Development and validation of the living with chronic obstructive pulmonary disease questionnaire.

PURPOSE: Available patient-reported outcome (PRO) measures for chronic obstructive pulmonary disease (COPD) focus primarily on impairment (symptoms) and activities (functioning). The purpose of the study was to develop a patient-based PRO measure for COPD that captures the overall everyday impact of living with COPD from the patient's perspective. METHODS: LCOPD items (Living with COPD Questionnaire) were generated from qualitative interviews in the U.K. and focus groups in the U.S.A. The draft measure was tested for face and content validity in both countries. Item reduction and testing for reproducibility and construct validity was conducted via Rasch and traditional psychometric analyses. RESULTS: The draft LCOPD was found to be relevant and acceptable to patients in the U.K. (N = 19) and U.S. (N = 16). Application of Rasch analysis to data collected in validation studies (n = 162 in the U.K. and 145 in U.S.) identified a 22-item scale that measured a single construct in both countries. Psychometric analyses indicated that this version was internally consistent and reproducible. Scores on the measure were related as expected to clinician ratings of disease severity and patient ratings of COPD severity and general health. CONCLUSIONS: The LCOPD is a new measure examining the everyday impact of living with COPD. It demonstrates good scaling properties and may prove valuable in understanding treatment benefits.

Quality of life in patients with newly diagnosed chronic phase chronic myeloid leukemia on imatinib versus interferon alfa plus low-dose cytarabine: results from the IRIS Study.

PURPOSE: Quality of life (QOL) outcomes in patients with chronic myeloid leukemia (CML) were evaluated in an international phase III study. PATIENTS AND METHODS: Newly diagnosed patients with chronic phase CML were randomly assigned to imatinib or interferon alfa plus subcutaneous low-dose cytarabine (IFN+LDAC). Cross-over to the other treatment was permitted because of intolerance or lack of efficacy. Patients completed cancer-specific QOL (Functional Assessment of Cancer Therapy-Biologic Response Modifiers) and utility (Euro QoL-5D) questionnaires at baseline and during treatment (n = 1,049). The primary QOL end point was the Trial Outcome Index (TOI; a measure of physical function and well-being). Secondary end points included social and family well-being (SFWB), emotional well-being (EWB), and the utility score. Primary analyses were intention to treat with secondary analyses accounting for cross-over. RESULTS: Patients receiving IFN+LDAC experienced a large decline in the TOI, whereas those receiving imatinib maintained their baseline level. Treatment differences at each visit were significant (P <.001) and clinically relevant in favor of imatinib. Mean SFWB, EWB, and utility scores were also significantly better for those patients taking imatinib. Patients who crossed over to imatinib experienced a large increase in TOI; significant (P <.001) differences were observed between patients who did and did not cross over in favor of imatinib. CONCLUSION: Imatinib offers clear QOL advantages compared with IFN+LDAC as first-line treatment of chronic phase CML. In addition, patients who cross over to imatinib from IFN+LDAC experience a significant improvement in QOL compared with patients who continue to take IFN+LDAC.

Quality of life on imatinib.

Imatinib (Gleevec), a highly effective specific tyrosine kinase inhibitor, demonstrates a better side effect profile than interferon-alpha (IFN), which impairs patients' quality of life (QoL). This phase III international study evaluated QoL outcomes in 1,106 newly diagnosed patients with chronic-phase chronic myeloid leukemia (CML) who were randomized to receive either imatinib 400 mg daily or IFN up to 5 MU/m(2)/d with cytarabine (Ara-C) 20 mg/m(2)/d added for 10 days every month (IFN + LDAC). Crossover to the other treatment arm was permitted due to a lack of efficacy or treatment intolerance. QoL was assessed with the Functional Assessment of Cancer Therapy-Biologic Response Modifiers (FACT-BRM) at baseline, monthly for 6 months and then at months 9, 12, and 18. The Trial Outcome Index (TOI; a composite endpoint of physical/functional/treatment-specific subscales) was the primary endpoint. Secondary endpoints measured were social/family well-being (SFWB) and emotional well-being (EWB). QoL was analyzed for the first 18 months of treatment using mixed effects growth curve models. The primary analyses were intention-to-treat (ITT); secondary analyses incorporated crossover as a time-dependent covariate. A total of 1,049 patients completed at least one QoL assessment. Two hundred sixty-one patients (50%) crossed over from IFN to imatinib and 11 (2%) crossed over from imatinib to IFN. There was a significant decline in TOI scores for the IFN treatment arm compared with preservation of baseline TOI scores in the imatinib arm (P <.001, ITT). Mean social/family and EWB scores were 22.8 and 19.5, respectively, for imatinib and 21.6 and 17.6, respectively, for IFN (P <.001, ITT). After crossing over from IFN to imatinib, patients experienced a significant (P <.001) increase in TOI scores. Imatinib offers clear QoL advantages over IFN as first-line treatment of chronic-phase CML. In addition, patients who crossed over to imatinib reported higher QoL than those who remained on IFN. Semin Hematol 40(suppl 2):31-36.

Development and validation of the Asthma Life Impact Scale (ALIS).

BACKGROUND: Current asthma patient-reported outcome (PRO) measures focus on symptoms and functioning and may not capture the holistic impact of asthma on the quality of life of the patient. OBJECTIVE: To develop a PRO measure capturing the overall impact of asthma on patient's quality of life. METHODS: Items for the Asthma Life Impact Scale (ALIS) were generated from patients with asthma during interviews in the UK and focus groups in the US. The ALIS was tested with UK and US asthma patients during cognitive debriefing interviews and included in large, two-administration, validation studies in the UK and US. RESULTS: Issues raised by asthma patients during interviews (n = 39 patients) and focus groups (n = 16 patients) were included in the draft ALIS. Cognitive debriefing interviews with 29 UK and US asthma patients showed that the scale was relevant and comprehensive. 140 UK and 185 US asthma patients participated in the validation study. The analysis showed that the ALIS measures a single construct, namely the overall impact of asthma on patients' quality of life. Internal consistency (Cronbach's Alpha) was high (UK = 0.94; US = 0.92) as was test-retest reliability (UK = 0.93; US = 0.83). Patients reporting worse general health or more severe asthma had significantly higher ALIS scores (p < 0.001) (indicating greater negative impact of asthma). Correlations with the Asthma Quality of Life Questionnaire were moderate to high. CONCLUSIONS: The final 22-item ALIS is unidimensional, reliable and valid, and a valuable tool for comprehensively assessing the holistic impact of asthma from the patient's perspective.

Economic evaluation of zoledronic acid versus pamidronate for the prevention of skeletal-related events in metastatic breast cancer and multiple myeloma.

Skeletal complications of cancer decrease health-related quality of life. Bisphosphonates can prevent skeletal-related events. We collected resource use data prospectively for 930 patients alongside a multinational trial of zoledronic acid versus pamidronate for patients with metastatic multiple myeloma or breast cancer and > or =1 bone lesion. Country-specific unit costs were assigned to counts of resource use from randomization through last trial visit. Total costs were calculated by summing costs for medical resources, plus costs of institutional care and study medications and administration. Resource use was similar for both groups. Approximately half of the patients were hospitalized at least once during the mean follow-up of 10 months (52.8% for zoledronic acid versus 52.6% for pamidronate; P = 0.9504). The average number of hospital days was 8.9 for zoledronic acid versus 9.2 for pamidronate (P = 0.728). The mean total cost was 16,434 dollars for zoledronic acid and 15,735 dollars for pamidronate, an incremental cost of 699 dollars (95% confidence interval [CI], -1047 to 2163). Mean total costs for patients with multiple myeloma were 1982 dollars (95% CI, -1491 to 5335) higher for zoledronic acid (17,958 dollars) than for pamidronate (15,976 dollars). However, among patients with breast cancer, total costs in both groups were approximately equal (15,703 dollars for zoledronic acid versus 15,680 dollars for pamidronate; 95% CI for the difference: -1875 to 2012). There were no significant cost differences between patients receiving zoledronic acid and those receiving pamidronate.

Using multiple anchor- and distribution-based estimates to evaluate clinically meaningful change on the Functional Assessment of Cancer Therapy-Biologic Response Modifiers (FACT-BRM) instrument.

OBJECTIVE: The interpretation of health-related quality of life (HRQL) data from clinical trials can be enhanced by understanding the degree of change in HRQL scores that is considered meaningful. Our objectives were to combine distribution-based and two anchor-based approaches to identify minimally important differences (MIDs) for the 27-item Trial Outcome Index (TOI), the seven-item Social Well-Being (SWB) subscale, and the six-item Emotional Well-being (EWB) subscale from the Functional Assessment of Cancer Therapy-Biological Response Modifiers (FACT-BRM) instrument. METHODS: Distribution-based MIDs were based on the standard error of measurement. Anchor-based approaches utilized patient-reported global rating of change (GRC) and change in physician-reported performance status rating (PSR). Correlations and weighted kappa statistics were used to assess association and agreement between the two anchors. FACT-BRM changes were evaluated for three time periods: baseline to month 1, month 2 to month 3, and month 5 to month 6. RESULTS: Association between GRC and change in PSR was poor. Correlation between the anchors and HRQL change scores was largest at month 1 and decreased through month 6. Combining results from all approaches, the MIDs identified were 5-8 points for the TOI, 2 points for the SWB subscale, and 2-3 points for the EWB subscale. CONCLUSIONS: We combined patient-reported estimates, physician-reported estimates, and distribution-based estimates to derive MIDs for HRQL outcomes from the FACT-BRM. These results will enable interpretation of treatment group effects in a clinical trial setting, and they can be used to estimate sample size or power when designing future studies.

Barriers to adherence of deferoxamine usage in sickle cell disease.

BACKGROUND: We hypothesized that child cognitive disability would be a significant risk factor for non-adherence with home deferoxamine (DFO) administration and that a factor that would contribute to improved adherence would be sharing of responsibilities for chelation between parents and patients. We explored the influences on adherence of behavioral and psychological adjustment; family stress; perceived convenience of and satisfaction with the DFO regimen; and parent and patient knowledge about DFO. PROCEDURE: Fifteen pediatric patients with sickle cell disease (SCD) who had evidence of excessive iron stores, and their parents, were interviewed about adherence and responsibility for chelation therapy. A neuropsychological assessment battery was administered to the patients. Family stress, the child's emotional and behavioral status, knowledge about chelation and iron overload were explored. Adherence was rated objectively using pharmacy refill patterns and observable signs of chelation. RESULTS: Sharing of responsibilities for chelation between parents and children was related to better adherence while neuropsychological status bore a complex relation to adherence. Of the exploratory variables, low family stress were related to better adherence while satisfaction with the home care regimen and convenience ratings were not useful in predicting adherence. No one element of adherence, even objective measures, was capable of classifying adherence, while a multifactorial scheme categorizing adherent, partially adherent and non-adherent groups demonstrated good face validity. CONCLUSIONS: Supporting developmentally appropriate sharing of responsibilities for self-care is critical, taking patient neurocognitive status into consideration. Clinicians should evaluate adherence using a multifactorial model that highlights the most salient targets for intervention.

Cost-effectiveness of zoledronic acid for the prevention of skeletal complications in patients with prostate cancer.

PURPOSE: We estimated the cost-effectiveness of zoledronic acid vs placebo for decreasing skeletal complications in men with prostate cancer. MATERIALS AND METHODS: We performed a cost-effectiveness analysis alongside a multinational clinical trial of zoledronic acid. Cost estimation was based on prospectively collected resource use data for 85.3% of enrolled patients. Cost-effectiveness ratios were based on within-trial data on clinical outcomes, quality of life and study medication cost. RESULTS: Patients receiving zoledronic acid experienced fewer hospital days during a mean followup of 9 months (average 5.6 vs 8.0 days; p = 0.1910). Mean direct costs excluding study medication were US dollars 5365 for patients receiving zoledronic acid and US dollars 5689 for patients receiving placebo, a difference of US dollars 324 (95% CI US dollars 1781 to US dollars 1146). The global average cost of zoledronic acid plus its administration during the trial was US dollars 5677 (US dollars 450 per dose). The nominal cost per skeletal complication avoided was US dollars 112300 (95% CI US dollars 6900 to US dollars 48700) and the cost per additional patient free of skeletal complications was US dollars 51400 (95% CI US dollars 26900 to US dollars 243700). Nominal within-trial cost per quality adjusted life-year was US dollars 159200, which varied widely in sensitivity analyses. CONCLUSIONS: The nominal base case estimate of the cost per quality adjusted life-year for zoledronic acid in the prevention of skeletal complications of prostate cancer is consistent with that of bisphosphonates in breast cancer. However, the cost-effectiveness ratios for bisphosphonates are higher than commonly cited thresholds for conferring cost-effectiveness.

Health-related quality of life among patients with breast cancer receiving zoledronic acid or pamidronate disodium for metastatic bone lesions.

BACKGROUND: Research on individual differences in health-related quality of life (HRQOL) can identify intervention targets and important covariates in analyses of treatment outcomes. OBJECTIVES: The objectives of this study were to describe HRQOL trajectories for women with metastatic breast cancer in a randomized trial of bisphosphonates and to identify characteristics associated with variations in HRQOL. RESEARCH DESIGN: We conducted a prospective quality-of-life study within a randomized, controlled trial. SUBJECTS: We studied women with metastatic breast cancer receiving zoledronic acid or pamidronate disodium to reduce the incidence of skeletal-related events (SREs). MAIN OUTCOME MEASURES: HRQOL was measured at fixed time points during the trial. Individual growth-curve modeling was used to describe longitudinal trajectories and to identify predictors of trajectories. RESULTS: For most domains of HRQOL, the mean trajectory reflected a mild increase, which leveled off later in the trial. Older age and full-time employment were associated with higher baseline HRQOL. Longer time from cancer diagnosis to randomization, lower Eastern Cooperative Oncology Group (ECOG) status (score of 2 ["inactive"]), and a history of SREs were associated with lower baseline HRQOL. Significant differences across geographic regions were observed for all domains. Active ECOG status (score of 0-1) at baseline was predictive of greater increases in all domains of HRQOL except Social/Family Well-Being. Age, geographic region, and time from first bone metastases to randomization were associated with longitudinal changes in some domains. CONCLUSIONS: Women with metastatic breast cancer receiving bisphosphonates for prevention of SREs experienced an overall increase in HRQOL. Variations among women's experiences are explained partly by such characteristics as a history of SREs.

Long-term survival estimates for imatinib versus interferon-alpha plus low-dose cytarabine for patients with newly diagnosed chronic-phase chronic myeloid leukemia.

BACKGROUND: The authors estimated survival among patients with chronic myeloid leukemia for a cost-effectiveness analysis of imatinib versus interferon-alpha plus low-dose cytarabine (IFN+LDAC). METHODS: Two-year survival and cytogenetic response were determined using data from 553 patients who received first-line imatinib in the International Randomized Interferon versus ST571 Study (IRIS). Long-term survival was modeled on complete cytogenetic response (CCyR) after 2 years. Long-term survival for patients with a CCyR was modeled using data from a cohort study of 317 patients with CCyRs. Long-term survival for patients without a CCyR was modeled using data from a trial of 275 patients who were treated with IFN+LDAC. Computation of lifetime survival estimates for imatinib assumed a proportional hazards relation between survival for an age-matched and gender-matched cohort and survival for patients with and without a CCyR. RESULTS: For IRIS patients receiving imatinib, the estimated survival was 95.8% and the CCyR rate was 73.8%. The average residual life expectancy was estimated to be 16.71 years for CCyR patients and 5.78 years for non-CCyR patients. The estimated life expectancy after treatment with imatinib was 15.30 years, compared with 9.07 years for patients who were treated with IFN+LDAC in previous studies. CONCLUSIONS: Assuming the relation between CCyR and survival with interferon-alpha holds for imatinib, higher CCyR rates with imatinib therapy will result in an estimated 6.23 life-years gained compared with treatment with IFN+LDAC.

Cost-effectiveness of imatinib versus interferon-alpha plus low-dose cytarabine for patients with newly diagnosed chronic-phase chronic myeloid leukemia.

BACKGROUND: Despite a lack of long-term data, imatinib has become standard therapy for patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML) who are not candidates for allogeneic stem cell transplantation. In the current study, the authors estimated the incremental cost-effectiveness of imatinib versus interferon-alpha plus low-dose cytarabine (IFN+LDAC) as first-line therapy for these patients. METHODS: Data from the International Randomized Interferon versus STI571 Study and the literature were used to estimate lifetime costs, survival, and quality-adjusted survival. Survival estimates were based on published survival curves for patients who achieved and those who did not achieve a complete cytogenetic response after treatment with interferon-alpha. RESULTS: The mean estimated survival with first-line imatinib therapy was 15.30 years, compared with 9.07 years with IFN+LDAC. Undiscounted lifetime costs were approximately $424,600 with imatinib and $182,800 with IFN+LDAC. Using a 3% discount rate, the incremental survival gain with imatinib was 3.93 life-years and 3.89 quality-adjusted life-years (QALYs). Incremental discounted lifetime costs were found to be $168,100 higher with imatinib, resulting in incremental cost-effectiveness ratios of $43,100 per life-year saved (95% confidence interval [95% CI], $37,600-51,100) and $43,300 per QALY (95% CI, $38,300-49,100). CONCLUSIONS: The results of the current study demonstrate that compared with IFN+LDAC, imatinib is a cost-effective first-line therapy in patients with newly diagnosed chronic-phase CML.