Understanding the impact of non-alcoholic steatohepatitis with metabolic comorbidities on adults: a real-world qualitative study.

OBJECTIVE: Limited real-world evidence exists to better understand the patient experience of living with symptoms and impacts of non-alcoholic steatohepatitis (NASH). This study aimed to (1) describe patient-reported perspectives of NASH symptoms and impacts on patients' daily lives and (2) develop a patient-centered conceptual NASH model. METHODS: A cross-sectional study using semi-structured qualitative interviews was conducted among adults (≥18 years) in the United States living with NASH. Eligible participants were diagnosed with NASH, had mild to advanced fibrosis (F1-F3), and no other causes of liver disease. The interview guide was informed by a targeted literature review (TLR) to identify clinical signs, symptoms, impacts, and unmet treatment needs of NASH. Participants described their experiences and perspectives around NASH and the symptoms, symptom severity/bother, and impact of NASH on their daily activities. Interviews were audio-recorded and transcribed verbatim for coding and thematic analysis. RESULTS: Twenty participants (age: 42.4 years; female: 50.0%) were interviewed. Participants discussed their experience with NASH symptoms (most frequent: fatigue [75.0%]; weakness/lethargy [70.0%]) and impacts (most frequent: physical and psychological/emotional [70.0% each]; dietary [68.4%]). Participants considered most symptoms to be moderately severe or severe and moderately or highly bothersome. Findings from the TLR and qualitative interviews were incorporated into a conceptual model that describes patient-reported symptoms and impacts of NASH, clinical signs, risk factors, and unmet treatment needs. CONCLUSION: Our study provides insights into patients' perspectives of NASH symptoms and their impact on their daily lives. These findings may guide patient-physician conversations, supporting patient-centered treatment decisions and disease management.

Study findings help to address the gap in current literature about patients' perspectives on NASH and its symptoms as well as its impact on daily life.The study proposes a holistic conceptual model that describes patients' perspectives of living with NASH, including symptoms and their impact, the clinical signs and risk factors of NASH, and the unmet treatment needs of the disease.Healthcare providers can use study findings to inform patient-focused decisions around treatment strategies for NASH.

Development and Validation of the Eyelash Satisfaction Questionnaire.

BACKGROUND: Patient-reported outcome (PRO) measures have been used to assess treatment benefit in a variety of therapeutic areas and are now becoming increasingly important in aesthetic research. OBJECTIVES: The objective of the current study was to develop and validate a new PRO measure (Eyelash Satisfaction Questionnaire [ESQ]) to assess satisfaction with eyelash prominence. METHODS: The content of the questionnaire (including conceptual framework and questionnaire items) was generated by review of literature, participant interviews, and expert opinion. Cognitive interviews were conducted to pilot test the questionnaire. Psychometric properties of the questionnaire were examined in a combined sample of participants (n = 970) completing Internet- (n = 909) and paper-based (n = 61) versions. Item- and domain-level properties were examined using modern and classical psychometrics. RESULTS: Content-based analysis of qualitative data demonstrated the presence of 3 distinct domains (Length, Fullness, Overall Satisfaction; Confidence, Attractiveness, and Professionalism; and Daily Routine). Initial confirmatory factor analysis (CFA) results of 23 items revealed insufficient model-data fit (comparative fit index [CFI] of 0.86 and a non-normed fit index [NNFI] of 0.82). A revised model using 9 items (3 per domain) achieved appropriate fit (CFI of 0.99 and NNFI of 0.97). Analyses revealed measurement equivalence across the Internet- and paper-based versions. The 3 ESQ domains had strong internal consistency reliability (Cronbach's α [range] = 0.919-0.976) and adequate convergent and discriminant validity. CONCLUSIONS: The ESQ was found to be a reliable and valid PRO measure for assessing satisfaction with eyelash prominence. LEVEL OF EVIDENCE 3: Therapeutic.

Development and validation of a novel patient-reported treatment satisfaction measure for hyperfunctional facial lines: facial line satisfaction questionnaire.

BACKGROUND: Facial lines or wrinkles are among the most visible signs of aging, and minimally invasive cosmetic procedures are becoming increasingly popular. AIMS: The aim of this study was to develop and validate the Facial Line Satisfaction Questionnaire (FLSQ) for use in adults with upper facial lines (UFL). METHODS: A literature review, concept elicitation interviews (n = 33), and cognitive debriefing interviews (n = 23) of adults with UFL were conducted to develop the FLSQ. The FLSQ comprises Baseline and Follow-up versions and was field-tested with 150 subjects in a US observational study designed to assess its psychometric performance. Analyses included acceptability (item and scale distribution [i.e. missingness, floor, and ceiling effects]), reliability, and validity (including concurrent validity). RESULTS: In total, 69 concepts were elicited during patient interviews. Following cognitive debriefing interviews, the FLSQ-Baseline version included 11 items and the Follow-up version included 13 items. Response rates for the FLSQ were 100% and 73% at baseline and follow-up, respectively; no items had excessive missing data. Questionnaire scale scores were normally distributed. Most domain scores demonstrated good internal consistency reliability (Cronbach's α ≥ 0.70). Most items within their respective domains exhibited good convergent (item-scale correlations > 0.40) and discriminant (items had higher correlation with their hypothesized scales than other scales) validity. Concurrent validity correlation coefficients of the FLSQ domain scores with the associated concurrent measures were acceptable (range: r = 0.40-0.70). Six FLSQ items demonstrated reliability and validity as stand-alone items outside their domains. CONCLUSIONS: The FLSQ is a valid questionnaire for assessing treatment expectations, satisfaction, impact, and preference in adults with UFL.

The impact of upper facial lines and psychological impact of crow's feet lines: content validation of the Facial Line Outcomes (FLO-11) Questionnaire.

BACKGROUND: Treatments for upper facial lines (UFL), the most visible sign of aging, are of interest to patients and clinicians alike. Patient-reported outcomes (PROs) are valuable in evaluating the impact of such treatments; however, regulatory recommendations have stipulated that the patient perspective be central in developing these assessments. OBJECTIVES: (1) To evaluate the content validity of the Facial Lines Outcomes Questionnaire, a PRO instrument developed to assess upper facial line impacts, according to the regulatory guidance of the United States Food and Drug Administration and (2) assess whether it adequately measures the psychological impacts associated with crow's feet lines (CFL) (lateral canthal lines) from the patient perspective. METHODS: Two patient groups participated in face-to-face qualitative interviews. One group included patients with UFL (Group 1, n = 25 interviews), and the other included patients specifically with CFL (Group 2, n = 41 interviews). Each interview consisted of a concept elicitation and cognitive debriefing phase. RESULTS: Interviews with both groups elicited all key concepts of the instrument, including "bothered by facial lines"; "looking older"; "looking less attractive"; and looking "tired," "stressed," or "angry." Most Group 2 patients (n = 35, 85%) agreed that the instrument adequately assessed the psychological impacts associated with CFL. During cognitive debriefing, the majority of patients in both groups agreed the instrument was understandable, comprehensive, and easy to complete. CONCLUSIONS: The Facial Line Outcomes Questionnaire is an appropriate and valid tool to assess the impact of UFL and the psychological impacts associated with CFL.

Development of a new patient-reported outcome measure for facial acne: the Acne Symptom and Impact Scale (ASIS).

OBJECTIVE: Facial acne has been associated with impaired health-related quality of life, which is an essential patient outcome for evaluating the success of acne treatment. In consideration of the US Food and Drug Administration's (FDA) new recommendations on patient reported outcome (PRO) measures, the objectives of this study were to (1) establish the need for a new PRO measure that assesses facial acne outcomes and satisfies the criteria set forth by the FDA and (2) develop the content of a new facial acne PRO measure appropriate for use in both adolescents and adults as well as adherent to the FDA PRO Guidance. METHODS: A literature and PRO review, patient interviews (concept elicitation), and input from clinical experts were used to develop a conceptual framework for the outcomes deemed important to facial acne patients, and to construct items for a preliminary PRO measure: the Acne Symptom and Impact Scale (ASIS). Cognitive interviews were conducted to pilot test the ASIS. RESULTS: A review of the literature and PROs revealed that, of the 34 measures identified, no suitable PRO measure for the population of interest was available. The conceptual framework comprised two main themes: symptoms and psychosocial impacts. Concept elicitation interviews included a diverse set of patients (n=48) with facial acne, of various ages: 12-17 years (n=15), 18-25 years (n=20), and 26-50 years (n=13). The most frequently reported symptoms were: pimples, oily skin, scabs/scars/marks, blackheads, acne, and whiteheads. The most frequently reported impacts were impacts on appearance, self-consciousness, annoyance, bothersomeness, mood, social criticism, embarrassment, confidence, and social withdrawal. These reported symptoms and impacts constituted the 15-item draft ASIS. The draft ASIS was modified following the analysis of 20 cognitive interviews, resulting in the current 17-item ASIS. CONCLUSIONS: Results from both the concept elicitation and cognitive interviews demonstrated that the ASIS is content valid in both adolescents and adults with facial acne. The ASIS will undergo psychometric evaluation to further support its validity in both adolescents and adults with facial acne.

Incorporating indirect costs into a cost-benefit analysis of laparoscopic adjustable gastric banding.

OBJECTIVES: The objective of this study was to estimate the time to breakeven and 5-year net costs of laparoscopic adjustable gastric banding (LAGB) taking both direct and indirect costs and cost savings into account. METHODS: Estimates of direct cost savings from LAGB were available from the literature. Although longitudinal data on indirect cost savings were not available, these estimates were generated by quantifying the relationship between medical expenditures and absenteeism and between medical expenditures and presenteeism (reduced on-the-job productivity) and combining these elasticity estimates with estimates of the direct cost savings to generate total savings. These savings were then combined with the direct and indirect costs of the procedure to quantify net savings. RESULTS: By including indirect costs, the time to breakeven was reduced by half a year, from 16 to 14 quarters. After 5 years, net savings in medical expenditures from a gastric banding procedure were estimated to be $4970 (±$3090). Including absenteeism increased savings to $6180 (±$3550). Savings were further increased to $10,960 (±$5864) when both absenteeism and presenteeism estimates were included. CONCLUSIONS: This study presented a novel approach for including absenteeism and presenteeism estimates in cost-benefit analyses. Application of the approach to gastric banding among surgery-eligible obese employees revealed that the inclusion of indirect costs and cost savings improves the business case for the procedure. This approach can easily be extended to other populations and treatments.

Direct and indirect costs and potential cost savings of laparoscopic adjustable gastric banding among obese patients with diabetes.

OBJECTIVE: To estimate the time to breakeven and 5-year net costs for laparoscopic adjustable gastric banding among obese patients with diabetes taking direct and indirect costs into account. METHODS: Indirect cost savings were generated by quantifying the cross-sectional relationship between medical expenditures and absenteeism and between medical expenditures and presenteeism (reduced on-the-job productivity) and simulating indirect cost savings based on these multipliers and reductions in direct medical costs available in the literature. RESULTS: Time to breakeven was estimated to be nine quarters with and without the inclusion of indirect costs. After 5 years, net savings increase from $26570 (±$9000) to $34160 (±$10 380) when indirect costs are included. CONCLUSION: This study presented a novel approach for incorporating indirect costs into cost-benefit analyses. Application to gastric banding revealed that inclusion of indirect costs improves the financial outlook for the procedure.

Financial implications of coverage for laparoscopic adjustable gastric banding.

BACKGROUND: Employers and insurers have become increasingly concerned about the cost implications of providing coverage for bariatric procedures. We sought to quantify the costs and potential cost savings resulting from coverage for laparoscopic adjustable gastric banding (LAGB) using a claims analysis. METHODS: U.S. healthcare claims data of >7000 LAGB patients and a propensity score-matched control group were used to quantify the costs and potential cost savings resulting from LAGB for the overall surgery-eligible population and for the subset of the surgery-eligible population with diabetes mellitus. The matched control group consisted of those with a morbid obesity diagnosis code and/or a body mass index >35 kg/m(2) as reported in the Health Risk Assessment data. RESULTS: Including the related medical payments in the 90 days before and after the procedure, the mean cost of LAGB was approximately $20,000. After placement, a modest reduction occurred in the health expenditures relative to the preoperative payments. In the postoperative period, these decreases were maintained for the LAGB sample. In contrast, the payments for the comparison sample continued to increase. As a result, the net cost of coverage for LAGB was reduced to 0 by approximately 4 years after band placement. For those with diabetes, the net costs resulting from LAGB were reduced to 0 in just >2 years. CONCLUSION: These results suggest that the LAGB procedure pays for itself within a relatively short period, especially for those with diabetes.

The costs of obesity in the workplace.

OBJECTIVE: To quantify per capita and aggregate medical expenditures and the value of lost productivity, including absenteeism and presenteeism, because of overweight, and grade I, II, and III obesity among U.S. employees. METHODS: Cross-sectional analysis of the 2006 Medical Expenditure Panel Survey and the 2008 National Health and Wellness Survey. RESULTS: Among men, estimates range from -$322 for overweight to $6087 for grade III obese men. For women, estimates range from $797 for overweight to $6694 for grade III. In aggregate, the annual cost attributable to obesity among full-time employees is $73.1 billion. Individuals with a body mass index >35 represent 37% of the obese population but are responsible for 61% of excess costs. CONCLUSIONS: Successful efforts to reduce the prevalence of obesity, especially among those with a body mass index >35, could result in significant savings to employers.

Patient perspectives on the impact of fibromyalgia.

OBJECTIVE: The objective of this study was to elicit and assess important symptom domains and the impact of fibromyalgia on patients' quality of life and functioning from a patient's perspective. The intention was to collect this information as part of an overall effort to overcome shortcomings of existing outcome measures in fibromyalgia. METHODS: This was a qualitative study in which six focus group sessions with 48 women diagnosed with fibromyalgia were conducted to elicit concepts and ideas to assess the impact of fibromyalgia on their lives. RESULTS: The focus groups conducted with fibromyalgia patients identified symptom domains that had the greatest impact on their quality of life including pain, sleep disturbance, fatigue, depression, anxiety, and cognitive impairment. Fibromyalgia had a substantial negative impact on social and occupational function. Patients reported disrupted relationships with family and friends, social isolation, reduced activities of daily living and leisure activities, avoidance of physical activity, and loss of career or inability to advance in careers or education. CONCLUSION: The findings from the focus groups revealed that fibromyalgia has a substantial negative impact on patients' lives. PRACTICE IMPLICATIONS: A comprehensive assessment of the multiple symptoms domains associated with fibromyalgia and the impact of fibromyalgia on multidimensional aspects of function should be a routine part of the care of fibromyalgia patients.

Development and cross-sectional validation of the Childhood Asthma Control Test.

BACKGROUND: For children younger than 12 years old with asthma, there are several quality-of-life instruments, clinical diaries, and questionnaires assessing symptoms; however, a validated tool for assessing asthma control is currently lacking. OBJECTIVE: To develop and validate the Childhood Asthma Control Test (C-ACT), a self-administered tool for identifying children aged 4-11 years whose asthma is inadequately controlled. METHODS: A 21-item questionnaire was administered to 343 patients with asthma and their caregivers, randomly assigning 75% (n = 257) for development and cross-sectional validation of the tool and 25% (n = 86) to a confirmatory sample. Stepwise logistic regression was used to reduce the 21 items to those best able to discriminate control as defined by the specialist's rating of asthma control. RESULTS: Seven items were selected from regression analyses of the development sample to comprise the C-ACT. The scores of each item were summed for a total score (0-27), with lower scores indicating poorer control. Summed scores discriminated between groups of patients differing in the specialists' rating of asthma control (F = 36.89; P < .0001), the need for change in patients' therapy (F = 20.07; P < .0001), and % predicted FEV(1) (F = 2.66; P = .0494). A score of 19 indicated inadequately controlled asthma (specificity 74%, sensitivity 68%). These analyses were confirmed in the confirmatory sample. CONCLUSION: The C-ACT is a validated tool to assess asthma control and identify children with inadequately controlled asthma. CLINICAL IMPLICATIONS: The C-ACT can be valuable in clinical practice and research based on its validation, ease of use, input from the child and caregiver, and alignment with asthma guidelines.

Frequency, predictors, and economic impact of upward dose adjustment of infliximab in managed care patients with rheumatoid arthritis.

OBJECTIVE: To examine dosing patterns and costs among rheumatoid arthritis (RA) patients newly treated with infliximab in a large national health care claims database. METHODS: Using data from a proprietary database of pharmacy and medical claims for 75 U.S. health plans, RA patients newly treated with infliximab between June 2000 and June 2002 were selected and assigned an .index date. based on the first infusion. A pretreatment period of 6 months was created; patients were also followed for a minimum of 6 months after the initial infusion. Follow-up was allowed to vary beyond this minimum 6 months in order to preserve all available patient data. A maintenance number of infliximab vials was determined as of the second infusion; patients with 1 subsequent increase in vials used or 2 intervals between infusions of <49 days were considered to have had an upward dose adjustment. Differences (i.e., between those with upward dose adjustment and those with no upward dose) in patient characteristics were examined using descriptive statistics. In addition, time to upward dose adjustment and factors influencing its likelihood were analyzed using Kaplan-Meier and Cox proportional hazards techniques. Finally, differences in RA-related and unrelated costs (medication, outpatient, inpatient, and total, expressed in 2003 dollars) were examined using Wilcoxon rank-sum tests and were also stratified by a number of patient characteristics found to differ between the 2 groups. RESULTS: A total of 1,236 patients met all study entry criteria and were included in these analyses. One or more upward dose adjustments were experienced by 61.7% (N=762) of patients during an average of 15 months of follow-up (median =13 months, range=6 to 31 months). The majority (63.3%) of upward dose adjustments were due to increases in the number of billed vials. Median time to upward dose adjustment was 254 days and declined steadily based on year of initiation (from 330 days in 2000 to 224 days in 2002). Factors significantly influencing upward dose adjustment included pretreatment use of leflunomide, comorbid Crohn.s disease, and pretreatment liver function testing. During followup, patients in the upward dose adjustment group used a mean (SD) of 30.28 (20.90) vials of infliximab, compared with 15.90 (14.28) among those not adjusting dose (P<0.001). Annualized (i.e., standardized to a 365-day rate) RA-related costs were higher by more than 50% among patients with upward dose adjustment (SD $22,283 [$20,517] versus $14,425 [$10,828] for those without upward dose adjustment; P<0.001); differences were driven almost entirely by the costs of infliximab itself ($16,336 [$9,490] versus $9,573 [$6,790], P<0.001). CONCLUSIONS: In a cohort of managed care members with RA, upward dose adjustment with infliximab was frequent and appeared to occur earlier in the drug therapy in 2002 compared with 2000. Upward dose adjustment was associated with significant increases in drug treatment costs; therefore, payers and providers should consider the impact of current dosing trends when monitoring the use of biologics for autoimmune diseases.

How much is enough and who says so?

BACKGROUND: One of the challenges of health-related quality of life research is to translate statistically significant health-related quality of life changes into interpretable clinical or medically important ones. OBJECTIVE: To calculate the minimal important difference of the King's Health Questionnaire, a condition-specific health-related quality of life questionnaire for the assessment of men and women with lower urinary tract dysfunction. METHODS: The King's Health Questionnaire was administered to patients suffering from overactive bladder enrolled in two multinational studies. Minimal important differences were calculated using an anchor-based approach with both a global rating of patient-perceived treatment benefit and one of perceived disease impact. A distribution-based method using effect size was calculated for comparison purposes. RESULTS: Minimal important difference values varied slightly with each method. Using the anchor-based approach, the King's Health Questionnaire minimal important difference ranged between 5-10 points when the calculation factored out patients who reported no change and 6-12 points for patients who experienced a small improvement. The effect size method indicated a minimal important difference of 5 to 6 points for a small effect and 10 to 15 points for a medium effect. CONCLUSIONS: In the case of the King's Health Questionnaire, the anchor-based approaches and the distribution-based approach provide similar results. A change from baseline of at least 5 points on King's Health Questionnaire domains indicates a change that is meaningful to patients and is indicative of a clinically meaningful improvement in health-related quality of life after treatment. Convergence of the estimates using different approaches should give us confidence in the values derived for the quality of life domains measured by the King's Health Questionnaire.

Long-term health-related quality of life of patients receiving extended-release tolterodine for overactive bladder.

OBJECTIVE: To evaluate the long-term effects of tolterodine on the health-related quality of life (HRQoL) of patients diagnosed with overactive bladder with incontinence. METHODS: Patients who completed a 12-week randomized, double-blind, safety and efficacy trial comparing tolterodine with placebo were invited to enroll in a 12-month open-label continuation trial to assess the long-term safety and efficacy of tolterodine. This study reports the HRQoL results from the King's Health Questionnaire (KHQ) and the Short Form-36 (SF-36) that were administered at baseline, at the end of the 12-week trial, and 3 and 12 months following open-label treatment with tolterodine. RESULTS: One thousand seventy-seven patients were included in the intent-to-treat (ITT(B)) population. KHQ translations were available for 838 patients (mean age, 61.1 years; 80.9% women) in the ITT(B) population. HRQoL, as measured by the KHQ, significantly improved from baseline to months 3 and 12 on the following domains: incontinence impact, role limitations, physical limitations, social limitations, personal relationships, emotions, sleep and energy, severity (coping) measures, and symptom severity. Improvements were generally consistent across all analyses for the 3- and 12-month measurements and for the ITT(B) and completer (C(B)) populations. Patients receiving tolterodine in the double-blind study showed additional improvement at the 3-month open-label assessment on all but the general health domain. At 12 months from treatment rollover, all improvements from rollover to 3 months were sustained with additional improvement seen on the incontinence impact and role limitations domains. The general health perceptions domain showed a slight decline from rollover that might be attributable to a natural decline in patients' health status at this life stage. These findings were consistent with other efficacy results whereby efficacy was maintained over the 12-month open-label period. SF-36 results were consistent with previous experience of reduced sensitivity, as population groups were similar to the SF-36 Physical Component and Mental Component scores at various time points and with all populations. CONCLUSION: Continued treatment with tolterodine provides additional benefits in HRQoL as measured by the KHQ. Of particular importance are improvements on the psychological aspects after longer-term treatment not detected after a short-term trial. Treatment effects on HRQoL are evident even after a 12-week placebo run-in supporting the true clinical effect of active treatment.