Understanding the migraine treatment landscape prior to the introduction of calcitonin gene-related peptide inhibitors: Results from the Assessment of TolerabiliTy and Effectiveness in MigrAINe Patients using Preventive Treatment (ATTAIN) study.

BACKGROUND: Calcitonin gene-related peptide (CGRP) inhibitors were introduced in the United States (US) in 2018. To understand the changing patterns of preventive treatment following the introduction of these new agents, we must first characterize the patterns which preceded their introduction. OBJECTIVE: To characterize the burden, unmet need, and treatment patterns in patients with migraine initiating preventive migraine medications before the introduction of CGRP inhibitors in the US. METHODS: Between March 2016 and October 2017, we enrolled episodic (EM) and chronic migraine (CM) patients initiating or changing preventive treatment at primary care or neurology clinic visits in the US, in a real-world observational study using a prospective cohort design. At baseline and monthly thereafter for 6 months, we collected data from study sites and patients on migraine frequency, treatment modifications, migraine impact on functioning, and work productivity for a descriptive analysis of migraine patient experience and treatment patterns. RESULTS: From the sample of 234 completers, 118 had EM (50.4%) and 116 had CM (49.6%). Mean age at enrollment was 41 years (SD = 12) and mean age at first migraine diagnosis was 22 years (SD = 11). Most participants were females (n = 204/234; 87.2%) and white (n = 178/234; 76.1%). The majority (n = 164/234; 70.1%) had not used preventive migraine treatment in the 5 years prior to enrollment (treatment naïve). At baseline, mean monthly migraine days were 9.6 days (SD = 5.0) for the preventive treatment naïve group and 12.4 days (SD = 7.0) for treatment experienced patients. The majority had severe Migraine Disability Assessment (Grade IV, total score ≥21), including 67.1% (n = 110/164) of the preventive treatment naïve and 77.1% (n = 54/70) of the preventive treatment experienced patients. Headache Impact Test total scores indicating severe impairment (score >59) occurred in 88.4% (n = 145/164) of the treatment naïve and 88.6% (n = 62/70) of treatment experienced patients. Mean work productivity loss as measured by the Work Productivity and Activity Impairment questionnaire in the subsample of employed patients was 53.3% loss. The most used acute medications at baseline were nonsteroidal anti-inflammatory agents (n = 124/234; 53.0%), acetaminophen-based products (n = 112/234; 47.9%), and triptans (n = 105/234; 44.9%). The most commonly initiated preventive treatments were topiramate (n = 100/234; 42.7%), tricyclic antidepressants (n = 39/234; 16.7%), beta-blockers (n = 26/234; 11.1%), and onabotulinumtoxinA (n = 24/234; 10.3%). Over the 6-month follow-up period, almost half of patients (n = 116/234, 49.6%) modified their preventive treatment and discontinued treatment (n = 88/312 total modifications; 28.2%) or modified their pattern of use by increasing, decreasing, or skipping doses (n = 224/312 total modifications; 71.8%), often without seeking medical advice. Avoiding side effects was the main reason reported among patients who discontinued (n = 52/88; 59.1%), decreased frequency or dose (n = 37/89; 41.6%), and skipped doses (n = 29/86; 33.7%). Perceived lack of efficacy was another frequent reason reported among those who discontinued (n = 20/88; 22.7%), decreased frequency or dose (n = 15/89; 16.9%), and skipped doses (n = 18/86; 20.9%). Despite initiation of preventive treatment and improvements observed in number of headache and migraine days, migraine patients continued to experience substantial disability, headache impact, and reduced productivity throughout the 6-month follow-up period. CONCLUSIONS: Prior to 2018, the burden of migraine was high for patients initiating preventive treatments. Despite having more than 9 days of migraine per month on average, the majority (70.1%) of patients initiating prevention had been treatment naïve, indicating underuse of preventive treatments. The preventive treatments used in this study were poorly tolerated and were reported by patients to lack efficacy, resulting in suboptimal adherence. The high discontinuation rates suggest that the preventive medications being offered during the period of the study did not meet the treatment needs of patients. In addition, the decisions by about half of patients to alter their prescribed treatment plan without consulting their provider can pose substantial health risks. These findings pertain to the broad set of preventive treatments initiated in this study and do not support inferences about individual preventive treatments, due to limitations in sample size. These findings suggest the need for more effective and better tolerated preventive treatment options.

The association of lung function and St. George's respiratory questionnaire with exacerbations in COPD: a systematic literature review and regression analysis.

BACKGROUND: This study investigated the relationship between changes in lung function (as measured by forced expiratory volume in one second [FEV1]) and the St. George's Respiratory Questionnaire (SGRQ) and economically significant outcomes of exacerbations and health resource utilization, with an aim to provide insight into whether the effects of COPD treatment on lung function and health status relate to a reduced risk for exacerbations. METHODS: A systematic literature review was conducted in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials of adult COPD patients published in English since 2002 in order to relate mean change in FEV1 and SGRQ total score to exacerbations and hospitalizations. These predictor/outcome pairs were analyzed using sample-size weighted regression analyses, which estimated a regression slope relating the two treatment effects, as well as a confidence interval and a test of statistical significance. RESULTS: Sixty-seven trials were included in the analysis. Significant relationships were seen between: FEV1 and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.001); between FEV1 and moderate-to-severe exacerbations (time to first exacerbation, patients with at least one exacerbation, or annualized rate, p = 0.045); between SGRQ score and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.0002) and between SGRQ score and moderate-to-severe exacerbations (time to first exacerbation or patients with at least one exacerbation, p = 0.0279; annualized rate, p = 0.0024). Relationships between FEV1 or SGRQ score and annualized exacerbation rate for any exacerbation or hospitalized exacerbations were not significant. CONCLUSIONS: The regression analysis demonstrated a significant association between improvements in FEV1 and SGRQ score and lower risk for COPD exacerbations. Even in cases of non-significant relationships, results were in the expected direction with few exceptions. The results of this analysis offer health care providers and payers a broader picture of the relationship between exacerbations and mean change in FEV1 as well as SGRQ score, and will help inform clinical and formulary-making decisions while stimulating new research questions for future prospective studies.

Impact of female acne on patterns of health care resource utilization.

BACKGROUND: Limited data are available on acne treatment patterns in females through their adult years. OBJECTIVE: The purpose of this analysis was to evaluate health care resource utilization (HRU) and treatment patterns in cohorts with and without the use of acne medication and predictors of use. METHODS: A cross-sectional, web-based survey was administered to US females (25-45 years) with facial acne (≥ 25 visible lesions). Data collected included: sociodemographics and self-reported clinical characteristics, acne treatments, and health care professional (HCP) visits. Subject characteristics associated with medication use were examined by logistic regression. RESULTS: Approximately half of the total sample (N=208, mean age: 35 ± 6) ever visited an HCP for acne and reported more over-the counter (OTC) medication use (51.0%) than prescription (Rx) medication use (15.4%). Subjects did not use medications daily, averaging from 12-18 days over the previous 4 weeks. Logistic regression showed that race and prior HCP visits for acne were significant predictors of medication use (P<.05). CONCLUSIONS: Adult females generally self-treated their acne using primarily OTC medications; however, poor compliance was observed for Rx and OTC. Race and prior HCP visits for acne were significant predictors of current medication use.

Patterns of use and reasons for discontinuation of prophylactic medications for episodic migraine and chronic migraine: results from the second international burden of migraine study (IBMS-II).

OBJECTIVE: Our objective was to characterize patterns of preventive medication use in persons with episodic migraine (EM) and chronic migraine (CM). BACKGROUND: Several classes of medications are used both on- and off-label for the prevention of migraine, including ß-blockers (eg, propranolol, timolol), tricyclic antidepressants (eg, amitriptyline), anti-epileptic drugs (eg, topiramate, valproic acid), and neurotoxins (eg, onabotulinumtoxinA). METHODS: Preventive medication use and reasons for discontinuation were collected in an international, Web-based, cross-sectional survey of adults with migraine during 2010. Descriptive analyses were conducted on demographics and headache-related disability as measured by the Migraine Disability Assessment Scale, stratified by use of preventive medication, and EM or CM. Univariate and multivariate logistic regression models were constructed to assess predictors of preventive medication use. RESULTS: One thousand one hundred and sixty-five respondents completed the survey. Only 28.3% of EM and 44.8% of CM respondents were currently using preventive medication; any use of prophylaxis (prior or current) was reported by 43.4% of those with EM and 65.9% with CM. The mean number of prophylactic medications ever used was 2.92 for EM and 3.94 for CM. Antidepressants were used most frequently (EM 60.9%; CM 54.7%), followed by ß-blockers (EM 35.4%; CM 36.8%) and anti-epileptics (EM 28.6%; CM 36.3%). Odds of preventive medication use were higher among CM than EM, adjusting for age, gender, race, years of daily headache, and country (odds ratio 2.72; 95% confidence interval 2.15 to 3.57). Greater headache-related disability and older age were also associated with greater odds of ever having used prophylaxis, regardless of headache frequency. CONCLUSIONS: Less than half the persons with EM and CM were currently using preventive medication for migraine, with treatment rates being higher for CM, as expected. Those with CM tried more medications than those with EM, possibly reflecting higher levels of treatment need.

Item selection, reliability and validity of the Shortness of Breath with Daily Activities (SOBDA) questionnaire: a new outcome measure for evaluating dyspnea in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible, progressive obstruction of lung airflow. Dyspnea (shortness of breath [SOB]) is the COPD symptom which most negatively impacts patients' daily activities. To assess how SOB affects daily activities, 37 items were drafted through focus group discussions and cognitive interviews with COPD patients to develop a patient-reported outcome instrument: the Shortness of Breath with Daily Activities questionnaire (SOBDA). Psychometric analysis was conducted to reduce the number of items and evaluate the measurement properties of the final SOBDA. METHODS: Prospective, observational study of 334 COPD patients, recruited from 24 pulmonology and internal medicine clinics in the United States. The 37-item SOBDA was administered to patients each evening for 28 days using an electronic diary. Patients answered every item and rated their level of SOB experienced that day during specific activities. Item selection was conducted by examining item characteristics, dimensionality, and Rasch model analysis results. The decision to delete an item was based on psychometric evidence, content validity, and expert clinical input. The final SOBDA instrument was evaluated for internal consistency, reproducibility, convergent validity, known-groups validity, and responsiveness. RESULTS: Twenty-four items from the 37-item pool were removed following the item selection process: nine items were removed due to high item-to-item correlations; five due to floor effects; three due to infrequent activity; one due to gender bias; two due to low factor loadings; three due to unordered response options; and one due to expert's discretion. Internal consistency and reproducibility of the final SOBDA were demonstrated by Cronbach Alpha = 0.87, and intra-class correlation coefficient = 0.91. Convergent validity was demonstrated by high correlation with the CRQ-SAS (0.60) and SGRQ-C (0.61). Known groups validity was demonstrated by significant difference between ratings of the mMRC and clinical global rating of severity. Evaluation of the ability to detect change was not performed owing to too few responders at the end of the study. CONCLUSIONS: Through the empirical item reduction process, 13 items were selected from the 37-item pool generated during qualitative development. The final 13-item SOBDA is a reliable and valid instrument for use in clinical trials.

Patients' experience and utilization patterns of diclofenac gel in Germany: a real-world study with a prospective longitudinal survey and a retrospective analysis of pharmacy data.

OBJECTIVE: Describe and characterize treatment patterns, satisfaction, improvement in pain and functional impairment (health-related quality of life [HRQoL]) in users of over the counter (OTC) Voltaren gel diclofenac (VGD) 2.32% and 1.16% in a real-world setting. METHODS: This observational real-world German study had prospective and retrospective components. The prospective data were collected from electronic surveys completed by adults who purchased VGD to treat their musculoskeletal pain at baseline and 4 and 12 weeks after baseline. Retrospective data were from a 12-month (March 2019 to February 2020) abstraction from dispensing software platforms used in select German pharmacies. RESULTS: Surveys from 467 participants (mean age 60.8 years) were analyzed. Average pain severity at baseline was 6.0 on an 11-point Numeric Rating Scale (0 = no pain, 10 = worst possible pain), improving by 0.8 and 1.2 points at Weeks 4 and 12, respectively. Performance of functional activities (daily/physical/social activities and errands/chores) improved and the proportion of participants with at least moderate interference decreased at both follow-up timepoints. Retrospective analyses indicated that majority of patients receiving VGD (n = 95,085) were ≥65 years old (67.9%), had one dispensed tube (70.8%) and did not switch to another topical treatment (including other NSAIDs) (77.3%), and were co-prescribed at least one cardiovascular medication (74.3%). CONCLUSIONS: This study provides the first real-world insights into OTC VGD use in Germany. The participants using VGD reported a decrease in pain severity and an improvement of HRQoL while under treatment, as well as resulting satisfaction with treatment. Patients infrequently switched to alternate topical therapies/NSAIDs.

Standardizing measurement of chronic obstructive pulmonary disease exacerbations. Reliability and validity of a patient-reported diary.

RATIONALE: Although exacerbations are an important problem in chronic obstructive pulmonary disease (COPD) and a target of intervention, there is no valid, standardized tool for assessing their frequency, severity, and duration. OBJECTIVES: This study tested the properties of the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a new patient-reported outcome diary. METHODS: A prospective, two-group, observational study was conducted in patients with COPD. The acute group (n = 222) was enrolled during a clinic visit for exacerbation with follow-up visits on Days 10, 29, and 60. The stable group (n = 188), recruited by telephone or during routine visits, was exacerbation free for at least 60 days. MEASUREMENTS AND MAIN RESULTS: Acute patients completed the diary on Days 1-29 and 60-67; stable patients for 7 days. All patients provided stable-state spirometry and completed the St. George Respiratory Questionnaire-COPD (SGRQ-C). Acute patient assessments included clinician and patient global ratings of exacerbation severity and recovery. Mean age of the sample (n = 410) was 65 (± 10) years; 48% were male; stable FEV1 was 51% predicted (± 20). Internal consistency (Pearson separation index) for the EXACT was 0.92, 1-week reproducibility (stable patients; intraclass correlation) was 0.77. EXACT scores correlated with SGRQ-C (r = 0.64; P < 0.0001) and differentiated acute and stable patients (P < 0.0001). In acute patients, scores improved over time (P < 0.0001) and differentiated between degrees of clinician-rated exacerbation severity (P < 0.05). EXACT change scores differentiated responders and nonresponders on Day 10, as judged by clinicians or patients (P < 0.0001). CONCLUSIONS: Results suggest the EXACT is reliable, valid, and sensitive to change with exacerbation recovery.

The International Burden of Migraine Study (IBMS): study design, methodology, and baseline cohort characteristics.

OBJECTIVE: To describe a survey methodology to evaluate headache characteristics and burden and to present baseline characteristics for the international cohort of survey participants. METHODS: A targeted, web-based methodology was used to recruit and survey subjects with migraine in 10 countries. Based on reported symptoms, subjects meeting ICHD-2 criteria for migraine were included; eligible subjects were classified as chronic (≥ 15 headache days per month) or episodic (< 15 headache days per month). Outcomes included sociodemographic and clinical characteristics, resource utilization, disability, health-related quality of life, anxiety, depression and productivity. RESULTS: Of 23,312 survey respondents, 11,897 were eligible and 9715 (81.7%) completed the survey; subjects were 81.5% female; 5.7% (n = 555) had chronic migraine. CONCLUSIONS: This is the first large international cohort of persons with chronic and episodic migraine studied using a web-based approach, a methodology well suited to the study of the burden of migraines.

Cost of health care among patients with chronic and episodic migraine in Canada and the USA: results from the International Burden of Migraine Study (IBMS).

OBJECTIVE: To evaluate and compare healthcare resource use and related costs in chronic migraine and episodic migraine in the USA and Canada. BACKGROUND: Migraine is a common neurological disorder that produces substantial disability for sufferers around the world. Several studies have quantified overall costs associated with migraine in general, with recent estimates ranging from $581 to $7089 per year. Although prior studies have characterized the clinical and humanistic burden of chronic migraine relative to episodic migraine, to the best of our knowledge only 1 previous study has compared chronic migraine and episodic migraine healthcare costs. The purpose of this study was to quantify and compare the direct medical costs of chronic migraine and episodic migraine using medical resource use data collected as part of the International Burden of Migraine Study. METHODS: Cross-sectional data were collected from respondents in 10 countries via a Web-based survey. Respondents were classified as chronic migraine (≥15 headache days/month) or episodic migraine (<15 headache days/month). Data collection included socio-demographic and clinical characteristics and medical resource use for headache (clinician and emergency department visits and hospitalizations over the preceding 3 months and medications over the preceding 4 weeks). Unit cost data were collected outside of the Web-based survey using publicly available sources and then applied to resource use profiles. Cost estimates are presented in 2010 US and Canadian dollars. RESULTS: In this manuscript, the analysis included data from respondents with migraine in the USA (N=1204) and Canada (N=681). The most common medical services utilized by all respondents included headache-specific medication, healthcare provider visits, emergency department visits, and diagnostic testing. In the USA, approximately one-quarter (26.2%) of chronic migraine participants vs 13.9% of episodic migraine participants reported visiting a primary care physician in the preceding 3 months (P<.001). In Canada, one-half (48.2%) of chronic migraine participants had a primary care physician visit, compared with 12.3% of episodic migraine subjects (P< .0001). Total mean headache-related costs for participants with chronic migraine in the USA were $1036 (±$1334) over 3 months compared to $383 (±807, P< .001) for persons with episodic migraine. In Canada, total mean headache-related costs among chronic migraine subjects were $471 (±1022) compared to $172 (±920, P< .001) for episodic migraine subjects. CONCLUSIONS: Chronic migraine was associated with higher medical resource use and total costs compared to episodic migraine. Therapies that reduce headache frequency could become important approaches for containing or reducing headache-related medical costs.

Development of the EXAcerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT): a patient-reported outcome (PRO) measure.

BACKGROUND: This article describes the qualitative methods used to develop the EXAcerbation of Chronic Pulmonary Disease Tool (EXACT), a new patient-reported outcome (PRO) instrument for evaluating frequency, severity, and duration of exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: Focus groups and interviews were conducted in the United States with COPD patients treated for exacerbations during the past 6 months. Participants were asked to describe exacerbation attributes, care-seeking cues, and indications of progression and recovery. An iterative process was used to identify themes in the data to inform instrument content and structure. Cognitive debriefing interviews were performed to evaluate and revise the draft item pool. Experts in COPD, instrument development, and clinical research participated in the process. RESULTS: Eighty-three subjects participated in elicitation focus groups or interviews (n=48); elicitation interviews with cognitive debriefing (n=23), or cognitive interviews alone (n=12). Mean age of the sample was 65 years (SD=10); 45% were male; mean FEV-1% predicted was 44% (SD=16). Participants characterized exacerbations as a persistent increase in the severity of respiratory symptoms and other systemic manifestations accompanied by a dramatic reduction in activity. Specific attributes included shortness of breath, chest congestion, cough, sputum, chest discomfort, feeling weak or tired, sleep disturbances, and concern or worry. The diary card of 23 candidate items was debriefed in booklet and electronic format. CONCLUSIONS: Qualitative data from patients and input from experts formed the basis of the EXACT's structure and item pool, ready for empirically based item reduction and reliability and validity testing.

Retrospective claims study of fluticasone propionate/salmeterol fixed-dose combination use as initial asthma controller therapy in children despite guideline recommendations.

BACKGROUND: According to current asthma treatment guidelines, single-entity inhaled corticosteroids (ICSs) should be used as initial controller therapy in children with mild to moderate persistent asthma. Long-acting beta(2)-agonists (LABAs) can be added to therapy for those patients whose asthma is not well controlled with a single-entity ICS. OBJECTIVES: The goal of this study was to examine whether the claims history for children in a US insured population indicate proper fluticasone propionate/ salmeterol (FPS) fixed-dose combination use in accordance with recommended asthma guidelines and a US Food and Drug Administration (FDA) advisory and black box warning regarding LABA use. A comparison of study-drug charges was also conducted. METHODS: Data from a US commercial insurance database were used in this retrospective study to evaluate pharmacy and medical claims for children between October 2004 and September 2006 (ie, the index period). An index date corresponding to the date of the first FPS claim was assigned to each patient. Eligible patients were aged 4 to 11 years and had >/=1 pharmacy claim for FPS during the index period. Those patients receiving 1 FPS prescription dose strength on the index date who were continuously enrolled for benefits during the preindex period (ie, the 365 days before the index date) were included in the study. Disease severity was assigned based on asthma-related pharmacy (frequency and/or incidence of oral corticosteroid, LABA, montelukast, and >365 doses of a short-acting beta(2)-agonist) and medical (asthma-related urgent care clinic or emergency department visits or hospitalizations) claim histories during the preindex period. RESULTS: A total of 13,306 patients between the ages of 4 and 11 years on the index date were included in the study; their mean (SD) age was 8.9 (1.9) years. The majority of the patients were male (60.7%). Of the total FPS claims, 55.2% were for patients with no evidence of pharmacy or medical claims in the 365 days before the first FPS claim that would warrant ICS/LABA combination therapy according to asthma treatment guidelines. There were no large changes in preindex ICS claims over the course of the study in response to an FDA-issued advisory and black box warning regarding the use of LABAs. Median drug charges for single-entity ICS use were $98 compared with $168 for FPS therapy. CONCLUSIONS: ICS/LABA combination treatment was used as initial therapy in 55.2% of children with mild to moderate asthma in this claims database population, contrary to the recommendations of current asthma treatment guidelines. The FDA advisory and black box warning for LABA use had little observed impact on the number of single-entity ICS claims.

Women manifest more severe COPD symptoms across the life course.

BACKGROUND: Previous studies suggest that gender differences exist in COPD diagnosis and symptoms; these differences may be more pronounced in younger adults. Our objective was to explore age-associated gender differences across a range of COPD severities. MATERIALS AND METHODS: A total of 4,484 current and former smokers with COPD from the Genetic Epidemiology of COPD cohort were investigated using regression modeling to explore the association between gender, age, disease severity, and the contributing elements of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification system (symptoms, exacerbation risk, airflow limitation). RESULTS: The age-gender interaction was observed across multiple age categories. Compared to men with COPD, younger women with COPD had a greater likelihood of more severe dyspnea, airflow limitation, greater risk for exacerbations, and categorization in GOLD groups B and D. These differences were less pronounced in older women with COPD. However, older women remained more likely to experience severe dyspnea and to manifest more severe COPD (B vs A) than older men, despite lower pack-years of smoking. CONCLUSION: These data demonstrate the significant symptom burden of COPD in women, especially younger women. More research is needed to understand the pathogenesis of increased severity of COPD in women and to develop gender-targeted clinical assessment and management approaches to improve outcomes for women and men with COPD at all ages.

Initiation of triple therapy maintenance treatment among patients with COPD in the US.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids) for patients with only the most severe COPD. Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated. Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy. Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines. PATIENTS AND METHODS: This retrospective study used claims from the IMS PharMetrics Plus database from 2009 to 2013. Cohort 1 was selected to assess Objective 1 only; descriptive analyses were conducted in Cohort 2 to answer Objective 2. A validated claims-based algorithm and severity and frequency of exacerbations were used as proxies for COPD severity. RESULTS: Of all 199,678 patients with COPD in Cohort 1, 7.5% received triple therapy after diagnosis, and 25.5% of all treated patients received triple therapy. In Cohort 2, 30,493 COPD patients (mean age =64.7 years) who initiated triple therapy were identified. Using the claims-based algorithm, 34.5% of Cohort 2 patients were classified as having mild disease (GOLD 1), 40.8% moderate (GOLD 2), 22.5% severe (GOLD 3), and 2.3% very severe (GOLD 4). Using exacerbation severity and frequency, 60.6% of patients were classified as GOLD 1/2 and 39.4% as GOLD 3/4. CONCLUSION: In this large US claims database study, one-quarter of all treated COPD patients received triple therapy. Although triple therapy is recommended for the most severe COPD patients, spirometry is infrequently assessed, and a majority of the patients who receive triple therapy may have only mild/moderate disease. Any potential overprescribing of triple therapy may lead to unnecessary costs to the patient and health care system.

Acne treatment patterns, expectations, and satisfaction among adult females of different races/ethnicities.

BACKGROUND: Limited data are available on acne treatment patterns, expectations, and satisfaction in the adult female subpopulation, particularly among different racial and ethnic groups. OBJECTIVE: Describe acne treatment patterns and expectations in adult females of different racial/ethnic groups and analyze and explore their potential effects on medication compliance and treatment satisfaction. METHODS: A cross-sectional, Web-based survey was administered to US females (25-45 years) with facial acne (≥25 visible lesions). Data collected included sociodemographics, self-reported clinical characteristics, acne treatment use, and treatment expectations and satisfaction. RESULTS: Three hundred twelve subjects completed the survey (mean age, 35.3±5.9 years), comprising black (30.8%), Hispanic (17.6%), Asian/other (17.3%), and white (34.3%). More than half of the subjects in each racial group recently used an acne treatment or procedure (black, 63.5%; Hispanic, 54.5%; Asian/other, 66.7%; white, 66.4%). Treatment use was predominantly over-the-counter (OTC) (47.4%) versus prescription medications (16.6%). OTC use was highest in white subjects (black, 42.7%; Hispanic, 34.5%; Asian/other, 44.4%; white, 59.8%; P<0.05). The most frequently used OTC treatments in all racial/ethnic groups were salicylic acid (SA) (34.3%) and benzoyl peroxide (BP) (32.1%). Overall, compliance with acne medications was highest in white versus black (57.0±32.4 vs 42.7±33.5 days, P>0.05), Hispanic (57.0±32.4 vs 43.2±32.9 days, P>0.05), and Asian/other (57.0±32.4 vs 46.9±37.2 days, P>0.05) subjects. Most subjects expected OTC (73.7%) and prescription (74.7%) treatments to work quickly. Fewer than half of the subjects were satisfied with OTC treatment (BP, 47.0%; SA, 43.0%), often due to skin dryness (BP, 26.3%; SA, 44.3%) and flakiness (BP, 12.3%; SA, 31.1%). No statistically significant differences were observed among racial/ethnic groups in their level of satisfaction with OTC or prescription acne treatments. CONCLUSION: Racial/ethnic differences were observed in acne treatment patterns in adult females, while treatment expectations were similar. Results indicate that treatment patterns and expectations may impact treatment satisfaction and medication compliance.

Acne-Related Quality of Life Among Female Adults of Different Races/Ethnicities.

BACKGROUND: Acne impairs quality of life, but its effect on different races/ethnicities is unclear. This study evaluated racial/ethnic differences in acne-related quality of life and psychological symptoms among female adults. METHODS: A Web-based survey was conducted with U.S. female adults (25-45 years old) with facial acne (≥25 visible lesions). Outcomes included sociodemographics, clinical characteristics, acne-related quality of life (Acne-Specific Quality of Life Questionnaire), psychological symptoms (Patient Health Questionnaire), and work/school productivity. Racial/ethnic differences were evaluated using descriptive statistics and analysis of variance/chi-square analyses. RESULTS: Three-hundred twelve subjects (Black = 30.8%, Hispanic = 17.6%, Asian/other = 17.3%, White = 34.3%) completed the survey (mean age = 35.3 ± 5.9 years). Acne negatively impacted quality of life for all subjects. Black subjects reported significantly less negative impact on self-perception versus Asian/other (Black = 12.6 ± 9.9, Asian/other = 8.4 ± 8.6; p = .05). Social functioning was less negatively impacted in White and Black subjects versus Asian/other (White = 12.7 ± 7.5, Asian/other = 8.4 ± 7.8, p < .05; Black = 12.1 ± 9.2, Asian/other = 8.4 ± 7.8, p = .06). Over one third (total sample = 40.7%, Black = 31.3%, Hispanic = 36.4%, Asian/other = 50.0%, White = 46.7%) reported moderate/severe anxiety/depression symptoms. Acne also impacted ability to concentrate on work/school. CONCLUSION: Racial/ethnic differences were observed in acne-related quality of life and psychological symptoms in female adults; acne negatively impacted self-perceptions and social/emotional functioning.

Racial differences in clinical characteristics, perceptions and behaviors, and psychosocial impact of adult female acne.

OBJECTIVE: Limited data are available on racial differences in clinical characteristics and burden in adult female acne. The objective was to describe racial differences in clinical characteristics, psychosocial impact, perceptions, behaviors, and treatment satisfaction in facial adult female acne. DESIGN: Cross-sectional, web-based survey. SETTING: Diverse sample of United States women. PARTICIPANTS: Women between the ages of 25 and 45 years with facial acne (≥25 visible lesions). MEASUREMENTS: Outcomes included sociodemographic characteristics, psychosocial impacts, perceptions, behaviors, and treatment satisfaction. Racial differences were evaluated using descriptive statistics and t-test/chi-square analyses. RESULTS: 208 females participated (mean age 35±6 years); 51.4 percent were White/Caucasian and 48.6 percent were non-White/Caucasian women [Black/African American (n=51); Hispanic/Latina (n=23); Asian (n=16); Other (n=ll)]. Age of acne onset (mean 14.8±5 vs. 17.0±8 years, p<0.05) and acne concern occurred earlier (16.6±7 vs. 19.3±9 years, p<0.05) in White/Caucasian than non-White/Caucasian subjects. Facial acne primarily presented on chin (28.0%) and cheeks (30.8%) for White/Caucasian women versus cheeks (58.4%) for non-White/Caucasian women. Non-White/Caucasian women experienced more postinflammatory hyperpigmentation than White/Caucasian women (p<0.0001). Facial acne negatively affected quality of life (QoL) in both groups, and most participants (>70%) reported some depression/anxiety symptoms. More White/Caucasian than non-White/Caucasian women were troubled by facial acne (88.8% vs. 76.2%, p<0.05). Lesion clearance was most important to White/Caucasian women (57.9 vs. non-White/Caucasian 31.7%, p<0.001); non-White/Caucasian females focused on postinflammatory hyperpigmentation clearance (41.6% vs. Caucasian 8.4%, p<0.0001). CONCLUSION: RESULTS highlight racial differences in participant-reported clinical characteristics, attitudes, behaviors, and treatment satisfaction. These findings may inform clinicians about racial differences in facial adult female acne and guide treatment recommendations toward improving care.

Shortness of Breath with Daily Activities questionnaire: validation and responder thresholds in patients with chronic obstructive pulmonary disease.

OBJECTIVES: To test the reliability, validity and responsiveness of the 13-item Shortness of Breath with Daily Activities (SOBDA) questionnaire, and determine the threshold for response and minimal important difference (MID). DESIGN: 6 week, randomised, double-blind, placebo-controlled study. SETTING: 40 centres in the USA between 29 October 2009 and 1 July 2010. PRIMARY AND SECONDARY OUTCOME MEASURES: 547 patients with chronic obstructive pulmonary disease (COPD) were enrolled and 418 entered the 2-week run-in period. Data from the run-in period were collected to test internal consistency, test-retest reliability, convergent validity and known-groups validity of the SOBDA. Three hundred and sixty six patients were randomised 2:2:1 to fluticasone propionate/salmeterol 250/50 µg, salmeterol 50 µg or placebo, twice daily. Results from the SOBDA questionnaire, Patient Global Assessment of Change Question, modified Medical Research Council Dyspnoea Scale (mMRC), Clinician Global Impression of Dysponea Severity (CGI-S), Clinician Global Impression of Change Question and Chronic Respiratory Disease Questionnaire self-administered standardised version (CRQ-SAS) were evaluated; spirometry and safety parameters were measured. Study endpoints were selected to investigate the cross-sectional and longitudinal validity of the SOBDA questionnaire in relation to the clinical criteria. RESULTS: Internal consistency of the SOBDA questionnaire (Cronbach α) was 0.89. Test-retest reliability (intraclass correlation) was 0.94. The SOBDA weekly scores correlated with the patient-reported and clinician-reported mMRC, CGI-S and CRQ-SAS dyspnoea domain scores (0.29, 0.24, 0.24 and -0.68, respectively). The SOBDA weekly scores differentiated between the responders and the non-responders as rated by the patients and the clinicians. Anchor-based and supportive distribution-based analyses produced a range of the potential values for the threshold for the responders and MID. CONCLUSIONS: The 13-item SOBDA questionnaire is reliable, valid and responsive to change in patients with COPD. On using anchor-based methods, the proposed responder threshold shows a -0.1 to -0.2 score change. A specific threshold value will be identified as more data are generated from future clinical trials. TRIAL REGISTRATION: NCT00984659; GlaxoSmithKline study number: ASQ112989.

Health economics and outcomes research within drug development: challenges and opportunities for reimbursement and market access within biopharma research.

Healthcare decision makers who determine funding for new medical technologies depend on manufacturers to provide evidence of the technology's efficacy, safety and cost-effectiveness. Constrained budgets and increasing reliance on formal health technology assessment (HTA) have created an abundance of external hurdles that manufacturers must navigate to ensure successful product commercialization. These demands have pushed pharmaceutical companies to adjust their internal structures to coordinate generation of appropriate evidence. In this article we summarize internal and external opportunities for manufacturers to establish a foundation of evidence for successful market access, starting in Phase I of development and continuing throughout the post-approval product lifecycle.

A new measure of caregiver burden in Alzheimer's disease: the caregiver-perceived burden questionnaire.

OBJECTIVE: To validate the Caregiver-Perceived Burden Questionnaire (CPBQ) and report its psychometric properties. METHODS: The CPBQ was administered to caregivers of patients with moderate-to-severe AD in a double-blind randomized trial comparing extended-release memantine to placebo (n = 676). Measurement properties were analyzed using factor analysis, classical test theory, and Rasch analysis. RESULTS: Two subscales were identified: the Caregivers' Assessment of the Patient (CAP) and the Caregivers' Assessment of Themselves (CAT). The reliability was .89 (CAP) and .83 (CAT). The CAP scores were significantly correlated (r > .3) with scores from the Severe Impairment Battery (SIB) and the Neuropsychiatric Inventory (NPI). The CAT scores were significantly correlated with NPI scores. The CAT discriminated among patients by clinician-rated severity and significantly differentiated between responders and nonresponders. CONCLUSION: The CPBQ appears to be a reliable, valid, and responsive measure that enables linking caregiver's perceptions about burden and patient function in patients with moderate-to-severe AD.

Characterizing and quantifying the symptomatic features of COPD exacerbations.

BACKGROUND: There is a need for a standardized, valid, and reliable instrument for quantifying exacerbations of COPD. The objective of this study was to identify symptom items that characterize COPD exacerbations to form a new patient diary for evaluating exacerbation frequency, severity, and duration. METHODS: Twenty-three symptom items identified from patient interviews were administered to 410 patients with COPD aged (mean ± SD) 65 ± 10 years with stable FEV(1) of 51% predicted ± 20% predicted and 1.8 ± 1.8 exacerbations in the preceding 12 months. A total of 222 patients had a physician-diagnosed exacerbation; 188 were stable. Item-level analyses (floor and ceiling effects, criterion keying, item-total correlation) were used in the first stage of item reduction. Further reduction was conducted using Rasch model and descriptive item analyses. Exploratory factor analysis was performed on the items that survived the exclusion process. RESULTS: No item behaved differently between stable and exacerbation conditions. One item was removed after item-level analysis, and eight were removed following Rasch analysis. Together, the surviving 14 items met the criteria for a unidimensional measure of exacerbation severity. Internal consistency (person separation index) was excellent at 0.92. Post hoc exploratory factor analysis revealed one dominant factor, with three domains (breathlessness, cough and sputum, and chest symptoms) that accounted for 68% of the variance. CONCLUSIONS: An exacerbation appears to be a quantitative rather than qualitative change from the stable state. This analysis identified a range of symptoms that form a unidimensional construct of overall exacerbation severity. The 14 items identified form the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a daily diary for detecting and quantifying exacerbation severity in COPD.