Cost-Effectiveness of Canagliflozin Added to Standard of Care for Treating Diabetic Kidney Disease (DKD) in Patients with Type 2 Diabetes Mellitus (T2DM) in England: Estimates Using the CREDEM-DKD Model.

INTRODUCTION: On the basis of reductions in diabetic kidney disease (DKD) progression and major adverse cardiovascular events observed in the landmark CREDENCE trial, canagliflozin 100 mg received an extension to its EU marketing authorisation in July 2020 to include the treatment of DKD in people with type 2 diabetes mellitus (T2DM) making it the first pharmacological therapy to receive regulatory authorisation for treatment of DKD since the RENAAL and IDNT trials in nearly 20 years. Efficient allocation of limited healthcare resources requires evaluation not only of clinical safety and efficacy but also economic consequences. The study aim was to estimate the cost-effectiveness of canagliflozin when added to current standard of care (SoC) versus SoC alone from the perspective of the NHS in England. METHODS: A microsimulation model was developed using patient-level data from CREDENCE, including risk equations for the key clinical outcomes of start of dialysis, hospitalisation for heart failure, nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality. DKD progression was modelled using estimated glomerular filtration rate and urinary albumin-to-creatinine ratio evolution equations. Risk for kidney transplant was sourced from UK-specific sources given the near absence of events in CREDENCE. Patient characteristics and treatment effects were sourced from CREDENCE. Unit costs (£2019) and disutility weights were sourced from the literature and discounted at 3.5% annually. The time horizon was 10 years in the base case, and sensitivity analysis was performed. RESULTS: Canagliflozin was associated with sizable gains in life-years and quality-adjusted life-year (QALYs) over 10 years, with gains increasing with simulation duration. Cost offsets associated with reductions in cardiovascular and renal complications were sufficient to achieve overall net cost savings. The findings were generally confirmed in the sensitivity analyses. CONCLUSION: Model results suggest that adding canagliflozin 100 mg to SoC can improve patient outcomes while reducing overall net costs from the NHS perspective in England. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02065791.

CANadian CAnagliflozin REgistry: Patient-Reported Outcomes of Canagliflozin in the Treatment of Type 2 Diabetes Mellitus in Canadian Clinical Practice.

OBJECTIVES: To describe patient-reported outcomes (PROs) after initiation of treatment with canagliflozin (CANA) for type 2 diabetes mellitus (T2DM) in a real-world Canadian setting. METHODS: CANadian CAnagliflozin REgistry (CanCARE) is a prospective, observational, single-arm, real-world Canadian study of the effectiveness and safety of CANA for the treatment of T2DM in 527 subjects. PRO measures were collected in CanCARE using the Current Health Satisfaction Questionnaire (CHES-Q) at baseline and after 3, 6 and 12 months of CANA treatment to examine patient satisfaction regarding weight and overall health. Associations between changes in satisfaction with weight, systolic blood pressure (SBP) and glycated hemoglobin (A1C) levels were also investigated. RESULTS: Proportion of patients satisfied with their body weight and overall health increased from 22.1% and 26.9% at baseline to 32.4% and 49.2% after 12 months of CANA treatment, respectively. Satisfaction rates also increased on CHES-Q domains representing physical and emotional health. Correlations were found between improvement in satisfaction with body weight and weight loss (r=-0.29; p<0.01) and between improvements in satisfaction with overall health and weight loss (r=-0.13; p=0.03) and SBP (r=-0.17; p<0.01), but not with changes in A1C level. CONCLUSIONS: Treatment with CANA is associated with improvements in satisfaction with body weight and overall health, which may be important drivers of patient self-management and hold the potential to positively influence long-term outcomes in T2DM.

A call to action to inform patient-centred approaches to obesity management: Development of a disease-illness model.

Patient-centred care is an essential component of high-quality health care, shown to improve clinical outcomes and patient satisfaction, and reduce costs. While there are several authoritative models of obesity pathophysiology and treatment algorithms, a truly patient-centred model is lacking. We describe the development of a patient-centric obesity model. A disease-illness framework was selected because it emphasizes each patient's unique experience while capturing biomedical aspects of the disease. Model input was obtained from an accumulation of research including contributions from experts in obesity and patient-reported outcomes, qualitative research with adults living in the United States, and two targeted literature searches. The model places the patient with obesity at its core and links pathologic imbalances of energy intake and expenditure to environmental, sociodemographic, psychological, behavioural, physiological and medical health determinants. It highlights relationships between obesity signs and symptoms, comorbid conditions, impacts on health-related quality of life, and some barriers to obesity management that must be considered to attain better outcomes. Providers need to evaluate patients holistically, understand what changes each patient is motivated to make, and recognize what challenges might impede weight reduction, improvements in comorbid conditions, signs and symptoms, and health-related quality of life before pursuing individualized treatment goals. Patients living with obesity who do lose weight perceive benefits beyond weight loss. Ideally, this model will increase awareness of the complex, heterogeneous impacts of obesity on patients' well-being and recognition of obesity as a chronic disease, and prompt a call to action among stakeholders to improve quality of care.

CANadian CAnagliflozin REgistry: Effectiveness and safety of canagliflozin in the treatment of type 2 diabetes mellitus in Canadian clinical practice.

AIM: There is limited information concerning the effects of canagliflozin (CANA), a sodium-glucose co-transporter 2 inhibitor (SGLT2i) in a real-world clinical setting in Canada. CanCARE is a 12-month, prospective, observational analysis to demonstrate the effectiveness and safety of CANA in usual clinical practice in Canada. MATERIALS AND METHODS: SGLT2i-naïve adult patients with type 2 diabetes mellitus (T2DM) (n = 527) on a stable antihyperglycemic agent (AHA) regimen with glycated hemoglobin (A1C) ≥ 7%, an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2 , were initiated on CANA as part of their usual treatment approach, and were followed for a period of 12 months. The primary effectiveness objective was the mean change in HbA1c from baseline to 6 and 12 months. RESULTS: Significant improvement from baseline in mean HbA1c levels were observed at 6 months (-0.90%; 95% CI, -1.02, -0.78) and at 12 months (-1.04%; 95% CI, -1.15, -0.92), regardless of duration of diabetes or background AHA treatment regimen. Similarly, significant decreases in systolic blood pressure (-4.65 mm Hg); body weight (-3.24 kg), waist circumference (-2.91 cm) and body mass index (-1.15 kg/m2 ) were observed at 12 months. Additionally, 40.5% of patients achieved the double endpoint (≥0.5% HbA1c reduction and ≥ 3% weight loss), while 24.3% of patients achieved the triple composite endpoint (≥0.5% HbA1c reduction, ≥3% weight loss and ≥ 4 mm Hg systolic blood pressure reduction). No unexpected adverse events were reported. CONCLUSION: CANA provided sustained clinically meaningful improvements in cardiometabolic parameters in this study in a real-world setting, confirming findings from randomized controlled trials.

Impact of Canagliflozin Treatment on Health-Related Quality of Life among People with Type 2 Diabetes Mellitus: A Pooled Analysis of Patient-Reported Outcomes from Randomized Controlled Trials.

BACKGROUND: Evidence from patient-reported outcomes in clinical trials may explain health-related behaviors observed in the real world. OBJECTIVE: The purpose of this analysis was to evaluate the effect of treatment with canagliflozin, a sodium glucose co-transporter 2 inhibitor, compared with placebo or sitagliptin on health-related quality-of-life outcomes in participants with type 2 diabetes mellitus from the clinical development program. METHODS: Patient-reported outcomes data from four randomized controlled trials of canagliflozin (n = 2536) were pooled and analyzed to evaluate participants' interest in continuing study medication; satisfaction with weight; and physical, mental, and emotional health after 26-52 weeks of treatment with canagliflozin vs. placebo or sitagliptin. RESULTS: Upon trial completion, participants treated with canagliflozin were more likely to express interest in continuing study medication than participants treated with placebo or sitagliptin [odds ratio (95% confidence interval) of 1.54 (1.19-1.99); p = 0.001]. Those treated with canagliflozin were also more likely to be satisfied with their weight and report favorable outcomes (score improvement or maintenance of good scores) related to physical and emotional health. CONCLUSIONS: The results of this pooled analysis suggest that people with type 2 diabetes mellitus treated with canagliflozin generally had positive experiences with treatment and improvements in health-related quality of life. Future research is needed to determine if these improvements result in improved type 2 diabetes mellitus management and treatment adherence. CLINICALTRIALS. GOV IDENTIFIERS: NCT01106625, NCT01106677, NCT01137812, NCT02025907.

Improvement of fatigue, physical functioning, and well-being among patients with severe impairment at baseline receiving ibrutinib in combination with bendamustine and rituximab for relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma in the HELIOS study.

Health-related quality of life (HRQoL) is an important endpoint, especially in clinical trials for malignancies with a long course of disease, such as chronic lymphocytic leukemia (CLL). Patient-reported outcomes were examined in the randomized, double-blind, placebo-controlled HELIOS study to assess the impact of treatment with the Bruton's tyrosine kinase inhibitor ibrutinib, added to bendamustine plus rituximab (BR) background therapy. Measures included FACIT-Fatigue, EORTC QLQ-C30, QLQ-CLL16, and EQ-5D-5L. Of 578 patients enrolled, 540 (93%) provided FACIT-Fatigue responses at baseline. Most had only a moderate degree of impairment at baseline; mean values did not appear to change over time in either treatment arm, suggesting that adding ibrutinib to BR did not impact health-related quality of life. However, post-hoc analyses showed that subgroups of patients with the worst fatigue, physical functional status, and well-being at baseline had greater improvements in these outcomes with ibrutinib plus BR treatment versus placebo.

An Indirect Comparison of Changes in the Impact of Weight on Quality of Life Among Subjects with Type 2 Diabetes Treated with Antihyperglycemic Agents in Dual Therapy with Metformin.

INTRODUCTION: It is important to capture the patient experience with a diabetes treatment in clinical trials; however, use of instruments to assess patient-reported outcomes (PROs) in diabetes trials is inconsistent and results may not be reported alongside primary efficacy data. In lieu of head-to-head data, indirect comparisons can be used to compare competing interventions. In this study, we used indirect comparison methods to assess differences in PRO score changes between canagliflozin and other antihyperglycemic agents as add-on to metformin. METHODS: Literature searches were performed to identify studies that reported the same PRO instruments that were collected across four trials of canagliflozin in dual or triple therapy. Extensive searches identified only one study that was sufficiently similar in design and reported common PRO results using the Impact of Weight on Quality of Life-Lite (IWQoL-Lite): the DURATION-2 study of exenatide once-weekly (QW) versus sitagliptin and pioglitazone. This study was compared with the CANTATA-D study of canagliflozin versus sitagliptin. Bayesian indirect comparisons were performed to assess mean change in IWQoL-Lite total score. A fixed-effects model with noninformative priors was used to estimate between-treatment differences. Sensitivity analyses examined differences in trial populations. RESULTS: In the primary analysis, the probability that canagliflozin treatment results in greater improvement in IWQoL-Lite total score versus exenatide, sitagliptin, and pioglitazone was 60.0%, 89.9%, and 99.5%, respectively. When the CANTATA-D population was restricted using DURATION-2 inclusion/exclusion criteria, canagliflozin was also associated with a higher probability of having greater improvement in IWQoL-Lite than exenatide, sitagliptin, and pioglitazone. CONCLUSIONS: These findings suggest that improvements in the impact of weight on health-related quality of life may be greater with canagliflozin than exenatide, sitagliptin, and pioglitazone. This analysis also demonstrates the application of indirect comparison methodology to PRO data and provides examples of advantages and challenges associated with performing indirect comparisons of PRO data.

Health-related quality of life data from a phase 3, international, randomized, open-label, multicenter study in patients with previously treated mantle cell lymphoma treated with ibrutinib versus temsirolimus.

Mantle cell lymphoma (MCL) is a rare, aggressive, incurable B-cell malignancy. Ibrutinib has been shown to be highly active for patients with relapsed/refractory (R/R) MCL. The RAY trial (MCL3001) was a phase 3, randomized, open-label, multicenter study that compared ibrutinib with temsirolimus in patients with R/R MCL. Active disease is frequently associated with impaired functional status and reduced well-being. Therefore, the current study employed two patient-reported outcome instruments, the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and the EQ-5D-5L, to assess symptoms, well-being, health status, and health-related quality of life of patients on treatment within the RAY trial. We found that patients on ibrutinib had substantial improvement in FACT-Lym subscale and total scores, and had improvement in EQ-5D-5L utility and VAS scores compared with temsirolimus patients, indicating a superior well-being. These improvements in well-being correlated with clinical response, indicating that better health-related quality of life was associated with decreased disease burden.

The Effect of Canagliflozin, a Sodium Glucose Cotransporter 2 Inhibitor, on Glycemic End Points Assessed by Continuous Glucose Monitoring and Patient-Reported Outcomes Among People With Type 1 Diabetes.

OBJECTIVE: To assess the effects of canagliflozin, a sodium glucose cotransporter 2 inhibitor, on glycemic parameters and measures of glucose variability assessed by a 9-point self-monitoring blood glucose (SMBG) and continuous glucose monitoring (CGM) profiles, and patient-reported outcomes as an add-on to insulin among participants with type 1 diabetes. RESEARCH DESIGN AND METHODS: In this randomized, double-blind study, 351 participants received canagliflozin 100 or 300 mg or placebo for 18 weeks. Change from baseline in daily mean glucose and SD was measured using a 9-point SMBG profile. In a subset of 89 participants who underwent CGM, the change from baseline in mean glucose, measures of glycemic variability (SD, coefficient of variation, and mean amplitude of glycemic excursions), and time spent in glycemic ranges were assessed. Change in treatment satisfaction was evaluated using the Diabetes Treatment Satisfaction Questionnaire (n = 328). RESULTS: At week 18, reductions in daily mean glucose and SD measured using the 9-point SMBG profile were seen with canagliflozin 100 and 300 mg versus placebo. Reductions in mean glucose (-1.2, -0.7, and 0.6 mmol/L) and measures of glycemic variability assessed by CGM, such as changes in glucose SD (-0.3, -0.7, and 0.1 mmol/L), were also seen with canagliflozin 100 and 300 mg versus placebo, respectively. Canagliflozin 100 and 300 mg were associated with increases in time spent within target (glucose >3.9 to ≤10.0 mmol/L) compared with placebo (11.6%, 10.1%, and -3.5%, respectively) and commensurate reductions in time spent above the target level (glucose >10.0 mmol/L; -12.7%,-7.6%, and 5.7%, respectively). Participants showed greater improvement in treatment satisfaction with canagliflozin versus placebo; reductions in insulin dose, SD of glucose, and body weight contributed to the relationship between canagliflozin and satisfaction change. CONCLUSIONS: Canagliflozin improved indices of glycemic variability and was associated with improvement in treatment satisfaction versus placebo over 18 weeks among participants with type 1 diabetes. Although these data from this study demonstrate the potential benefits of canagliflozin in people with type 1 diabetes, canagliflozin is not approved for the treatment of type 1 diabetes and should not currently be used in people with type 1 diabetes.

The Diabetes Intention, Attitude, and Behavior Questionnaire: evaluation of a brief questionnaire to measure physical activity, dietary control, maintenance of a healthy weight, and psychological antecedents.

BACKGROUND: This study assessed measurement properties of the 17-item Diabetes Intention, Attitude, and Behavior Questionnaire (DIAB-Q), which measures intention to engage in self-care behaviors, including following a diabetes diet and engaging in appropriate physical activity. METHODS: The DIAB-Q includes questions based on the Theory of Planned Behavior. Items were developed using published literature, input from health care professionals, and qualitative research findings in patients with and without type 2 diabetes mellitus (T2DM). In Stage I of the study, 23 adults with T2DM were interviewed to evaluate the content and clarity of the DIAB-Q. In Stage II 1,015 individuals with T2DM completed the DIAB-Q and supplemental questionnaires, including the Short Form-36 acute (SF-36), section III of the Multidimensional Diabetes Questionnaire, the Summary of Diabetes Self-Care Activities questionnaire, and self-administered items relevant to the treatment and management of T2DM (eg, blood pressure and glycated hemoglobin [HbA1c]) at baseline and 3-7 days later. Once the DIAB-Q scale structure was determined, its test-retest reliability, construct validity, and known-groups validity were evaluated, and minimal clinically important change was estimated. RESULTS: In Stage I, the 23 respondents surveyed generally reported that the DIAB-Q was clear and comprehensive and endorsed questions as relevant to their intentions to engage in diabetes-related self-care activities. Most subjects in Stage II were male, Caucasian, and married. Mean age was 63 years. Factor analysis revealed six psychological constructs (Behavior, Planning, Intention, Perceived Behavioral Control, Attitude, and Subjective Norm). Test-retest reliability was acceptable (≥0.70) for all scales, except Perceived Behavioral Control. Construct validity was demonstrated based on correlations with diabetes-specific items/scales and the SF-36. Known-groups validity was confirmed for Behavior, Planning, and Intention when respondents were categorized into groups that differed based on body mass index, disease severity, and HbA1c. Item scores were transformed to a 100-point scale, and minimal clinically important change estimates ranged from 6-11 points, representing the change that would be considered important to a respondent. CONCLUSION: The DIAB-Q is a brief, psychometrically sound, patient-reported outcome that can be used among individuals with T2DM to evaluate intention to engage in self-care behaviors.

Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study.

BACKGROUND: Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma. METHODS: This randomised, open-label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell lymphoma confirmed by central pathology in 21 countries who had received one or more rituximab-containing treatments. Patients were stratified by previous therapy and simplified mantle-cell lymphoma international prognostic index score, and were randomly assigned with a computer-generated randomisation schedule to receive daily oral ibrutinib 560 mg or intravenous temsirolimus (175 mg on days 1, 8, and 15 of cycle 1; 75 mg on days 1, 8, and 15 of subsequent 21-day cycles). Randomisation was balanced by using randomly permuted blocks. The primary efficacy endpoint was progression-free survival assessed by a masked independent review committee with the primary hypothesis that ibrutinib compared with temsirolimus significantly improves progression-free survival. The analysis followed the intention-to-treat principle. The trial is ongoing and is registered with ClinicalTrials.gov (number NCT01646021) and with the EU Clinical Trials Register, EudraCT (number 2012-000601-74). FINDINGS: Between Dec 10, 2012, and Nov 26, 2013, 280 patients were randomised to ibrutinib (n=139) or temsirolimus (n=141). Primary efficacy analysis showed significant improvement in progression-free survival (p<0·0001) for patients treated with ibrutinib versus temsirolimus (hazard ratio 0·43 [95% CI 0·32-0·58]; median progression-free survival 14·6 months [95% CI 10·4-not estimable] vs 6·2 months [4·2-7·9], respectively). Ibrutinib was better tolerated than temsirolimus, with grade 3 or higher treatment-emergent adverse events reported for 94 (68%) versus 121 (87%) patients, and fewer discontinuations of study medication due to adverse events for ibrutinib versus temsirolimus (9 [6%] vs 36 [26%]). INTERPRETATION: Ibrutinib treatment resulted in significant improvement in progression-free survival and better tolerability versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma. These data lend further support to the positive benefit-risk ratio for ibrutinib in relapsed or refractory mantle-cell lymphoma. FUNDING: Janssen Research & Development, LLC.

Demystifying "patient-centered" care in type 2 diabetes: the role of systematic measurement.

Questionnaires are noninvasive, inexpensive measures that can identify key elements of the patient perspective that are important for the achievement of better outcomes in diabetes care.

The Importance of Weight Change Experiences for Performance of Diabetes Self-Care: A Patient-Centered Approach to Evaluating Clinical Outcomes in Type 2 Diabetes.

INTRODUCTION: The aim of this study was to examine the influence of weight change experiences over time on motivation to perform diabetes self-care behaviors using data from a study of canagliflozin (an agent that inhibits sodium glucose co-transporter 2) versus glimepiride in dual therapy with metformin and background diet/exercise. METHODS: Weight and motivation for performing healthy behaviors were collected at baseline and over time. The motivation questionnaire enabled categorization into two groups: those performing or not performing health behaviors. Four distinct patterns of weight change were determined: losing weight, gaining weight, and two patterns for fluctuating weight. The relationships between these patterns and motivation for weight loss, following a diet, and exercise were examined using logistic regression models. RESULTS: Of 1182 subjects, more than half were already performing behaviors to lose weight, diet, and exercise at baseline. Among those who were not, 52% (246/474) started taking action to lose weight after baseline, 54% (241/448) started following a diet, and 42% (232/556) started exercising. Weight change patterns were significantly related to performance of healthy behaviors at follow-up (week 36). Compared to the weight gain pattern, those who experienced a continuous weight loss pattern from baseline to week 36 were 2.2 (95% confidence interval 1.49, 3.37) times more likely to perform the healthy behaviors. Baseline behavior and confidence were also predictive of performing healthy behaviors. CONCLUSION: The current work highlights the importance of weight change patterns for performance of diabetes self-care. Tracking weight patterns over time, assessing confidence for performance of healthy behaviors, and being aware of the relationship between weight changes and diabetes self-care behaviors are viable, concrete ways to practice patient-centered care. FUNDING: Janssen Global Services, LLC.

Pragmatic measurement of health satisfaction in people with type 2 diabetes mellitus using the Current Health Satisfaction Questionnaire.

BACKGROUND: The concept of diabetes-related health satisfaction encompasses issues specifically related to living with diabetes (eg, blood glucose, blood pressure levels, body weight). Health satisfaction is more specific than overall health-related quality of life because it considers disease-related factors, and is different from diabetes treatment satisfaction because it addresses issues not specifically related to treatment. Low levels of health satisfaction in people with type 2 diabetes mellitus (T2DM) may negatively affect self-care behaviors and treatment outcomes; however, there are currently no instruments available to assess health satisfaction in this population. This study assessed the measurement properties of a newly constructed, 14-item Current Health Satisfaction Questionnaire (CHES-Q) designed to assess diabetes-related health satisfaction and knowledge of the disease and important laboratory results. METHODS: In-depth interviews were conducted in 23 adults with T2DM to confirm the content and clarity of the CHES-Q. The revised instrument was administered to 1,015 individuals with T2DM, along with supplemental questionnaires, including the Short Form-36. All subjects completed the questionnaires again 3 to 7 days later. CHES-Q test-retest reliability, construct validity, and known-groups validity were evaluated. RESULTS: In general, respondents found the CHES-Q to be clear and comprehensive. Test-retest reliability was generally acceptable for all items (≥0.70), except for three that fell just below the widely accepted cut-point of 0.70 (range 0.63-0.69). Convergent and divergent validity was demonstrated based on hypothesized correlations with the Short Form-36. Known-groups validity was confirmed for most CHES-Q items when respondents were split into groups known to differ clinically by body mass index, disease severity, or glycated hemoglobin. CONCLUSION: Health satisfaction is a unique and important concept to consider when developing individualized strategies for managing T2DM because health satisfaction is a key element of patient-centered care. The CHES-Q allows for the pragmatic assessment of many aspects of diabetes-related health satisfaction in a single questionnaire.

The impact of weight loss on weight-related quality of life and health satisfaction: results from a trial comparing canagliflozin with sitagliptin in triple therapy among people with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is primarily a self-managed disease in which self-care behaviors play an important role in achieving optimal outcomes. Because self-care does not result in immediate tangible or noticeable benefits, adherence to such a regimen can be confusing, difficult, and frustrating. People are more likely to adhere to treatment regimens that offer benefits from the patient perspective, such as convenience, avoidance of hypoglycemic episodes, and weight loss, compared with regimens that do not. In this study, we explored the impact of the average weight loss amount demonstrated with canagliflozin treatment on improvement in 3 patient-relevant outcomes that have been linked to performance of healthy behaviors and better outcomes in T2DM: weight-related quality of life, as measured by the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire, and satisfaction with physical health and emotional health, as measured by the Current Health Satisfaction Questionnaire (CHES-Q), using data from a previously reported study. Weight loss of an amount demonstrated in clinical trials of canagliflozin was associated with improvements in weight-related quality of life and satisfaction with physical and emotional health, concepts shown to be important to the persistent and consistent performance of healthy behaviors.

Rapid and sustained improvement in health-related quality of life and utility for 72 weeks in patients with ankylosing spondylitis receiving etanercept.

OBJECTIVE: To examine the longterm effect of etanercept (ETN) therapy on health-related quality of life (HRQOL) and utility in patients with ankylosing spondylitis. METHODS: Patients completing a 24-week placebo-controlled trial were continued on ETN in a 72-week open-label extension study. Short Form-36 (SF-36), EuroQOL-5D (EQ-5D), and EuroQOL visual analog scale (EQ-VAS) scores were collected at open-label baseline and every 12 weeks thereafter. Mental and physical component scores (MCS and PCS) of the SF-36, EQ-5D and SF-6D utility scores, and quality-adjusted life-years (QALY) were calculated. RESULTS: 257 patients [129 previous placebo (PLA) and 128 ETN recipients] enrolled in this open-label extension study, and 85% completed the 72-week followup. PCS, EQ-5D and SF-6D utilities, and EQ-VAS were significantly lower at open-label baseline in the previous PLA group (PLA/ETN group) than in the previous ETN group (ETN/ETN group; all p < 0.001). At week 12, PCS and MCS, EQ-5D and SF-6D utility scores, and EQ-VAS were similar in the PLA/ETN and ETN/ETN groups. As expected, mean change in EQ-5D in the PLA/ETN group was significantly greater than that for SF-6D (0.18 vs 0.06; p < 0.0001). HRQOL and utility improvements were maintained in both groups for up to 72 weeks. The average 72-week QALY gain per person in the PLA/ETN group was 0.24 and 0.10 for EQ-5D and SF-6D, respectively. CONCLUSION: Patients continuing ETN therapy sustained HRQOL and utility improvements attained during the original PLA-controlled trial. Patients previously taking PLA showed rapid and sustained improvements in HRQOL and utility and substantial QALY gain with ETN therapy.

Symptoms and treatment burden associated with cancer treatment: results from a cross-sectional national survey in the U.S.

GOALS: To examine the prevalence of chemotherapy-or radiotherapy-associated side effects and related treatment burden, and correlates of fatigue and missed work days among cancer patients. MATERIALS AND METHODS: A cross-sectional survey was conducted using a dual sampling frame of 63,949 cancer patients (35,751 from an online panel and 28,198 from telephone listings) > or = 18 years receiving chemotherapy and/or radiotherapy at the time of the survey or during the previous 12 months. Data were collected on cancer type, time since diagnosis, treatment side effects, visits, caregiver burden, missed work days, and sociodemographic characteristics. Data are presented only for patients receiving cancer treatment at the time of the survey. MAIN RESULTS: Of the 15,532 patients (24%) who responded to the screening questionnaire, 1,572 met the eligibility criteria and 1,569 completed the survey; 814 received chemotherapy and/or radiotherapy at the time of the survey. The most common side effects were fatigue (80%), pain (48%), and nausea/vomiting (48%). Patients spent 4.5 h, on average, per visit to treat side effects. Approximately 43% of the patients were employed; of these, 78% were actively working. Employed patients missed, on average, 18 work days annually for side effect treatment. Females, younger and unemployed patients, and those with higher levels of anxiety and depression experienced more fatigue; patients with a greater number of side effects endured more missed work days. CONCLUSIONS: In addition to the symptomatic experience of side effects, patients reported a considerable time burden for treatment. It is important to consider supportive care strategies that may effectively reduce side effects and their associated treatment burden.

The complexity of care for patients with rheumatoid arthritis: metrics for better understanding chronic disease care.

BACKGROUND: Patients with rheumatoid arthritis (RA) provide an important opportunity for understanding care of patients with a serious chronic condition. OBJECTIVES: We sought to characterize the complexity of care for patients with RA, including metrics describing the patient, the disease, and use of the health care system across time and place. METHODS: We undertook a prospective cohort study of 568 community-dwelling patients with RA by using observational data from clinically detailed telephone interviews at baseline and 2 years later in addition to medical record abstraction. Health status, comorbidity, use of disease-modifying antirheumatic drugs, visits, providers, provider types, encounter settings, and the discontinuity between patients and providers were studied. RESULTS: Within a 12-month window, 568 patients had 8686 outpatient encounters with the health care system with a mean of 3.41 unique providers per patient associated with a mean of 5 primary care and 6 rheumatologist visits. Half did not see a primary care physician, and 20% did not see a rheumatologist during 6-month periods despite their use of potentially toxic drugs, a mean of 4 comorbidities and progressive RA. Over the course of 24 months, 29% of patients changed their primary care provider, and 15% changed their rheumatologist. Patients were moderately impaired with mean SF-12 physical component score 37 (SD, 9). CONCLUSION: Patients with RA have frequent encounters with multiple providers and also frequent discontinuity of care. Recognizing the complexity of the care of patients with a chronic disease across multiple dimensions provides an opportunity to better understand challenges and opportunities in delivering high quality care.

Measuring process of arthritis care: the Arthritis Foundation's quality indicator set for rheumatoid arthritis.

OBJECTIVE: To describe the scientific evidence that supports each of the explicit process measures in the Arthritis Foundation's Quality Indicator Set for Rheumatoid Arthritis. METHODS: For each of the 27 measures in the Arthritis Foundation's Quality Indicator set, a comprehensive literature review was performed for evidence that linked the process of care defined in the indicator with relevant clinical outcomes and to summarize practice guidelines relevant to the indicators. RESULTS: Over 7500 titles were identified and reviewed. For each of the indicators the scientific evidence to support or refute the quality indicator was summarized. We found direct evidence that supported a process-outcome link for 15 of the indicators, an indirect link for 7 of the indicators, and no evidence to support or refute a link for 5. The processes of care described in the indicators for which no supporting/refuting data were found have been assumed to be so essential to care that clinical trails assessing their importance have not, and probably never will be, performed. The process of care described in all but 2 of the indicators is recommended in 1 or more practice guidelines. CONCLUSION: There are sufficient scientific evidence and expert consensus to support the Arthritis Foundation's Quality Indicator Set for Rheumatoid Arthritis, which defines a minimal standard of care that can be used to assess health care quality for patients with rheumatoid arthritis.

Effects of omega-3 fatty acids on cancer risk: a systematic review.

CONTEXT: Omega-3 fatty acids are purported to reduce the risk of cancer. Studies have reported mixed results. OBJECTIVE: To synthesize published and unpublished evidence to determine estimates of the effect of omega-3 fatty acids on cancer risk in prospective cohort studies. DATA SOURCES: Articles published from 1966 to October 2005 identified through MEDLINE, PREMEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CAB Health; unpublished literature sought through letters to experts in the neutraceutical industry. STUDY SELECTION: A total of 38 articles with a description of effects of consumption of omega-3 fatty acids on tumor incidence, prospective cohort study design, human study population; and description of effect of omega-3 among groups with different levels of exposure in the cohort were included. Two reviewers independently reviewed articles using structured abstraction forms; disagreements were resolved by consensus. DATA EXTRACTION: Two reviewers independently abstracted detailed data about the incidence of cancer, the type of cancer, the number and characteristics of the patients, details on the exposure to omega-3 fatty acids, and the elapsed time between the intervention and outcome measurements. Data about the methodological quality of the study were also abstracted. DATA SYNTHESIS: Across 20 cohorts from 7 countries for 11 different types of cancer and using up to 6 different ways to categorize omega-3 fatty acid consumption, 65 estimates of the association between omega-3 fatty acid consumption were reported. Among these, only 8 were statistically significant. The high degree of heterogeneity across these studies precluded pooling of data. For breast cancer 1 significant estimate was for increased risk (incidence risk ratio [IRR], 1.47; 95% confidence interval [CI], 1.10-1.98) and 3 were for decreased risk (RR, 0.68-0.72); 7 other estimates did not show a significant association. For colorectal cancer, there was 1 estimate of decreased risk (RR, 0.49; 95% CI, 0.27-0.89) and 17 estimates without association. For lung cancer one of the significant associations was for increased cancer risk (IRR, 3.0; 95% CI, 1.2-7.3), the other was for decreased risk (RR, 0.32; 95% CI, 0.13-0.76), and 4 other estimates were not significant. For prostate cancer, there was 1 estimate of decreased risk (RR, 0.43; 95% CI, 0.22-0.83) and 1 of increased risk (RR, 1.98; 95% CI, 1.34-2.93) for advanced prostate cancer; 15 other estimates did not show a significant association. The study that assessed skin cancer found an increased risk (RR, 1.13; 95% CI, 1.01-1.27). No significant associations between omega-3 fatty acid consumption and cancer incidence were found for aerodigestive cancer, bladder cancer, lymphoma, ovarian cancer, pancreatic cancer, or stomach cancer. CONCLUSIONS: A large body of literature spanning numerous cohorts from many countries and with different demographic characteristics does not provide evidence to suggest a significant association between omega-3 fatty acids and cancer incidence. Dietary supplementation with omega-3 fatty acids is unlikely to prevent cancer.