Development and validation of a novel patient-reported outcome measure in people with episodic migraine and chronic migraine: The Activity Impairment in Migraine Diary.

OBJECTIVE: To evaluate the content validity and psychometric properties of the Activity Impairment in Migraine Diary (AIM-D). BACKGROUND: Measuring treatment effects on migraine impairment requires a psychometrically sound patient-reported outcome (PRO) measure developed consistent with U.S. Food and Drug Administration guidance. METHODS: The AIM-D was created from concepts that emerged during qualitative interviews with five clinicians experienced in treating migraine and concept elicitation (CE) interviews with 40 adults with episodic migraine (EM) or chronic migraine (CM). The initial version was refined based on three waves of cognitive interviews with 38 adults with EM or CM and input from a panel of clinical and measurement experts. The AIM-D was psychometrically evaluated using data from 316 adults with EM or CM who participated in a 13-week prospective observational study. Study participants completed PRO assessments including the AIM-D and a daily headache diary. Exploratory and confirmatory factor analysis were used to determine the factor structure. The reliability, validity, and responsiveness of the AIM-D were assessed. Additional PRO measures including the Patient Global Impression - Severity (PGI-S), Migraine Specific Quality of Life Questionnaire, Version 2.1 Role Function-Restrictive domain, and Headache Impact Test were used for psychometric evaluation of the AIM-D. RESULTS: Based on CE interviews with adults with migraine and input from an expert panel, activity impairment was identified as the target in the preliminary conceptual framework, which had two domains: performance of daily activities (PDAs) and physical impairment (PI). Revision of the draft AIM-D through multiple rounds of cognitive interviews and expert panel meetings resulted in a content valid 11-item version. Exploratory factor analysis supported both one- and two-domain structures for the AIM-D, which were further supported by confirmatory factor analysis (factor loadings all >0.90). The AIM-D domains (PDA and PI) and total score showed high internal consistency reliability (Cronbach's alpha 0.95-0.97), acceptable test-retest reliability for weekly average scores (intraclass correlation coefficient >0.60 for participants with no change in PGI-S between baseline and week 2), and good convergent and known-groups validity. There was evidence of responsiveness based on changes in PGI-S score and monthly migraine days. CONCLUSION: The AIM-D is a content valid and psychometrically sound measure designed to evaluate activity impairment and is suitable for use in clinical trials of preventive treatments for EM or CM.

Evaluation of the 6-item Identify Chronic Migraine screener in a large medical group.

OBJECTIVE: To evaluate the sensitivity and specificity of the 6-item Identify Chronic Migraine screener (ID-CM[6]), designed to improve the detection of chronic migraine (CM). BACKGROUND: CM is often undertreated and underdiagnosed. Survey-based studies have found that approximately 75-80% of people meeting criteria for CM do not report having received an accurate diagnosis. METHODS: This study used claims data of patients enrolled in a large medical group who had at least one medical claim with an International Classification of Diseases 9th/10th revision diagnostic code for migraine in the 12-month prescreening period. The Identify Chronic Migraine survey was administered by e-mail, in-person, or over the telephone to all enrolled patients. A Semi-Structured Diagnostic Interview (SSDI) was administered by telephone by a trained physician. The ID-CM(6) and SSDI classifications of CM status were compared to evaluate sensitivity and specificity of the ID-CM(6) screening tool. RESULTS: The analysis of the ID-CM(6) screening tool included 109 patients, with 65/109 (59.6%) positive for CM based on the SSDI. The mean (standard deviation) age of the patient sample was 49 (15) years and 100/109 (91.7%) were female. Using the SSDI as the diagnostic gold standard, the ID-CM(6) had a sensitivity of 70.8% (46/65) and a specificity of 93.2% (41/44). CONCLUSION: The ID-CM(6) demonstrated acceptable sensitivity and good specificity in determining CM status. The results of this analysis support the real-world utility of the ID-CM(6) as a simple and useful tool to identify patients with CM.

Comparison of healthcare resource utilization and costs among patients with migraine with potentially adequate and insufficient triptan response.

BACKGROUND: Triptans are the most commonly prescribed acute treatments for migraine; however, not all triptan users experience adequate response. Information on real-world resource use and costs associated with triptan insufficient response are limited. METHODS: A retrospective claims analysis using US commercial health plan data between 2012 and 2015 assessed healthcare resource use and costs in adults with a migraine diagnosis newly initiating triptans. Patients who either did not refill triptans but used other non-triptan medications or refilled triptans but also filled non-triptan medications over a 24-month follow-up period were designated as potential triptan insufficient responders. Patients who continued filling only triptans (i.e. triptan-only continuers) were designated as potential adequate responders. All-cause and migraine-related resource use and total (medical and pharmacy) costs over months 1-12 and months 13-24 were compared between triptan-only continuers and potential triptan insufficient responders. RESULTS: Among 10,509 new triptan users, 4371 (41%) were triptan-only continuers, 3102 (30%) were potential triptan insufficient responders, and 3036 (29%) did not refill their index triptan or fill non-triptan medications over 24 months' follow-up. Opioids were the most commonly used non-triptan treatment (68%) among potential triptan insufficient responders over 24 months of follow-up. Adjusted mean all-cause and migraine-related total costs were $5449 and $2905 higher, respectively, among potential triptan insufficient responders versus triptan-only continuers over the first 12 months. CONCLUSIONS: In a US commercial health plan, almost one-third of new triptan users were potential triptan insufficient responders and the majority filled opioid prescriptions. Potential triptan insufficient responder patients had significantly higher all-cause and migraine-related healthcare utilization and costs than triptan-only continuers.

Acute treatment patterns in patients with migraine newly initiating a triptan.

BACKGROUND: Triptans are the most commonly used acute treatment for migraine. This study evaluated real-world treatment patterns following an initial triptan prescription to understand refill rates and use of non-triptan medications for the acute treatment of migraine. METHODS: Commercially-insured adult patients over 18 years of age with a triptan prescription between 1/1/2013 to 31/12/2013 were identified from the Optum Clinformatics™ Data Mart database, with date of the first triptan fill designated as index date. Inclusion was limited to those with no fills for a triptan in the 12 months prior to index date (i.e. new users or initiators of triptans) and continuous enrollment in the 12 months pre- and 24 months post-index date. Fills for index triptan, non-index triptan, and other acute treatments for migraine were assessed for up to 24 months post-index. RESULTS: Among 10,509 patients, 50.8% did not refill the initial triptan within 12 months and 43.6% did not refill within 24 months. In the 12 months post-index, 90.5% of patients used only one type of triptan, 8.4% used two different triptans, and 1.0% used three or more triptans. Among patients with and without a triptan refill, use of opioids (39% vs. 42%), non-steroidal anti-inflammatory drugs (22% vs. 22%), and butalbital-containing products (9% vs. 10%) were similar. CONCLUSION: More than half of those who newly initiated a triptan did not refill their initial prescription, and less than 1 in 10 used two or more triptans within 12 months. High rates of non-triptan acute medication use were found over 12 and 24 months of follow-up, most commonly opioids.

Ubrogepant, an Acute Treatment for Migraine, Improved Patient-Reported Functional Disability and Satisfaction in 2 Single-Attack Phase 3 Randomized Trials, ACHIEVE I and II.

OBJECTIVE: To evaluate the efficacy of ubrogepant on patient-reported functional disability, satisfaction with study medication, and global impression of change. BACKGROUND: Ubrogepant is a small-molecule, oral calcitonin gene-related peptide receptor antagonist indicated for the acute treatment of migraine. In 2 phase 3 trials (ACHIEVE I and II), ubrogepant demonstrated efficacy vs placebo on the 2 co-primary endpoints of headache pain freedom and absence of the most bothersome migraine-associated symptom at 2 hours post dose for the 50 and 100 mg doses. Patient-reported outcomes, such as functional disability, satisfaction, and patient global impression of change, can provide additional evidence of the efficacy of an acute treatment for migraine on clinically meaningful and patient-relevant outcomes. METHODS: ACHIEVE I and ACHIEVE II were multicenter, randomized, double-blind, placebo-controlled, parallel-group, single-attack trials in adults (18-75 years) with migraine. In ACHIEVE I, participants were randomized 1:1:1 to placebo or ubrogepant 50 or 100 mg; in ACHIEVE II, participants were randomized 1:1:1 to placebo or ubrogepant 25 or 50 mg to treat a migraine attack with moderate or severe headache pain. Participants rated ability to perform daily activities on the Functional Disability Scale, before dosing and at 1, 2, 4, and 8 hours after the initial dose; satisfaction with study medication at 2 and 24 hours; and impression of overall change in migraine on the Patient Global Impression of Change scale at 2 hours. In prespecified analyses for each trial, each outcome was compared between each ubrogepant dose group and the relevant placebo group. Data were pooled from the ubrogepant 50 mg and placebo groups of the 2 trials in a post hoc analysis. RESULTS: In ACHIEVE I, 559 participants were randomized to placebo, 556 to ubrogepant 50 mg, and 557 to ubrogepant 100 mg; in ACHIEVE II, 563 were randomized to placebo, 561 to ubrogepant 25 mg, and 562 to ubrogepant 50 mg. At 2 hours post dose, significantly higher proportions of ubrogepant-treated participants vs placebo-treated participants reported being able to function normally (ACHIEVE I: ubrogepant 50 mg, 40.6% [171/421], P = .0012 vs placebo; ubrogepant 100 mg, 42.9% [192/448], P < .0001 vs placebo; placebo, 29.8% [136/456]; ACHIEVE II: ubrogepant 25 mg, 42.6% [185/434], P = .0015 vs placebo; ubrogepant 50 mg, 40.5% [188/464], P = .0118 vs placebo; placebo, 34.2% [156/456]; pooled 50 mg, 40.6% [359/885], vs pooled placebo, 32.0% [292/912]; P < .0001), were satisfied/extremely satisfied with study medication (ACHIEVE I: 50 mg, 36.3% [147/405], P < .0001 vs placebo; 100 mg, 35.8% [149/416], P = .0002 vs placebo; placebo, 24.1% [104/432]; ACHIEVE II: 25 mg, 35.1% [141/402], P = .0018 vs placebo; 50 mg, 37.8% [163/431], P < .0001 vs placebo; placebo, 24.8% [106/427]; pooled ubrogepant 50 mg, 37.1% [310/836], vs pooled placebo, 24.5% [210/859]; P < .0001), and indicated that their migraine was much/very much better on the Patient Global Impression of Change scale (ACHIEVE I: 50 mg, 34.4% [103/299], P = .0006 vs placebo; 100 mg, 34.3% [102/297], P = .0009 vs placebo; placebo, 22.0% [69/313]; ACHIEVE II: 25 mg, 34.1% [124/364], P < .0001 vs placebo; 50 mg, 33.4% [131/392], P = .0002 vs placebo; placebo, 20.7% [78/376]; pooled 50 mg, 33.9% [234/691], vs pooled placebo, 21.3% [147/689]; P < .0001). CONCLUSIONS: A significantly higher proportion of participants treated with ubrogepant were able to function normally, were satisfied with the study medication, and reported clinically meaningful improvement compared with those receiving placebo. The results reinforce the potential benefits of ubrogepant on patient-centered outcomes in the acute treatment of migraine.

Development of a claims-based algorithm to identify potentially undiagnosed chronic migraine patients.

OBJECTIVE: To develop a claims-based algorithm to identify undiagnosed chronic migraine among patients enrolled in a healthcare system. METHODS: An observational study using claims and patient survey data was conducted in a large medical group. Eligible patients had an International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) migraine diagnosis, without a chronic migraine diagnosis, in the 12 months before screening and did not have a migraine-related onabotulinumtoxinA claim in the 12 months before enrollment. Trained clinicians administered a semi-structured diagnostic interview, which served as the gold standard to diagnose chronic migraine, to enrolled patients. Potential claims-based predictors of chronic migraine that differentiated semi-structured diagnostic interview-positive (chronic migraine) and semi-structured diagnostic interview-negative (non-chronic migraine) patients were identified in bivariate analyses for inclusion in a logistic regression model. RESULTS: The final sample included 108 patients (chronic migraine = 64; non-chronic migraine = 44). Four significant predictors for chronic migraine were identified using claims in the 12 months before enrollment: ≥15 versus <15 claims for acute treatment of migraine, including opioids (odds ratio = 5.87 [95% confidence interval: 1.34-25.63]); ≥24 versus <24 healthcare visits (odds ratio = 2.80 [confidence interval: 1.08-7.25]); female versus male sex (odds ratio = 9.17 [confidence interval: 1.26-66.50); claims for ≥2 versus 0 unique migraine preventive classes (odds ratio = 4.39 [confidence interval: 1.19-16.22]). Model sensitivity was 78.1%; specificity was 72.7%. CONCLUSIONS: The claims-based algorithm identified undiagnosed chronic migraine with sufficient sensitivity and specificity to have potential utility as a chronic migraine case-finding tool using health claims data. Research to further validate the algorithm is recommended.

Measurement Properties of the Psoriasis Symptom Inventory Electronic Daily Diary in Patients with Moderate to Severe Plaque Psoriasis.

OBJECTIVES: The Psoriasis Symptom Inventory (PSI) is a patient-reported outcome instrument that measures the severity of psoriasis signs and symptoms. This study evaluated measurement properties of the PSI in patients with moderate to severe plaque psoriasis. METHODS: This secondary analysis used pooled data from a phase 3 brodalumab clinical trial (AMAGINE-1). Outcome measures included the PSI, Psoriasis Area and Severity Index (PASI), static Physician's Global Assessment (sPGA), psoriasis-affected body surface area, 36-item Short-Form Health Survey version 2, and the Dermatology Life Quality Index (DLQI). The PSI was evaluated for dimensionality, item performance, reliability (internal consistency and test-retest), construct validity, ability to detect change, and agreement between PSI response and response measures based on the PASI, sPGA, and DLQI. RESULTS: Results supported unidimensionality, good item fit, ordered responses, and PSI scoring. The PSI demonstrated reliability: baseline Cronbach's alpha ≥ 0.92 and intraclass correlation coefficients ≥ 0.95. Correlations between PSI total score and DLQI item 1 (r = 0.86), DLQI symptoms and feelings (r = 0.87), and 36-item Short-Form Health Survey version 2 bodily pain (r = -0.61) supported convergent validity. PSI scores differed significantly (P < 0.001) among severity groups based on the PASI (< 12/≥ 12), sPGA (0-1/2-3/4-5), body surface area (< 5%/5%-10%/> 10%), and DLQI (≤ 5/> 5) at weeks 8 and 12. At week 12, the PSI detected significant changes in severity based on PASI responses (< 50/50- < 75/≥ 75) and sPGA (0-1/≥ 2), and showed good agreement (k ≥ 0.66) between PSI response and PASI, sPGA, and DLQI responses. CONCLUSION: The PSI demonstrated excellent validity, reliability, and ability to detect change in the severity of psoriasis signs and symptoms.

Biologic therapy adherence, discontinuation, switching, and restarting among patients with psoriasis in the US Medicare population.

BACKGROUND: Studies indicate adherence to biologics among patients with psoriasis is low, yet little is known about their use in the Medicare population. OBJECTIVE: We sought to investigate real-world utilization patterns in a national sample of Medicare beneficiaries with psoriasis initiating infliximab, etanercept, adalimumab, or ustekinumab. METHODS: We conducted a retrospective claims analysis using 2009 through 2012 100% Medicare Chronic Condition Data Warehouse Part A, B, and D files, with 12-month follow-up after index prescription. Descriptive and multivariate analyses were used to examine rates of and factors associated with biologic adherence, discontinuation, switching, and restarting. RESULTS: We examined 2707 patients initiating adalimumab (40.0%), etanercept (37.9%), infliximab (11.7%), and ustekinumab (10.3%); during 12-month follow-up, 38% were adherent and 46% discontinued treatment, with 8% switching to another biologic and 9% later restarting biologic treatment. Being female and being ineligible for low-income subsidies were associated with increased odds of decreased adherence. Outcomes varied by index biologic. LIMITATIONS: Patient-reported reasons for nonadherence or gaps in treatment are unavailable in claims data. CONCLUSION: Medicare patients initiating biologics for psoriasis had low adherence and high discontinuation rates. Further investigation into reasons for inconsistent utilization, including exploration of patient and provider decision-making and barriers to more consistent treatment, is needed.

Clinical meaningfulness of complete skin clearance in psoriasis.

BACKGROUND: New psoriasis therapies have increased the ability to achieve skin clearance. However, insufficient evidence exists on the impact of total skin clearance from the patient perspective. OBJECTIVE: We sought to determine if complete skin clearance is clinically meaningful compared with treatment responses without clearance. METHODS: Pooled data from 3 phase-III trials were used to compare results for patients with complete skin clearance (Psoriasis Area and Severity Index [PASI] 100 or static Physician Global Assessment score 0) with patients without complete skin clearance (PASI 75 to <100 or static Physician Global Assessment score 1) based on Psoriasis Symptom Inventory and Dermatology Life Quality Index. RESULTS: Percentages of patients with Psoriasis Symptom Inventory score 0 were 45% for those achieving PASI 100 and 8% for PASI 75 to <100 (P < .001). Respective percentages with Dermatology Life Quality Index score 0/1 were 80% and 55% (P < .001). PASI 100 resulted in incremental improvement over PASI 90 to <100 (incremental differences of 28% for Psoriasis Symptom Inventory score 0 and 18% for Dermatology Life Quality Index score 0). Similar results were observed for static Physician Global Assessment scores 0 versus 1. CONCLUSIONS: Complete skin clearance represents a clinically meaningful end point and outcome for patients, reflected in experiences of no psoriasis symptoms and no impairment on health-related quality of life.

Equivalence and measurement properties of an electronic version of the Psoriasis Symptom Inventory.

PURPOSE: To evaluate the equivalence of electronic and paper versions of the Psoriasis Symptom Inventory and to examine measurement properties of the electronic version. METHODS: In a prospective, randomized, crossover, non-interventional study in adult subjects (age ≥18 years) with plaque psoriasis conducted over a period of 15 days, subjects were randomized to two groups, completing either the paper or electronic Psoriasis Symptom Inventory daily for 7 consecutive days followed by the alternate version. Equivalence was assessed by the intraclass correlation coefficient (ICC) between both administration modes. Differences in scores were also tested using paired Student's t test. Measurement properties included internal consistency reliability, test-retest reliability, and convergent and discriminant validity between the Psoriasis Symptom Inventory and (1) disease-specific (Dermatology Life Quality Index) and (2) general health (SF-36v2) status. RESULTS: Eighty subjects [74 % (59/80) moderate-to-severe psoriasis; 26 % (21/80) mild psoriasis receiving systemic treatment] were enrolled from 8 sites in the USA. The two modes were highly concordant for both total (ICC = 0.97) and individual item scores (ICC range = 0.93-0.97). Response bias testing showed no differences based on completion order with all ICC values >0.91. All mean score differences, except for one item ("flaking"), were non-significant (P > 0.05). Minimum values for reliability (>0.70) and validity (convergent, r ≥ 0.40) were exceeded for the electronic Psoriasis Symptom Inventory. CONCLUSIONS: Equivalence between paper and electronic versions of the Psoriasis Symptom Inventory and strong measurement properties of the electronic mode indicated a successful migration from paper to electronic format of the Psoriasis Symptom Inventory.

Validation of the Osteoporosis-Specific Morisky Medication Adherence Scale in long-term users of bisphosphonates.

PURPOSE: To examine the psychometric properties and validity of the 8-item Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS-8) in postmenopausal women prescribed bisphosphonates (BPs) for at least 15 months. METHODS: A random sample of women aged ≥55 years with osteoporosis prescribed daily or weekly BPs was identified. Pharmacy fill data were extracted to calculate the medication possession ratio (MPR). Eligible women were stratified by low (<0.50), medium (0.50-0.79), or high (≥0.80) MPR, with the a priori goal of recruiting 133 participants in each group. OS-MMAS-8 scores can range from 0 to 8 and were categorized as low (<6), medium (6 to <8), and high (8) adherence. Internal consistency reliability (Cronbach's alpha), test-retest reliability [intraclass correlation coefficients (ICCs)] and convergent validity (correlating OS-MMAS-8 with MPR and other self-reported measures) were assessed. RESULTS: A total of 400 women out of 449 respondents reported that they were still taking their BPs at the time of the survey and completed OS-MMAS-8. Overall, 38.5, 34.3, and 27.3% of participants had low, medium, and high OS-MMAS-8 scores, respectively. The mean (SD) MPRs according to OS-MMAS-8 scores (<6, 6 to <8 and 8) were 56.9 (22.6), 69.0 (24.9), and 76.7 (26.4), respectively. The correlation between OS-MMAS-8 and MPR was 0.36; p < 0.0001. Cronbach's alpha was 0.74, and the ICC was 0.83 (95% CI 0.76-0.88). CONCLUSIONS: OS-MMAS-8 has acceptable psychometric properties for assessing medication adherence in postmenopausal women prescribed therapy for osteoporosis. Additional studies are needed to investigate the psychometric properties of OS-MMAS-8 in other settings and populations.

Psychometric properties of the Osteoporosis-specific Morisky Medication Adherence Scale in postmenopausal women with osteoporosis newly treated with bisphosphonates.

BACKGROUND: Poor adherence to oral osteoporosis medications is common. Strategies for improving adherence begin with identification of the problem. The 8-item Morisky Medication Adherence Scale for self-reported adherence to antihypertensive medications was modified for assessing adherence to oral osteoporosis medications. An evaluation of the measurement properties of the Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) was needed. OBJECTIVE: To examine the psychometric properties of the OS-MMAS in women with postmenopausal osteoporosis. METHODS: Five hundred women aged 55 years and older with osteoporosis who were newly prescribed daily or weekly oral bisphosphonates between May 15, 2010, and August 15, 2010, were randomly selected from Kaiser Permanente Southern California, a large integrated health care delivery system, and mailed a self-administered survey that included the 8-item OS-MMAS, Self-Efficacy for Appropriate Medication Use Scale (SEAMS), Beliefs about Medicines Questionnaire (BMQ), Treatment Satisfaction Questionnaire for Medication (TSQM), Gastrointestinal Symptom Rating Scale (GSRS), and 12-item Short-Form Health Survey (SF-12v2). OS-MMAS scores can range from 0 to 8, with higher scores indicating better medication adherence. Internal consistency reliability was evaluated using Cronbach α coefficient. Test-retest reliability was assessed using intraclass correlation coefficients (ICCs) in a subset of 102 participants. Construct validity was assessed using confirmatory factor analysis and correlations between OS-MMAS and related measures. RESULTS: Of 197 participants, 150 reported that they were still taking their bisphosphonate at the time of the survey and completed the OS-MMAS. Overall, 30.7%, 32.7%, and 36.7% had low, medium, and high OS-MMAS scores (<6, 6 to <8, and 8, respectively). Cronbach α was 0.82 and the ICC was 0.77. Convergent validity was supported by significant correlations with SEAMS, BMQ necessity, and TSQM scores. In confirmatory factor analysis, a single-factor scale was supported. CONCLUSIONS: The OS-MMAS showed strong psychometric properties with good reliability and construct validity and may provide a valuable assessment of self-reported medication adherence in women newly prescribed oral osteoporosis medications.

Assessing the effect of darbepoetin alfa on patient-reported fatigue in chemotherapy-induced anemia in four randomized, placebo-controlled clinical trials.

PURPOSE: This analysis examined the effects of darbepoetin alfa on hemoglobin and fatigue outcomes in patients with cancer using latent growth curve modeling (LGM). METHODS: Data from 4 clinical trials of darbepoetin alfa in lung cancer (2 studies; n = 547; n = 288), lymphoproliferative malignancies (n = 339), and non-myeloid malignancies (n = 320) were analyzed separately. Fatigue was assessed using the FACT-Fatigue (FACT-F) scale. Effects of darbepoetin alfa on changes in hemoglobin and FACT-F scores were evaluated using LGM, controlling for age, gender, Eastern Cooperative Oncology Group performance status, health status, and total transfusions. RESULTS: Patients receiving darbepoetin alfa had higher rates of change in hemoglobin (standardized regression coefficient [[Formula: see text]] = 0.30 to 0.53, all P < 0.05) than placebo. Patients with greater rates of change in hemoglobin reported improvements in fatigue outcomes ([Formula: see text] = 0.28 to 0.59, all P < 0.05). The total standardized effect of darbepoetin alfa on fatigue outcomes corresponded to a mean change of 0.9 to 3.5 points in FACT-F scores, with one trial demonstrating changes exceeding the minimal important difference of 3 points. CONCLUSIONS: Darbepoetin alfa improved hemoglobin which was associated with improved fatigue across the 4 trials. Clinically, meaningful improvement in fatigue was seen in 2 trials. More complex statistical analysis models of treatment may assist in understanding the effects of erythropoiesis-stimulating agents on patient-reported outcomes.

The anemia impact measure (AIM): development and content validation of a patient-reported outcome measure of anemia symptoms and symptom impacts in cancer patients receiving chemotherapy.

PURPOSE: To develop a patient-reported outcome instrument for measuring anemia symptoms and their impact in patients with chemotherapy-induced anemia (CIA). METHODS: Qualitative research was conducted using six focus groups and 24 interviews with 46 CIA patients, eight interviews in patients receiving chemotherapy with no CIA history and two interviews in patients successfully treated for CIA. Atlas.ti 5.0 was used to organize key concepts. Cognitive interviews with 16 CIA patients and assessment of relevance of each item to CIA by 10 clinicians were also conducted to evaluate content validity. RESULTS: Most CIA patients were white (76%) and female (83%), and the average age was 60 years. The most common cancer types were breast cancer (54%) and lung cancer (17%). Tiredness was the most prevalent symptom and rated as the most important by 83% of CIA patients; weakness, shortness of breath, lightheadedness, and dizziness were ranked next in importance. The final anemia impact measure (AIM) contains: (1) daily CIA symptom diary (9 items), and (2) impact of CIA-related tiredness (29 items covering daily living activities, social activities, cognitive function, and emotions). Cognitive interviews found that the AIM was relevant and easy to understand. CONCLUSIONS: The AIM assesses important patient-perceived CIA symptoms and their impact and was developed using extensive patient qualitative data.

Migraine Patients With Cardiovascular Disease and Contraindications: An Analysis of Real-World Claims Data.

INTRODUCTION: Triptans, the most commonly prescribed acute treatments for migraine attacks are, per FDA labeling, contraindicated in cardiovascular (CV) disease patients and have warnings and precautions for those with CV risk factors. METHODS: Headache specialists, cardiologists, and health economics and outcomes researchers convened to identify diagnostic codes for: (1) CV diseases contraindicating triptans based on FDA labeling; (2) conditions comprising "other significant underlying CV disease"; and (3) CV risk factors included as warnings and precautions for triptans. A retrospective, cross-sectional analysis of commercially insured adult US migraine patients in the 2017 Optum® Clinformatics® Data Mart (CDM) and the 2017 IBM® Watson Health MarketScan® Commercial Claims database was used to estimate the proportion of migraine patients with CV contraindications and warnings and precautions to triptans. RESULTS: Of the 56,662 migraine patients analyzed from Optum CDM, 13.5% had ≥1 CV disease as specified in triptan labeling and an additional 8.5% had ≥1 "other CV disease" judged by the panel to constitute a "significant underlying CV disease" (total: 22.0% migraine patients). Of 176 724 migraine patients analyzed from MarketScan, 12.2% had ≥1 CV disease as specified in the labeling and an additional 8.0% had ≥1 "other significant underlying CV disease" (total: 20.2% of migraine patients). An additional 25.4% and 25.1% of migraine patients had ≥2 CV risk factors in Optum CDM and MarketScan. In total, 47.4% and 45.3% of migraine patients in both databases had a CV disease specified as a contraindication, an "other CV disease" endorsed as significant, or ≥2 CV risk factors identified as warnings and precautions to triptans. CONCLUSIONS: Analyses of more than 230,000 people with migraine showed that ≥20% of commercially insured US migraine patients have a CV condition that specifically contraindicates triptan treatment, and an additional 25% have ≥2 CV risk factors identified as warnings and precautions to triptans.

Developing a preference-based utility scoring algorithm for the Psoriasis Area Severity Index (PASI).

Introduction: It is challenging to identify health state utilities associated with psoriasis because generic preference-based measures may not capture the impact of dermatological symptoms. The Psoriasis Area Severity Index (PASI) is one of the most commonly used psoriasis rating scales in clinical trials. The purpose of this study was to develop a utility scoring algorithm for the PASI. Methods: Forty health states were developed based on PASI scores of 40 clinical trial patients. Health states were valued in time trade-off interviews with UK general population participants. Regression models were conducted to crosswalk from PASI scores to utilities (e.g. OLS linear, random effects, mean, robust, spline, quadratic). Results: A total of 245 participants completed utility interviews (51.4% female; mean age = 45.3 years). Models predicting utility based on the four PASI location scores (head, upper limbs, trunk, lower limbs) had better fit/accuracy (e.g. R2, mean absolute error [MAE]) than models using the PASI total score. Head/upper limb scores were more strongly associated with utility than trunk/lower limb. The recommended model is the OLS linear model based on the four PASI location scores (R2 = 0.13; MAE = 0.03). An alternative is recommended for situations when it is necessary to estimate utility based on the PASI total score. Conclusions: The derived scoring algorithm may be used to estimate utilities based on PASI scores of any treatment group with psoriasis. Because the PASI is commonly used in psoriasis clinical trials, this scoring algorithm greatly expands options for quantifying treatment outcomes in cost-effectiveness analyses of psoriasis therapies. Results indicate that psoriasis of the head/upper limbs could be more important than trunk/lower limbs, suggesting reconsideration of the standard PASI scoring approach.

Budget impact analysis of darbepoetin alfa every 3 weeks versus epoetin alfa every week for the treatment of chemotherapy-induced anaemia from a US payer's perspective.

OBJECTIVE: This analysis was conducted to compare the direct medical costs of treatment with darbepoetin alfa every 3 weeks (Q3W) and epoetin alfa every week (QW) in patients with chemotherapy-induced anaemia (CIA) from the payer's perspective. METHODS: An analysis was conducted from a US health plan perspective to compare the annual budget impact for CIA with darbepoetin alfa Q3W and epoetin alfa QW over a 16-week treatment period. Dosing regimens were obtained from registration clinical trials. RESULTS: Mean doses, including dose adjustments, were 375.6 microg Q3W for darbepoetin alfa and 43,187 U QW for epoetin alfa. Costs of medical resources included drug acquisition and administration costs. The base case analysis resulted in a per-patient budget impact of $8,544 and $8,667 for darbepoetin alfa and epoetin alfa, respectively. Per member per month cost was $0.90 for darbepoetin alfa and $0.91 for epoetin alfa, based on an estimate of 2,735 CIA patients in a health plan population of 2.17 million. The analysis was most sensitive to drug dose, treatment period and drug price. CONCLUSIONS: Results suggest that per-patient direct medical costs of CIA treatment, when initiated at labelled starting doses, are comparable for darbepoetin alfa Q3W and epoetin alfa QW.

Development and validation of the Ulcerative Colitis patient-reported outcomes signs and symptoms (UC-pro/SS) diary.

BACKGROUND: The clinical course of ulcerative colitis (UC) and the effects of treatment are assessed through patient-reported signs and symptoms (S&S), and endoscopic evidence of inflammation. The Ulcerative Colitis Patient-Reported Outcomes Signs and Symptoms (UC-PRO/SS) measure was developed to standardize the quantification of gastrointestinal S&S of UC in clinical trials through direct report from patient ratings. DESIGN: The UC-PRO/SS was developed by collecting data from concept elicitation (focus groups, and individual interviews), then refined through a process of cognitive interviews of 57 UC patients. Measurement properties, including item-level statistics, scaling structure, reliability, and validity, were evaluated in an observational, four-week study of adults with mild to severe UC (N = 200). RESULTS: Findings from qualitative focus groups and interviews identified nine symptom items covering bowel and abdominal symptoms. The final UC-PRO/SS daily diary includes two scales: Bowel S&S (six items) and Abdominal Symptoms (three items), each scored separately. Each scale showed evidence of adequate reliability (α = 80 and 0.66, respectively); reproducibility (intraclass correlation coefficient = 0.81, 0.71) and validity, including moderate-to-high correlations with the Partial Mayo Score (0.79; 0.45) and Inflammatory Bowel Disease Questionnaire (IBDQ) total score (- 0.70; - 0.61). Scores discriminated by level of disease severity, as defined by the Partial Mayo Score, Patient Global Rating, and Clinician Global Rating (p < 0.0001). CONCLUSIONS: Results suggest that the UC-PRO/SS is a reliable and valid measure of gastrointestinal symptom severity in UC patients. Additional longitudinal data are needed to evaluate the ability of the UC-PRO/SS scores to detect responsiveness and inform the selection of responder definitions.

Development and validation of the Crohn's disease patient-reported outcomes signs and symptoms (CD-PRO/SS) diary.

BACKGROUND: The clinical course of Crohn's disease (CD) and the effect of its treatment are monitored through patient-reported signs and symptoms (S&S), and endoscopic evidence of inflammation. The Crohn's Disease Patient-reported Outcomes Signs and Symptoms (CD-PRO/SS) measure was developed to standardize the quantification of gastrointestinal S&S of CD through direct report from patient ratings. METHODS: The CD-PRO/SS was developed based on data from concept elicitation (focus groups, interviews; n = 29), then refined through cognitive interviews of CD patients (n = 20). Measurement properties, including item-level statistics, scaling structure, reliability, and validity, were examined using secondary analyses of baseline and two-week clinical trial data of adults with moderate-to-severe CD (n = 238). RESULTS: Findings from qualitative interviews identified nine S&S items covering bowel and abdominal symptoms. The final CD-PRO/SS daily diary includes two scales: Bowel S&S (three items) and Abdominal Symptoms (three items), each scored separately. Each scale showed evidence of adequate reliability (α = 0.74 and 0.67, respectively); reproducibility (intraclass correlation coefficient > 0.80), and validity, with the last including moderate correlations with the Inflammatory Bowel Disease Questionnaire bowel symptom score and select items (ranging from r = 0.43-0.54). Scores distinguished patients categorized by patient global ratings of disease severity (p < 0.0001). CONCLUSIONS: Results suggest the CD-PRO/SS is a reliable and valid measure of gastrointestinal symptom severity in CD patients. Additional longitudinal data are needed to evaluate the ability of the CD-PRO/SS scores to detect responsiveness and inform the selection of responder definitions.

Psychometric Properties of the Asthma Symptom Diary (ASD), a Diary for Use in Clinical Trials of Persistent Asthma.

BACKGROUND: No currently available asthma symptom diary has sufficient validation to be recommended for use as a core asthma outcome measure. OBJECTIVE: The objective of this study was to provide validation data for the 10-item asthma symptom diary (ASD). METHODS: Data were collected in a 4-week prospective, observational study. Subjects completed 3 study visits, completing the ASD twice daily at home for 28 days. Psychometric properties in terms of dimensionality, reliability, validity, and responsiveness were assessed. RESULTS: Data from 276 subjects were analyzed; mean age was 42.9 (standard deviation [SD] = 16.4) years, mean asthma duration was 23.3 (SD = 16.8) years, and 69.6% were female. Confirmatory factor and Rasch analysis supported the ASD as unidimensional and adequately measuring the spectrum of asthma symptom severity. High Cronbach's α (0.94) and intraclass correlation coefficients (0.89-0.95) supported reliability. A high correlation between the 7-day average ASD score and the Asthma Control Questionnaire (ACQ) total score (r = 0.75) and Asthma Quality of Life Questionnaire total scores (r = -0.76), and a moderate correlation with FEV1% predicted (r = -0.30) supported convergent validity. Significant differences (P < .001) between groups classified by ACQ scores supported known-group validity. The 7-day average ASD scores were responsive to change, with significantly higher score changes (P < .001) in responders versus nonresponders. Minimally important differences were calculated and found to be in the range of 0.1-0.3. CONCLUSION: Results of this study indicated that the ASD is a reliable and valid asthma symptom measure for use in adult and adolescent asthma patients to evaluate the effect of treatment on asthma in clinical trials.