The emotional and physical impact of wet age-related macular degeneration: findings from the wAMD Patient and Caregiver Survey.

OBJECTIVES: This was a cross-sectional survey to evaluate the physical and emotional impact of wet age-related macular degeneration (wAMD) on a global cohort of patients who were receiving (or had previously received) antivascular endothelial growth factor injections, and caregivers (paid and unpaid). METHODS: The survey was performed in nine countries using an ophthalmologist-devised questionnaire. RESULTS: A total of 910 patients and 890 caregivers completed the questionnaire. Most patients had been diagnosed and receiving antivascular endothelial growth factor injections for more than 1 year (74.7% and 63.8%, respectively), and many patients (82.1%) received support from a caregiver (usually a child/grandchild [47.3%] or partner [23.3%]). wAMD had a negative impact on most patients (71.6%); many rated fear (44.9%), sadness (39.9%), frustration (37.3%), and depression (34.0%) as common. It was linked to physical consequences, such as difficulty in reading (61.1%). Many effects were significantly greater in patients with a longer duration of disease or with wAMD in both eyes. Some caregivers (unpaid) also reported that caregiving had a negative impact on them (31.1%); many reported emotions such as sadness (34.9%) and depression (24.4%), but many also felt useful (48.4%). Overall, 27.2% of caregivers (unpaid) rated caregiving as inconvenient; this was linked to days of employment/personal obligations missed. CONCLUSION: wAMD has a significant negative impact on the lives of patients, including vision-related depression, poor mobility, and limitations in day-to-day activities. The impact on nonprofessional caregivers may be underestimated in terms of emotional impact (such as depression) and loss of productivity.

Current barriers to treatment for wet age-related macular degeneration (wAMD): findings from the wAMD patient and caregiver survey.

PURPOSE: A cross-sectional survey to evaluate the current management of wet age-related macular degeneration (wAMD) and to identify barriers to treatment from a patient and caregiver perspective. METHODS: An ophthalmologist-devised questionnaire was given to a global cohort of patients who were receiving (or had previously received) antivascular endothelial growth factor injections and to caregivers (paid and unpaid) to evaluate the impact of wAMD on their lives. RESULTS: Responders included 910 patients and 890 caregivers; wAMD was diagnosed in both eyes in 45% of patients, and 64% had been receiving injections for > 1 year. Many caregivers were a child/grandchild (47%) or partner (23%) of the patient; only 7% were professional caregivers. Most (73%) patients visited a health care professional within 1 month of experiencing vision changes and 54% began treatment immediately. Most patients and caregivers reported a number of obstacles in managing wAMD, including the treatment itself (35% and 39%, respectively). Sixteen percent of patients also missed a clinic visit. CONCLUSION: Most patients seek medical assistance promptly for a change in vision; however, about a quarter of them do not. This highlights a lack of awareness surrounding eye health and the impact of a delayed diagnosis. Most patients and caregivers identified a number of obstacles in managing wAMD.

Improvement in vision-related function with intravitreal aflibercept: data from phase 3 studies in wet age-related macular degeneration.

PURPOSE: To evaluate the effect of intravitreal aflibercept injection on visual function in wet age-related macular degeneration (AMD). DESIGN: Prospective, multicenter, double-masked, active-controlled, parallel-group, randomized phase 3 clinical studies (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD [VIEW] 1 and 2 [clinicaltrials.gov identifiers, NCT00509795 and NCT00637377, respectively]). PARTICIPANTS: Patients (n=2419) with active, treatment-naïve, exudative AMD. This analysis included patients who received intravitreal aflibercept 2.0 mg every 8 weeks (2q8; n=607) or ranibizumab 0.5 mg every 4 weeks (0.5q4; n=595). INTERVENTION: Patients were randomized 1:1:1:1 to receive intravitreal aflibercept 2q8 (after 3 initial monthly doses), intravitreal aflibercept 2q4, intravitreal aflibercept 0.5q4, or ranibizumab 0.5q4 in the study eye. Patients in the intravitreal aflibercept 2q8 group received a sham injection alternating with active treatment. MAIN OUTCOME MEASURES: The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was administered at baseline and at weeks 12, 24, 36, and 52. The NEI VFQ-25 subscale scores were compared between intravitreal aflibercept 2q8 and ranibizumab 0.5q4 treatment arms, the approved dosing for each agent worldwide. Change in composite NEI VFQ-25 score was evaluated based on categorical change in visual acuity (worsened, unchanged, improved). RESULTS: Baseline NEI VFQ-25 scores were similar for both treatments in both studies. Mean change from baseline to 52 weeks was similar for ranibizumab 0.5q4 and intravitreal aflibercept 2q8 across all 12 subscales, with the greatest improvements noted for mental health and general vision (9.0-11.6 points, both treatments, both studies). Improvement of 4 points or more (both treatments, both studies) also was observed for subscales near vision, distance vision, role difficulties, and dependency. Mean change from baseline to 52 weeks in NEI VFQ-25 composite score (pooled data) stratified by clinical response showed meaningful improvement only in patients who gained 5 Early Treatment Diabetic Retinopathy letters or more (7.3 and 7.8 points for intravitreal aflibercept 2q8 and ranibizumab 0.5q4, respectively). CONCLUSIONS: Visual function outcomes were similar across all NEI VFQ-25 subscales over 52 weeks for intravitreal aflibercept 2q8 and ranibizumab 0.5q4, with clinically meaningful improvement recorded in 6 of 12 subscales.

Impact of estradiol valerate/dienogest on work productivity and activities of daily living in women with heavy menstrual bleeding.

OBJECTIVES: To quantify the change in work productivity and activities of daily living in North American women with heavy menstrual bleeding (HMB) treated with estradiol valerate/dienogest (E2V/DNG; Qlaira(®)/Natazia(®)) compared to placebo. METHODS: Women in the United States and Canada, aged 20-53 years with an objective diagnosis of HMB and no recognizable anatomical pathology, were treated with E2V/DNG or placebo for seven cycles (196 days). Main outcome measures included work productivity (i.e., productivity while at work) and activities of daily living measured using a modified Work Productivity and Activity Impairment Questionnaire (mWPAI) on a Likert scale from 0 to 10 (higher values denote higher impairment levels). RESULTS: In both countries, significant improvement was observed between baseline and end of treatment in work productivity and activities of daily living impairment. The improvements in work productivity and activities of daily living with E2V/DNG treatment relative to placebo ranged from 37.2% to 39.2% across both countries. Monthly gains due to E2V/DNG treatment (net of placebo improvement) associated with improvement in work productivity were estimated to be US$80.2 and Can$70.8 (US$58.5) and those associated with improvement in activities of daily living were estimated to be US$84.9 and Can$73.5 (US$60.7). CONCLUSIONS: E2V/DNG was shown to have a consistent positive impact on work productivity and activities of daily living in U.S. and Canadian women with HMB. In addition, these improvements in work productivity and activities of daily living were associated with a reduction in HMB-related monetary burden compared to the placebo group.

Impact of estradiol-valerate/dienogest on work productivity and activities of daily living in European and Australian women with heavy menstrual bleeding.

BACKGROUND: The purpose of this study was to quantify the impact of estradiol-valerate/dienogest (E(2)V/DNG; Qlaira(®)/Natazia(®)) on work productivity and activities of daily living in European and Australian women with heavy menstrual bleeding. METHODS: Women aged 18-54 years with a confirmed diagnosis of heavy menstrual bleeding and no recognizable pathology were recruited across nine European countries (the Czech Republic, Finland, Germany, Hungary, The Netherlands, Poland, Sweden, UK, and Ukraine) and Australia. The women were randomized to receive either E(2)V/DNG (n = 149) or placebo (n = 82) for seven treatment cycles (196 days). The outcomes assessed included work productivity (ie, productivity while at work) and activities of daily living, measured on a Likert scale from 0 to 10 (with higher values denoting higher impairment levels) at baseline and at the end of the third and seventh cycles (days 84 and 196). The equivalent monetary value associated with the changes in work productivity and activities of daily living was also calculated. RESULTS: Across all the countries, greater improvements from baseline to the end of treatment were observed with E(2)V/DNG treatment than placebo in work productivity (46.0% versus 15.1%) and activities of daily living (55.6% versus 30.8%). In 2008, savings associated with improvements in work productivity and activities of daily living due to E(2)V/DNG treatment (net of placebo improvement) were estimated to be between US$22-62 and US$18-56 per month (in purchasing power parity of US$), respectively. CONCLUSION: E(2)V/DNG has a consistent positive impact on work productivity and activities of daily living in European and Australian women with heavy menstrual bleeding. These improvements were associated with a reduction in monetary burden of heavy menstrual bleeding compared with the placebo group, consistent with the response to treatment observed.

Potential economic impact of increasing low dose aspirin usage on CVD in the US.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death in the US and Western Europe, but regular use of preventive low-dose aspirin has proven effective in preventing CVD events. The purpose of this study was to explore the potential economic impact in the US if preventive aspirin usage were to be increased in line with clinical guidelines for primary and secondary prevention. METHODS: The risk profile of the US population was characterized using NHANES data, and Framingham cardiovascular risk equations were applied to calculate risk for myocardial infarction, angina and ischemic stroke according to age and gender. Primary and secondary patients were considered separately. Using publicly available unit costs, a budget impact model calculated the annual impact of increased preventive aspirin usage considering gastrointestinal bleeding and hemorrhagic stroke adverse events and diminishing aspirin adherence over a 10-year time horizon. RESULTS: In a base population of 1,000,000 patients, full implementation of clinical guidelines would potentially prevent an additional 1273 myocardial infarctions, 2184 angina episodes and 565 ischemic strokes in primary prevention patients and an additional 578 myocardial infarctions, and 607 ischemic strokes in secondary prevention patients. This represents a total savings of $79.6 million for primary prevention and $32.2 million for secondary and additional out-of-pocket expense to patients of $29.0 million for primary prevention and $2.6 million for secondary prevention for the cost of aspirin. CONCLUSIONS: This budgetary model suggests that there is a strong economic case, both for payers and society, to encourage aspirin use for patients at appropriate risk and per clinical guidelines. It also provides an example of how minimizing costs do not necessarily have to imply a rationing of care. Limitations include the exclusion of other CVD interventions in the analysis.

Economic costs of overactive bladder in the United States.

OBJECTIVES: To calculate, from a societal perspective, current direct (medical and nonmedical) and indirect costs of overactive bladder (OAB) in the United States and project them to future years. Existing cost assessments of OAB in the United States are incomplete and outdated. METHODS: A prevalence-based model was developed incorporating age- and sex-specific OAB prevalence rates, usage data, and productivity data. On the basis of the information gathered from the recent 5 years of the medical literature, practice guidelines, Medicare and managed care fee schedules, and expert panel input, the annual per capita and total US costs were calculated for 2007. US census population forecasts were used to project the costs of OAB to 2015 and 2020. RESULTS: In 2007, average annual per capita costs of OAB were $1925 ($1433 in direct medical, $66 in direct nonmedical, and $426 in indirect costs). Applying these costs to the 34 million people in the United States with OAB results in total national costs of $65.9 billion (billion = 1000 million), ($49.1 billion direct medical, $2.3 billion direct nonmedical, and $14.6 billion indirect). Average annual per capita costs in 2015 and 2020 would be $1944 and $1969 and total national costs would be $76.2 billion and $82.6 billion, respectively. CONCLUSIONS: These data suggest that the economic burden of OAB is about 5-fold higher than older, noncomprehensive estimates. These costs are higher than previously published data for the United States and Europe because this analysis relies on more current data, real world age- and sex-specific treatment patterns and costs, and includes a more complete set of cost components.

Generation of a Danish TTO value set for EQ-5D health states.

AIMS: Health policy decisions should be based on national social preferences. In the absence of a set of Danish health preferences, patient outcome studies using the EQ-5D instrument have typically used UK health state valuations. This article describes the development of a Danish EQ-5D value set. METHODS: Regression modelling was based on Time Trade-Off (TTO) data derived from computer-assisted interviews conducted with 1,332 respondents from the Danish general population. Using a split-sample technique, 46 health states were directly valued by the respondents. Five different model types were tested and compared on statistical and theoretical grounds. Eleven different specifications were then tested for the chosen model type to identify the most appropriate model that had high explanatory power and parameters that were both consistent (positively signed) and statistically significant. RESULTS: An additive random effects model was found to be superior to ordinary least squares, fixed effects, random coefficient and censored Tobit modelling approaches. From the 11 model specifications tested, the TTO3 model (main effects model, without an N3 factor) performed best and was used to generate a Danish set of health state preferences. CONCLUSIONS: An additive random effects model appears to adequately generate a Danish set of EQ-5D health state preferences. The model has high explanatory power and produces consistent and significant parameters for EQ-5D dimensions and levels. It is recommended that this value set be used in Danish cost-utility studies using EQ-5D.

Measuring the impact of diabetes through patient report of treatment satisfaction, productivity and symptom experience.

OBJECTIVE: Diabetes is a common, debilitating chronic illness with multiple impacts. The impact on treatment satisfaction, productivity impairment and the symptom experience may be among the most important for patient-reported outcomes. This study developed and validated disease-specific, patient-reported measures for these outcomes that address limitations in currently available measures. METHODS: Data was collected from the literature, experts and patients and a conceptual model of the patient-reported impact of diabetes was created. Item pools, based on the conceptual model, were then generated. The items were administered to 991 diabetes patients via a web-based survey to perform item reduction, identify relevant factor structures and assess reliability and validity following an a-priori analysis plan. RESULTS: All validation criteria and hypotheses were met resulting in three new, valid measures: a 21-item Satisfaction Measure (three sub-scales: burden, efficacy and symptoms), a 30-item Symptom Measure and a 14-item Productivity Measure assessing both life and work productivity impairments. CONCLUSION: This triad of measures captures important components of the multifaceted diabetes patient experience and can be considered as valid, viable options when choosing measures to assess patient-reported outcomes. Addressing these outcomes may assist researchers and clinicians to develop more patient-centered diabetes interventions and care.

Cost-effectiveness of detemir-based basal/bolus therapy versus NPH-based basal/bolus therapy for type 1 diabetes in a UK setting: an economic analysis based on meta-analysis results of four clinical trials.

BACKGROUND: A meta-analysis of results from four clinical trials in type 1 diabetes patients showed that insulin detemir (IDet)-based basal/bolus treatment of type 1 diabetes led to improved HbA1c (0.15%-points lower), reduced risk of major hypoglycaemic events (by 2%) and reduction in body mass index (BMI) (0.26 kg/m2) compared to protamine Hagedorn human (NPH) insulin-based basal/bolus therapy in type 1 patients. METHODS: A published, validated, peer-reviewed Markov simulation model (the CORE Diabetes Model) projected short-term results obtained from the fixed-effects (weighted average) meta-analysis to long-term incidence of complications, improvements in quality-adjusted life years (QALY), long-term costs and the cost-effectiveness for IDet combinations versus NPH combinations in type 1 diabetes patients. Probabilities of complications and HbA1c-dependent adjustments were derived from the DCCT and other studies. Costs of treating complications in the UK were retrieved from published sources. Total direct costs (complications + treatment costs) for each arm were projected over patient lifetimes from a UK National Heath Service perspective. Both costs and clinical outcomes were discounted at 3.5% annually. RESULTS: Improved glycaemic control, decreased hypoglycaemic events and BMI with IDet-based basal/bolus therapy led to fewer diabetes-related complications, an increase in quality-adjusted life expectancy of 0.09 years, increased total lifetime costs/patient of 1707 pounds sterling and an incremental cost-effectiveness ratio of 19,285 pounds sterling per QALY gained. Results were stable under a wide range of reasonable assumptions. CONCLUSIONS: Short-term improvements seen with IDet combinations versus NPH combinations led to decreased complications, improvements in QALYs and reductions in complication costs, which partially offset the additional costs of detemir, leading to a cost-effectiveness ratio which fell within a range considered to represent excellent value for money (< 35,000 pounds sterling/QALY gained).

Ability to perform activities of daily living is the main factor affecting quality of life in patients with dementia.

BACKGROUND: Dementia is a chronic illness associated with a progressive loss of cognitive and intellectual abilities, such as memory, judgment and abstract thinking. The objective of this study was to assess the health utilities of patients with dementia in Europe and identify the key factors influencing their Health-Related Quality of Life (HRQol). METHODS: This study used cross-sectional data from the Odense study; a Danish cohort of patients aged 65-84 living in Odense, Denmark. A total of 244 patients with mild to severe dementia were interviewed together with a caregiver about their health status and activities of daily living (ADL). Alzheimer's disease was diagnosed according to the NINCDS-ADRDA criteria for probable dementia. Vascular dementia and other types of dementia were diagnosed according to the DSM-IIIR criteria. Severity of dementia was defined by score intervals on the Mini Mental State Examination score: mild (MMSE 20-30), moderate (MMSE 10-19), and severe (MMSE 0-9). Based on the ADL information, the patients' dependency level was defined as either dependent or independent. Questions from the Odense Study were mapped into each of the five dimensions of the EQ-5D in order to assess patients' HRQol. Danish EQ-5D social tariffs were used to value patients' HRQol.A regression analysis of EQ-5D values was conducted with backward selection on gender, age, severity, ADL level and setting in order to determine the main factor influencing HRQoL. RESULTS: The EQ-5D weight in patients independent upon others in ADL was 0.641 (95% CI: [0.612-0.669]), and in those dependent upon others was 0.343 (95% CI: [0.251-0.436]). CONCLUSION: Dependency upon others to perform ADL was the main factor affecting HRQoL.