and Food Bureau of Hong Kong
- oropharyngeal mucositis;
- health-related quality of life;
- cancer treatment;
- psychometric properties
Oropharyngeal mucositis (OM) causes profound impairment of patients' health-related quality of life (HQoL). The aim of the article is to describe the development and preliminary validation of an HQoL instrument, OMQoL, specifically for patients with OM.
First, a qualitative phase was conducted to generate items (n = 23). Face validity was assessed by focus group interviews (n = 13). Expert content review (n = 7) was used to ensure content validity. The second step was a quantitative validation phase comprised a multicenter study (n = 210) to help identify subscales of the instrument addressing different dimensions of OM and to measure reliability.
The qualitative interview generated 171 items. Using focus group discussion and expert content review, items were reduced to 41 items. Factor and scaling analyses of these 41 items resulted in 4 subscales, contributed by 31 items, depicting problems with symptoms, diet, social function, and swallowing. The floor effect was modest. The factorial structure was satisfactory with loading >0.40 on each subscale for all items. All corrected item-total corrections were higher than 0.40 (r = 0.457–0.874). The internal consistency reliability of each subscale was high, with Cronbach alpha coefficients ranging from 0.906 to 0.934. The test-retest reliability of the individual items using weighted kappa was good (kappa values 0.610–0.895). The intraclass correlation results for the subscale totals were all in excess of 0.70 (0.864–0.934).
An initial psychometric analysis of the OMQoL was encouraging. The OMQoL could provide a valuable tool for the assessment of HQoL of patients with OM. Cancer 2007. © 2007 American Cancer Society.
Oropharyngeal mucositis (OM) is an acute inflammatory and ulcerative oral complication that commonly occurs during cancer therapy. The incidence of OM reported in the literature varies widely, with estimates ranging from 20% in patients who received standard-dose 5-fluorouracil (5-FU)-based stomatotoxic chemotherapy for the treatment of colorectal cancer to 50% of patients being treated with standard-dose 5-FU, Adriamycin, and cytoxan-based stomatotoxic chemotherapy for breast cancer.1 Approximately 97% and 89% of head and neck cancer patients receiving conventional radiotherapy and chemoradiotherapy, respectively, will develop OM.2 For patients subjected to high-dose myeloablative chemotherapy with or without concomitant total body irradiation before hematopoietic stem cell transplantation (HSCT), the incidence of OM is reported to be approximately 75% to 100%.3, 4
Clinically, OM presents with an initial mucosal erythema that often progresses to patchy mucositis and then to extensive ulceration and desquamation.5, 6 In addition to the clinical and economic burdens,7–9 OM often causes substantial physical and psychosocial suffering to patients. Pain, inability to eat/chew, drink, swallow, or speak, compromised oral intake and nutritional status, and colonized infection and bleeding can have profound functional, nutritional, and emotional impacts on patients. These are particularly damaging to the cancer patients' well-being and health-related quality of life (HQoL).7, 10, 11 The literature indicates that 46% of patients with OM report 3 to 4 simultaneous OM-related dysfunctions.12 The HQoL was severely compromised for patients with OM,11, 13, 14 especially in the functional sphere.11 Patients with cancer have always identified OM as 1 of the major troubling symptoms and the primary cause of distress in their cancer treatment. It is estimated that about 38% of the patients with OM suffer from depression.14
The latest advance in OM has been the detailed understanding of the cellular and molecular biology of mucosal injury.6 The refined 5-stage model of OM suggests that the most rational approach for managing OM is to use mechanistically based agents directing at multiple pathways involved in OM pathogenesis.15 Until recently, there has been no scientifically demonstrated intervention or agent in any setting to reduce the incidence and duration of OM, and the treatment of OM was limited to palliative strategies. The most recent Cochrane systematic review of interventions for preventing oral mucositis evaluated 29 interventions and recruited 5217 patients. The reviewers concluded that of those 29, only 10 interventions showed some evidence of a benefit (albeit sometimes weak) in preventing or reducing the severity of OM.16 In its 2005 update of the MASCC/ISOO Clinical Practice Guidelines for OM, the MASCC/ISOO Mucositis Study Group recommends few agents for OM, specific to certain cancer types or cancer treatments.17 Palifermin (recombinant human keratinocyte growth factor) is the only pharmacologic agent approved by the US Food and Drug Administration (FDA) for reduction of the incidence and duration of OM in patients with hematologic malignancies undergoing autologous HSCT. The introduction of palifermin represents an important first in the management of OM.4, 17, 18 More clinical trial efficacy data for palifermin should be available in the next few years.
Given the multifaceted nature of OM, the evaluation of its incidence and duration does not reflect the full impact of the oral condition on a patient. Trials of potential therapeutic agents or interventions should, therefore, not only include assessments of biomedical outcomes but also HQoL parameters because they are an integral part of efficacy studies. Nevertheless, since its introduction HQoL has been 1 of the most debated concepts in the literature. The debate centers around the issues of dimensionality of the operationalized concept and the measurement of each dimension. The majority argue that HQoL is a subjective, multifaceted construct that encompasses perceptions of both positive and negative aspects of dimensions such as physical symptoms and toxicities, physical functioning, emotional functioning, role functioning and social well-being and functioning.19–21 Because there are so many potential dimensions, controversy remains over which components should be included. Nevertheless, most researchers agree that a number of the above dimensions should be included in HQoL instruments and that the HQoL is neither a unidimensional nor bidimensional construct.21, 22 There are other unifying and noncontroversial features of the HQoL instruments: the patients themselves are asked, there are frequently several subscales, the scales are often based on multiple items, and the scales represent constructs that cannot be measured directly.22
HQoL was increasingly assessed in clinical trials of therapeutic agents or interventions for OM using the generic measure of Functional Assessment of Cancer Therapy-General Scale (FACT-G) as an important part of the evaluation of treatment outcome.4, 18 This instrument, however, may lack sensitivity and would be unable to discriminate differences in OM between groups of patients. Currently, 1 of the major barriers in the HQoL assessment of patients with OM has been the lack of an instrument to specifically tap dimensions of health status that are particularly salient and relevant to OM in cancer therapy. Whereas many generic HQoL instruments, such as the FACT-G19 and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30),23 are available for the assessment of HQoL in cancer patients, none sufficiently cover the aspects specifically relevant for patients with OM. Of the published disease- or site-specific instruments, only the EORTC Quality of Life-Head and Neck 35 Questionnaire (EORTC QLQ-H&N35),24 the FACT-Head and Neck Scale (FACT-H&N),25 the Quality of Life Radiation Therapy Instrument with Head and Neck Companion Module (QOL-RTI/H&N)26 and the Performance Status Scale for Head and Neck Cancer (PSS-HN)25 contain items related to oral dysfunction, such as swallowing and speech. Nevertheless, they were developed for use in patients with head and neck cancer and so focus on the effects associated with radiotherapy and surgical treatment of head and neck cancer: facial disfigurement and permanent impairment of vasculature, connective tissue, salivary glands, muscle, and bone. They may fail to fully address the distinct problems arising from the acute erythematous and ulcerative mucosal changes in OM during chemotherapy and radiotherapy. Another drawback of the EORTC QLQ-H&N35, FACT-H&N, and QOL-RTI/H&N instruments is that they must be used in conjunction with their core questionnaires24–26; the whole panel of items would be much more demanding for patients, particularly in the acute stage of complication. Indeed, OM is a unique, acute complication very common to stomatotoxic chemotherapy and high-dose myeloablative chemotherapy, as well as head/neck irradiation. Neither generic nor disease-specific instruments can specifically and concisely address the important issues in OM. These instruments may therefore not be suitable for assessing patients with OM because of their limitations in sensitivity and validity.
The purpose of this article is to describe the development and preliminary validation of the OMQoL, an OM-specific HQoL measure, which is intended to provide an accurate summary of the patient's perspective of the impact of OM while undergoing cancer therapy.
MATERIALS AND METHODS
The study was conducted in the 2 regional university-affiliated hospitals and 1 regional hospital in Hong Kong after approval from their Institutional Review Boards. Subjects were recruited who were over 18 years of age, diagnosed with hematologic malignancies or solid tumors, able to understand the study, and give informed consent. They were treated with 1 of the following cancer therapies and presented with OM: stomatotoxic chemotherapy (eg, 5-FU, etoposide, melphalan, Adriamycin, methotrexate, etc), head/neck irradiation, combined chemotherapy and head/neck irradiation, high-dose myeloablative chemotherapy for HSCT or combined high-dose myeloablative chemotherapy and total body irradiation for HSCT. Subjects with such cancer therapies were selected because they are considered to be at high risk for OM and thus are representative of the group targeted by the developed scale. The study was conducted in accordance with the Declaration of Helsinki; all the subjects provided written informed consent before enrolling in the study.
The OMQoL instrument was developed and tested in 2 stages: first, to perform item generation; second, to perform psychometric evaluation of the developed scale.
The approach to developing the OMQoL used a combination of empirical item generation and theoretical item selection.19 The degree to which these OMQoL elements, including individual items, response format, and instructions, is relevant to and representative of the targeted construct for HQoL assessment in OM patients was determined by focus group discussion and expert content review.27, 28
Exploratory, in-depth qualitative interviews were carried out with OM patients in order to identify areas of salience and concern, which enabled us to generate a large number of candidate questionnaire items.29 Interviews were conducted with 23 patients (11 male, 12 female) with a mean (±SD) age of 42 ± 13 years (range, 21–58 years). The majority of them were diagnosed with nasopharyngeal cancer (NPC) (n = 9, 39%) and acute lymphoblastic leukemia (ALL) (n = 7, 30%). The respondents were well distributed with respect to cancer treatment modality: 6 (26%) were treated with stomatotoxic chemotherapy and 6 (26%) received a combination of chemotherapy and head/neck irradiation. The majority of the respondents (n = 11, 48%) had World Health Organization (WHO) grade 2 OM during cancer therapy (Table 1). The analysis of respondent interviews resulted in the generation of 171 items. Three researchers went on to independently select and devise questionnaire items from these 171 items, which were then discussed and scrutinized for repetition and ambiguity until a final set of items was agreed upon. To avoid possible omission of items that could be clinically significant, recent literature and previous validated HQoL instruments, including the EORTC QLQ-H&N35, the FACT-H&N, and the QOL-RTI/H&N, were also searched for additional items.24–26 After removal of duplicate and idiosyncratic items the item selection process yielded 63 items for the first version of the OMQoL. All the items were formulated both in English and Chinese by a linguistics expert and 2 bilingual investigators. A 4-point Likert scale with descriptors (1 = not at all, 2 = a little bit, 3 = quite a bit, 4 = very much) response format was selected because previous HQoL studies indicated that this is the most appropriate scoring format for such an instrument.23, 24
|Individual interview||Focus group||Focus group|
|N = 23||Patients, n = 9||Family, n = 4|
|Mean (SD)||Mean (SD)||Mean (SD)|
|Age, y||42 (13)||38 (15)||38 (15)|
|Sex||f (%)||f (%)||f (%)|
|Men||11 (48)||5 (56)||2 (50)|
|Women||12 (52)||4 (44)||2 (50)|
|Primary to junior secondary||7 (30)||4 (44)||0 (0)|
|Secondary graduate||12 (52)||4 (44)||3 (75)|
|Post-secondary and above||4 (17)||1 (11)||1 (25)|
|NPC||9 (39)||2 (22)||—|
|Colorectal cancer||1 (4)||2 (22)||—|
|Breast cancer||3 (13)||1 (11)||—|
|Lung cancer||1 (4)||0 (0)||—|
|ALL||7 (30)||3 (33)||—|
|AML||2 (9)||1 (11)||—|
|Stomatotoxic CT||6 (26)||3 (33)||—|
|Head and neck RT||3 (13)||2 (22)||—|
|CT+Head and neck RT||6 (26)||0 (0)||—|
|High-dose myeloablative CT followed by HSCT||4 (17)||3 (33)||—|
|High-dose myeloablative CT+TBI followed by HSCT||4 (17)||1(11)||—|
|WHO grade for mucositis||—|
|1||5 (22)||3 (33)||—|
|2||11 (48)||3 (33)||—|
|3||6 (26)||3 (33)||—|
|4||1 (4)||0 (0)||—|
Focus group interviews,28 made up of a combination of OM patients and their family caregivers, were used to assess the face validity of the OMQoL and refine the questionnaire if necessary. Ten patients and 6 family caregivers were enrolled in focus group interviews. Nine patients and 4 family caregivers actually attended the group discussions, with 6 respondents in 1 group and 7 in another. The mean age of the patient respondents was 38 ± 15 years (range, 18–55 years) with 5 (56%) males. About one-third of the respondents were diagnosed with ALL (n = 3, 33%). Patients treated with stomatotoxic chemotherapy and high-dose myeloablative chemotherapy for HSCT represented 66% of the study sample. Patient respondents were well distributed by OM severity, with the exception of WHO grade 4. The mean age of the family caregiver respondents was 38 ± 15 years (range, 22–54 years) (Table 1). In focus group interviews respondents were asked to comment on the clarity, understandability, and appropriateness of all instructions, questionnaire items, and response continua and to check on the most appropriate wording. Items that were problematic or not well understood were reworded to improve comprehension. It was also possible for respondents to exclude items or suggest additional ones. The first author facilitated the process of group interview. After focus group discussion it was decided for reasons of irrelevance, ambiguity, and repetition to remove 20 items and add 1. The remaining 44 items went to expert review to assess the content validity.
Expert review for clarity and relevance was undertaken by 2 clinical oncologists (29%), a HSCT oncologist (14%), a specialist oncology nurse (14%), 2 specialist HSCT nurses (29%), and an oral mucositis researcher (14%). The mean oncology/HSCT experience of the experts was 14.4 ± 2.9 years (range, 9–17 years). A separate, 4-point rating scale was used to assess the clarity and relevance parameters: 1, not clear, not relevant; 2, somewhat clear, somewhat relevant; 3, clear, relevant; and 4, very clear, very relevant. The interrater agreement (IR) and content validity index (CVI) for theses 2 parameters were computed, which have been presented elsewhere.30 The experts' review showed 37 of the 44 items (CVI 0.82) to be ‘relevant’ and ‘very relevant.’ As a result of the content validity testing, minor revisions were made to improve clarity and logic, which resulted in the deletion of 3 items and the modification of 4. The iteration with 41 items had a clarity IR of 0.71, a relevancy IR of 0.72, a clarity CVI of 0.97 (range, 0.57–1), and a relevancy CVI of 0.88 (0.71–1), which were greater than the predetermined acceptable IR and CVI levels of 0.70 and 0.80, respectively. The resultant OMQoL contained 41 items. A single item with rating of 1–7 was also developed to assess the overall QoL during OM.22
To determine the psychometric properties of the OMQoL, the above 41-item version of the OMQoL was administered to 210 patients with OM during their cancer therapies to test its scaling properties, internal consistency, and test-retest reliability using an iterative process. The statistical analysis began with assessment of the pattern of missing values among the OMQoL items. In addition, the degree of variability among individual items was assessed using summary statistics. An exploratory factor analysis was undertaken to extract factors in order to explore how the items of the OMQoL were combined into relevant subscales. For this purpose a principal axis factoring31 with promax rotation32 was used. Only factors that gained an eigen value in excess of 1 and items with factor loadings above 0.40 were retained.33 The correlations of items with their subscales total were also determined. Items with a low corrected item-total correlation (r<0.20) with the other items were considered for deletion.33 Cronbach alpha coefficient was used to assess the internal consistency reliability for the subscales total. Items that tapped different aspects of the same attribute by too low a correlation (alpha coefficient <0.70)29, 34 and showed redundancy of measurement by too high a correlation (alpha coefficient >0.95)33 were omitted. In addition, items were removed from each of the subscales if they inflated the alpha coefficient.29 The test-retest pairs for each individual item were analyzed using a weighted kappa coefficient35, 36 and the test-retest analysis of the subscale total scores was performed using intraclass correlation (ICC).37 Values greater than 0.40 and 0.70 for weighted kappa and ICC, respectively, were accepted as satisfactory level for test-retest reliabilities.35–37 Scale-level analysis was evaluated by the floor and ceiling effects. The floor effect refers to a high percentage of subjects scoring the lowest possible score (not at all), whereas ceiling effect refer to a high percentage of subjects achieving the highest possible score (very much).38 A percentage of 20% at floor or at ceiling was considered a significant effect. Likewise, a percentage of 70% was considered a high floor or ceiling effect, which indicates a scale that is limited in its responsiveness to clinical change.38 In this study, items with a high floor or ceiling effect, ie, items where more than 70% subjects scored ‘not at all’ or ‘very much’ were considered for removal.
Table 2 describes the demographic and clinical characteristics of the 210 patients. The mean age of the patients was 51 ± 12 years (range, 21–84 years) with 120 (57%) females. Almost half of the patients were diagnosed with NPC (n = 91, 43%). One-third of the patients were treated with stomatotoxic chemotherapy (n = 76, 36%), and another 34% (n = 71) treated with combined chemotherapy and head/neck irradiation. Patient respondents were quite well distributed by OM severity, with the exception of WHO grade 4.
|Age, y||50.7 (12)|
|Informal education||4 (2)|
|Primary to junior secondary||94 (45)|
|Secondary graduate||82 (39)|
|Tertiary or above||30 (14)|
|Non-NPC head and neck||18 (9)|
|Colorectal cancer||18 (9)|
|Breast cancer||35 (17)|
|Lung cancer||8 (4)|
|Lymphoma/Hodgkin disease||7 (3)|
|Gynecological cancer||10 (5)|
|Other cancers||10 (5)|
|Stomatotoxic CT||76 (36)|
|Head and neck RT||43 (21)|
|CT+Head and neck RT||71 (34)|
|High-dose myeloablative CT followed by HSCT||16 (8)|
|High-dose myeloablative CT+TBI followed by HSCT||4 (2)|
|WHO grade for mucositis|
Exploratory factor analysis extracted 4 distinct factors that included 31 items denoting symptoms (Factor 1, items 1–9), diet (Factor 2, items 10–19), social function (Factor 3, items 20–26), and swallowing (Factor 4, items 27–31). These 4 factors accounted for 62.8% of the total variance. The factors with their respective factor loadings are presented in Table 3. The factorial structure was satisfactory, with loading >0.40 on each subscale for all items. Item 8 had moderate loading on both Factors 1 and four; however, this item was retained because of its clinical relevance and this item would reduce the coefficient alpha for Factor 1 if they were removed. Internal consistency reliability of OMQoL was good. Each of the 4 factors had a similarly high coefficient alpha value ranging from 0.906 (Factor 4, swallowing) to 0.934 (Factor 3, social function). All corrected item-total correlations were higher than 0.40.
|Item||EFA||Internal consistency||Test-retest reliability|
|Factors||Corrected item-total correlation||Cronbach α||α if item deleted||Weighted kappa||ICC|
|1||I have swelling inside my mouth.||0.550||0.651||0.916||0.910||0.688||0.864|
|2||I have mouth ulcer.||0.645||0.657||0.909||0.718|
|3||Mouth pain makes me distressed.||0.788||0.346||0.874||0.893||0.754|
|4||I have oozing/bleeding on my lips, or inside my mouth.||0.602||0.457||0.920||0.697|
|5||I feel discomfort while tooth brushing/mouth rinsing.||0.655||0.695||0.907||0.649|
|6||Mouth pain makes me have trouble sleep.||0.525||0.312||0.758||0.903||0.791|
|7||I have mouth pain.||0.868||0.353||0.832||0.897||0.687|
|8||I have burning sensation inside my mouth.||0.569||0.353||0.742||0.904||0.610|
|9||I have difficulty in opening my mouth.||0.448||0.656||0.909||0.792|
|10||I am unable to enjoy food.||0.802||0.813||0.929||0.917||0.762||0.914|
|11||I reduce outside social dining due to mucosal discomfort.||0.558||0.681||0.924||0.757|
|12||My saliva becomes thick/sticky and need to spit out frequently.||0.491||0.335||0.680||0.924||0.775|
|13||I have taste changes.||0.690||0.621||0.927||0.718|
|14||Eating difficulty makes me distressed.||0.463||0.822||0.916||0.841|
|15||I use longer time to drink/eat.||0.465||0.745||0.920||0.835|
|16||I have weight loss.||0.663||0.598||0.928||0.895|
|17||I modify my diet (e.g. food type, texture and size).||0.859||0.802||0.918||0.742|
|18||I reduce my soft/solid food intake.||0.553||0.729||0.921||0.808|
|19||I worry my inadequate nutritional intake.||0.720||0.745||0.921||0.762|
|20||I speak with lower quality/voice.||0.687||0.785||0.934||0.924||0.726||0.934|
|21||I have difficulty in talking.||0.640||0.815||0.921||0.826|
|22||I need to use other means (e.g. paper/pen, body language) to communicate with others.||0.742||0.742||0.928||0.698|
|23||I feel embarrassed at mealtimes with my family/friends.||0.528||0.702||0.932||0.722|
|24||Speaking difficulty makes me distressed.||0.726||0.864||0.916||0.895|
|25||I do not want to talk to others (including talking on phone) due to mouth discomfort.||0.715||0.790||0.924||0.786|
|26||I have my expression (including smiling to others) and communication affected.||0.680||0.812||0.922||0.800|
|27||I have throat discomfort.||0.642||0.709||0.906||0.896||0.756||0.896|
|28||I have difficulty in swallowing liquids (e.g. water, juice, soup).||0.686||0.797||0.878||0.643|
|29||I have difficulty in swallowing soft/solid food.||0.460||0.764||0.886||0.757|
|30||I feel easily choked while swallowing.||0.500||0.732||0.891||0.684|
|31||I have difficulty in swallowing saliva.||0.751||0.827||0.871||0.695|
|Alpha = 0.971 standardized item alpha = 0.970|
Forty-seven subjects were selected at random to fill in the OMQoL again within 3 days in order to assess the reliability of the OMQoL over time. The test-retest reliability of the individual items using weighted kappa was good (kappa values 0.610–0.800) for 25 items, and very good for 6 items (kappa values 0.808–0.895).39 The test-retest ICC for the subscale totals ranged from 0.864 to 0.934, which were all in excess of 0.70 (Table 3).
Table 4 summarizes the OMQoL data at the level of each item. All items showed a noteworthy degree of variation. Results also showed that the proportion of missing responses per item was low. Of 210 patients, only 11 (5%) had at least 1 missing item, and 199 (95%) had completed data on the OMQoL. The item most commonly left missing pertained to the item of “I reduce outside social dining due to mucosal discomfort.” All of those with missing responses did not have outside social dining due to reverse isolation for HSCT. The other items left missing are likely due to patients failing to follow the directions to answer “not at all” under those circumstances. A floor effect (>20% of scores at the lowest possible score) was shown for 25 out of 31 items. In contrast, only 4 out of 31 items had a ceiling effect (>20% of scores at the highest possible score). A high floor effect (>70% of scores at the lowest possible score) was evident for item 22. However, this item was retained because of its clinical relevance. A high ceiling effect (>70% of scores at the highest possible score) was not observed for any items.
|Item||Response categories||Mean||SD||Missing, f||Floor, %||Ceiling, %|
|Not at all, f||A little bit, f||Quite a bit, f||Very much, f|
OM is a multifaceted clinical problem causing profound psychological distress and impairment of HQoL for patients with cancer. Whereas the measurement of HQoL in this patient population is increasingly being recognized as an important part of the evaluation of treatment outcome, systematic attempts to assess the impact of OM from the perspective of the patient have been relatively scarce and have utilized generic or disease-specific measures.4, 18 However, there are a number of aspects of OM that are not addressed by these HQoL measures. Problems and symptoms such as burning, bleeding, and difficulty in swallowing saliva are not addressed by the existing measures, even though they can have a major clinical impact on patients with OM. In addition, none of these measures can thoroughly address the levels of distress caused by these symptoms or many aspects of the impact on the HQoL resulting from acute mucosal damage. Thus, these measures for accurately assessing the HQoL related to OM would have limited utility.
The OMQoL developed in this study addresses those experiences judged to be of great importance to patients with OM. Content validity was addressed by developing items on the basis of in-depth qualitative interviews, focus groups, and expert content review. This patient-as-expert method of item generation fulfills a basic requirement of HQoL instruments, in which the content should be generated from relevant patients.19, 40 The expert content review revealed a high degree of agreement between 7 experts in terms of clarity and relevancy, indicating that the items were representative of OM-related HQoL, thereby revealing the content validity of the OMQoL. Content validity is a fundamental requirement of all assessment instruments.41 Fayers and Machin22 and Haynes et al.27 also indicated that these initial stages of instrument development are the most crucial and are what distinguishes successful from unsuccessful instruments, and no amount of psychometric analyses can recover a poorly conceived questionnaire.
The OMQoL is designed to assess all specific aspects of the HQoL that tap dimensions of health status of particular salience to patients with OM. Our factor analysis supported the creation of symptoms, diet, social function, and swallowing subscales. Such dimensions of OMQoL are distinctive and of special importance in OM. The OMQoL subscales had a high degree of internal consistency, confirming its reliability. In addition, the test-retest reliabilities were good, meeting all weighted kappa and ICC coefficient requirements.35–37 The symptoms scale consists of 9 items that assess various symptoms, such as pain, edema, burning, and bleeding in relation to OM. The diet scale includes 10 items that assess different degrees of dietary and eating problems. The social function scale includes 7 items that assesses problems with communicating to other people and assesses embarrassment at mealtimes with family and friends. The swallowing scale consists of 5 items related to swallowing problems. It is interesting to note that items 12 and 27, pertaining to sticky saliva and throat discomfort, respectively, may assess the aspects of symptoms and thus may be in the symptom subscale. On the basis of psychometric theory, we decided to retain these items in the diet and swallowing subscales, respectively. Nevertheless, for item of sticky saliva, patients may have eating problems if they have sticky saliva. For item of throat discomfort, patients may have swallowing problems if they report discomfort in the throat. It could be argued that item 12, “My saliva becomes thick/sticky and need to spit out frequently” is indeed a double-barreled question addressing the problems of diet and symptom at the same time. However, clinical experience and content validation suggest that there is a close correspondence between thick/sticky saliva and the need to spit frequently; thus, shared variance is to be expected. This interpretation is supported by sufficient variation among response categories of this item. In addition, none of the subjects in this sample found it confusing or difficult to answer this item.
The floor effect of the sample was modest, whereas the ceiling effect was negligible. One possible explanation for the floor effect is that about one-third of subjects in this sample had WHO grade 1 OM, who would be expected to score at floor. Nevertheless, the sample size for the WHO grade 4 group was small, and thus the results should be interpreted with caution. Further evaluation of the floor and ceiling effects including a larger population with severe OM is warranted. In addition, further research using item response analysis investigating the performance of individual item response choices should be conducted.
Chemotherapy and head/neck irradiation often cause substantial injury to the epithelial lining of the oral mucosa. Patients with OM are a heterogeneous group of the population affected by cancer therapy. The OMQoL is designed to address problems experienced over the whole spectrum of cancer treatment modalities. Although patients were not well distributed by the type of cancer therapy for psychometric evaluation, the study sample represented the full diversity of patients with OM. Nevertheless, it could be argued that a possible bias was present in the item generation and validation phases due to younger patients being overrepresented in the samples. Although we cannot rule out that possible bias, in future studies an attempt should be made to determine if the OMQoL behaves differently across age based on differential item functioning. In addition, a further validation study with a larger sample of patients with high-dose myeloablative chemotherapy and total body irradiation followed by HSCT is warranted.
The OMQoL was developed as a self-report measure of the multidimensional construct of OM-related HQoL. HQoL instruments have been shown to have the ability to assess treatment outcomes and predict clinical outcomes. Clinical trials of efficacy should be conducted to evaluate OM using both objective and patient-reported HQoL data; the OMQoL could be crucial to such assessments. The OMQoL is the first patient-based outcome measure that is specific to OM; this could allow evaluation of new drugs and interventions from the patient's perspective and thus help map avenues for effective OM intervention. In addition, the OMQoL will provide a unique and common platform for clinicians to assess, care for, and treat patients with OM. Stiff et al.18 indicated that the patient's perspective, in conjunction with observer-rated clinical scales, is crucial when assessing the patient's condition and determining a therapeutic agent's effectiveness in the management of OM. A patient-rated appraisal of the effect on HQoL is also an important aspect of the cost/benefit ratio in cost-effectiveness studies.19
These initial validation results of OMQoL appear promising. Further validation is ongoing to assess the construct validity of OMQoL in relation to clinical and other health outcomes, as well as responsiveness to change. Nevertheless, instrument development and validation is by no means a 1-time event.42 Additional research is needed in order to determine the item response, sensitivity, usefulness, and psychometric robustness of OMQoL that will allow more reliably assessing the HQoL for patients with OM. Knowledge of minimal clinically important differences in HQoL are important for interpreting the meaning of the HQoL results.38 Further research determining minimal important difference for the OMQoL is therefore warranted.
We thank the physicians and nursing staff that were involved in various aspects of the study and the patients and their families for taking the time to thoughtfully complete the interview process and to fill in the questionnaire.
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