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Background: This study aimed to elicit and quantify preferences for treatments for juvenile idiopathic arthritis (JIA). Methods: We conducted a discrete-choice experiment among adolescents with JIA in the United States (US) (n = 197) and United Kingdom (UK) (n = 100) and caregivers of children with JIA in the US (n = 207) and UK (n = 200). In a series of questions, respondents chose between experimentally designed profiles for hypothetical JIA treatments that varied in efficacy (symptom control; time until next flare-up), side effects (stomachache, nausea, and vomiting; headaches), mode and frequency of administration, and the need for combination therapy. Using a random-parameters logit model, we estimated preference weights for these attributes, from which we derived their conditional relative importance. Results: On average, respondents preferred greater symptom control; greater time until the next flare-up; less stomachache, nausea, and vomiting; and fewer headaches. However, adolescents and caregivers in the US were generally indifferent across varying modes and frequencies of administration. UK adolescents and caregivers preferred tablets, syrup, or injections to intravenous infusions. US and UK adolescents were indifferent between treatment with monotherapy or combination therapy; caregivers in the UK preferred treatment with combination therapy to monotherapy. Subgroup analysis showed preference heterogeneity across characteristics including gender, treatment experience, and symptom experience in both adolescents and caregivers. Conclusions: Improved symptom control, prolonged time to next flare-up, and avoidance of adverse events such as headache, stomachache, nausea, and vomiting are desirable characteristics of treatment regimens for adolescents with JIA and their caregivers. [ABSTRACT FROM AUTHOR]

COVID-19 infection adversely impacts patients' wellbeing and daily lives. This survey-based study examined differences in patient-reported COVID-19 symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Activity Impairment (WPAI) among groups of patients defined based on age and symptom-based long COVID status. Symptomatic, COVID-19-positive US outpatients were recruited from 31 January–30 April 2022. Outcomes were collected via validated instruments at pre-COVID, Day 3, Week 1, Week 4, Month 3 and Month 6 following infection, with changes assessed from pre-COVID and between groups, adjusting for covariates. EQ-5D-5L HRQoL and WPAI scores declined in all groups, especially during the first week. Long COVID patients reported significantly higher symptoms burden and larger drops in HRQoL and WPAI scores than patients without long COVID. Their HRQoL and WPAI scores did not return to levels comparable to pre-COVID through Month 6, except for absenteeism. Patients without long COVID generally recovered between Week 4 and Month 3. Older (>50) and younger adults generally reported comparable symptoms burden and drops in HRQoL and WPAI scores. During the first week of infection, COVID-19-related health issues caused loss of 14 to 26 work hours across the groups. These data further knowledge regarding the differential impacts of COVID-19 on clinically relevant patient groups. [ABSTRACT FROM AUTHOR]

Background: Although there is extensive literature on the clinical benefits of COVID-19 vaccination, data on humanistic effects are limited. This study evaluated the impact of SARS-CoV-2 infection on symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Impairment (WPAI) prior to and one month following infection between individuals vaccinated with BNT162b2 and those unvaccinated. Methods: Subjects with ≥ 1 self-reported symptom and positive RT-PCR for SARS-CoV-2 at CVS Health US test sites were recruited between 01/31/2022 and 04/30/2022. Socio-demographics, clinical characteristics and vaccination status were evaluated. Self-reported symptoms, HRQoL, and WPAI outcomes were assessed using questionnaires and validated instruments (EQ-5D-5L, WPAI-GH) across acute COVID time points from pre-COVID to Week 4, and between vaccination groups. Mixed models for repeated measures were conducted for multivariable analyses, adjusting for several covariates. Effect size (ES) of Cohen's d was calculated to quantify the magnitude of outcome changes within and between vaccination groups. Results: The study population included 430 subjects: 197 unvaccinated and 233 vaccinated with BNT162b2. Mean (SD) age was 42.4 years (14.3), 76.0% were female, 38.8% reported prior infection and 24.2% at least one comorbidity. Statistically significant differences in outcomes were observed compared with baseline and between groups. The EQ-Visual analogue scale scores and Utility Index dropped in both cohorts at Day 3 and increased by Week 4 but did not return to pre-COVID levels. The mean changes were statistically lower in the BNT162b2 cohort at Day 3 and Week 4. The BNT162b2 cohort reported lower prevalence and fewer symptoms at index date and Week 4. At Week 1, COVID-19 had a large impact on all WPAI-GH domains: the work productivity time loss among unvaccinated and vaccinated was 65.0% and 53.8%, and the mean activity impairment was 50.2% and 43.9%, respectively. Except for absenteeism at Week 4, the BNT162b2 cohort was associated with statistically significant less worsening in all WPAI-GH scores at both Week 1 and 4. Conclusions: COVID-19 negatively impacted HRQoL and work productivity among mildly symptomatic outpatients. Compared with unvaccinated, those vaccinated with BNT162b2 were less impacted by COVID-19 infection and recovered faster. [ABSTRACT FROM AUTHOR]

The expanding number of potential treatment options for atopic dermatitis (AD) highlights the need to better understand the treatment preferences of individuals with AD. This study identified attributes that most greatly influenced treatment preferences of adults/adolescents/caregivers of children with mild/moderate/severe AD. Adults (≥18 years), adolescents (12–17 years), and caregivers of children (2–11 years) with mild, moderate, or severe AD in the United States (US) and United Kingdom (UK) participated in semistructured interviews. Thematic analysis was used to identify and generate themes across the interview results describing the treatment attributes of greatest importance to participants. Qualitative interviews were conducted with 35 adults, 35 caregivers, and 33 adolescent participants across both countries (n = 103; US = 51; UK = 52) and all severity groups (mild = 43; moderate = 47; severe = 13). The most important treatment attributes included efficacy (96.1%; speed and duration of symptom relief), mode of administration (66.0%; route of administration, frequency, and convenience), and side effects (55.3%, short-term, long-term, and general). Efficacy, mode of administration, and side effects were the most important attributes that influenced AD treatment preferences for patients and caregivers across different countries, ages, and disease severity. These results may assist patients/caregivers/clinicians in shared decision-making discussions to improve treatment adherence and outcomes. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is typically associated with pain, but many patients are not treated.Methods: This point in time study explored factors associated with treatment status, using logistic regression of data from the Adelphi OA Disease Specific Programme conducted in the United States. Patients' treatment status was based on physician-reported, current: 1) prescription medication for OA vs. none; and 2) physician treatment (prescription medication and/or recommendation for specified nonpharmacologic treatment for OA [physical or occupational therapy, acupuncture, transcutaneous electrical nerve stimulation, or cognitive behavior therapy/psychotherapy]) vs. self-management (no prescription medication or specified nonpharmacologic treatment).Results: The 841 patients (including 57.0% knee OA, 31.9% hip OA) reported mild (45.4%) or moderate or severe (54.6%) average pain intensity over the last week. The majority were prescribed medication and/or recommended specified nonpharmacologic treatment; 218 were not prescription-medicated and 122 were self-managed. Bivariate analyses showed less severe patient-reported pain intensity and physician-rated OA severity, fewer joints affected by OA, lower proportion of joints affected by knee OA, better health status, lower body mass index, and lower ratings for cardiovascular and gastrointestinal risks, for those not prescribed medication (vs. prescription-medicated). Multivariate analyses confirmed factors significantly (p < 0.05) associated with prescription medication included (odds ratio): physician-rated current moderate OA severity (vs. mild, 2.03), patient-reported moderate OA severity 6 months ago (vs. mild, 1.71), knee OA (vs. not, 1.81), physician-recommended (0.28) and patient-reported (0.43) over-the-counter medication use (vs. not), prior surgery for OA (vs. not, 0.37); uncertain income was also significant. Factors significantly (p < 0.05) associated with physician treatment included (odds ratio): physician-recommended nonpharmacologic therapy requiring no/minimal medical supervision (vs. not, 2.21), physician-rated current moderate OA severity (vs. mild, 2.04), patient-reported over-the-counter medication use (vs. not, 0.26); uncertain time since diagnosis was also significant. Patient-reported pain intensity and most demographic factors were not significant in either model.Conclusions: Approximately 1 in 4 patients were not prescribed medication and 1 in 7 were self-managed, although many were using over-the-counter medications or nonpharmacologic therapies requiring no/minimal medical supervision. Multiple factors were significantly associated with treatment status, including OA severity and over-the-counter medication, but not pain intensity or most demographics. [ABSTRACT FROM AUTHOR]

To identify meaningful treatment attributes and quantify patient preferences for attributes of systemic atopic dermatitis (AD) treatments. Qualitative interviews were conducted with adults with moderate-to-severe AD (N = 21) to identify AD treatment attributes that patients consider most important and inform attribute selection for an online discrete-choice experiment (DCE) survey administered to patients in the United States with moderate-to-severe AD. Participants identified probability of clear/almost clear skin at 16 weeks, time to itch relief, mode of administration, and safety risks as very important. DCE data were analyzed using a random-parameters logit model to estimate the relative importance of treatment attributes and maximum acceptable risk. A total of 320 respondents completed the DCE survey (74% female; mean age, 35 years). Annual risk of malignancy was the most important attribute, followed by mode of administration, probability of clear skin at 16 weeks, and time to onset of itch relief. Respondents preferred daily oral treatment over injectable treatment. Respondents were willing to accept increases in adverse event risks for improvements in efficacy and mode of administration. The findings of this study can help inform joint patient-physician decision making in managing moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Introduction: Satisfaction with medications prescribed for osteoarthritis (OA) varies; this study aimed to determine the factors associated with satisfaction in US patients and their physicians. Methods: This point-in-time study used the Adelphi OA Disease Specific Programme (physicians identified from public lists reported on nine consecutive patients diagnosed with OA [any joint]: physicians and patients completed questionnaires). Patient's demographic, clinical, and treatment characteristics associated with patient-reported and physician-rated overall satisfaction with, and expectations of effectiveness of, medication for OA were assessed using multivariate linear regression. Results: Responses from 572 patients (mean age 64.9 years, 60.5% female) currently prescribed medication for OA and 153 physicians (81 primary care, 35 rheumatologists, 37 orthopedic surgeons) were analyzed. Pain intensity was moderate or severe for 59.4% of patients. Greater patient-reported overall satisfaction with medication was significantly associated with (standardized beta, 95% confidence interval) exercise (0.12, 0.03–0.20), comorbid other musculoskeletal or painful conditions (vs none) (0.15, 0.06–0.24), and physicians' report that the best control had been achieved (0.12, 0.03–0.20); lack of efficacy was among factors associated with worse satisfaction. Greater patient-reported expectation of effectiveness was significantly associated with exercise (0.12, 0.03–0.21) and the most troublesome joint not being a knee, hip, or their back (0.08, 0.01–0.14). Greater physician-rated overall satisfaction with medication was significantly associated with their report that the best control had been achieved (0.18, 0.11–0.26), the most troublesome joint being a knee (0.08, 0.01–0.14), comorbid other musculoskeletal or painful conditions (0.07, 0.01–0.12), obesity (0.06, 0.00–0.11), and female patients (0.06, 0.00–0.11); lack of efficacy and adverse events/tolerability issues were among factors associated with worse satisfaction. For physicians, their report that the best control had been achieved (0.19, 0.11–0.27), the most troublesome joint being a knee (0.08, 0.00–0.15), improving (vs stable) OA (0.15, 0.07–0.24), and uncertain duration of OA (0.11, 0.02–0.21) were associated with greater perception that the medication was meeting patients' efficacy expectations. Conclusion: Although efficacy was strongly associated with both patients' and physicians' satisfaction with medication, other factors were also important, including exercise (for patients), tolerability (for physicians), and knee OA (for physicians). [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this research was to conceptualize and develop a tool for identifying persons who are, or are likely to be, non-adherent to medications prescribed by their healthcare provider(s) by identifying concerns that patients have regarding their treatments. Patients and Methods: The target populations were persons diagnosed with atrial fibrillation or osteoarthritis, who were prescribed anticoagulants or over-the-counter or prescription pain medications, respectively. In this two-stage, multi-year, qualitative research study, relevant concepts were explored, confirmed and refined. The focus was on non-adherence due to active (thus potentially modifiable) patient decisions to forego taking medications as prescribed. Results: The most common concerns among participants with atrial fibrillation were medication-related side effects and fear of bleeding. Participants with osteoarthritis were most concerned about short-term stomach problems and long-term kidney and liver side effects. The Concerns Influencing Medication Adherence (CIMA) instrument was developed based on these concerns and those identified in the literature. It is comprised of 16 items: a core set of 11 items potentially applicable to multiple disease states, 3 items specific to atrial fibrillation, and 2 items unique to osteoarthritis. The instrument is intended to be completed electronically, and publicly available for use in direct patient care in the United States or in population health management. Conclusion: To our knowledge, this is the first instrument focused on medication adherence that includes documented details of patient input as recommended by the United States Food and Drug Administration guidance. Patient input is considered a key component of content validity. In this research, for example, the concerns that patients have regarding their treatments can be expected to have affected past medication adherence and can potentially impact future adherence. Although applicability outside atrial fibrillation or osteoarthritis was not assessed, the general items may be useful in assessing adherence in other chronic diseases. [ABSTRACT FROM AUTHOR]

To evaluate healthcare resource utilization (HCRU) by osteoarthritis (OA) pain severity. Cross-sectional surveys of US physicians and their patients were conducted between February and May 2017. Using the Numeric Rating Scale, patients were classified by self-reported pain intensity in the last week into mild (0–3), moderate (4–6), and severe (7–10) cohorts. Parameters assessed included clinical characteristics, HCRU, and current caregiver support. Descriptive statistics were obtained, and analysis of variance and chi-square tests were performed. Patients (n = 841) were mostly female (60.9%) and white (77.8%), with mean age of 64.6 years. Patients reported mild (45.4%), moderate (35.9%), and severe (18.7%) OA pain. Mean number of affected joints varied by pain severity (range mild: 2.7 to severe: 3.6; p < 0.0001). Pain severity was associated with an increased number of physician-reported and patient-reported overall healthcare provider visits (HCPs; both p < 0.001). As pain increased, patients reported an increased need for mobility aids, accessibility modifications to homes, and help with daily activities due to functional disability. The number of imaging tests used to diagnose OA was similar across pain severity but varied when used for monitoring (X-rays: p < 0.0001; computerized tomography scans: p < 0.0447). Hospitalization rates for OA were low but were significantly associated with pain severity (mild: 4.9%; severe: 11.5%). Emergency department visits were infrequent but increasing pain severity was associated with more prior and planned surgeries. Greater current pain was associated with more prior HCRU including imaging for monitoring progression, HCP visits including more specialty care, hospitalizations, surgery/planned surgery, and loss of independence due to functional disability. Yet rates of hospitalizations and X-ray use were still sizable even among patients with mild pain. These cross-sectional findings warrant longitudinal assessment to further elucidate the impact of pain on HCRU. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess how patient-reported pain is related to osteoarthritis (OA) treatment patterns in routine clinical practice. Patients and Methods: Data were collected between February and May 2017 from 153 United States (US) primary care physicians, rheumatologists, and orthopedic surgeons. Each invited up to nine consecutive patients to rate their OA pain in the last week. Physicians provided demographic, clinical, and treatment information for patients, including nonpharmacologic therapies ever recommended, currently recommended over-the-counter (OTC) medications, and currently and ever prescribed medications for the management of OA. Findings for patients with mild (0─3), moderate (4─6), and severe current pain (7─10) were compared using appropriate statistics. Results: Among the 841 patients (61% female; mean 65 years; 57% knee OA), 45% reported mild, 36% moderate, and 19% severe current OA pain. Current treatment modalities differed by pain severity (P< 0.05). Most patients (70%) had been recommended nonpharmacologic therapy and 40% were currently recommended OTC medications. More patients with moderate (81%) or severe pain (78%) currently received prescription medications, with or without nonpharmacologic therapy, versus those with mild pain (67%). Overall, 47% of patients currently received just one prescription drug, while 49% had received one prescription drug ever. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most common current (58%) and ever received (88%) prescriptions. Current NSAID prescriptions were not associated with pain severity. Acetaminophen recommendations, opioid prescriptions (current and ever), and multiple prescription medications tried were numerically highest in the severe pain group (all P< 0.05 by pain severity). In all groups, > 80% of treatment switches were due to lack of efficacy. Conclusion: Real-life treatment patterns for OA in the US are significantly associated with current patient-reported pain. Combining nonpharmacologic and pharmacologic treatments is common but higher pain ratings are associated with multiple failed prescription treatments. Current use of acetaminophen and opioids, but not NSAIDs, increases alongside pain severity. [ABSTRACT FROM AUTHOR]

Purpose: Alopecia areata (AA) is an autoimmune disease characterized by the development of non-scarring alopecia. The prevalence is not well known, and estimates vary considerably with no recent estimates in the United States (US). The objective of this study was to define the current AA point prevalence estimate among the general population in the US overall and by severity. Patients and Methods: We administered an online, cross-sectional survey to a representative sample of the US population. Participants self-screening as positive for AA using the Alopecia Assessment Tool (ALTO) also completed the Severity of Alopecia Tool (SALT) to measure the severity of disease as a percent of scalp hair loss. Self-reported AA participants were invited to upload photographs for adjudication of AA by 3 clinicians. Results: The average age of participants was 43 years. Approximately half of the participants (49.2%) were male, and the majority were white (77.1%) and not of Hispanic origin (93.2%). Among the 511 self-reported AA participants, 104 (20.4%) uploaded photographs for clinician evaluation. Clinician-adjudicated point prevalence of AA was 0.21% (95% CI: 0.17%, 0.25%) overall, 0.12% (95% CI: 0.09%, 0.15%) for "mild" disease (≤ 50% SALT score), and 0.09% (95% CI: 0.06%, 0.11%) for "moderate to severe" disease (> 50% SALT score) with 0.04% (95% CI: 0.02%, 0.06%) for the alopecia totalis/alopecia universalis (100% SALT score) "moderate to severe" subgroup. The average SALT score was 44.4% overall, 8.8% for "mild", and 93.4% for "moderate to severe". Conclusion: This study suggests that the current AA prevalence in the US is similar to the upper estimates from the 1970s at approximately 0.21% (700,000 persons) with the current prevalence of "moderate to severe" disease at approximately 0.09% (300,000 persons). Given this prevalence and the substantial impact of AA on quality of life, the burden of AA within the US is considerable. [ABSTRACT FROM AUTHOR]

Background: Patients with ulcerative colitis (UC) experience periods of recurring and episodic clinical signs and symptoms. This study sought to establish the association between disease activity and health-related quality of life (HRQoL) and other patient-reported outcomes.Methods: United States (US) and European Union 5 ([EU5]; i.e., France, Germany, Italy, Spain, and the United Kingdom) data from the 2015 and 2017 Adelphi Inflammatory Bowel Disease-Specific Programme (IBD-DSP) were used. The IBD-DSP is a database of retrospective patient chart information integrated with patient survey data (EuroQoL-5 Dimensions [EQ-5D], Short Quality of Life in Inflammatory Bowel Disease Questionnaire [SIBDQ], and Work Productivity and Activity Impairment-Ulcerative Colitis [WPAI-UC] questionnaire). Using available chart information, physicians classified their moderate-to-severe patients into one of the following categories: remission with a Mayo endoscopic score = 0 ("deep remission"), remission without a Mayo endoscopic score = 0 ("remission"), or active disease. Differences among disease activity categories with respect to patient-reported outcomes were analyzed using generalized linear models, controlling for confounding variables.Results: N = 289 and N = 1037 patient charts with linked surveys were included from the US and EU5, respectively. The disease activity distribution was as follows: active disease = 40.1% (US) and 33.6% (EU5); remission = 48.0 and 53.0%; deep remission = 11.9 and 13.3%. Patients with active disease reported significantly lower levels of EQ-5D health state utilities (adjusted mean [AdjM] = 0.87 [US] and 0.78 [EU5]) compared with remission (AdjM = 0.92 and 0.91) and deep remission (AdjM = 0.93 and 0.91) (all P < 0.05 compared with active disease within each region). Similar findings were observed with the scores from the SIBDQ and the WPAI-UC. No significant differences were observed between remission categories.Conclusions: Among patients with moderate-to-severe UC in the US and EU5, active disease was associated with significant impairments in HRQoL, work and leisure activities. These results reinforce the importance, to both the patient and society, of achieving some level of remission to restore generic and disease-related HRQoL and one's ability to work productively. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study is to examine how moderate-to-severe ulcerative colitis (UC) is currently managed in real-world clinical practice across the United States (US) and European Union Five (EU5; France, Germany, Italy, Spain, and the United Kingdom). Methods: Data from the 2017 Adelphi Inflammatory Bowel-Disease Specific Programme (IBD-DSP) were used. The IBD-DSP is a database of patient chart information abstracted by selected gastroenterologists across the US and EU5. Eligible gastroenterologists who agreed to participate were asked to complete patient record forms for the next seven consecutive eligible adult patients with UC. Only charts from patients with moderate-to-severe UC were included in the analysis (defined as those with documented administration of either an immunosuppressant [IM] or a biologic). Treatment patterns were reported descriptively. Results: 411 and 1191 patient charts were included in the US and EU5 (mean ages 44.2 and 39.6 years; 53.0% and 43.5% female), respectively. For those with complete treatment history, 40.7% and 52.9% used either an IM or biologic as their first treatment (with or without steroids). Usage of these therapies increased in subsequent lines. The percentage of patients treated with combination therapy (i.e., biologic therapy with a concomitant IM) in first line generally varied between 10–20% (e.g., US: adalimumab (ADA), 10.8%; infliximab (IFX), 18.2%; EU5: ADA, 12.5%; IFX, 19.9%), though increased in later lines in the EU5. Among patients currently using a biologic therapy, between 10–40% of patients used a higher than indicated dose or greater than indicated dosing frequency during maintenance (e.g., US: IFX, 37.1%; ADA, 13.4%; EU5: IFX, 39.1%; ADA, 36.1%). In both the US and EU5, the primary reason for switching therapy was efficacy-related. Conclusions: In this analysis, many patients with moderate-to-severe UC use an IM or biologic as their first therapy after diagnosis. Combination therapy and dose escalation are also common, and underscore the challenges with managing this patient population. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to elicit patient and physician preferences for ulcerative colitis (UC) treatments in the United States (US). Patients and methods: The following UC treatment attributes included in the discrete-choice experiment (DCE) were identified during qualitative interviews with both patients and physicians: time to symptom improvement, chance of long-term symptom control, risks of serious infection and malignancy, mode and frequency of administration, and need for steroids. The DCE survey instruments were developed and administered to patients and physicians. A random-parameters logit model was used to estimate preference weights and conditional relative importance for these attributes. Results: A total of 200 patients with moderate to severe UC (status determined using self-reported medication history) and 200 gastroenterologists completed the survey. Patients' average age was 42 years; most (59%) were female. Patients considered symptom control 2.5 times as important as time to symptom improvement and 5-year risk of malignancy almost as important as long-term symptom control (relative importance, 0.79 vs 0.96 for long-term symptom control); they preferred oral to subcutaneous or intravenous administration (relative importance, 0.47 vs 0.11 and 0.18, respectively). For physicians, symptom control was the most important attribute and was five times as important as the risk of malignancy. Conclusion: Both patients and physicians considered long-term symptom control the most important attribute relative to others; however, risk of malignancy was of almost-equal importance to patients but not physicians. Differences between patients' and physicians' preferences highlight the need for improved communication about the relevant benefits and risks of different UC treatments to improve therapeutic decision-making. [ABSTRACT FROM AUTHOR]

Objective: The Chronic Pain Questions (CPQ) were developed for clinical use with the aim of supporting primary care physicians in the screening, assessment and monitoring of patients with chronic pain. the purpose of this study was to examine the ability of the cpq CPQ to discriminate between patients with neuropathic pain (nep) versus those with sensory hypersensitivity (sh).Methods: Adult men and women with a diagnosis of a NeP or SH condition were recruited from 5 clinical sites across the United States. Participants completed a series of self-administered questionnaires, including the CPQ. Continuous variables were compared between groups with independent t-tests; categorical variables were compared with chi-square analyses. A series of exploratory logistic regressions were performed to discern optimal screening criteria for SH using CPQ responses.Results: 98 participants, 68 with physician-confirmed diagnoses of SH and 30 with NeP, participated. 81.6% were female, 73.5% Caucasian, and mean (± SD) age was 58.4 ± 12.6 years. SH participants included significantly more females compared to the NeP group (94.1% vs. 53.3%). Differences in CPQ responses between groups were statistically significant for six of the 14 CPQ items with SH participants having significantly lower scores on specific pain quality questions and significantly higher scores on trouble thinking/remembering (5.3 ± 3.5 vs. 3.0 ± 2.8) and sensitivity to lights/noises/smells (4.8 ± 3.5 vs. 2.7 ± 3.0). No significant differences were found between groups for chronic pain intensity, pain made worse with touch, pain limited to joints, or pain interference with usual activity, sleep or mood. Logistic regression analyses revealed strong c indices (≥0.89) for all models. Consistent findings demonstrated that younger age, female gender, and scores ≥6 for the CPQ question on sensitivity to lights/noises/smells were all predictive of SH.Conclusions: The CPQ can help differentiate between patients with NeP and SH. More research is warranted. [ABSTRACT FROM AUTHOR]

Objective To quantify the prevalence of potential drug-drug/drug-condition interactions ( DDI/ DCI) among fibromyalgia patients initiating pregabalin or duloxetine, and to determine the impact of potential DDI/ DCI on health care expenditures. Design Retrospective cohort study. Setting U. S. clinical practice, as reflected within a large administrative claims database. Subjects Fibromyalgia patients newly initiating pregabalin or duloxetine between July 1, 2008 and October 1, 2010 (initiation date = index). Outcome Measures Potential DDI measured using clinical software that identifies co-prescription of medications that potentially interact with pregabalin or duloxetine. Potential DCI, drawn from the contraindications and warnings and precautions sections of pregabalin and duloxetine prescribing information, measured using administrative claims-based algorithms. All-cause health care expenditures measured throughout a 6-month postindex period. Analyses included univariate, bivariate, and multivariable statistical approaches. Results Seven thousand seven hundred fifty-one pregabalin and 7,785 duloxetine initiators were selected for study: mean age 49 years, 88% female. Only 1.4% of pregabalin initiators had ≥1 potential pregabalin DCI; none had potential pregabalin DDI. In contrast, 67% of duloxetine initiators had potential duloxetine DDI/ DCI, driven mostly by potential duloxetine DDI (62% of duloxetine initiators). Compared between pregabalin and duloxetine initiators, differences in the prevalence of potential DDI/ DCI were statistically significant ( P < 0.001). Multivariable analyses indicated that, among duloxetine initiators, those with potential duloxetine DDI/ DCI had postinitiation health care expenditures that were $670 higher ( P < 0.001) than those without potential duloxetine DDI/ DCI. Among pregabalin initiators, potential pregabalin DDI/ DCI were not associated with health care expenditures. Conclusions Among fibromyalgia patients initiating pregabalin or duloxetine, potential duloxetine DDI could be highly prevalent. Among duloxetine initiators, potential duloxetine DDI/ DCI were significantly associated with increased health care expenditures. [ABSTRACT FROM AUTHOR]

Background: The study aimed to evaluate health care resource utilization (HRU) and costs for neuropathic pain (NeP) secondary to spinal cord injury (SCI) among Medicaid beneficiaries. Methods: The retrospective longitudinal cohort study used Medicaid beneficiary claims with SCI and evidence of NeP (SCI-NeP cohort) matched with a cohort without NeP (SCI-only cohort). Patients had continuous Medicaid eligibility 6 months pre- and 12 months postindex, defined by either a diagnosis of central NeP (ICD-9-CM code 338.0x) or a pharmacy claim for an NeP-related antiepileptic or antidepressant drug within 12 months following first SCI diagnosis. Demographics, clinical characteristics, HRU, and expenditures were compared between cohorts. Results: Propensity score-matched cohorts each consisted of 546 patients. Postindexpercentages of patients with physician office visits, emergency department visits, SCI- and pain-related procedures, and outpatient prescription utilization were all significantly higher for SCI-NeP (P,0.001). Using regression models to account for covariates, adjusted mean expenditures were US$47,518 for SCI-NeP and US$30,150 for SCI only, yielding incremental costs of US$17,369 (95% confidence interval US$9,753 to US$26,555) for SCI-NeP. Factors significantly associated with increased cost included SCI type, trauma-related SCI, and comorbidity burden. Conclusion: Significantly higher HRU and total costs were incurred by Medicaid patients with NeP secondary to SCI compared with matched SCI-only patients. [ABSTRACT FROM AUTHOR]

Objective: To compare comorbidities, drug use, benefit costs, absences, medication persistence/adherence between employees with fibromyalgia initiating treatment with pregabalin (PGB) vs. antidepressant Standard of Care ([SOC] amitriptyline, duloxetine, or venlafaxine). Methods: Retrospective study of 240 adults initiating PGB or SOC after 7/1/2007. Multivariate regression models on propensity-score-matched cohorts compared postindex costs, absences, and adherence between cohorts. Results: Pregabalin users had significantly more preindex muscle pain and dizziness and less depression than SOC (each P < 0.05). Use of some non-PBG/SOC drugs differed. No differences were found in total medical, drug, or absenteeism cost. PGB had more sick leave (9.8 vs. 6.8 days, P = 0.04), but other absence types were similar. All adherence metrics were nonsignificantly greater for PGB vs. SOC. Conclusion: Despite several comorbidity and drug use differences, most employee benefit outcomes and adherence did not differ between the cohorts. [ABSTRACT FROM AUTHOR]

ackground: This study was designed to develop a diabetes-specific questionnaire on parents' quality of life and satisfaction with their child's diabetes treatment, the WEll-being and Satisfaction of CAREgivers of Children with Diabetes Questionnaire, and to conduct psychometric validation of the WE-CARE. Methods: Parents of 116 children aged 6 to 11 years were enrolled in the United States. Children had type 1 diabetes mellitus for > 1 year, had been treated with subcutaneous insulin for ≥ 2 months, and had a recent glycosylated hemoglobin (HbA1C) measurement. Recruiting clinicians provided clinical information on the children. Over a two-week period, parents completed WECARE (initial 68 items) and two other questionnaires (the 36-item Short Form of the Medical Outcomes Study and the 50-item Child Health Questionnaire-Parent Form) twice. Results: A literature review and one-on-one interview with caregivers and pediatricians led to the development of a draft questionnaire consisting of 68 items. Factor analysis suggested retention of 37 of the 68 initial items grouped into four multi-item scales (Psychosocial Well-being, Ease of Insulin Use, Treatment Satisfaction, and Acceptance of Insulin Administration as well as a Total Score). The four multi-item domains of WE-CARE were found to be psychometrically robust -- they had negligible floor and ceiling effects, excellent internal consistency and test-retest reliability, high item-discriminant validity and good concurrent, divergent, known-group and clinical validity. Moderate interscale correlations among the four WE-CARE domains indicated that the concepts they measure were related but distinct. Conclusion: These data suggest that WE-CARE provides a reliable and valid measure of parents' well-being and treatment satisfaction related to their child's diabetes. While these results show promise, additional validation of WE-CARE is warranted. [ABSTRACT FROM AUTHOR]

Background: To evaluate the measurement properties (e.g. content validity, reliability and ability to detect change) of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale in patients with active psoriatic arthritis (PsA). Methods: One-on-one semi-structured qualitative interviews with adult patients with active PsA evaluated the content validity of FACIT-Fatigue. Quantitative measurement properties were evaluated using data from phase III tofacitinib randomized controlled trials (RCTs) in PsA: OPAL Broaden (NCT01877668) and OPAL Beyond (NCT01882439). Results: Of 12 patients included in the qualitative study, 2 (17%) had mild, 8 (67%) had moderate, and 2 (17%) had severe PsA disease activity; 7 (58%) attributed fatigue to PsA, and 7 (58%) rated fatigue as important or extremely important. Most patients considered the FACIT-Fatigue items relevant to their PsA experience and understood item content and response options as intended. In the psychometric analysis of RCT data, a second-order confirmatory factor model fit the data well (Bentler's Comparative Fit Index ≥0.92). FACIT-Fatigue demonstrated good internal consistency (Cronbach's coefficient α ≥ 0.90), test-retest reliability (Intraclass Correlation Coefficient ≥ 0.80) and a strong correlation with SF-36 Vitality (r > 0.80). A robust relationship between disease activity (based on Patient's Global Assessment of Psoriasis and Arthritis) and FACIT-Fatigue was observed (effect sizes > 1.4), with clinically important difference for the FACIT-Fatigue total score estimated as 3.1 points, and the responder definition estimated as a 4-point improvement for FACIT-Fatigue total score. Conclusion: Fatigue was confirmed to be an important symptom to patients with PsA, and FACIT-Fatigue was found to be a reliable and valid measure in this population. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare the health status of fibromyalgia patients assessed by EuroQol (EQ-5D) with healthy controls and patients with chronic conditions, and to identify modifiable clinical factors associated with the EQ-5D. Study Design: EQ-5D scores were calculated using US preference weights for patients with fibromyalgia from a published patient survey. Scores were compared with healthy controls and individuals with chronic conditions (cancer, diabetes, asthma, headache, hypertension, myocardial infarction, coronary atherosclerosis, congestive heart failure, osteoarthritis, rheumatoid arthritis, and spondylopathies) from the Medical Expenditure Panel Survey. Demographic and clinical factors associated with the EQ-5D were identified using regression analyses. Results: Adjusted for age and sex, the mean (±SD) EQ-5D score was 0.56±0.18 among fibromyalgia patients; significantly lower, that is, worse (P <.0001), than that of healthy controls (0.89±0.46) and other chronic conditions (P <.0001). Differences in scores between fibromyalgia patients and comparators were ≥.074, indicating clinical significance. Patient self-reported fibromyalgia symptom severity was a significant factor associated with the EQ-5D. Compared with “very severe” patients, those with “moderate,” “mild,” and “very mild” symptoms had significantly (P <.05) higher mean EQ-5D scores. Major depressive disorder also was a significant factor, but anxiety, cognitive dysfunction, and chronic fatigue syndrome were not; neither were fibromyalgia duration and number of tender points. Conclusions: EQ-5D scores in fibromyalgia patients were significantly lower than healthy controls and individuals with other chronic conditions. Self-reported symptom severity was significantly associated with the EQ-5D. A substantial health burden for fibromyalgia has been highlighted and results suggest that effective symptom management is necessary to improve the health status of fibromyalgia patients. [Copyright &y& Elsevier]

The US Food and Drug Administration and the Critical Path Institute's Patient-Reported Outcome (PRO) Consortium convened a cosponsored workshop on the use of PRO measures to inform the assessment of safety and tolerability in cancer clinical trials. A broad array of international stakeholders involved in oncology drug development and PRO measurement science provided perspectives on the role of PRO measures to provide complementary clinical data on the symptomatic side effects of anticancer agents. Speakers and panelists explored the utility of information derived from existing and emerging PRO measures, focusing on the PRO version of the National Cancer Institute's Common Terminology Criteria for Adverse Events. Panelists and speakers discussed potential ways to improve the collection, analysis, and presentation of PRO data describing symptomatic adverse events to support drug development and better inform regulatory and treatment decisions. Workshop participants concluded the day with a discussion of possible approaches to the patient-reported assessment of an investigational drug's overall side effect burden as a potential clinical trial end point. The Food and Drug Administration reiterated its commitment to collaborate with international drug development stakeholders to identify rigorous methods to incorporate the patient perspective into the development of cancer therapeutics. [ABSTRACT FROM AUTHOR]

Introduction: Clostridioides difficile (C.diff) infection (CDI) causes significant morbidity and mortality among older adults. Vaccines to prevent CDI are in development; however, data on the target population's preferences are needed to inform vaccination recommendations in the United States (US). This study assessed US adults' willingness to receive a C.diff vaccine and examined how vaccine attributes influence their choices., Methods: A cross-sectional online survey with a discrete choice experiment (DCE) was conducted among US adults aged ≥50 years. DCE attributes included effectiveness, duration of protection, reduction in symptom severity, out-of-pocket (OOP) costs, number of doses, and side effects. The DCE included 11 choice tasks, each with two hypothetical vaccine profiles and an opt-out (i.e., no vaccine). Attribute-level preference weights were estimated using hierarchical Bayesian modeling. Attribute relative importance (RI) was compared between select subgroups., Results: Of 1216 adults in the analyses, 29.9% reported they knew either 'a little' (20.7%) or 'a lot' (9.2%) about C.diff before the study. A C.diff vaccine was chosen 58.0% of the time (vs. opt-out) across choice tasks. It was estimated that up to 75.0% would choose a vaccine when OOP was $0. Those who were immunocompromised/high-risk for CDI (vs. not) more frequently chose a C.diff vaccine. Decreases in OOP costs (RI = 56.1), improvements in vaccine effectiveness (RI = 17.7), and reduction in symptom severity (RI = 10.3) were most important to vaccine choice. The rank ordering of attributes by importance was consistent across subgroups., Conclusion: OOP cost, improvements in vaccine effectiveness, and reduction in CDI severity were highly influential to vaccine selection. Most adults aged ≥50 years were receptive to a C.diff vaccine, especially with little-to-no OOP cost, suggesting that mandating insurance coverage of vaccination with no copayment may increase uptake. The limited awareness about C.diff among adults presents an opportunity for healthcare providers to educate their patients about CDI prevention., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jeffrey Vietri reports financial support was provided by Pfizer Inc. Jeffrey Vietri reports a relationship with Pfizer Inc. that includes: employment and equity or stocks. Joseph C. Cappelleri reports a relationship with Pfizer Inc. that includes: employment and equity or stocks. Holly Yu reports a relationship with Pfizer Inc. that includes: employment and equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Pfizer Inc. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Associations between increased functional disability and higher healthcare resource utilization (HCRU) and costs were reported in patients with psoriatic arthritis (PsA). We assessed characteristics/outcomes of patients with PsA receiving tofacitinib monotherapy vs combination therapy with conventional synthetic disease-modifying antirheumatic drugs., Methods: Claims data from Optum ® Clinformatics ® Data Mart (OC) and Merative™ MarketScan ® (MS) databases between December 2017 and February 2020 were analyzed. Outcomes assessed were adherence/persistence by therapy type (monotherapy/combination therapy); HCRU/costs (per patient per month) by periods on-treatment (sum time on tofacitinib) and off-treatment (sum time off tofacitinib [gap of > 60 days]) plus therapy type., Results: This analysis included 274 and 395 tofacitinib-treated patients in OC (70.4% female, mean age 54.4 years) and MS (68.9% female, mean age 51.4 years), respectively. Percentages of patients with a proportion of days covered ≥ 0.8 at 12 months for monotherapy vs combination therapy were OC, 44.5% vs 53.8%; MS, 36.4% vs 45.7%. Generally similar trends were seen over 24 months and for medication possession ratio ≥ 0.8. Median (95% confidence interval) times to treatment discontinuation for monotherapy vs combination therapy were OC, 10.1 (7.4-11.8) vs 16.7 (8.3-26.6) months; MS, 6.9 (5.6-9.4) vs 11.0 (6.1-13.9) months. During off-treatment vs on-treatment periods, numerical decreases were observed for all-cause (OC, $5383 vs $6149; MS, $4145 vs $5180) and PsA-related costs (OC, $3237 vs $4515; MS, $2703 vs $3907) regardless of therapy type. During off-treatment vs on-treatment periods, numerical increases in outpatient visits for all-cause (OC, 2.37 vs 2.05; MS, 2.15 vs 1.99) and PsA-related visits (OC, 0.60 vs 0.46; MS, 0.47 vs 0.44) were observed, and PsA-related medications numerically decreased (OC, 1.21 vs 1.53; MS, 1.05 vs 1.48)., Conclusion: In this USA-based claims analysis, tofacitinib adherence was numerically lower for patients with PsA receiving monotherapy vs combination therapy. Costs numerically decreased off-treatment vs on-treatment, irrespective of therapy type, driven by lower medication costs., (© 2024. The Author(s).)

A maternal vaccine and long-acting monoclonal antibody (mAb) were recently approved to protect infants against respiratory syncytial virus (RSV). We identified subgroups of pregnant people with different preferences for RSV preventives and respondent characteristics associated with subgroup membership. An online survey, including a discrete choice experiment (DCE), was conducted among US pregnant people. RSV preventive attributes included effectiveness, duration of protection during RSV season, injection recipient/timing, preventive type (vaccine or mAb), and type of visit required to receive injection. In DCE choice tasks, pregnant people selected between two hypothetical preventive profiles with varying attribute-levels and a no-preventive option. Logistic regression, including latent class analysis (LCA), was used to analyze the data. Of 992 pregnant people (mean age: 30.0 years), 60.3% were expecting their second/later birth. LCA identified three preference subgroups: 'Effectiveness' (preventive choice mostly driven by increases in effectiveness; 51.4% class membership probability), 'Season' (preventive choice mostly driven by improvement in duration of protection during the RSV season; 39.2% class membership probability), and 'No Preventive' (frequently chose no-preventive option; 9.4% class membership probability). 'Effectiveness' and 'Season' preferred maternal vaccine over mAb; mAb was preferred by 'No Preventive.' Perceiving RSV as serious for infants, higher health literacy, and lower household income were associated with 'Effectiveness.' Perceiving RSV as serious for pregnant people was associated with 'Season.' Perceiving RSV to not be serious for pregnant people and not being employed were associated with 'No Preventive.' Subgroups of pregnant people vary in preferences for RSV preventives. Most pregnant people preferred a maternal vaccine, although some may be more willing to accept alternative preventive options.

Background: Percentage uptake of some meningococcal vaccines is low in the US. Understanding what drives vaccination preferences may help to increase vaccination rates., Objectives: To determine how attributes of meningococcal vaccines and the availability of a pentavalent (MenABCWY) vaccine profile drive adolescents' and young people's (AYP's) willingness to be vaccinated and parents' and legal guardians' (PLG') willingness for their child to be vaccinated (WTV). To also explore how preferences for meningococcal vaccines vary by participant characteristics., Methods: Vaccine preferences were elicited in a discrete choice experiment (DCE) with AYP aged 16-23 years and PLG of adolescents aged 11-17 years. Participants chose between two hypothetical vaccine profiles that differed in level of protection, dosing, and risks of mild-to-moderate and severe side effects, and a no vaccination profile. Main outcome measures were relative attribute importance (RAI) and WTV. RAI measured the maximum contribution of an attribute to vaccination choice relative to other attributes. WTV compared predicted choice probabilities for the three vaccine profiles., Results: 407 AYP and 394 PLG participated (50.9% male, 78.4% White/Caucasian). Irrespective of vaccine attributes, 59.5% always opted into vaccination and 3.6% always opted out of vaccination. The most important attributes were level of protection (RAI: 33.7%) and risk of mild-to-moderate side effects (RAI: 32.3%). Dosing was more important to PLG (RAI: 5.9%) than AYP (RAI: 2.0%; p < .01). Adding a pentavalent vaccine alternative increased WTV by 3.7 percentage points (PP) for PLG, 2.4 PP for AYP, 16.4 PP for vaccine-hesitant participants, 13.4 PP for participants without health insurance, and 9.6 PP for adults., Conclusion: Level of protection and risk of mild-to-moderate side effects were the most important vaccine attributes. Adding a pentavalent vaccine alternative increased WTV particularly among adults, individuals who were vaccine-hesitant, and individuals without health insurance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Katharina Schley reports a relationship with Pfizer Pharma GmbH that includes: employment. Brett Hauber reports a relationship with Pfizer Inc. that includes: employment. Joseph C. Cappelleri reports a relationship with Pfizer Inc. that includes: employment. Paula Peyrani reports a relationship with Pfizer Inc. that includes: employment. Jessica Vespa Presa reports a relationship with Pfizer Inc. that includes: employment. Joshua Coulter reports a relationship with Pfizer Inc. that includes: employment. Chiara Whichello reports a relationship with Evidera Ltd. that includes: employment. Nicolas Krucien reports a relationship with Evidera Ltd. that includes: employment. Sebastian Heidenreich reports a relationship with Evidera Ltd. that includes: employment. The following co-authors are employees of Pfizer and may hold stocks in Pfizer: KS, BH, JC, JCC, PP, and JVP. The following co-authors are employees of Evidera Ltd.: CW, SH, and NK. SH holds minor stocks in Thermo Fisher Scientific as part of his employment with Evidera. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Qualitative research is fundamental for designing discrete choice experiments (DCEs) but is often underreported in the preference literature. We developed a DCE to elicit preferences for vaccination against invasive meningococcal disease (IMD) among adolescents and young people (AYP) and parents and legal guardians (PLG) in the United States. This article reports the targeted literature review and qualitative interviews that informed the DCE design and demonstrates how to apply the recent reporting guidelines for qualitative developmental work in preference studies., Methods: This study included two parts: a targeted literature review and qualitative interviews. The Medline and Embase databases were searched for quantitative and qualitative studies on IMD and immunization. The results of the targeted literature review informed a qualitative interview guide. Sixty-minute, online, semi-structured interviews with AYP and PLG were used to identify themes related to willingness to be vaccinated against IMD. Participants were recruited through a third-party recruiter's database and commercial online panels. Interviews included vignettes about IMD and vaccinations and three thresholding exercises examining the effect of incidence rate, disability rate, and fatality rate on vaccination preferences. Participant responses related to the themes were counted., Results: The targeted literature review identified 31 concepts that were synthesized into six topics for the qualitative interviews. Twenty AYP aged 16-23 years and 20 PLG of adolescents aged 11-17 years were interviewed. Four themes related to willingness to be vaccinated emerged: attitudes towards vaccination, knowledge and information, perception of IMD, and vaccine attributes. Most participants were concerned about IMD (AYP 60%; PLG 85%) and had positive views of vaccination (AYP 80%; PLG 60%). Ninety percent of AYP and 75% of PLG always chose vaccination over no vaccination, independent of IMD incidence rate, disability rate, or fatality rate., Conclusion: Willingness to be vaccinated against IMD was affected by vaccine attributes but largely insensitive to IMD incidence and severity. This article provides an example of how to apply the recent reporting guidelines for qualitative developmental work in preference studies, with 21 out of 22 items in the guidelines being considered., (© 2024. The Author(s).)

Background: The Ulcerative Colitis (UC) Narrative global survey assessed aspects of living with UC. This analysis aimed to identify health care disparities, social determinants of health, and emotional impacts related to UC disease management, patient experience, and quality of life., Methods: The survey was conducted by The Harris Poll from August 2017 to February 2018 among adults with UC. Responses from 1000 patients in the United States, Canada, Japan, France, and Finland were analyzed based on patient income, employment status, educational level, age, sex, and psychological comorbidities. Odds ratios (ORs) with significant P values (P < .05) from multivariate logistic regression models are reported., Results: Low-income vs high-income patients were less likely to have participated in a peer mentoring (OR, 0.30) or UC education program (OR, 0.51). Patients not employed were less likely to report being in "good/excellent" health (OR, 0.58) than patients employed full time. Patients with low vs high educational levels were less likely to have reached out to patient associations/organizations (OR, 0.59). Patients aged younger than 50 years vs those aged 50 years and older were less likely to have visited an office within an inflammatory bowel disease center/clinic in the past 12 months (OR, 0.53). Males were less likely to be currently seeing their gastroenterologist than females (OR, 0.66). Patients with vs without depression were less likely to agree that UC had made them more resilient (OR, 0.51)., Conclusions: Substantial differences in disease management and health care experience were identified, based on categories pertaining to patient demographics and psychological comorbidities, which may help health care providers better understand and advance health equity to improve patient care., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: To describe variations in treatment patterns, clinical outcomes, patient-reported outcomes (PRO), and physician and patient satisfaction in patients with moderate-to-severe ulcerative colitis (UC) treated with tofacitinib in a real-world setting., Methods: Data were drawn from the Adelphi UC Disease Specific Programme™, a point-in-time survey of physicians and their consulting patients in the US and Europe. For inclusion in this analysis, gastroenterologists completed medical record forms for the next seven consecutive consulting patients with confirmed UC, plus a further two patient record forms for patients treated with tofacitinib. Those same patients then completed a patient-reported questionnaire., Results: Gastroenterologists (n = 340) provided data for 2049 patients with UC, including 642 patients receiving tofacitinib. Physicians' most frequent reason for choosing tofacitinib was overall efficacy (71.3% of patients). The proportion of patients in remission increased with length of treatment, from 13.7% at [0, 4) weeks to 68.3% at [52+] weeks. Both physicians and patients reported that the Mayo components of stool frequency and blood in stool were reduced with time on treatment. Improvement in symptoms (bloody diarrhea, abdominal pain/cramps, urgency, rectal bleeding, fatigue/tiredness) was reported in the first weeks of treatment, and increased with time. At week [52+], mean score reductions from treatment initiation to current in overall symptom severity, pain, and fatigue were 2.2 (to a current mean score of 1.1), 2.2 (to 0.9), and 2.1 (to 1.0), respectively. Comparing patients at weeks [0, 4) and [52+] (all PROs, p < 0.0001), the increase in EQ-5D-5L index total score was 0.29 points and in SIBDQ total score was 20.5 points; percent reductions in WPAI absenteeism was 34.4%, presenteeism 26.8%, overall work impairment 40.9% and activity impairment was 28.3%. These changes reached the thresholds for minimally clinically important differences. The majority of physicians (91.9%) and patients (93.5%) were satisfied with tofacitinib at week [52+]., Conclusion: Patients with moderate-to-severe UC treated with tofacitinib show considerable improvement in symptoms and quality of life from tofacitinib initiation to one year and beyond, with high rates of remission. Physicians and patients report satisfaction with UC control at recommended doses in a mostly biologic experienced population., (© 2023. The Author(s).)

Introduction: Atopic dermatitis (AD) is associated with significant quality-of-life and economic burdens. Real-world evidence is needed to identify optimal treatment pathways for AD. Here we evaluate real-world effectiveness of systemic therapies for moderate-to-severe AD in the USA., Methods: Data (September 2016 to December 2019) were from the IQVIA Health Plan Claims data set (IQVIA, Danbury, CT) from patients aged 12 years or older with AD (ICD-9/10-CM, 691.8/L20.x) initiating a systemic immunosuppressive (SIS) agent (methotrexate, cyclosporine, mycophenolate, or azathioprine) or dupilumab and continuously enrolled for at least 6 months before and after the index date. Indicators of non-response (i.e., adding on/switching systemic therapy, AD-related inpatient/emergency room visits, or incident staphylococcal/streptococcal skin infection) and predictors of non-response were evaluated. Descriptive statistics and Kaplan-Meier rates and times were obtained; Cox regression models were used., Results: In 3249 patients, 45.4% exhibited at least one indicator of non-response, with median time to non-response being longer for dupilumab than for any SIS therapy (27.0 vs 4.0-7.7 months, respectively). Key non-response predictors were age, geographic region, and baseline number of annual AD-related medical visits., Conclusion: Non-response was common in patients with AD who required systemic treatment, and non-response indicators occurred significantly more frequently with SIS treatment than with dupilumab treatment., (© 2022. Pfizer Inc.)

Background: Psoriatic arthritis (PsA) is a chronic progressive inflammatory condition associated with significant direct and indirect costs. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Economic evaluations, alongside clinical data, help inform papers and formulary decisions in the United States., Objective: To evaluate outcomes and costs of including tofacitinib in treatment strategies for PsA from a third-party U.S. payer perspective, using a health economic model., Methods: A decision tree model was developed to evaluate treatment sequences (up to 4 lines of advanced PsA therapy) with or without tofacitinib. Patients included in the model had active PsA and a previous inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drug (csDMARD) or tumor necrosis factor inhibitor (TNFi) therapy. The analysis time horizon was 2 years; decision points for continuing/switching treatments occurred quarterly, based on clinical response (assessed using the primary rheumatoid measure of efficacy, American College of Rheumatology [ACR]20 response only) and adverse drug reactions (ADRs). Costs included those related to ADRs and drug acquisition, monitoring, and administration. Other endpoints of PsA, such as assessment of enthesitis and dactylitis, were not integrated into the model., Results: Treatment strategies including tofacitinib were associated with cost savings versus strategies without tofacitinib across all modeled scenarios, with an estimated 2-year cost saving of up to $8,454,858, based on 1 million insurants. Similarly, costs per member per month and per ACR20 responder were lower for sequences including tofacitinib versus sequences without. These savings arose because of lower ADR and drug acquisition/administration costs for sequences including tofacitinib. Deterministic sensitivity analyses showed these results to be robust., Conclusions: This analysis suggests that including tofacitinib in the treatment of active PsA in csDMARD-IR or TNFi-IR patients is a cost-saving alternative to sequences without tofacitinib, potentially reducing costs for PsA advanced therapies by up to $8.4 million over 2 years for payers insuring 1 million individuals., Disclosures: This work was sponsored by Pfizer Inc. Bungey is an employee of Decision Resources Group, which received financial support from Pfizer Inc to develop the treatment-cost model used in the development of this manuscript. Chang-Douglass was an employee of Decision Resources Group at the time of the analysis. During development of this publication, Chang-Douglass started a role at the National Institute for Health and Care Excellence (NICE). The publication only reflects her views and does not reflect the views of NICE. Hsu, Cappelleri, Young, and Woolcott are employees of Pfizer Inc and own stock or stock options in Pfizer Inc. The data reported in this manuscript have been previously presented at the American College of Rheumatology Annual Scientific Meeting; October 19-24, 2018; Chicago, IL, and the AMCP Annual Meeting and Expo; March 25-28, 2019; San Diego, CA.

Aim: To analyze real-world data relating to treatment decision-making in stage III-IV ovarian cancer (OC). Materials & methods: Real world data were collected from a survey of physicians and their patients (n = 2413) across Europe and the USA in 2017-2018. Results: 49% had stage IVb disease. 39, 54 and 7% of patients received first-line (1L), second-line, or 7% third-line or later treatment. In the 1L (ongoing or completed), 93% received platinum-containing regimens, 26% bevacizumab-containing regimens and 1% a PARP inhibitor-containing regimen. In 1L maintenance treatment, 81% received bevacizumab, 17% platinum-containing treatments and 6% a PARP inhibitor. Conclusion: The most common 1L treatment for advanced ovarian cancer was platinum-containing chemotherapy. Of those receiving 1L maintenance therapy, 70-99% (across countries) received targeted therapy.

Aims: To evaluate the cost differences between a treatment strategy including tofacitinib (TOFA) vs treatment strategies including adalimumab (ADA), golimumab (GOL), infliximab (IFX), and vedolizumab (VEDO) among all patients with moderate-to-severe ulcerative colitis (UC) (further stratified by patients naïve/exposed to tumor necrosis factor inhibitors [TNFis]). Materials and methods: An Excel-based decision-analytic model was developed to evaluate costs from the perspective of a third-party US payer over 2 years. Efficacy and safety parameters were taken from prescribing information and published trials. All patients started induction therapy on the first treatment in the strategy and continued if efficacy criteria were met and no major adverse event occurred (in which cases they proceeded to the next treatment in the strategy). Results: The cost per member per month (PMPM) of the TOFA->IFX->VEDO->GOL strategy ($1.11) was lower than that of the ADA->IFX->VEDO->GOL strategy ($1.34; Δ = $-0.23) among the TNFi-naïve population ( n  = 204 patients out of a plan of one million members). Similarly, the use of TOFA before ADA (i.e. TOFA->ADA->IFX-> VEDO) was also associated with lower PMPM costs than the use of ADA before TOFA (i.e. ADA->TOFA->IFX->VEDO): $1.15 vs $1.25 (Δ = $-0.10). Similar, and often larger, differences were observed in both the overall moderate-to-severe population and the TNFi-exposed population. Sensitivity analyses resulted in the same conclusions. Limitations: Our model relied on efficacy data from prescribing information and published trials, which were not head-to-head and slightly differed with respect to methods. Additionally, our model used representative minor and major ADRs (and the associated costs) to represent toxicity management, which was a simplifying assumption. Conclusions: This analysis, the first of its kind to evaluate TOFA vis-à-vis other advanced therapies in the US, suggests the early use of TOFA among both TNFi-naïve and TNFi-failure patients results in lower PMPM costs compared with other treatment alternatives.

Aim: We used Adelphi Real World Disease-Specific Programme data to characterize adults with newly diagnosed or relapsed/refractory de novo acute myeloid leukemia (AML). Materials & methods: Community-practice hematologists/oncologists completed patient record forms for their regular AML patients. Patients were invited to complete patient self-completion forms including 3-Level EuroQol 5-Dimensions (EQ-5D-3L) and Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaires. Results: Physicians provided patient record forms for 389 patients (339 newly diagnosed, 50 relapsed/refractory); 68 patients completed patient self-completion forms. Mean EQ-5D visual-analog scale and index and FACT-General scores were significantly lower than US population norms (p < 0.0001); health-related quality of life (HRQoL) scores were generally lower than 11 other cancers. Conclusion: HRQoL impairment is grave in AML. Efforts are needed to improve HRQoL in affected patients.

Although well developed to assess efficacy questions, meta-analyses and, more generally, systematic reviews, have received less attention in application to safety-related questions. As a result, many open questions remain on how best to apply meta-analyses in the safety setting. This appraisal attempts to: (i) summarize the current guidelines for assessing individual studies, systematic reviews, and network meta-analyses; (ii) describe several publications on safety meta-analytic approaches; and (iii) present some of the questions and issues that arise with safety data. A number of gaps in the current quality guidelines are identified along with issues to consider when performing a safety meta-analysis. While some work is ongoing to provide guidance to improve the quality of safety meta-analyses, this review emphasizes the critical need for better reporting and increased transparency regarding safety data in the systematic review guidelines. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Comprehensive studies on costs of moderate to severe plaque psoriasis (MSPP) have not been conducted in the United States., Objective: We sought to evaluate current health care resource use, productivity, and costs among patients with MSPP in routine practice., Methods: A total of 200 adults seeking MSPP treatment enrolled in 9 US sites. Consented patients reported symptoms, treatment, lost productivity, and costs; 6-month retrospective chart review captured health care resource use and clinical characteristics. Costs were assigned to health care resource use and lost productivity using standard algorithms. Differences by Psoriasis Area and Severity Index (PASI) group, based on PASI score (≤10, >10-≤20, >20) at enrollment, were evaluated. Analyses included descriptive statistics and analysis of variance or Kruskal-Wallis tests., Results: Most patients (79.5%) were prescribed 1 or more MSPP medications (mean: 1.5); 36.0% and 9.0% received self-administered biologics and systemic therapies, respectively. Mean number of nonprescription treatments was 12.3. Differences by PASI group were observed for overall work and activity impairment (P < .02). Six-month total MSPP direct costs per patient were $11,291; indirect costs were $2101 and differed across PASI groups (P = .0008)., Limitations: This study enrolled patients with MSPP actively seeking care., Conclusion: Despite treatment, a number of patients with MSPP continue to experience moderate to severe PASI scores, impaired functioning, and high costs suggesting a need for new treatment options., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Managed healthcare organizations often utilize formulary management strategies such as prior authorization and step therapy to guide appropriate medication use and to control medication expenditures. The objective of this study was to examine clinical and economic outcomes associated with implementation of a pregabalin step therapy (ST) policy among Medicare Advantage Prescription Drug (MAPD) members., Methods: Pharmacy and medical claims data from Humana (restricted cohort; ST policy implemented 01/01/2009) and Thomson Reuters MarketScan(®) (unrestricted cohort) were analyzed for MAPD members aged 65 to 89 years receiving treatment for painful diabetic peripheral neuropathy (pDPN), postherpetic neuralgia (PHN) or fibromyalgia (FM). Difference-in-differences (DID) was used to examine year-over-year changes in disease-related and all-cause utilization and costs. Regression analyses examined medication utilization and healthcare expenditures after controlling for between-group compositional differences., Results: We identified 13,911 members in the restricted cohort and matched to members from unrestricted health plans. FM (51.0%) and pDPN (41.8%) were the most common diagnoses. Members in the unrestricted cohort were older and had a greater level of comorbidity than members in the restricted cohort. The restricted cohort demonstrated greater year-over-year decrease in pregabalin utilization and increase in year-over-year gabapentin utilization compared with the unrestricted cohort. ST restriction was associated with an increase in disease-related pharmacy costs and a decrease in total medical costs for the restricted cohort compared with the unrestricted cohort. There was no difference between cohorts in total healthcare cost., Conclusion: After controlling for differences in age and comorbidity burden between the groups, implementation of a pregabalin ST restriction was associated with increased disease-related pharmacy costs and decreased total medical costs; however, there was no net difference in total healthcare cost or total pharmacy cost., (© 2013 Pfizer Inc and Humana, Inc. Pain Practice © 2013 World Institute of Pain.)

Background: The US Food and Drug Administration's guidance for industry document on patient-reported outcomes (PRO) defines content validity as "the extent to which the instrument measures the concept of interest" (FDA, 2009, p. 12). According to Strauss and Smith (2009), construct validity "is now generally viewed as a unifying form of validity for psychological measurements, subsuming both content and criterion validity" (p. 7). Hence, both qualitative and quantitative information are essential in evaluating the validity of measures., Methods: We review classical test theory and item response theory (IRT) approaches to evaluating PRO measures, including frequency of responses to each category of the items in a multi-item scale, the distribution of scale scores, floor and ceiling effects, the relationship between item response options and the total score, and the extent to which hypothesized "difficulty" (severity) order of items is represented by observed responses., Results: If a researcher has few qualitative data and wants to get preliminary information about the content validity of the instrument, then descriptive assessments using classical test theory should be the first step. As the sample size grows during subsequent stages of instrument development, confidence in the numerical estimates from Rasch and other IRT models (as well as those of classical test theory) would also grow., Conclusion: Classical test theory and IRT can be useful in providing a quantitative assessment of items and scales during the content-validity phase of PRO-measure development. Depending on the particular type of measure and the specific circumstances, the classical test theory and/or the IRT should be considered to help maximize the content validity of PRO measures., (Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.)

Purpose: The frequency and financial impact of potential drug-drug interactions (DDIs) and drug-condition interactions (DCIs) in patients with painful diabetic peripheral neuropathy (DPN) treated with either pregabalin or duloxetine were compared., Methods: This retrospective cohort study was conducted using a large U.S. administrative claims database. Patients selected for study inclusion had a diagnosis of DPN and were newly initiated on either pregabalin or duloxetine between July 1, 2008, and October 1, 2010. Data on potential DDIs and DCIs were collected. Health care costs were measured as the sum of gross covered payments for all medical and prescription claims incurred during the six months after the index date., Results: The study sample comprised 2499 pregabalin users and 1354 duloxetine users. Among pregabalin users, 48 (1.8%) had at least one potential pregabalin DCI; none had potential pregabalin DDIs. Among duloxetine users, 966 (71%) had at least one potential duloxetine DDI or DCI. The frequencies of potential DDIs and DCIs differed significantly between pregabalin and duloxetine users (p < 0.001). Potential duloxetine DDIs and DCIs were associated with a significant increase in mean health care costs in duloxetine users (p = 0.002). Potential pregabalin DDIs and DCIs were not associated with additional health care costs in pregabalin users., Conclusion: Among patients with painful DPN treated with either pregabalin or duloxetine, the frequency of potential duloxetine DDIs and DCIs was substantially higher than that of pregabalin. Potential DDIs and DCIs were associated with significantly increased health care costs in duloxetine users.

Objective: The prevalence of non-steroidal anti-inflammatory drug (NSAID) and concurrent gastroprotective agent (GPA) use in the US is not known. As such, the prevalence of GPA use among arthritis patients taking NSAIDs was examined., Methods: Men and women aged ≥ 40 with self-reported arthritis and members of a web-based community panel were invited via e-mail to participate in a web survey. Interested panelists consented and completed the survey. Participants using NSAIDs in the last 30 days were eligible. Questions regarding NSAID and GPA use were asked, likewise adherence to GPA (Morisky scale), comorbid conditions, gastrointestinal (GI) history, and other risk factors. Descriptive analyses and logistic regressions were performed to assess associations with GPA use and adherence., Results: Invitations were sent to 7605 adults; 4108 (54%) responded; 2208 completed. Final sample was 1525 (76%) with osteoarthritis (OA), 354 (18%) with rheumatoid arthritis (RA), and 121 (6%) with both OA and RA. Mean age was 62.0; 64% were female; 83% white; 25% worked full-time, and 39% were retired. Mean duration with arthritis was 13.0 years; 47% and 19% experienced arthritis symptoms 'daily' and 'almost always', respectively. Nearly 43% reported using a GPA and 39% of daily NSAID users reported taking a GPA. Fifty-eight participants (2.9%) were classified as low GI risk, 342 (17.1%) were moderate risk, and 1600 (80.0%) were high risk. Variables significantly associated with GPA use included older age; male gender; being white (vs. Hispanic); taking an NSAID at least daily; taking fewer NSAIDs; taking a Cox-2 inhibitor or prescription NSAID; history of GI conditions; prescription antiplatelet use; and having GI symptoms. Similar variables were associated with GPA adherence., Conclusion: Less than half of adult men and women in the US taking a daily NSAID used GPAs and only 37% of high-risk participants were taking GPAs.

Objective: The aim of the current study was to examine the health outcomes of patients suffering from painful diabetic peripheral neuropathy (pDPN) over a 3-year period, relative to patients with diabetes but without neuropathic pain and controls., Design: The current study included participants who completed three consecutive waves of the National Health and Wellness Survey (2006-2008). These participants were categorized into one of three groups: those with pDPN (N=290), those with diabetes but without pDPN ("diabetes without pDPN group"; N=1,037), and those not diagnosed with diabetes ("control group"; N=8,162)., Outcome Measures: Health status (Short Form-12v2), work productivity (Work Productivity and Activity Impairment Questionnaire), and resource use were examined with repeated-measures models adjusting for demographic and clinical factors., Results: The pDPN group reported significantly lower levels of physical quality of life. Moreover, physical quality of life scores for the pDPN group decreased at a significantly faster rate over a 3-year period relative to other groups. In addition, the pDPN patients reported significantly higher levels of impairment of work productivity and activity, greater resource use, and higher total 3-year per-patient costs., Conclusions: Confirming and expanding upon the literature, our results indicate a significantly worse trajectory of quality of life outcomes over time and long-term increased total costs for pDPN patients relative to non-pDPN diabetes patients and controls., (Wiley Periodicals, Inc.)

Objective: To compare the incidence of serious gastrointestinal (GI) complications and associated medical costs in a population with either osteoarthritis (OA) or rheumatoid arthritis (RA) enrolled in Medicare plans with celecoxib formulary restrictions versus plans without such restrictions., Methods: This study was a retrospective cohort analysis of Medicare members in plans with and without celecoxib restrictions. Members diagnosed with OA or RA were identified and followed for 1 year., Results: The restricted group had higher levels of nonselective nonsteroidal anti-inflammatory drug use (51% vs 40%, p <.001), and celecoxib use was double in the unrestricted group (16% vs 8%, p <.001). The incidence of a serious GI complication was slightly higher in the restricted group (5.4% vs 4.6%, P <.001). The adjusted mean serious GI complication-related cost for the restricted group was more than 15 times higher than that for the nonrestricted group ($1559 [95% confidence interval (CI) $1341-$1811] vs $101 [95% CI $87-$117]), adjusted mean arthritis-related medical costs were $5733 per year (95% CI $5097-$6448) for the restricted group and $3170 (95% CI $2816-$3569) for the unrestricted group., Conclusions: The restricted group had significantly less use of celecoxib, indicating that restriction was effective at reducing celecoxib utilization. Although limitations exist when comparing populations from different health plans, and the underlying causes of serious GI complications are multifactorial, the restricted group had a higher incidence of serious GI complications and higher costs related to serious GI complications and arthritis.

Background: Sleep disturbances are a common and bothersome symptom of fibromyalgia (FM). This study reports psychometric properties of a single-item scale to assess sleep quality among individuals with FM., Methods: Analyses were based on data from two randomized, double-blind, placebo-controlled trials of pregabalin (studies 1056 and 1077). In a daily diary, patients reported the quality of their sleep on a numeric rating scale ranging from 0 ("best possible sleep") to 10 ("worst possible sleep"). Test re-test reliability of the Sleep Quality Scale was evaluated by computing intraclass correlation coefficients. Pearson correlation coefficients were computed between baseline Sleep Quality scores and baseline pain diary and Medical Outcomes Study (MOS) Sleep scores. Responsiveness to treatment was evaluated by standardized effect sizes computed as the difference between least squares mean changes in Sleep Quality scores in the pregabalin and placebo groups divided by the standard deviation of Sleep Quality scores across all patients at baseline., Results: Studies 1056 and 1077 included 748 and 745 patients, respectively. Most patients were female (study 1056: 94.4%; study 1077: 94.5%) and white (study 1056: 90.2%; study 1077: 91.0%). Mean ages were 48.8 years (study 1056) and 50.1 years (study 1077). Test re-test reliability coefficients of the Sleep Quality Scale were 0.91 and 0.90 in the 1056 and 1077 studies, respectively. Pearson correlation coefficients between baseline Sleep Quality scores and baseline pain diary scores were 0.64 (p < 0.001) and 0.58 (p < 0.001) in the 1056 and 1077 studies, respectively. Correlations between the Sleep Quality Scale and the MOS Sleep subscales were statistically significant (p < 0.01), except for the MOS Snoring subscale. Across both studies, standardized effect sizes were generally moderate (0.46 to 0.52) for the 300 mg group and moderate (0.59) or moderate-to-large (0.70) for the 450 mg group. In study 1056, the effect size for the 600 mg group was moderate-to-large (0.73). In study 1077, the effect size for the 600 mg group was large (0.82)., Conclusion: These results provide evidence of the reproducibility, convergent validity, and responsiveness to treatment of the Sleep Quality Scale and provide a foundation for its further use and evaluation in FM patients.

Introduction: The absence of a single brief measure that assesses function and health-related quality of life (HRQoL) hinders evaluation of the sexual experience in men with erectile dysfunction (ED)., Aim: To psychometrically analyze the Sexual Experience Questionnaire (SEX-Q)., Methods: Two data sets were studied. A randomized, double-blind, placebo-controlled trial of flexible-dose sildenafil for ED treatment provided the final clinical trial data set (213 men enrolled, 4 of whom did not receive treatment) and the interim clinical trial data set (190 men screened and 165 men enrolled). The survey data set consisted of 902 respondents to a U.S. community health survey, of whom two-thirds had ED and one-third did not., Main Outcome Measures: Quality and distribution of responses, comparative fit, item-level discriminant testing, internal consistency (Cronbach alpha), test-retest reliability (intraclass correlation coefficient), known-groups validity (vs. International Index of Erectile Function [IIEF] ED severity groups), convergent validity (Pearson correlation coefficients with scores on the IIEF, Self-Esteem and Relationship [SEAR] questionnaire, and Quality of Erection Questionnaire [QEQ]), responsiveness, and clinically important difference (CID)., Results: The original 15 items were reduced to 12 items in three domains (erection, individual satisfaction, and couple satisfaction), which demonstrated good quality responses for all items; a strong factor structure; excellent internal consistency; good test-retest reliability; clear known-groups validity across the severity groups; moderate to strong convergent validity against the IIEF, SEAR, and QEQ; and high treatment responsiveness. The estimated CID ranged from 16.0 to 22.3 across domains., Conclusions: The SEX-Q is the first questionnaire to solely and exclusively combine functional and HRQoL concepts (erection, individual satisfaction, and couple satisfaction domains) in a brief questionnaire, which allows a more focused and less burdensome evaluation of the sexual experience, making it a potentially useful measure for clinical trial research.

There is a broad agreement that patient-reported outcome (PRO) assessment in health care should proceed from a strong conceptual basis, with rationales clearly articulated in advance concerning what is to be measured and how this is to be accomplished. The representation of the patient's perspective has been part of clinical trials for some time; but the formalization of, and broader emphasis on PROs has become increasingly important with the release of the draft guidance for industry on patient-reported outcomes. In response, we address the challenges in constructing the conceptual foundations for PRO assessment to support drug product labeling claims submitted to regulatory agencies worldwide. After discussing what constitutes a PRO concept and an adequate basis for framing a PRO assessment, we examine the consequences of choosing PRO instruments without reference to a well-established conceptual framework for measurement. Then we illustrate through a hypothetical example the important interplay between the sponsor's proposed product claim, the corresponding conceptual model that depicts hypotheses involving the PRO concept(s) in the claim, and the resulting conceptual framework(s) for measurement to guide instrument selection and psychometric analyses. We discuss how these conceptual issues may vary or evolve over time depending on the phase of product development. As the science of PRO measurement continues to develop and experience accumulates, a consensus may emerge on how best to articulate the conceptual basis of PRO measurement for purposes of product labeling and regulation. In the meantime, one point is imminently clear: in regulatory decisions expected to affect not only the quantity but the quality of life, it is imperative to incorporate the patient's own perspective on the illness experience and the effects of therapy.

Purpose: We assessed the change in confidence, relationships and self-esteem, and its correlation with erectile function in men with ED treated with sildenafil citrate in the first United States based, double-blind, placebo controlled, randomized trial assessed by the validated SEAR., Materials and Methods: This 12-week flexible dose (25, 50 or 100 mg) trial determined change scores from baseline to end of treatment for the 5 SEAR components (Sexual Relationship domain, Confidence domain, Self-Esteem subscale [prespecified as the primary end point], Overall Relationship subscale and Overall score), and their correlations with the IIEF and event log data, as well as correlations between SEAR components and a general efficacy question at the end of treatment., Results: Compared with the placebo group (125 patients, mean age +/- SD 55 +/- 13 years, mean years ED 3.8 +/- 4.2), the sildenafil group (128 patients, mean age +/- SD 56 +/- 12, mean years ED 4.6 +/- 4.3) had significantly greater improvements in all 5 SEAR components (p < 0.0001) and all sexual function measures. SEAR component scores showed significant correlations with IIEF Erectile Function domain scores (r range 0.34 to 0.69, p < 0.0001), other IIEF domain scores (p < 0.0001), percentage of successful intercourse attempts (p < 0.0001) and frequency of erection that allowed satisfactory intercourse (p < 0.0001)., Conclusions: In this study of men with ED, sildenafil produced substantial improvements in self-esteem, confidence and relationship satisfaction as measured by SEAR scores, which showed moderate to high positive correlations with IIEF scores.

Objectives: Research is lacking on the correlation between treatment satisfaction and confidence, self-esteem, and relationships for men receiving treatment for erectile dysfunction (ED). We sought to correlate scores between the validated Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) index and the validated Self-Esteem And Relationship (SEAR) questionnaire following treatment with sildenafil citrate (VIAGRA)., Methods: This study was based on an open-label, flexible-dose trial of 93 sildenafil-naive patients with ED. Pearson correlation coefficients between EDITS index and SEAR questionnaire scores, each of which can range from 0 to 100 (most favorable), were calculated at end of treatment (EOT). An analysis of covariance model was applied to associate changes from baseline to EOT in SEAR scores with EDITS score at EOT, controlling for baseline SEAR score., Results: Significant and sizable Pearson's correlations between SEAR and EDITS scores (P < or = 0.0001; range: 0.49-0.84) were observed. A 10-point higher EDITS scores at EOT corresponded to a significant and tangible average improvement in SEAR scores from baseline to EOT (P < or = 0.0001; range: 6.6-8.7). Average SEAR scores at EOT were markedly different between patients with greater treatment satisfaction at EOT (EDITS score > or = median EDITS score of 88.6; n = 50) and those with lesser treatment satisfaction at EOT (EDITS score <88.6; n = 43)., Conclusions: The data add to the validity of the SEAR questionnaire, suggest a tangible relationship between treatment satisfaction and psychosocial benefit among men with ED treated with sildenafil, and highlight the importance of assessing the psychosocial impact of ED in men undergoing treatment.

We consider the problems of interval estimation and hypothesis testing for the intraclass correlation coefficient in an interrater reliability study when both raters and subjects are assumed to be randomly selected from populations of raters and subjects, respectively. We propose a novel approach for the confidence interval estimation and hypothesis testing using the concepts of generalized confidence interval (GCI) and generalized P-values. A simulation study is conducted to investigate the coverage probabilities of the GCI approach relative to the modified large sample (MLS) approach. Both methods tend to provide somewhat conservative coverage. Relative to the MLS approach, the GCI approach is closer to the correct (nominal) coverage for a two-sided interval, but farther to the correct coverage for a one-sided lower interval. Unlike the MLS approach, the GCI approach can also easily provide P-values. The fact that the GCI approach is suitable for confidence interval estimation and obtaining P-values makes the GCI approach a suitable candidate for making inference about interrater reliability., (Copyright 2004 John Wiley & Sons, Ltd.)

We consider the problem of constructing a confidence interval for the intraclass correlation coefficient in an interrater reliability study when both raters and subjects are random effects in a two-way random effects model. A simulation study is conducted to investigate and compare the interval coverage per cents of three methods of approximation: (i) Satterthwaite's two moments, the standard approach; (ii) modified three moments, a newer approach; and (iii) modified large sample, the newest approach for this particular problem. One-sided lower and two-sided bounds are examined. For the two-moment approach, coverage of confidence intervals can be understated for not only one-sided bounds but also two-sided bounds. Coverage of confidence intervals for the modified large-sample approach is either correct or conservative and provides narrower two-sided widths than the modified three-moment approach, which can understate coverage on one-sided and two-sided bounds for two or three raters. The competing methods are illustrated with data from a reliability study of four raters evaluating the number of decayed, missing, and filled surfaces in the permanent teeth of ten subjects. Overall, the modified large-sample approach provides the most satisfactory performance of the three methods., (Copyright 2003 John Wiley & Sons, Ltd.)

Introduction: Health-related quality-of-life (HRQL) can be defined as the impact of disease and treatment across the physical, psychological, social and somatic domains of functioning and well-being. Health-related quality-of-life measures are included in clinical trials of drug treatment to assess the impact of therapy on the patient's functioning. HRQL guidance could allow for use of this data in drug labeling and promotion., Objectives: The aim of our study was to provide recommendations with respect to regulatory issues important to the development of guidelines for HRQL research., Methods: The HRQL workshop was planned jointly by members of the Pharmaceutical Research and Manufacturers of America Health Outcomes Committee and the Division of Drug Marketing, Advertising, and Communications of the Food and Drug Administration. The workshop was limited to six regulatory issues related to HRQL research in clinical trials of pharmaceutical therapies. These six issues were: instrument selection and validation, study design, data analysis, HRQL and safety, clinical meaning, and promotional use. Before the meeting, a consensus was reached that HRQL does not measure, nor should it be used to measure, safety. Therefore, five work groups discussed HRQL issues and made recommendations., Results: Overall, the workshop recommended that HRQL measures be treated as any other clinical end point. The workshop recognized that research in HRQL methods is ongoing and that any guidance should be flexible to allow for changes in this developing research area., Conclusions: HRQL provides a patient perspective on the impact of disease and therapy on patients' daily life and functioning. Including HRQL information in promotion could be beneficial to decision making on the use of therapies. HRQL is a measure of effectiveness, not safety, and should be treated as any other clinical end point.