MEdical Database AnaLysIS of Japanese multiple myeloma patienTs with apheresis #2 (MEDALIST-2): the impact of plerixafor use on costs and healthcare resources during mobilization and stem cell transplantation.

Treatment for multiple myeloma (MM) can involve apheresis to mobilize hematopoietic stem cells for later autologous stem cell transplantation (ASCT), which can become costly over time. This retrospective claims database study examined healthcare resource use and medical costs associated with plerixafor, a selective CXCR4 inhibitor that mobilizes hematopoietic stem cells and minimizes apheresis times. Medical data were sampled from Japanese MM patients between April 2017 and September 2019, after the Japanese launch of plerixafor. The study population (190 plerixafor users and 180 non-users) was identified from the Medical Data Vision database, and further stratified into those using granulocyte-colony stimulating factor in monotherapy or in combination with cyclophosphamide to trigger apheresis. A descriptive comparison of patient characteristics, healthcare resource use, and medical costs across the mobilization and ASCT phases indicated plerixafor is associated with higher average total medical costs. However, plerixafor-treated patients received fewer concomitant medications and spent less time in apheresis than non-users. A comparison of non-users with a similar analysis conducted pre-plerixafor launch (2013-2017) showed general improvements to treatment independent of plerixafor. The results of this research can inform guidelines for the role of plerixafor in balancing cost-effectiveness and drug efficacy in MM treatment.

Cost drivers associated with diffuse large B-cell lymphoma (DLBCL) in Japan: A structural equation model (SEM) analysis.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin's lymphoma of increasing prevalence in Japan. However, patients with relapsed or refractory disease to first line treatment (rrDLBCL) have been found to shoulder greater economic burden and have poor survival with subsequent lines of therapy. The relative impact of individual patient attributes on total medical cost among patients with rrDLBCL receiving second or third line (2L/3L) therapy was assessed. Structural equation modelling was used to identify potential cost drivers of total medical costs incurred by treatment and procedures in a Japanese retrospective claims database. From the database, rrDLBCL patients on 2L or 3L of treatment were grouped into respective cohorts. The mean [median] (SD) total medical cost of care for the 2L cohort was 73,296.40 [58,223.11] (58,409.79) US dollars (USD) and 75,238.35 [60,477.31] (59,583.66) USD for the 3L cohort. The largest total effect on medical cost in both cohorts was length of hospital stay (LOS) (ß: 0.750 [95%CI: 0.728, 0.772] vs ß: 0.762 [95%CI: 0.729, 0.794]). Length of hospital stay and potential heart disease complications due to line of treatment were the primary drivers of total cost for patients who had received at least 2L or 3L therapy for rrDLBCL.

Effectiveness of Current Treatments for Wet Age-Related Macular Degeneration in Japan: A Systematic Review and Pooled Data Analysis.

PURPOSE: We conducted a systematic review to investigate the effectiveness of clinical treatments for wet age-related macular degeneration (wAMD) in Japanese patients in the decade since anti-vascular endothelial growth factor (VEGF) therapies were introduced. METHODS: PubMed was searched for articles published in English between 1 January 2008 and 30 September 2018 using a multistring search strategy. Reviews were scanned for additional relevant studies and select gray literature was evaluated. Mean and/or median for the logarithm of the minimum angle of resolution (logMAR) visual acuity (VA), central retinal thickness (CRT), and the number of injections after 12 months of treatment were calculated using extracted data. Data were stratified by disease type and treatment modality. RESULTS: Of 335 studies identified, 94 were selected for data extraction (147 treatment arms; typical AMD, n = 25; polypoidal choroidal vasculopathy [PCV], n = 85). Mean (median) logMAR VA was 0.44 (0.32) for typical AMD and 0.34 (0.31) for PCV; the respective mean number of anti-VEGF injections was 5.6 and 4.6. The mean CRT was approximately 220 µm for both groups. For typical AMD, anti-VEGF monotherapy resulted in better VA outcomes than photodynamic therapy (PDT) alone. For PCV, anti-VEGF monotherapy or anti-VEGF plus PDT combination therapy resulted in better VA and CRT outcomes than PDT monotherapy. Combination therapy required fewer injections than anti-VEGF monotherapy (PCV, 3.2 versus 5.3). CONCLUSION: wAMD treatment has advanced dramatically in the years since anti-VEGF drugs were introduced in Japan. Discrete patient populations may benefit from differing management regimens, including the fewer injections required with combination therapy.

Systematic review of survival outcomes for relapsed or refractory adult T-cell leukemia-lymphoma.

INTRODUCTION: Adult T-cell leukemia-lymphoma (ATL) is a mature T-cell lymphoproliferative neoplasm caused by human T-cell leukemia virus type-1 infection. There is no standard treatment for relapsed or refractory (r/r) ATL, and clinical outcomes are poor. This systematic review examined the survival outcomes for r/r ATL treated with various systemic therapies. METHODS: EMBASE and PubMed were searched for studies on r/r ATL, published between January 2010 and January 2020. The main outcome of interest was overall survival (OS). Median OS and an exploratory 30% OS time were assessed based on published data and Kaplan-Meier curves. RESULTS: There were 21 unique treatment subgroups (from 14 studies), that met the eligibility criteria. Nine subgroups were mogamulizumab treatment, two were mogamulizumab prior to allogenic hematopoietic stem cell transplantation (allo-HSCT), five were allo-HSCT, and five were other chemotherapy. Respectively, the median OS and 30% OS varied considerably in range for mogamulizumab treatment (2.2-17.6 months and 8.7-27.1 months), allo-HSCT (3.8-6.2 months and 7.5-19.8 months), and other chemotherapy arms (4.1-20.3 months and 7.1-17.0 months). CONCLUSION: Mogamulizumab was the most frequently studied treatment regimen and can potentially provide longer survival compared with chemotherapy alone. Future comparisons with synthetic or historical control arms may enable clearer insights into treatment efficacy.

Real-world assessment of myelodysplastic syndrome: Japanese claims data analysis.

Aim: To describe the treatment landscape and associated economic burden for myelodysplastic syndrome in Japan. Methods: We studied nationwide retrospective claims data from 2008 to 2019. The study cohort was categorized into patients receiving transfusion, erythropoiesis-stimulating agent, erythropoiesis-stimulating agent + transfusion, azacitidine, azacitidine + transfusion and others. Results: Our study found that the azacitidine + transfusion group had the highest medical cost and severity of disease compared with the other groups. In those patients, healthcare resource utilization and the costs of transfusions, including iron chelation therapy, increased medical costs. Conclusion: Our retrospective analysis provides a current snapshot of real-world treatment patterns and associated incremental economic costs of iron chelation therapy with the presence of transfusions that drive an increase in total costs.

Economic burden in treated Japanese patients with relapsed/refractory large B-cell lymphoma.

Aim: To understand the economic burden of relapsed and refractory large B-cell lymphoma patients in Japan treated with salvage chemotherapy. Patients & methods: Patients who received systemic therapy after first-line treatment were analyzed to assess its associated cost and resource use using a retrospective claims database. The impact of COVID-19 was assessed separately. Results & conclusion: This study identified 2927 and 1085 patients in the second- (2L) and third-line (3L) cohorts. The median ages for the 2L and 3L cohorts were 71 and 70 years, respectively, with Charlson Comorbidity Score of 3. A majority of the patients had limited stem cell transplant due to advanced age. Median lengths of inpatient stay for the 2L and 3L cohorts were 118 and 116 days, respectively. The majority of costs were attributed to inpatient costs, and limited COVID-19 impact was observed in this study.

Medical database analysis of japanese multiple myeloma patients with planned stem cell transplantation (MEDALIST) - a focus on healthcare resource utilization and cost.

This study explored the burden associated with stem cell mobilization, with or without cyclophosphamide (CPA), in patients who intended to receive autologous stem cell transplantation (ASCT) for multiple myeloma (MM). A Japanese health care claims database (MDV) was used to analyze the health care resource utilization patterns and medical cost between 2013 and 2016 (pre-plerixafor launch). The patients were further categorized into groups who received granulocyte-colony stimulating factor (G-CSF) alone or G-CSF + CPA group and analyzed in both mobilization and ASCT phases of treatment. Overall, there were more MM patients who were treated with G-CSF + CPA combination therapy than G-CSF alone. Length-of-stay was 1.6 times longer in the combination group during the mobilization phase. A reverse trend was observed during the ASCT phase. Direct cost was approximately 1.2 million yen during the mobilization phase and 2.3 million yen during the ASCT phase, with hospitalization basic fee accounting for the highest proportion in both groups and phases. A substantial amount of healthcare resource and cost was consumed in both phases. This study may serve as a basic reference for further health technology assessment of new medicines such as plerixafor. Further investigation of differences between treatment groups is warranted.

Comparative effectiveness study of chemotherapy in follicular lymphoma patients in the rituximab era: a Japanese claims database study.

Aim: To evaluate comparative effectiveness of rituximub (R)-based versus non-R-based therapies for follicular lymphoma patients in Japan, where limited studies have been reported. Materials & methods: Patients who received R-based index regimens were propensity score matched to those who did not receive R, based on patient baseline attributes and clinical characteristics using Japanese retrospective claims database to assess clinical and economic outcomes. Results & conclusion: A total of 1947 patients remained in the overall follicular lymphoma cohorts: 1294 receiving an R-based and 653 a non-R-based regimen. Patients on R-based therapy underwent fewer hospitalizations and had a shorter length of stay, but had higher costs during the first year of intensive R-based therapy. Improved clinical outcomes were associated with patients who were younger, female and chose R-based regimens in first index line.

Nationwide claims database analysis of treatment patterns, costs and survival of Japanese patients with diffuse large B-cell lymphoma.

Limited data are available regarding treatment patterns, healthcare resource utilization (HCRU), treatment costs and clinical outcomes for patients with diffuse large B-cell lymphoma (DLBCL) in Japan. This retrospective database study analyzed the Medical Data Vision database for DLBCL patients who received treatment during the identification period from October 1 2008 to December 31 2017. Among 6,965 eligible DLBCL patients, 5,541 patients (79.6%) received first-line (1L) rituximab (R)-based therapy, and then were gradually switched to chemotherapy without R in subsequent lines of therapy. In each treatment regimen, 1L treatment cost was the highest among all lines of therapy. The major cost drivers i.e. total direct medical costs until death or censoring across all regimens and lines of therapy were from the 1L regimen and inpatient costs. During the follow-up period, DLBCL patients who received a 1L R-CHOP regimen achieved the highest survival rate and longest time-to-next-treatment, with a relatively low mean treatment cost due to lower inpatient healthcare resource utilization and fewer lines of therapy compared to other 1L regimens. Our retrospective analysis of clinical practices in Japanese DLBCL patients demonstrated that 1L treatment and inpatient costs were major cost contributors and that the use of 1L R-CHOP was associated with better clinical outcomes at a relatively low mean treatment cost.

Treatment Patterns and Lipid Profile in Patients with Familial Hypercholesterolemia in Japan.

AIM: To evaluate the epidemiology and real-world treatment patterns associated with lipid-modifying therapies (LMTs) among groups of Japanese patients with familial hypercholesterolemia (FH). METHODS: A retrospective observational study was conducted using an electronic hospital-based administrative claims database and electronic medical records. Patients with existing diagnosis of FH (FH-D) and patients with suspected FH (FH-S) defined by low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL were included, and medical records of hospitals across Japan were analyzed to assess the diagnostic status, management of LDL-C levels, and treatment patterns. RESULTS: Among the 3,495 patients who met the inclusion criteria, 193 patients were FH-D and 3,339 patients were FH-S. Among them, 83.5% had not achieved the LDL-C of ＜100 mg/dL recommended for patients with FH at the index date. Mean LDL-C levels for all patients and for FH-D and FH-S patients were 145.8 mg/dL, 119.2 mg/dL, and 147.6 mg/dL, respectively. 44.5% of the patients were not currently treated with LMTs. High-intensity statins were used only in 19.2% and 2.3% of the FH-D and FH-S patients, respectively. Furthermore, among the FH-D and FH-S statin-treated patients, 61 (69.3%) and 1,059 (89.7%) remained on monotherapy even when their LDL-C was ≥100 mg/dL. CONCLUSIONS: Treatment and management of LDL-C in Japanese FH patients remain suboptimal. The results suggest that FH is underdiagnosed in real-world, routine clinical practice in Japan. There is an urgent need to improve the diagnostic rate of FH and to provide the appropriate therapy to achieve the recommended LDL-C levels of ＜100 mg/dL or a more than 50% reduction for patients with FH in Japan.

Cost-effectiveness of EOB-MRI for Hepatocellular Carcinoma in Japan.

PURPOSE: The objective of the study was to evaluate the cost-effectiveness of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) in the diagnosis and treatment of hepatocellular carcinoma (HCC) in Japan compared with extracellular contrast media-enhanced MRI (ECCM-MRI) and contrast media-enhanced computed tomography (CE-CT) scanning. METHODS: A 6-stage Markov model was developed to estimate lifetime direct costs and clinical outcomes associated with EOB-MRI. Diagnostic sensitivity and specificity, along with clinical data on HCC survival, recurrence, treatment patterns, costs, and health state utility values, were derived from predominantly Japanese publications. Parameters unavailable from publications were estimated in a Delphi panel of Japanese clinical experts who also confirmed the structure and overall approach of the model. Sensitivity analyses, including one-way, probabilistic, and scenario analyses, were conducted to account for uncertainty in the results. FINDINGS: Over a lifetime horizon, EOB-MRI was associated with lower direct costs (¥2,174,869) and generated a greater number of quality-adjusted life years (QALYs) (9.502) than either ECCM-MRI (¥2,365,421, 9.303 QALYs) or CE-CT (¥2,482,608, 9.215 QALYs). EOB-MRI was superior to the other diagnostic strategies considered, and this finding was robust over sensitivity and scenario analyses. A majority of the direct costs associated with HCC in Japan were found to be costs of treatment. The model results revealed the superior cost-effectiveness of the EOB-MRI diagnostic strategy compared with ECCM-MRI and CE-CT. IMPLICATIONS: EOB-MRI could be the first-choice imaging modality for medical care of HCC among patients with hepatitis or liver cirrhosis in Japan. Widespread implementation of EOB-MRI could reduce health care expenditures, particularly downstream treatment costs, associated with HCC.

Clinical implementation and error sensitivity of a 3D quality assurance protocol for prostate and thoracic IMRT.

This work aims at three goals: first, to define a set of statistical parameters and plan structures for a 3D pretreatment thoracic and prostate intensity-modulated radiation therapy (IMRT) quality assurance (QA) protocol; secondly, to test if the 3D QA protocol is able to detect certain clinical errors; and third, to compare the 3D QA method with QA performed with single ion chamber and 2D gamma test in detecting those errors. The 3D QA protocol measurements were performed on 13 prostate and 25 thoracic IMRT patients using IBA's COMPASS system. For each treatment planning structure included in the protocol, the following statistical parameters were evaluated: average absolute dose difference (AADD), percent structure volume with absolute dose difference greater than 6% (ADD6), and 3D gamma test. To test the 3D QA protocol error sensitivity, two prostate and two thoracic step-and-shoot IMRT patients were investigated. Errors introduced to each of the treatment plans included energy switched from 6 MV to 10 MV, multileaf collimator (MLC) leaf errors, linac jaws errors, monitor unit (MU) errors, MLC and gantry angle errors, and detector shift errors. QA was performed on each plan using a single ion chamber and 2D array of ion chambers for 2D and 3D QA. Based on the measurements performed, we established a uniform set of tolerance levels to determine if QA passes for each IMRT treatment plan structure: maximum allowed AADD is 6%; maximum 4% of any structure volume can be with ADD6 greater than 6%, and maximum 4% of any structure volume may fail 3D gamma test with test parameters 3%/3 mm DTA. Out of the three QA methods tested the single ion chamber performed the worst by detecting 4 out of 18 introduced errors, 2D QA detected 11 out of 18 errors, and 3D QA detected 14 out of 18 errors.

WILLINGNESS TO PAY FOR LUNG CANCER TREATMENT: PATIENT VERSUS GENERAL PUBLIC VALUES.

OBJECTIVES: Lung cancer has been the most common cancer since 1985, accounting for 12-13 percent of cancer cases worldwide. Newer targeted therapies with potential increased survival benefits may not be affordable to patients. Many countries use arbitrary thresholds to determine whether a medical intervention is cost-effective. As such, many effective, albeit expensive, therapies are not being reimbursed. To understand the value placed on effective therapies, this study evaluates the patient and public willingness to pay (WTP) for a quality-adjusted life-year (QALY) for lung cancer treatments using Thailand as an example. METHODS: A total of 300 subjects responded to hypothetical lung cancer health states, described by three levels of severity and two levels of side effects, and provided their valuation of the level of quality of life and their WTP to improve from one state to another. RESULTS: The patients with the lowest income and general public were willing to pay more than twice the threshold for acceptability in Thailand (US Dollar 5,123/QALY [Thai Baht 160,000/QALY]). This increased significantly by wealth category. Patients' WTP was associated with quality of life, financial difficulties, health insurance, diarrhea, and wealth. CONCLUSIONS: The current study highlights the value patients and general public place on effective lung cancer therapies.

Validation of a COPD screening questionnaire and establishment of diagnostic cut-points in a Japanese general population: the Hisayama study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is highly prevalent worldwide. COPD is a treatable disease and it is important to identify COPD subjects, highlighting the need for an efficient screening measure. Although the COPD screening questionnaire (COPD Population Screener, COPD-PS) was developed as a screening tool, its validity is not clear in population-based studies. This study determines the validity of the COPD-PS in the general Japanese population. METHODS: All registered residents living in the town of Hisayama aged above 40 were solicited to participate in a health check-up in 2012. All subjects aged 40-79 without physician-diagnosed asthma or lung resection were recruited, and 2357 subjects with the COPD-PS recorded and valid spirometry measurements were analyzed. Persistent airflow obstruction (AO) was defined by post-bronchodilator FEV1/FVC < 0.7. The sensitivity and specificity of the COPD-PS score for identifying AO was assessed by logistic regression analysis. RESULTS: The prevalence of AO in this population was 6.5%. The overall area under the receiver operating characteristic (ROC) curve for the continuous COPD-PS score was 0.748. A cut-point of 4-points is recommended, resulting in a sensitivity of 67.1% and specificity of 72.9% with an area under the ROC curve of 0.70. The positive predictive value was 14.6% and negative predictive value was 97.0%. CONCLUSIONS: The COPD-PS appears to be an adequate measure for large scale screening of possible airflow obstruction requiring further testing with spirometry.

Economic Burden of Venous Thromboembolism in Patients Undergoing Major Abdominal Surgery.

BACKGROUND: Venous thromboembolism (VTE) is a serious complication that arises after major abdominal surgery. VTE poses risks of negative outcomes and health care burden. The literature on the cost of VTE in Japanese surgical patients, however, is scarce. OBJECTIVE: This study was conducted to investigate the economic consequences of VTE in Japanese patients with major abdominal surgery, using a hospital claims database. METHODS: This is a retrospective, matched cohort study. Patients who had a VTE event up to 90 days after their first major abdominal surgery and initiated warfarin or heparin within 1 day of VTE diagnosis with continued treatment for more than 4 weeks were matched with controls for surgery type, hospital, and date of surgery ± 6 months in a 1:2 scheme. The primary outcome was 90-day costs associated with major abdominal surgery. The secondary outcomes were 6-month total costs, average length of initial inpatient stay, and cost of initial inpatient stay. RESULTS: The 90-day cumulative incidence of VTE was 4.89%. The development of a VTE event in patients undergoing major abdominal surgery resulted in a 1.5-fold increase in the length of hospitalization and a 2.8-fold increase in total costs 90 days after the surgery. Total costs further increased to 3.4-fold at 6 months. Overall, costs incurred in patients with VTE are on average much higher than in patients without VTE throughout 6-month postsurgery. CONCLUSIONS: The preventive care for VTE using more effective prophylactic treatment is recommended to reduce the economic burden associated with major abdominal surgery.

Economic Impact of Venous Thromboembolism Following Major Orthopaedic Surgery in Japan.

OBJECTIVES: Venous thromboembolism (VTE) is the most frequent complication following major orthopaedic surgery (MOS). Although studies in Western populations have demonstrated significantly higher costs for patients with VTE versus those without VTE after MOS, there is a paucity of such data in Japan. This study was conducted to understand the costs and VTE rates in Japanese patients. METHODS: Data were extracted from a hospital claims database. MOS was defined as total hip replacement, total knee replacement, or hip fracture repair. Subjects who underwent more than one MOS during the same admission were excluded. Identified VTE cases were matched on a 1:2 matching scheme on the basis of surgery type, hospital, and date of surgery (±6 months). The primary outcome was the difference in 90-day costs. Secondary outcomes included differences in total 6-month costs postsurgery and average length and cost of initial hospital stay. RESULTS: The 90-day cumulative VTE incidence was 0.774%, with 94% of the cases occurring within 30 days postsurgery. Total 90-day costs were significantly higher in patients with VTE (difference of 864,153 Japanese yen [US $10,538]). Average length of stay was longer for patients with VTE (66 days vs. 42 days). Costs incurred by patients with VTE were on average much higher than those incurred by patients without VTE throughout 5 months postsurgery. CONCLUSIONS: The development of a VTE in patients undergoing MOS results in a 1.5-fold increase in the length of stay and a 1.7-fold increase in 90-day costs. Findings indicate that the avoidance of VTEs through more effective prophylaxis will help to reduce the economic burden associated with MOS.

Evaluation of the willingness-to-pay for cancer treatment in Korean metastatic breast cancer patients: a multicenter, cross-sectional study.

AIMS: To evaluate the inherent value of breast cancer therapy a willingness-to-pay (WTP) study was conducted in Korean patients with metastatic breast cancer. METHODS: Patients were prospectively enrolled from four study centers and completed quality of life questionnaires to reflect their status pre-cancer and their current health status. Clinical and socioeconomic data were collected to characterize the population and utilize during modeling. Patients' WTP for breast cancer treatment was assessed using an open-ended question following three rounds of bidding to better hone in on their maximal WTP, starting with one of three randomly assigned start bids. Predictors of patient WTP was evaluated using linear regression models. Associations between WTP and other parameters were evaluated with correlations. RESULTS: Korean metastatic breast cancer patients were WTP an average of KRW 8 696 329 (US$7555) per month to return to their pre-cancer health state, with those who were recently diagnosed as WTP the most (KRW 12 955 000 [$11 254]). WTP was closely associated with the patient's education level, income, personal financial difficulties, Eastern Cooperative Oncology Group performance status, and their experience of arm symptoms. CONCLUSION: The results suggest that patients are WTP significant amounts per month for treatment. Breast cancer patients are heavily burdened physically, mentally and financially, and the present study indicated this significant financial burden by disclosing its relationship with WTP. Providing a better understanding of the inherent value of treatment will allow Koreans to better evaluate treatment in the coming era of personalized medicine.

Development and validation of the self-completed ascites impact measure to understand patient motivation for requesting a paracentesis.

BACKGROUND: The Ascites Impact Measure (AIM) was developed to record patients' daily experiences of symptoms that trigger a request for a paracentesis. METHODS: Development of the AIM followed a rigorous step-wise approach, including a review of the literature, expert opinions, and qualitative research involving patients who experience symptomatic malignant ascites. The AIM's measurement properties were assessed using data from two international trials, including 59 ovarian cancer patients with symptomatic malignant ascites. RESULTS: Following the literature review and expert discussions to develop the conceptual model, ten patients with symptomatic malignant ascites were interviewed in the item elicitation phase, resulting in a draft questionnaire with four questions. Validation analyses consisted of 59 patients pooled from two international trials. Inter-items correlations for the AIM were good (r > 0.60), except for the Pain item. Internal consistency reliability (α = 0.89) improved after removing the Pain item from the Total Symptom score (TSS). Test-retest reliability was sufficient. Scores significantly improved after paracentesis except for the Pain item. Preliminary estimates indicate that a two-point improvement on the three-item TSS (without the Abdominal Pain item) could be interpreted as clinically meaningful. CONCLUSION: The Abdominal Pain item appears to behave differently than the other three items, and could be more related to cancer. While the validity of the AIM TSS (four-item) is acceptable, removing the Pain item from the TSS scoring algorithm demonstrated better construct validity. In addition, test-retest reliability and responsiveness were found to be similar to the results for the four-item AIM TSS. The Pain item should be used as a supplemental item to the three-item AIM TSS, as it provides additional information about the underlying cancer state.

Bortezomib is associated with better health-related quality of life than high-dose dexamethasone in patients with relapsed multiple myeloma: results from the APEX study.

Health-related quality of life (HRQL) was prospectively measured during the phase III APEX trial of bortezomib versus dexamethasone in relapsed multiple myeloma patients. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core (QLQ-C30) and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (NTX) side-effects questionnaires were administered at baseline and every 6 weeks up to 42 weeks. Patients receiving bortezomib (1.3 mg/m(2), days 1, 4, 8 and 11 for eight 3-week cycles, then days 1, 8, 15 and 22 for three 5-week cycles; n = 296) demonstrated significantly better mean Global Health Status over the study versus patients receiving dexamethasone (40 mg/d, days 1-4, 9-12, and 17-20 for four 5-week cycles, then days 1-4 only for five 4-week cycles; n = 302), plus significantly better physical health, role, cognitive, and emotional functioning scores, lower dyspnoea and sleep symptom scores, and better NTX questionnaire score, using multiple imputation to account for missing data. Results were similar using available-data analyses. Sensitivity analyses suggested that improved HRQL with bortezomib is at least partially explained by improved survival. These results show that bortezomib was associated with significantly better multidimensional HRQL compared with dexamethasone, consistent with the better clinical outcomes seen with bortezomib.

Development and validation of a cough and sputum assessment questionnaire.

Although cough and sputum production may impact patients' well being and functioning in COPD and chronic bronchitis, there is no validated instrument for cough and sputum symptoms and their impact on patients' daily activities. To fill that gap, we developed and validated a specific, multilingual Cough and Sputum Assessment Questionnaire (CASA-Q) that evaluates clinical symptoms and their impact on patients with COPD or chronic bronchitis. In a three-country validation study (n=671), there was adequate internal consistency (Cronbach's alphas, 0.80-0.91) and test-retest reliability (correlation coefficients>0.70) for the CASA-Q. The cough impact and sputum impact domains correlated with the SGRQ impact domain and SGRQ total score, as did the cough impact domain with the SF-36 social functioning domain. The cough symptom and sputum symptom domains correlated with sputum wet weight (p<0.05; r=-0.56), but not with cough recordings. The mean CASA-Q cough symptom and sputum symptom domain scores indicated responsiveness towards both worse and improved symptoms, whereas the impact domains scored already in the upper third of the scale range, indicating the need for further improvement of its properties. Differences in the CASA-Q domain scores by smoking status (current vs. former smokers) were highest for cough symptoms and lowest for sputum impact. These data indicate that the CASA-Q may be a useful measure of cough and sputum production, and their impact in patients with COPD and/or chronic bronchitis. Further validation will need to assess the responsiveness of the CASA-Q to changes in symptoms.