Using Patient-reported Outcomes to Compare Relative Burden of Cancer: EQ-5D and Functional Assessment of Cancer Therapy-General in Eleven Types of Cancer.

PURPOSE: The objective of this study was to compare the health-related quality of life (HRQL) burden across different types of advanced cancer with the use of 2 widely used patient-reported outcome measures, the generic EQ-5D and the cancer-specific Functional Assessment of Cancer Therapy-General (FACT-G). METHODS: Patients with advanced cancer of the bladder, brain, breast, colon/rectum, head/neck, hepatobiliary tract/pancreas, kidney, lung, lymphoma, ovary, or prostate completed the EQ-5D and FACT-G. HRQL domains and summary scores were compared across types of cancer, using regression models to adjust for age and sex. FINDINGS: Approximately 50 patients with each type of cancer were recruited (total, 534 patients). According to EQ-5D dimensions, the highest proportion of problems was associated with prostate (mobility); prostate and kidney (self-care); head/neck, bladder, and lung (usual activities); breast, head/neck, and lung (pain/discomfort); and lymphoma and lung (anxiety/depression) cancers. EQ-5D visual analogue scale scores were lowest for breast and head/neck cancers; US index-based scores were lowest for breast and lung cancers and highest for brain cancer. For the FACT-G, physical well-being scores were lowest for head/neck, hepatobiliary, and kidney cancers; emotional well-being scores were lowest for hepatobiliary cancer, and functional well-being scores were lowest for head/neck, hepatobiliary, and bladder cancers. IMPLICATIONS: The overall and dimension-specific HRQL burden of advanced cancer depended on the type of cancer. Such results may aid clinicians and patients in better understanding of how cancer site can affect HRQL and functioning in different ways.

Setting standards for severity of common symptoms in oncology using the PROMIS item banks and expert judgment.

BACKGROUND: Although the use of patient-reported outcome measures (PROs) has increased markedly, clinical interpretation of scores remains lacking. We developed a method to identify clinical severity thresholds for pain, fatigue, depression, and anxiety in people with cancer. METHODS: Using available Patient-Reported Outcomes Measurement Information System (PROMIS) item bank response data collected on 840 cancer patients, symptom vignettes across a range of symptom severity were developed and placed on index cards. Cards represented symptom severity at five-point intervals differences on the T score metric [mean = 50; standard deviation (SD) = 10]. Symptom vignettes for each symptom were anchored on these standardized scores at 0.5 SD increments across the full range of severity. Clinical experts, blind to the PROMIS score associated with each vignette, rank-ordered the vignettes by severity, then arrived at consensus regarding which two vignettes were at the upper and lower boundaries of normal and mildly symptomatic for each symptom. The procedure was repeated to identify cut scores separating mildly from moderately symptomatic, and moderately from severely symptomatic scores. Clinician severity rankings were then compared to the T scores upon which the vignettes were based. RESULTS: For each of the targeted PROs, the severity rankings reached by clinician consensus perfectly matched the numerical rankings of their associated T scores. Across all symptoms, the thresholds (cut scores) identified to differentiate normal from mildly symptomatic were near a T score of 50. Cut scores differentiating mildly from moderately symptomatic were at or near 60, and those separating moderately from severely symptomatic were at or near 70. CONCLUSIONS: The study results provide empirically generated PROMIS T score thresholds that differentiate levels of symptom severity for pain interference, fatigue, anxiety, and depression. The convergence of clinical judgment with self-reported patient severity scores supports the validity of this methodology to derive clinically relevant symptom severity levels for PROMIS symptom measures in other settings.

Developing an emotional distress item bank for cancer patients.

Emotional distress is common among cancer patients during and after treatment. Many instruments have been used to measure emotional distress; however, none of them has emerged as a standard. Although the diversity of instruments has some merit, the lack of a common measure limits our ability to compare studies. This paper describes how we constructed a 46-item emotional distress bank. Using expert judgment, we selected a pool of items with emotional content from this six-instrument set. Rasch rating scale analysis helped us identify a set of general distress items with good model fit and a measurement gap causing floor effects. Additional items were written to augment the measure where found deficient. The resulting set of items reflects a spectrum of positive and negative affect. The measure demonstrated excellent reliability (person separation reliability = .96) and a wide range of emotional distress and was able to distinguish among levels of disease severity.

Development and validation of a symptom index for advanced hepatobiliary and pancreatic cancers: the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy (NCCN-FACT) Hepatobiliary-Pancreatic Symptom Index (NFHSI).

BACKGROUND: The 45-item Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire assesses health-related quality of life in patients with liver, bile duct, and pancreatic cancers. Although the FACT-Hep was initially derived from patient input, this study's researchers sought to verify adequate coverage of items by soliciting open-ended input from patients with advanced disease. METHODS: As part of a larger study in collaboration with the National Comprehensive Cancer Network (NCCN), 50 people (60% male, 80% caucasian, average age 60.4 years) with stage 3 or 4 hepatobiliary or pancreatic cancer were recruited. Participants generated and ranked up to 10 important symptoms and concerns that physicians should monitor when assessing the value of chemotherapy. Patients were also able to provide open-ended, qualitative information that was evaluated systematically. Ten expert physicians also provided input on priority symptoms. RESULTS: The resulting 18-item NCCN-FACT Hepatobiliary-Pancreatic Symptom Index (NFHSI-18) demonstrated high internal consistency (α = .89) and moderate to strong correlations with measures of physical well-being (ρ = .76), emotional well-being (ρ = 0.52), and functional well-being (ρ = 0.57). Scores on the NFHSI-18 were also highly correlated with the original hepatobiliary scale of the FACT-Hep (ρ = .82; all P < .001). Compared with patients with better performance status, patients with poor performance status had worse NFHSI-18 symptom scores, F(3,47) = 9.74; P = .0003. CONCLUSIONS: The NFHSI-18 assesses symptoms of importance to patients with hepatobiliary and pancreatic cancers and demonstrates promising measurement properties. The scale is a good candidate for brief symptom assessment in clinical trials.

Priority symptoms in advanced breast cancer: development and initial validation of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16).

OBJECTIVES: By using methods consistent with recent regulatory guidance on patient-reported outcomes as endpoints in clinical trials, we created a new version of the Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (FBSI), with emphasis on patient input during the development process. METHODS: We obtained input on the most important symptoms to monitor during treatment for stage III or IV breast cancer from 52 patients recruited from National Comprehensive Cancer Network institutions as well as support service organizations. Participating patients shared their top-priority symptoms/concerns through open-ended interviews and symptom checklists. To ensure adequate content coverage, we evaluated results alongside the original version of the FBSI, which was created on the basis of a survey of oncology clinicians at National Comprehensive Cancer Network institutions and items in the Functional Assessment of Chronic Illness Therapy measurement system. We also obtained input from 10 National Comprehensive Cancer Network oncologists regarding whether symptoms were primarily related to disease or treatment. RESULTS: We selected breast cancer-related symptoms and concerns endorsed as high priority by both oncology patients and clinicians for inclusion in the new National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index-16 (NFBSI-16), which includes all eight items from the original FBSI and eight additional items from Functional Assessment of Chronic Illness Therapy measures. The NFBSI-16 is formatted by subscale: Disease-Related Symptom, Treatment Side-Effect, and General Function and Well-Being. Results provide preliminary support for NFBSI-16's internal consistency reliability (α = 0.87) and validity as evidenced by moderate-to-strong relationships with expected criteria. CONCLUSIONS: Reflecting the priority symptoms of breast cancer patients and clinicians, the NFBSI-16 can be used to help evaluate the effectiveness of treatments for advanced breast cancer in clinical practice and research.

The psychosocial impact of cancer: evidence in support of independent general positive and negative components.

PURPOSE: Considerable research has demonstrated the negative psychosocial impact of cancer. Recent work has highlighted positive psychosocial outcomes. Research is now needed to evaluate the relationship between negative and positive impacts. This paper reports the development and validation of a measurement model capturing positive and negative psychosocial illness impacts. METHODS: The sample included 754 cancer patients on- or post-treatment. Item development was informed by literature review, expert input patient interviews and the results of a pilot study of 205 cancer patients, resulting in 43 positive and 46 negative items. Factor analyses were used to evaluate the dimensionality of the item pools. Analysis of variance (ANOVA) was used to examine relationships between psychosocial illness impact and other variables. RESULTS: Unidimensionality was demonstrated within but not across negative and positive impact items. ANOVA results showed differential relationships between negative and positive impacts, respectively, and patient sociodemographic and clinical variables. CONCLUSION: Positive and negative psychosocial illness impacts are best conceptualized and measured as two independent factors. Computerized adaptive tests and short-form measures developed from this comprehensive psychosocial illness impact item bank may benefit future research and clinical applications.

A brief symptom index for advanced lung cancer.

BACKGROUND: Advanced lung cancer is often symptomatic; thus the goals of treatment include maintenance of function and palliation of symptoms. Symptom management requires accurate systematic symptom assessment. This study, which focused on lung cancer, is part of a larger study to obtain patient input that, in combination with previously obtained physician and nurse input, was used to develop symptom indexes for 11 advanced cancers. PARTICIPANTS AND METHODS: Fifty patients with advanced lung cancer were recruited from National Comprehensive Cancer Network (NCCN) member institutions and community support agencies; 10 physician experts were recruited from NCCN institutions. Patients reported symptoms associated with their disease in open-ended format and then completed a checklist of symptoms, rating their 5 most important symptoms. Patient and provider ratings of symptom importance were tabulated to construct the NCCN-Functional Assessment of Cancer Therapy (FACT) Lung Symptom Index-17 (NFLSI-17). Patients also completed the Functional Assessment of Cancer Therapy-Lung (FACT-L), which was used to preliminarily validate the NFLSI-17. RESULTS: Based on combined patient, physician, and nurse input, the NFLSI-17 is composed of 17 priority symptoms, 11 that are disease related, 3 that are treatment related, and 3 that are related to general functional well-being (FWB). Data on 15 of 17 NFLSI-17 symptoms showed good internal consistency (alpha = 0.74) and strong association with the FACT-L total and most subscale scores (r = 0.42-0.92). Both the NFLSI-15 (F(2,47) = 4.46; P = .017) and the NFLSI-disease related subscale (DRS) (F(2,47) = 5.56; P = .007) significantly discriminated patients among performance status groups. CONCLUSION: The NFLSI-17 reflects the most important patient- and clinician-rated targets of chemotherapy for advanced lung cancer; further validation will follow.

Development and validation of 11 symptom indexes to evaluate response to chemotherapy for advanced cancer.

Recent guidance from the FDA discusses patient-reported outcomes as end points in clinical trials. Using methods consistent with this guidance, the authors developed symptom indexes for patients with advanced cancer. Input on the most important symptoms was obtained from 533 patients recruited from NCCN Member Institutions and 4 nonprofit social service organizations. Diagnoses included bladder, brain, breast, colorectal, head and neck, hepatobiliary/pancreatic, kidney, lung, ovarian, and prostate cancers and lymphoma. Physician experts in each of these diseases were also surveyed to differentiate symptoms that were predominantly disease-based from those that were predominantly treatment-induced. Results are evaluated alongside previously published indexes for 9 of these 11 advanced cancers that were created based on expert provider surveys, also implemented at NCCN Member Institutions. Final results are 11 symptom indexes that reflect the highest priorities of people affected by these 11 advanced cancers and the experienced perspective of the people who provide their medical treatment. Beyond the clinical value of such indexes, they may also contribute significantly to satisfying regulatory requirements for a standardized tool to evaluate drug efficacy with respect to symptomatology.

A new index of priority symptoms in advanced ovarian cancer.

OBJECTIVE: This study sought to develop and examine preliminary validity of the NCCN-FACT Ovarian Symptom Index-18 (NFOSI-18), a new ovarian cancer-specific symptom index comprised of symptoms rated as highest priority by both oncology clinical experts and women with advanced ovarian cancer. METHODS: Fifty-one women with advanced ovarian cancer rated the importance of 30 symptoms associated with advanced ovarian cancer. Ten gynecologic oncologists then rated symptoms according to whether they were predominantly disease- or treatment-related. Patient priorities were then reconciled with previously-published clinician priorities for symptom measurement in ovarian cancer. This produced the NFOSI-18. Participants also completed measures of quality of life and performance status to examine preliminary validity of the NFOSI-18. RESULTS: An 18-item symptom index for advanced ovarian cancer was developed, including three subscales: disease-related symptoms, treatment-related symptoms, and general function/well-being. Lower NFOSI-18 scores indicate greater high-priority symptom burden. Preliminary reliability suggests good internal consistency (α=0.80). The NFOSI-18 and its subscales were significantly positively associated with quality of life validity criteria. Scores on the NFOSI-18 differed significantly by performance status, with poor performance status associated with lower NFOSI-18 scores. CONCLUSIONS: The NFOSI-18 shows preliminary evidence for reliability and validity as a brief assessment of the most important symptoms associated with treatment for advanced ovarian cancer.

Efficient assessment of the most important symptoms in advanced prostate cancer: the NCCN/FACT-P Symptom Index.

BACKGROUND: Owing to the spectrum of symptoms, side effects, and concerns in clinically advanced prostate cancer (PC), effective symptom assessment is imperative. In line with recent regulatory guidance on the development of patient-reported outcomes, we undertook a multistep/multistudy approach to develop and test a new symptom index (NCCN FACT-Prostate Symptom Index-17 that can be used to examine the effectiveness of noncurative treatments in advanced PC. METHODS: This included significant input from two waves of expert medical providers (n=66 and 11, respectively) and two waves of patient engagement and testing (n=50 and 24, respectively). The resulting 17-item symptom index for advanced PC was then divided into sets or categories based on whether the symptoms are predominantly disease or treatment related. RESULTS: Preliminary reliability estimates suggest good internal consistency (α=0.86) and relationships with expected outside validity criteria are moderate to strong. CONCLUSIONS: This new tool may help clinicians and researchers quickly target and measure important symptoms and concerns in advanced PC, leading to increased knowledge of treatment effectiveness of noncurative therapies and improvements in the quality of patient care. Copyright © 2010 John Wiley & Sons, Ltd.

Age-associated differences in fatigue among patients with cancer.

CONTEXT: There has been some suggestion that the fatigue experienced by older cancer patients is more severe than that of younger cohorts; however, there is little empirical evidence to support this claim. OBJECTIVES: The goal of the present study was to determine the differential impact of age and cancer diagnosis on ratings of fatigue using a validated self-report instrument. METHODS: The Functional Assessment of Chronic Illness Therapy-Fatigue subscale consists of 13 items measuring fatigue experience and its impact on daily life, with scores ranging from 0 (severe fatigue) to 52 (no fatigue). Fatigue data were available from the U.S. general population (n=1075; 51.3% female, 45.9+/-16.5 years) and a sample of mixed-diagnosis cancer patients (n=738; 64.3% female, 58.7+/-13.6 years). General population participants were recruited using an Internet-based survey panel; patients with cancer were recruited from Chicago-area oncology clinics. RESULTS: On average, the cancer patient group reported more severe fatigue than the general population group (36.9 vs. 46.6; F[1,1797]=271.95, P<0.001). There was evidence for increased fatigue with age (F[6,719]=2.56, P<0.02) among patients with cancer, but not in the general population (P=0.06). Furthermore, the group x age interaction was not significant (P=0.44). Hemoglobin (Hgb) was treated as a covariate for 430 patients with available data; there was no main effect for age in this analysis. CONCLUSION: Older adults, whether they had a cancer diagnosis, reported more fatigue than younger adults. These differences may be explained, in part, by Hgb level. Future research would be helpful to explore longitudinal changes in fatigue in the general population and guide fatigue management for the older cancer patient.

Alleviating distress during antepartum hospitalization: a randomized controlled trial of music and recreation therapy.

BACKGROUND: Pregnant women who are placed on hospitalized bed rest experience increased antepartum-related distress. We sought to examine the efficacy of a single session music or recreation therapy intervention to reduce antepartum-related distress among women with high-risk pregnancies experiencing extended antepartum hospitalizations. METHODS: In a randomized, single-blinded study, participants (n = 80) received 1 hour of music or recreation therapy or were placed in an attention-control group. Antepartum-related distress was measured by the Antepartum Bedrest Emotional Impact Inventory, which was administered before and after the intervention and at a follow-up period between 48 and 72 hours. RESULTS: Significant associations were found between the delivery of music and recreation therapy and the reduction of antepartum-related distress in women hospitalized with high-risk pregnancies. These statistically significant reductions in distress persisted over a period of up to 48-72 hours. CONCLUSIONS: Single session music and recreation therapy interventions effectively alleviate antepartum-related distress among high-risk women experiencing antepartum hospitalization and should be considered as valuable additions to any comprehensive antepartum program.

A Comparison of the Renal Cell Carcinoma-Symptom Index (RCC-SI) and the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI).

The development and validation of measures that provide disease-specific, patient-reported outcomes have become increasingly relevant in the care of cancer patients, especially for assessing symptoms from the patient's perspective. Recently, two patient symptom questionnaires were developed for kidney cancer patients, the Renal Cell Carcinoma-Symptom Index (RCC-SI) and the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI). This article describes the development of the revised FKSI scale (FKSI-19) and reconciles its use with the RCC-SI. Fifty participants with advanced kidney cancer commented on their symptoms and concerns about kidney cancer and this input was used to revise FKSI items. These patients also completed the RCC-SI, the Functional Assessment of Cancer Therapy-General (FACT-G), and an older version of the FKSI scale. We qualitatively reviewed item wording and content coverage across the two instruments, examined correlations between the scales, and calculated basic psychometrics on each scale. We found that the FKSI-19 and the RCC-SI addressed similar symptoms. Qualitative and descriptive statistical analyses demonstrated considerable overlap between the two instruments (rho=0.88, P<0.001). Cronbach's alpha for the FKSI-19 and RCC-SI were both good, at 0.86 and 0.92, respectively. The FKSI-19 has some advantages over the RCC-SI. The FKSI-19 has more clarity in item phrasing, is shorter in length, and covers a similar breadth of disease-based symptoms when compared to the RCC-SI.

Fatigue is the most important symptom for advanced cancer patients who have had chemotherapy.

Cancer fatigue has been defined and described as an important problem. However, few studies have assessed the relative importance of fatigue compared with other patient symptoms and concerns. To explore this issue, the authors surveyed 534 patients and 91 physician experts from 5 NCCN member institutions and community support agencies. Specifically, they asked patients with advanced bladder, brain, breast, colorectal, head and neck, hepatobiliary/pancreatic, kidney, lung, ovarian, or prostate cancer or lymphoma about their "most important symptoms or concerns to monitor." Across the entire sample, and individually for patients with 9 cancer types, fatigue emerged as the top-ranked symptom. Fatigue was also ranked most important among patients with 10 of 11 cancer types when asked to rank lists of common concerns. Patient fatigue ratings were most strongly associated with malaise (r = 0.50) and difficulties with activities of daily living, pain, and quality of life. Expert ratings of how much fatigue is attributable to disease versus treatment mostly suggested that both play an important role, with disease-related factors predominant in hepatobiliary and lung cancer, and treatment-related factors playing a stronger role in head and neck cancer.

Evaluating equivalency between response systems: application of the Rasch model to a 3-level and 5-level EQ-5D.

BACKGROUND: Expansion of the EQ-5D health state classifier to 5 levels (EQ-5D-5L) has been proposed to improve discriminative and evaluative properties, but current preference-based algorithms were developed for a 3-level (EQ-5D-3L) structure. The objectives were to examine equivalency of meaning between 3L and 5L response systems, and to psychometrically derive a system of weights that facilitate conversion of 3L preference-based algorithms to a 5L system. METHODS: Rasch models were used to examine the equivalency of the 3L and 5L systems using 2 datasets where health status was assessed using the 3L and 5L: a Dutch study of primarily hypothetical health state assessments and a US-based multicenter study of 423 cancer patients. Category-specific mean values of latent person parameters (using maximum likelihood estimation) for the levels of the 3L and 5L systems were estimated. RESULTS: Means on the latent continuum pertaining to level 3 in the 5L system and level 2 in the 3L (some problems) were similar for both datasets, suggesting equivalence of these levels. Extremes of the 5L response structure consistently broadened the measurement continuum. By anchoring "no problems" as 0 disutility, disutility weights from EQ-5D-3L were transformed into weights for EQ-5D-5L using ratios of logit distances between person means for 5L and 3L calibrated for each dimension using the Rasch model. CONCLUSIONS: This study illustrates the rich potential for modern psychometric techniques both to examine equivalency when health status measures are modified as well as to inform preference-based measurement systems using existing value sets.

Assessment is not enough: a randomized controlled trial of the effects of HRQL assessment on quality of life and satisfaction in oncology clinical practice.

The potential benefits of health-related quality of life (HRQL) assessment in oncology clinical practice include better detection of problems, enhanced disease and treatment monitoring and improved care. However, few empirical studies have investigated the effects of incorporating such assessments into routine clinical care. Recent randomized studies have reported improved detection of and communication about patients' concerns, but few have found effects on patient HRQL or satisfaction. This study examined whether offering interpretive assistance of HRQL results would improve these patient outcomes. Two hundred and thirteen participants with metastatic breast, lung or colorectal cancer were randomly assigned to one of three conditions: usual care; HRQL assessment or HRQL assessment followed by a structured interview and discussion. Interviews about patients' assessment responses were conducted by a research nurse, who then presented HRQL information to the treating nurse. HRQL and treatment satisfaction outcomes were assessed at 3 and 6 months. No significant differences were found between study conditions in HRQL or satisfaction. Results suggest that routine HRQL assessment, even with description of results, is insufficient to improve patient HRQL and satisfaction. It is suggested that positive effects may require supplementing assessment results with specific suggestions for clinical management changes.

Psychometric comparison of the standard EQ-5D to a 5 level version in cancer patients.

OBJECTIVE: The objectives of this study were: 1) to determine whether expanding the number of levels (ie, response categories) on the standard 3 level EQ-5D (EQ-5D-3L) to 5-levels (EQ-5D-5L) would improve the descriptive richness and ability of the measure to discriminate among different levels of health, and 2) to examine the psychometric properties of each EQ-5D version in patients with cancer. METHODS: U.S.-based cancer patients self-assessed their health using EQ-5D-3L and EQ-5D-5L. These versions were compared in terms of ceiling effects, convergent validity based on correlations with ECOG performance status and FACT-G, discriminative ability using Rasch analysis, and informational richness using Shannon's Evenness Index (J'). RESULTS: A ceiling effect was observed among a greater proportion of respondents to EQ-5D-3L, n=74/424 (17%), compared with EQ-5D-5L, n=47/424 (11%). Within the midlevel of EQ-5D-3L (some problems), substantial partitioning of the sample into the 3 nonextreme levels of the EQ-5D-5L was observed across dimensions. EQ-5D-5L demonstrated a trend towards slightly stronger correlations with ECOG performance status compared with EQ-5D-3L for all dimensions of health, ie, rs (5L/3L): rmobility=0.38/0.31; rself-care=0.35/0.31; rusual activities=0.55/0.47; rpain/discomfort=0.43/0.37; ranxiety/depression=0.23/0.16; rcrude summary score=0.56/0.49. EQ-5D-5L demonstrated a greater relative efficiency and ability to discriminate different levels of health. Informational richness and evenness of EQ-5D-5L was slightly higher (J'5L=0.75) than EQ-5D-3L (J'3L=0.69). CONCLUSION: Evidence supported the validity of both EQ-5D-3L and EQ-5D-5L in cancer. However, results suggest a 5-level classifier system has less ceiling effect and greater discriminative ability with potentially more power to detect differences between groups compared with EQ-5D-3L.

Item response theory and health-related quality of life in cancer.

Identifying health-related quality of life concerns is a priority when caring for people with cancer. Specific problem areas such as pain, fatigue, emotional distress, disease- and treatment-related symptoms, as well as physical functioning can be routinely assessed using applications that draw upon item response theory. Item response theory measurement models can improve on the classical approach to health-related quality of life assessment with advantages that include comparison of patients across diverse instruments, flexibility in degree of precision desired, availability of multiple short forms, interval measurement and capability for individual assessment (real-time clinical monitoring) using computerized adaptive testing. This review describes a model of health-related quality of life in oncology and the contribution of item response theory to assessment using that model.