Informal Care Time and Cost in a Large Clinical Trial Sample of Patients with Mild to Moderate Alzheimer's Disease: Determinants and Level of Change Observed.

INTRODUCTION: We evaluate the association between caregiver (informal) time/cost and illness severity from two recently completed clinical trials of an investigational drug for Alzheimer's disease (AD). METHODS: Changes from baseline caregiver time were calculated and treatment effects analyzed using a restricted maximum likelihood-based mixed model for repeated measures. Four separate models were then estimated to examine the association between caregiver time costs and the clinical endpoints measured during the trials, including cognition (MMSE), function (DAD), behavior (NPI), global disability (CDR) and dependence (DS). RESULTS: Caregiver time cost was significantly associated with all clinical measures of illness severity with a 1-unit change in MMSE, DAD, NPI, CDR and DS associated with a 11.57%, 4.81-4.97%, 3.58-3.67%, 42.52% and 71.05% change, respectively, in primary caregiver time cost. The association between caregiver time cost and DS was the strongest of all the associations examined. CONCLUSION: Caregiver time costs increase with increasing AD severity in all key domains of AD (cognition, function, behavior, global disability and dependence on others). Our analysis demonstrated that patient dependence is a particularly important predictor of caregiver time costs and should be considered as a potential outcome measure in intervention clinical trials in AD. FUNDING: Pfizer Inc. and Janssen Alzheimer Immunotherapy Research and Development.

Psychometric properties of the Dependence Scale in large randomized clinical trials of patients with mild and moderate Alzheimer's disease.

OBJECTIVE: The need for assistance from others is a hallmark concern in Alzheimer's disease (AD). The psychometric properties of the Dependence Scale (DS) for measuring treatment benefit were investigated in large randomized clinical trials of patients with mild to moderate AD. METHODS: Reliability, validity, and responsiveness of the DS were examined. Path models appraised relationships and distinctiveness of key AD measures. The responder definition was empirically derived. RESULTS: Generally acceptable reliability (α ≥ .65), significant (P < .001) known-groups tests, and moderate to strong correlations (r ≥ .31) confirmed the DS psychometric properties. Path models supported relationships and distinctiveness of key AD measures. A DS change of ≤ 1 point for patients with limited home care and ≤ 2 points for patients with assisted living care best described stability of the level of dependence on caregivers. CONCLUSION: The DS is a psychometrically robust measure in mild to moderate AD. The empirically derived responder definition aids in the interpretation of DS change.

Dependence as a unifying construct in defining Alzheimer's disease severity.

This article reviews measures of Alzheimer's disease (AD) progression in relation to patient dependence and offers a unifying conceptual framework for dependence in AD. Clinicians typically characterize AD by symptomatic impairments in three domains: cognition, function, and behavior. From a patient's perspective, changes in these domains, individually and in concert, ultimately lead to increased dependence and loss of autonomy. Examples of dependence in AD range from a need for reminders (early AD) to requiring safety supervision and assistance with basic functions (late AD). Published literature has focused on the clinical domains as somewhat separate constructs and has given limited attention to the concept of patient dependence as a descriptor of AD progression. This article presents the concept of dependence on others for care needs as a potential method for translating the effect of changes in cognition, function, and behavior into a more holistic, transparent description of AD progression.

Prevalence and impact of dementia-related functional limitations in the United States, 2001 to 2005.

These analyses examined the relationship between dementia and comorbid conditions with respect to degree of functional impairment and emotional impact. Analyses were conducted using National Health Interview Survey (2001 through 2005) data from a subset of individuals aged > or =60 years with activity limitations attributed to dementia, senility, or Alzheimer disease compared with those whose limitations were attributed to other conditions. The mean number of limited activities was 6.84 (95% confidence interval: 6.48-7.20) for persons with dementia-related limitations and 4.87 (95% confidence interval: 4.81-4.93) for those with limitations not dementia related. Both groups reported similar prevalence of diabetes, acute myocardial infarction, heart disease, prostate cancer, breast cancer, angina, and emphysema; respondents with dementia-related functional limitations were more likely to report diabetes, depression or anxiety, and vision problems as being related to functional limitations. Persons with dementia-related functional limitations were also more likely than persons with non-dementia-related functional limitations to report feeling sad, hopeless, worthless, nervous, and that "everything is an effort." Improving or maintaining functional independence in patients with dementia will likely require a multifaceted approach across disease states. Additional research will help define the impact of dementia on the development and progression of functional limitations related to comorbidities.

Burden of Alzheimer's disease and association with negative health outcomes.

OBJECTIVE: To examine the association of Alzheimer's disease (AD) with common chronic conditions, acute care events, and risk of hospitalization. STUDY DESIGN: Retrospective matched cohort analysis. METHODS: Community-dwelling subjects with a diagnosis of and/or medication for AD were matched to subjects without AD based on age, sex, and geographic region. Administrative claims from commercially insured health plans for medical and pharmacy services provided from January 1, 2000, to March 31, 2006 (inclusive) were analyzed. The Deyo Charlson Index (DCI) was used to assess the number of chronic conditions. The outcomes of interest were risk of fractures and hospitalization. RESULTS: Among 5396 persons with AD and a matched cohort of 5396 persons without the condition, subjects with AD were more likely to have a diagnosis for any of the DCI components, had a higher rate of fractures (17.7% vs 7.9%, P <.00) and other urgent medical events (eg, pneumonia 14.0% vs 6.3%, P <.00), and were more likely to be hospitalized (odds ratio = 1.7; 95% confidence interval = 1.5, 1.9). There were significant differences in the medication use between the 2 groups, with the use of psychotics/tranquilizers 9-fold higher among persons with AD. CONCLUSION: Persons with AD have higher odds of experiencing a fracture, being hospitalized, and requiring other acute care medical services than those without AD. The disease also is associated with a higher prevalence of common chronic conditions.

Older Americans' risk-benefit preferences for modifying the course of Alzheimer disease.

Alzheimer disease (AD) is a progressive, ultimately fatal neurodegenerative illness affecting millions of patients, families, and caregivers. Effective disease-modifying therapies for AD are desperately needed, but none currently exist on the market. Thus, accelerating the discovery, development, and approval of new disease-modifying drugs for AD is a high priority for individuals, physicians, and medical decision makers. Potentially disease-modifying drugs likely will have significant therapeutic benefits but also may have treatment-related risks. We quantified older Americans' treatment-related risk tolerance by eliciting their willingness to accept the risk of treatment-related death or permanent severe disability in exchange for modifying the course of AD. A stated-choice survey instrument was administered to 2146 American residents 60 years of age and older. On average, subjects were willing to accept a 1-year risk of treatment-related death or permanent severe disability from stroke of over 30% for a treatment that prevents AD from progressing beyond the mild stage. Thus, most people in this age cohort are willing to accept considerable risks in return for disease-modifying benefits of new AD drugs. These results are consistent with other studies indicating that individuals view AD as a serious, life threatening illness that imposes heavy burdens on both patients and caregivers.

Patient dependence and longitudinal changes in costs of care in Alzheimer's disease.

BACKGROUND/AIMS: To examine the incremental effect of patients' dependence on others, on cost of medical and nonmedical care, and on informal caregiving hours over time. METHODS: Data are obtained from 172 patients from the Predictors Study, a large, multicenter cohort of patients with probable Alzheimer disease (AD) followed annually for 4 years in 3 University-based AD centers in the USA. Enrollment required a modified Mini-Mental State Examination score >or=30. We examined the effects of patient dependence (measured by the Dependence Scale, DS) and function (measured by the Blessed Dementia Rating Scale, BDRS) on medical care cost, nonmedical care cost, and informal caregiving time using random effects regression models. RESULTS: A one-point increase in DS score was associated with a 5.7% increase in medical cost, a 10.5% increase in nonmedical cost, and a 4.1% increase in caregiving time. A one-point increase in BDRS score was associated with a 7.6% increase in medical cost, a 3.9% increase in nonmedical cost and an 8.7% increase in caregiving time. CONCLUSIONS: Both functional impairment and patient dependence were associated with higher costs of care and caregiving time. Measures of functional impairment and patient dependence provide unique and incremental information on the overall impact of AD on patients and their caregivers.

The effects of patient function and dependence on costs of care in Alzheimer's disease.

OBJECTIVES: To estimate incremental effects of patients' dependence and function on costs of care during the early stages of Alzheimer's disease (AD) and to compare strengths of their relationships with different cost components. DESIGN: Multicenter, cross-sectional, observational study. SETTING: Three university hospitals in the United States. PARTICIPANTS: One hundred seventy-nine community-living patients with probable AD, with modified Mini-Mental State Examination scores of 30 or higher. MEASUREMENTS: Patients' dependence was measured using the Dependence Scale (DS). Functional capacity was measured using the Blessed Dementia Rating Scale (BDRS). Total cost was measured by summing direct medical costs and informal costs. Direct medical costs included costs of hospitalization, outpatient treatment and procedures, assistive devices, and medications. Informal costs were estimated from time spent helping with basic and instrumental activities of daily living for up to three caregivers per patient using national average hourly earnings as wage rate. RESULTS: DS and BDRS were associated with higher total cost; a 1-point increase in DS was associated with a $1,832 increase in total cost, and a 1-point increase in BDRS was associated with a $3,333 increase. Examining component costs separately identified potential differences between DS and BDRS. A 1-point increase in BDRS was associated with a $1,406 increase in direct medical cost. A 1-point increase in DS was associated with a $1,690 increase in informal cost. CONCLUSION: Patients' dependence and function related differently to direct medical and informal cost, suggesting that measures of function and dependence provided unique information for explaining variations in cost of care for patients with AD, highlighting the value in measuring both constructs.

Risk of recurrent emergency department visits or hospitalizations in children with asthma receiving nebulized budesonide inhalation suspension compared with other asthma medications.

OBJECTIVE: To examine whether nebulized budesonide inhalation suspension treatment reduces asthma-related emergency department visit/hospitalization recurrence risk in children compared with other asthma medications, particularly non-nebulized inhaled corticosteroids. RESEARCH DESIGN AND METHODS: Longitudinal, retrospective claims analysis of data from a managed care organization database in the United States (July 1, 2000-June 30, 2002). Participants were children aged < or = 8 years with an asthma diagnosis and asthma-related emergency department visit or hospitalization (index event). Asthma medication use, evaluated by asthma-related prescriptions < or = 30 days after the index event, determined treatment groups. MAIN OUTCOME MEASURE: Emergency department visit/hospitalization recurrence risk from post-index day 31-180 across treatment groups. RESULTS: Of 10,176 patients with an index event, 13% experienced a post-index recurrence. For patients receiving asthma prescriptions < or = 30 days after the index event, those receiving budesonide inhalation suspension showed a significant reduction in emergency department visit/hospitalization recurrence risk compared with those not prescribed this treatment (adjusted hazard ratio, 0.71; 95% confidence interval, 0.57-0.89). For patients receiving asthma controller medication in the post-index period, those receiving budesonide inhalation suspension had a significantly lower recurrence risk than patients receiving prescriptions for other controller medications (hazard ratio, 0.71; 95% confidence interval, 0.52-0.97). Recurrence risk was significantly reduced (53%) in patients receiving budesonide inhalation suspension prescriptions compared with non-nebulized inhaled corticosteroid prescriptions (hazard ratio, 0.47; 95% confidence interval, 0.28-0.78). CONCLUSION: For children aged < or = 8 years, budesonide inhalation suspension treatment after an asthma-related emergency department visit/hospitalization was associated with a significantly reduced risk of recurrence compared with other asthma medications and with non-nebulized inhaled corticosteroids. Because this was an observational study, results should be interpreted cautiously. However, this study allowed evaluation of treatment in real-world practice settings not often included in clinical trials.

Inhaled corticosteroids vs leukotriene receptor antagonists: health care costs across varying asthma severities.

BACKGROUND: The burden of asthma is substantial, and the overall cost of its management is growing. OBJECTIVE: To compare asthma-related charges and resource utilization across disease severity levels in the year after initial asthma treatment with any inhaled corticosteroid (ICS) or leukotriene receptor antagonist (LTRA). METHODS: This was a longitudinal, retrospective cohort study of claims data from managed care plans in the United States. All patients had a new prescription for an ICS or an LTRA between January 1999 and December 2000 and were enrolled in a managed care plan for at least 12 months before (preindex) and 12 months after (postindex) the initial claim. Asthma-related charges, hospitalizations, emergency department (ED) visits, physician visits, and asthma medication use were compared between the 2 cohorts. Propensity scores were calculated to control for baseline differences in patient characteristics and types of health care coverage. RESULTS: Claims from 31,860 patients were evaluated. Total postindex asthma-related charges were significantly lower in the ICS cohort than in the LTRA cohort (dollars 613 vs dollars 902, respectively; P < .001), as were asthma-related pharmacy charges (dollars 305 vs dollars 564, respectively; P < .001). Results were consistent for all propensity subclasses and all age groups. CONCLUSIONS: Results from this cohort study suggest that, across varying disease severities, treating asthma with an ICS as initial controller therapy leads to less health care resource utilization than does using an LTRA as initial therapy.

Inhaled corticosteroid use and outcomes in pregnancy.

BACKGROUND: Current asthma management guidelines recommend aggressive asthma treatment for women who are pregnant. OBJECTIVE: To examine asthma medication use and asthma-related health care use before and during pregnancy. METHODS: Women aged 15 to 45 years with a pregnancy claim (index event) and an asthma claim (diagnosis or asthma medication prescription) were identified from a database of US managed care organizations (PharMetrics Patient-Centric Database). Medical claims 6 months before and after the index event were studied to determine the impact of pregnancy on asthma medication use (ie, prescription claims) and asthma-related physician visits, emergency department (ED) visits, and hospitalizations. RESULTS: Of 7,235 women with a pregnancy claim and 6 months of preindex and postindex data, 633 had an asthma claim (334 had an asthma-related medication claim and 299 had no asthma-related medication claim before the index event). During the preindex period, 142 patients were using asthma controller medications, with inhaled corticosteroids (ICSs) the most commonly used controller (n = 101); 283 were using short-acting beta2-adrenergic agonists (SABAs) with or without controllers. Among the 334 patients using asthma medication before pregnancy, the number using any controller decreased from 142 to 94 (-34%), those using ICSs decreased from 101 to 65 (-36%), and those using SABAs decreased from 283 to 137 (-52%) after the pregnancy claim. For these 334 patients, the number with an asthma-related ED visit increased from 14 to 17 (21%) after the pregnancy claim. Among those without a pharmacy record of medication use before pregnancy (n = 299), the number with an asthma-related ED visit increased from 4 to 7 (75%) after the pregnancy claim. For the 101 patients using ICSs before pregnancy, the number with an asthma-related physician visit decreased from 39 to 25 (-36%) and the number with an ED visit was unchanged. For the 532 patients not using an ICS before pregnancy, the number with an asthma-related physician visit increased from 84 to 107 (27%) and the number with an ED visit increased from 12 to 18 (50%). CONCLUSION: For patients using an ICS before pregnancy, the rate of asthma-related physician visits decreased and the number of ED visits was unchanged after pregnancy, whereas physician and ED visits increased after pregnancy for patients not using an ICS before pregnancy. Overall, the data suggest that asthma is undertreated in women contemplating pregnancy and in those who are pregnant.

Patient preferences for sensory attributes of intranasal corticosteroids and willingness to adhere to prescribed therapy for allergic rhinitis: a conjoint analysis.

BACKGROUND: Sensory attributes of intranasal corticosteroid (INS) products vary. OBJECTIVE: To evaluate patient preferences for INS sensory attributes and the degree to which attributes influence patients' willingness to adhere to therapy. METHODS: We conducted a cross-sectional study with 120 individuals across 4 US allergy/immunology clinics. Respondents chose between pairs of hypothetical INSs differing in sensory attribute composition. We measured the strength of preferences for 6 sensory attributes (smell, taste, aftertaste, throat rundown, nose runout, and feel of spray in nose or throat). Preferences were measured for 3 intensity levels of each sensory attribute (eg, no taste, weak taste, and strong taste). Other outcomes included an importance score for each sensory attribute and patients' willingness to adhere to therapy with an INS with the lowest intensity levels of each sensory attribute vs one with moderate intensity levels. RESULTS: Preferences decreased with increasing intensity levels of each sensory attribute. Aftertaste was the most important attribute in 28% of patients, taste in 19%, throat rundown in 18%, nose runout in 12%, smell in 11%, and feel of spray in 7%. If instructed to take an INS daily for 3 months, 77% of patients stated that they would definitely be able to follow their physician's advice (willingness to adhere) if given one containing the lowest level of each sensory attribute vs 4% if given one having moderate levels (P < .01). CONCLUSIONS: Patient preferences are inversely related to increasing intensity levels of sensory attributes and affect patients' willingness to adhere to therapy. Application of patient preferences when selecting INSs could improve adherence.

Evaluating the efficiency of treatment in the allergic rhinitis market.

BACKGROUND: In the present era of increasing health care expenditures, economic comparisons of therapeutic products play an important role in ensuring that limited health care resources are used appropriately. OBJECTIVE: To provide a model for the comparative analysis of alternative treatments, in terms of both cost and efficacy, in allergic rhinitis that will provide decision makers in a managed care environment an additional tool to help maximize health care benefit per dollar spent. We also review current treatments in the allergic rhinitis market and their impact on cost, availability, and utilization. SUMMARY: Efficacy estimates were derived from published reviews, meta-analyses, and guidelines, and cost data are based on average wholesale prices. Our results indicate that when cost and efficacy data are plotted on a cost-effectiveness plane, the intranasal corticosteroids appear to be the most efficient use of health care resources. Moreover, budesonide aqueous nasal spray was found to be the most efficient treatment for allergic rhinitis when compared with 3 other leading intranasal corticosteroids used at their recommended starting doses, the less-sedating/nonsedating antihistamines, and a leukotriene receptor antagonist. CONCLUSION: Evaluating products on an efficiency frontier platform, which integrates both the effectiveness and cost of products, will allow health plan decision makers to ensure the appropriate allocation of health care resources.

Cost efficiency of intranasal corticosteroid prescribing patterns in the management of allergic rhinitis.

BACKGROUND: Effective treatment of seasonal or perennial allergic rhinitis often requires use of topical intranasal corticosteroids (INSs). Despite differences in recommended starting dosages, the 4 leading INSs by market share are packaged in bottles containing 120 metered-dose sprays. OBJECTIVE: To determine the relative prescribed dosages of the leading INSs and compare economic differences resulting from these prescribing behaviors. METHODS: The IMS National Disease and Therapeutic Index (NDTI) was used to identify prescribing habits for the 4 leading INSs: fluticasone propionate nasal spray (FPNS), mometasone furoate aqueous nasal spray (MFNS), triamcinolone acetonide aqueous nasal spray (TANS), and budesonide aqueous nasal spray (BANS). The NDTI uses a national, randomly drawn, 2-stage stratified clustersampling methodology. Physicians are sampled during the first stage, with 2 workdays per month subsampled from each physician in the second stage. Each physician reports on all patient contacts during the 2 consecutive days, offering a continuing compilation of statistical information about patterns and treatment of disease encountered by office-based physicians. In a given month, the NDTI reports on 1180 unique physicians. RESULTS: From January 1, 2002, to December 31, 2002, 58% of prescriptions for FPNS were for 4 sprays daily with 37% for 2 sprays daily, MFNS: 44% for 4 sprays and 52% for 2, TANS: 65% for 4 sprays and 31% for 2, and BANS: 29% for 4 sprays and 68% for 2. These equated to mean prescribed daily dosages of 3.47 sprays per day for FPNS, 3.33 for MFNS, 3.50 for TANS, and 2.73 for BANS. Because each INS is packaged in a bottle with 120 metered-dose sprays, the differences in dosage offer varying days of supply per unit filled. BANS offered the most days of treatment (44 days), followed by MFNS (38 days) and FPNS and TANS (means of 35 and 34 days, respectively) per single prescription filled. Cost per day of treatment was calculated by multiplying the prescribed dosage with the average wholesale price of the products. BANS had the lowest cost per day of treatment at US dollars 1.54, with each other INS costing at least an additional US dollars 0.26 daily (MFNS US dollars 1.80; FPNS US dollars 1.88; TANS US dollars 1.97). CONCLUSION: Based on physician prescribing patterns of INSs from the NDTI database, BANS offers more days of treatment at a lower cost per day than other leading INSs.