Real-World Analysis of Dispensed International Units of Coagulation Factor VIII and Resultant Expenditures for Hemophilia A Patients: A Comparison Between Standard Half-Life and Extended Half-Life Products.

PURPOSE: To identify international units (IUs) dispensed and consequent expenditures for standard half-life (SHL) versus extended half-life (EHL) recombinant factor VIII (rFVIII) replacement products in hemophilia A patients in a real-world setting. DESIGN: Two U.S. claims databases were analyzed. METHODOLOGY: Number of IUs dispensed and quarterly expenditures for rFVIII products were collected from the Optum Clinformatics Data Mart and Truven Health MarketScan Databases. Truven claims were also analyzed for factor IUs dispensed and expenditures for patients with data for ≥3 months before and after switching to an EHL product. RESULTS: The Optum and Truven databases, respectively, included 276 (SHL, n=243; EHL, n=33) and 500 (SHL, n=409; EHL, n=91) hemophilia A patients. Median quarterly factor IUs dispensed in Optum were 10% higher with EHL versus SHL products over nine quarters, and 45% higher with EHL versus SHL products in Truven over 10 quarters. Median quarterly expenditures in the EHL cohort were 51% (individual quarterly medians range, 1%-101%) higher than in the SHL cohort in Optum and 122% higher (individual quarterly medians range, 1%-189%) in Truven. Twenty-nine Truven patients switched to an EHL product; median factor IUs dispensed varied quarterly. The lowest SHL and highest EHL values occurred in the quarter immediately before switching and the first quarter post-switch, respectively. Overall median quarterly expenditures were higher post-switch; this was consistent over seven quarters. CONCLUSION: We found higher expenditures over two years for hemophilia A patients using EHL versus SHL products. Switching to an EHL rFVIII product was associated with variable factor IUs dispensed and consistently higher expenditures.

Pediatric patient-reported outcome instruments for research to support medical product labeling: report of the ISPOR PRO good research practices for the assessment of children and adolescents task force.

BACKGROUND: Patient-reported outcome (PRO) instruments for children and adolescents are often included in clinical trials with the intention of collecting data to support claims in a medical product label. OBJECTIVE: The purpose of the current task force report is to recommend good practices for pediatric PRO research that is conducted to inform regulatory decision making and support claims made in medical product labeling. The recommendations are based on the consensus of an interdisciplinary group of researchers who were assembled for a task force associated with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). In those areas in which supporting evidence is limited or in which general principles may not apply to every situation, this task force report identifies factors to consider when making decisions about the design and use of pediatric PRO instruments, while highlighting issues that require further research. GOOD RESEARCH PRACTICES: Five good research practices are discussed: 1) Consider developmental differences and determine age-based criteria for PRO administration: Four age groups are discussed on the basis of previous research (<5 years old, 5-7 years, 8-11 years, and 12-18 years). These age groups are recommended as a starting point when making decisions, but they will not fit all PRO instruments or the developmental stage of every child. Specific age ranges should be determined individually for each population and PRO instrument. 2) Establish content validity of pediatric PRO instruments: This section discusses the advantages of using children as content experts, as well as strategies for concept elicitation and cognitive interviews with children. 3) Determine whether an informant-reported outcome instrument is necessary: The distinction between two types of informant-reported measures (proxy vs. observational) is discussed, and recommendations are provided. 4) Ensure that the instrument is designed and formatted appropriately for the target age group. Factors to consider include health-related vocabulary, reading level, response scales, recall period, length of instrument, pictorial representations, formatting details, administration approaches, and electronic data collection (ePRO). 5) Consider cross-cultural issues. CONCLUSIONS: Additional research is needed to provide methodological guidance for future studies, especially for studies involving young children and parents' observational reports. As PRO data are increasingly used to support pediatric labeling claims, there will be more information regarding the standards by which these instruments will be judged. The use of PRO instruments in clinical trials and regulatory submissions will help ensure that children's experience of disease and treatment are accurately represented and considered in regulatory decisions.

Psychometric assessment of the Injection Pen Assessment Questionnaire (IPAQ): measuring ease of use and preference with injection pens for human growth hormone.

PURPOSE: To examine the psychometric properties of the Injection Pen Assessment Questionnaire (IPAQ) including the following: 1) item and scale characteristics (e.g., frequencies, item distributions, and factor structure), 2) reliability, and 3) validity. METHODS: Focus groups and one-on-one dyad interviews guided the development of the IPAQ. The IPAQ was subsequently tested in 136 parent-child dyads in a Phase 3, 2-month, open-label, multicenter trial for a new Genotropin(®) disposable pen. Factor analysis was performed to inform the development of a scoring algorithm, and reliability and validity of the IPAQ were evaluated using the data from this two months study. Psychometric analyses were conducted separately for each injection pen. RESULTS: Confirmatory factor analysis provides evidence supporting a second order factor solution for four subscales and a total IPAQ score. These factor analysis results support the conceptual framework developed from previous qualitative research in patient dyads using the reusable pen. However, the IPAQ subscales did not consistently meet acceptable internal consistency reliability for some group level comparisons. Cronbach's alphas for the total IPAQ score for both pens were 0.85, exceeding acceptable levels of reliability for group comparisons. CONCLUSIONS: The total IPAQ score is a useful measure for evaluating ease of use and preference for injection pens in clinical trials among patient dyads receiving hGH. The psychometric properties of the individual subscales, mainly the lower internal consistency reliability of some of the subscales and the predictive validity findings, do not support the use of subscale scores alone as a primary endpoint.

Real-world outcomes associated with standard half-life and extended half-life factor replacement products for treatment of haemophilia A and B.

: Standard-of-care treatment for haemophilia A or B is to maintain adequate coagulation factor levels through clotting factor administration. The current study aimed to evaluate annualised bleeding rates (ABR) and treatment adherence for haemophilia A or B patients receiving standard half-life (SHL) vs. extended half-life (EHL) factor replacement products. We analysed data from the Adelphi Disease-Specific Programmes, a health record-based survey of United States and European haematologists. Analysis included 651 males with moderate-to-severe haemophilia A or B (the United States, n = 132; Europe, n = 519). The haemophilia A analysis included 501 patients (SHL, n = 435; EHL, n = 66). In the combined United States/European population, mean (SD) ABR was 1.7 (1.69) for the SHL group and 1.8 (2.00) for the EHL group. A total of 72% of patients receiving SHL factor VIII and 75% of patients receiving EHL factor VIII in the combined population were fully adherent (no doses missed of the last 10 doses), as reported by physicians. The haemophilia B analysis included 150 patients (SHL, n = 114; EHL, n = 36). The mean (SD) ABR in the combined population was 2.1 (2.16) for patients receiving SHL factor IX (FIX) and 1.4 (1.48) for patients receiving EHL FIX. The percentage of fully adherent patients (physician-reported) was similar in both treatment groups (SHL FIX, 68%; EHL FIX, 73%). In this preliminary real-world survey in a relatively small sample of patients, measures of ABR and adherence between SHL and EHL products were evaluated. Additional real-world research on prescribing patterns, SHL vs. EHL effectiveness, and adherence is warranted.

Development and Psychometric Evaluation of the Life Interference Questionnaire for Growth Hormone Deficiency (LIQ-GHD) to Assess Growth Hormone Injection Burden in Children and Adults.

BACKGROUND: Current recombinant human growth hormone (r-hGH) replacement therapy involves long-term daily subcutaneous injections to treat growth hormone deficiency (GHD) in children and adults. Daily r-hGH injections can be burdensome, often resulting in poor treatment compliance. Clinical outcome assessments (COAs) can capture the burden of these injections from the patient (and caregiver) perspective and may demonstrate the benefit of a less-frequent r-hGH injection regimen, which may ultimately improve treatment compliance and long-term outcomes. OBJECTIVE: To address this knowledge gap, qualitative research was conducted to inform the development of a new Life Interference Questionnaire for Growth Hormone Deficiency (LIQ-GHD), designed to measure the experiences of patients taking r-hGH GHD injections. A second objective was to evaluate the hypothesized factor structure and preliminary performance of the LIQ-GHD in a cross-sectional observational study. METHODS: An empirical literature review and expert advice meetings were conducted to inform development of the draft LIQ-GHD (pediatric and adult versions). In-person concept elicitation and cognitive debriefing interviews were conducted with GHD patients (and patient dyads including caregivers) to explore and confirm concept coverage and evaluate respondents' ability to understand the questionnaire. The draft LIQ-GHD was then tested in a cross-sectional field study involving pediatric and adult patients receiving daily r-hGH injections for GHD. The factor structure, reliability, and validity were analyzed for the overall sample and for pediatric, adolescent, and adult subgroups. RESULTS: Results from the literature review and input from six experts were used to develop and refine the LIQ-GHD, with content covering pen ease of use; regimen convenience; life interference due to regimen; benefit/satisfaction/willingness to continue treatment; regimen choice/preference; intent to comply with regimen; injection-related signs/symptoms; and reasons for missed injections. Twenty-one patient interviews confirmed comprehensive concept coverage and patient/caregiver comprehension of the LIQ-GHD. A total of 224 patients (n = 70 children/caregiver dyads, n = 79 adolescents/caregiver dyads, n = 75 adults) participated in the field study. While most items showed floor effects, confirmatory factor analysis fit statistics were good for the overall sample (root mean square error of approximation = 0.07, comparative fit index = 0.98) and for the full pediatric sample after dropping co-dependent questions from the model. Cronbach's alpha (α) ranged from 0.746 to 0.905 and intra-class correlation coefficients ranged from 0.761 to 0.918 for the overall sample on LIQ-GHD domains. Scores correlated as predicted with an existing criterion measure in the overall sample and LIQ-GHD domain scores distinguished known groups as expected. CONCLUSIONS: The LIQ-GHD is a new COA for the measurement of r-hGH injection treatment burden. This research provides evidence supporting its content validity, hypothesized factor structure, score reliability, and construct validity in pediatric and adult populations.

Predicting EQ-5D utility scores from the 25-item National Eye Institute Vision Function Questionnaire (NEI-VFQ 25) in patients with age-related macular degeneration.

PURPOSE: In this study, we explored different statistical approaches to identify the best algorithm to predict EQ-5D utility scores from the NEI-VFQ 25 in patients with age-related macular degeneration (AMD). METHODS: Ordinary least squares (OLS), Tobit, and censored least absolute deviation (CLAD) approaches were compared using cross-sectional data (primary dataset, n = 151) at screening from a phase I/II clinical trial in patients with AMD. Three models were specified in this study: full (includes all 12 dimensions of the NEI-VFQ 25), short (includes only the general health dimension and the composite score), and reduced model (using stepwise regression). To evaluate the predictive accuracy of the models, the mean absolute prediction error (MAPE), mean error, and root means squared error were calculated using in-sample cross-validation (within the primary dataset) and out-of-sample validation using an independent dataset (n = 393). The model that provided the lowest prediction errors was chosen as the best model. RESULTS: In-sample cross-validation and out-of-sample validation consistently demonstrated that, compared to other approaches, heteroscedasticity-adjusted OLS produced the lowest MAPE (mean values were 0.1400, 0.1593, respectively) for the full model, while CLAD performed best for the short and reduced models (mean values were 0.1299, 0.1483, respectively). The normality and homoscedasticity assumptions of both OLS and Tobit were rejected. CLAD, however, can accommodate these particular violations. CONCLUSIONS: The CLAD-short model is recommended for producing the EQ-5D utility scores when only the NEI-VFQ 25 data are available.

Cost-effectiveness model for neovascular age-related macular degeneration: comparing early and late treatment with pegaptanib sodium based on visual acuity.

OBJECTIVE: To compare the cost-effectiveness of pegaptanib and usual care within three distinct cohorts of subfoveal neovascular age-related macular degeneration (NV-AMD) patients, that is, those with early, moderate, and late disease, using a comprehensive economic model. METHODS: A Markov framework was used to model lifetime movement of a subfoveal NV-AMD cohort through health states based on visual acuity. The model takes a US payer perspective of patients over the age of 65 years. Clinical efficacy was based on published results for the 0.3 mg pegaptanib and usual care groups. Expert interviews were conducted to determine adverse event treatment patterns and vision rehabilitation resource use. Incidence and costs of comorbidities such as depression and fractures associated with the effects of declining visual acuity were based on our previously published analysis of Medicare data. Transition probabilities were derived from published clinical trial data for each 3-month cycle. Utilities were derived from published sources. Three runs of the model were conducted with cohorts of newly diagnosed patients. Patients were classified as having early, moderate, or late NV-AMD defined as visual acuity in the better-seeing eye of 20/40 to more than 20/80, 20/80 to more than 20/200, and 20/200 to more than 20/400, respectively. Costs and outcomes were discounted 3.0% per annum. RESULTS: Incremental costs per vision-year gained and per quality-adjusted life-year (QALY) gained for early NV-AMD patients were approximately one-third those of patients with late disease ($15,279 vs. $57,230 and $36,282 vs. $132,381, respectively). On average, patients treated early with either pegaptanib or usual care incurred lower lifetime total direct costs than those treated later. Sensitivity analysis showed that base-case incremental costs per QALY gained for pegaptanib versus usual care were relatively robust. CONCLUSIONS: For patients with subfoveal NV-AMD, treatment with pegaptanib should be started as early as possible to maximize the clinical and economic benefits.

Real-World Analysis of Dispensed IUs of Coagulation Factor IX and Resultant Expenditures in Hemophilia B Patients Receiving Standard Half-Life Versus Extended Half-Life Products and Those Switching from Standard Half-Life to Extended Half-Life Products.

BACKGROUND: Hemophilia B requires replacement therapy with factor IX (FIX) coagulation products to treat and prevent bleeding episodes. A recently introduced extended half-life (EHL) recombinant FIX replacement product provided the opportunity to compare the amount of dispensed factor and expenditures for EHL treatment compared with a standard half-life (SHL) product. OBJECTIVE: To determine factor international units (IUs) dispensed and expenditures associated with switching from nonacog alfa, the most commonly used SHL replacement product, to eftrenonacog alfa, an EHL FIX replacement product. METHODS: Two U.S. claims databases were analyzed. A large national specialty pharmacy dispensation claims database was used to identify the number of IUs dispensed and monthly charges for all patients with hemophilia B from April 2015 to June 2016. Truven Health MarketScan Research Databases (January 2010-July 2016) were used to identify IUs and expenditures for patients with claims data for at least 3 months before and after switching from the SHL to the EHL product. Medians for IUs and expenditures are presented to accommodate for skewness of data distribution. RESULTS: The national specialty pharmacy database analysis included 296 patients with moderate or severe hemophilia B (233 on SHL; 94 on EHL). Median monthly factor dispensed was 11% lower (2,142 IU) in the EHL versus SHL cohort over the study period, while individual monthly reductions ranged from 32% to 47% (9,838 IU to 16,514 IU). Using the wholesale acquisition cost, the median per-patient monthly factor expenditures over the 15-month study period were 94% higher ($23,005) for the EHL than for the SHL product. Individual median monthly expenditure differences ranged from 15% ($6,562) to 49% ($19,624). In the Truven database, 14 patients switched from the SHL to the EHL product. The amount of factor dispensed was variable; in the 1-year period before and after the switch from the SHL to the EHL product, mean IUs dispensed decreased by 3,005 IU, while median IUs dispensed increased by 4,775 IU. Factor replacement expenditures were higher after switching from the SHL to the EHL product in each of the 3-month periods examined before versus after the switch. CONCLUSIONS: This analysis of real-world data showed that switching from the SHL to the EHL product was associated with higher expenditures. Increased expenditures noted in the first 3 months after switching may be related to initial stocking up of the EHL product, but expenditures were sustained throughout the 1-year period of data analysis. Further analysis of these findings with larger numbers of patients should be explored. DISCLOSURES: This study was sponsored by Pfizer. Pfizer employees were involved in the study design; the collection, analysis, and interpretation of data; the review of the manuscript; and the decision to submit for publication. All authors are employees of Pfizer. No author received an honorarium or other form of payment related to the development of this manuscript. All authors participated in the study design, data interpretation, and manuscript review and revisions and granted approval for the submission of the manuscript. Alvir, McDonald, and Tortella also participated in data analysis. Data from this paper were presented in part at the European Association for Haemophilia and Allied Disorders Annual Meeting, February 1-3, 2017, Paris, France; at the International Society for Pharmacoeconomics and Outcomes Research Annual Meeting, May 20-24, 2017, Boston, MA; and at the International Society on Thrombosis and Haemostasis Congress, July 8-13, 2017, Berlin, Germany.

Health-related quality of life of patients receiving extended-release tolterodine for overactive bladder.

OBJECTIVE: To compare the health-related quality of life (HRQoL) of overactive bladder (OAB) patients foilowing treatment with tolterodine extended-release (ER) 4 mg once daily versus placebo. STUDY DESIGN: Multinational, placebo-controlled, randomized, double-blind 12-week study. POPULATION: Patients with urinary frequency ( > or = 8 micturitions/24 hours over a 7-day period), urge incontinence ( > or = 5 episodes/week), and symptoms of OAB for at least 6 months were eligible for inclusion. Patients (81% female) received oral therapy with tolterodine ER (n = 507) or placebo (n = 508) for 12 weeks. OUTCOMES MEASURED: HRQoL was assessed using the King's Health Questionnaire (KHQ) and Medical Outcomes Study Short Form 36-item questionnaire (SF-36). Patients also rated their bladder condition. Assessments were performed at baseline and at the end of treatment. RESULTS: At end of treatment, KHQ domains selected a priori as primary HRQoL end points (incontinence impact and role limitations) significantly improved (P < or = .001) with tolterodine ER. Domains selected a priori as secondary end points (physical limitations, sleep and energy, severity [coping] measures, and symptom severity) were also significantly improved (P < or = .006) following treatment with tolterodine ER. The tolterodine ER group had decreased symptom severity and statistically significant improvements in patient rating of bladder control compared with the placebo group at end of treatment. No treatment differences were detected using the SF-36. CONCLUSION: Many aspects of HRQoL, as measured by the KHQ, showed statistically significant improvement following treatment with tolterodine ER. These HRQoL improvements were consistent with clinical efficacy benefits. Patients receiving tolterodine ER experienced overall improvement in their condition that was associated with an important impact on their HRQoL.

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.

Results from an international multicenter trial evaluating the ease-of-use of and preference for a newly developed disposable injection pen for the treatment of growth hormone deficiency in treatment-naïve children and adults.

Previous research has reported that ease of use of and preference for a delivery device are associated with greater patient compliance - an important factor in achieving optimal therapeutic results. The objective of this study was to assess the ease-of-use of a new disposable pen (GoQuick(®), Pfizer, Inc.) versus the current reusable pen (GENOTROPIN Pen(®), Pfizer, Inc.) to inject a daily dose of recombinant DNA origin human growth hormone, Genotropin(®) (somatropin) in standard practice. In this randomized, crossover, multicenter, multinational, open-label study, ease-of-use of and preference for the two pens were assessed in three treatment-naïve populations: 1) parents of very young children; 2) parent-child dyads; and 3) adults via use of a validated self-report Injection Pen Assessment Questionnaire (IPAQ) after 2 months of at-home-use experience. The primary endpoint was the proportion of participants who reported the new disposable pen to be no different from or easier to use than the current reusable pen. Safety was also assessed and reported according to local legal requirements. Of the 120 screened patients, 119 were included in the ease-of-use analysis and all were included in the safety analyses. In all, 67.2% found the new somatropin disposable pen to be no different from or easier to use than the reusable pen (95% confidence interval: 58.8-75.7). Most adverse events were mild or moderate. No deaths or device- or treatment-related serious adverse events were reported. These results suggest that improvements made to the reusable somatropin pen are tangible and recognizable to treatment-naïve patients and their caregivers, child-caregiver dyads, and adults, and may positively impact continued compliance with therapy. REGISTRY INFORMATION: ClinicalTrials.gov identifier: NCT01112865.

Changes in vision- and health-related quality of life in patients with diabetic macular edema treated with pegaptanib sodium or sham.

PURPOSE: To compare vision function and self-reported quality of life (QoL) in patients with diabetic macular edema (DME) treated with intravitreous pegaptanib 0.3 mg or sham injection. METHODS: This randomized (1:1), controlled, multicenter trial included subjects with DME (center point thickness on OCT, ≥ 250 µm) and visual acuity (VA) ≤ 65 letters and ≥ 35 letters. In year 1, pegaptanib or sham was administered every 6 weeks with focal/grid photocoagulation at investigator discretion after week 18. Subjects received injections as often as every 6 weeks per pre-specified criteria in year 2. Primary efficacy endpoint: proportion gaining ≥10 letters of VA from baseline to week 54. Change in QoL from baseline to weeks 54 and 102 was assessed with the 25-item National Eye Institute-Visual Function Questionnaire (NEI-VFQ 25) and the EQ-5D. RESULTS: One hundred thirty-three pegaptanib- and 127 sham-treated subjects were in the year 1 intent-to-treat population. From baseline to week 54, ≥ 10 letter gains seen in 49 (36.8%) pegaptanib- and 25 (19.7%) sham-treated subjects (odds ratio [95% CI]: 2.38 [1.32-4.30]; P = 0.0047). At 2 years, the VA trend favored pegaptanib. The NEI-VFQ 25 domains of Near Vision, Distance Vision, and Social Functioning (week 54) and Distance Vision, Social Functioning, Mental Health, and Composite Score (week 102) demonstrated clinically meaningful (>5-point between-group difference) and statistically significant (P < 0.05) benefits favoring pegaptanib. No significant difference in the mean change in generic EQ-5D-weighted utility scores was seen. CONCLUSIONS: The VA improvement from pegaptanib treatment versus sham is reflected by improved vision-related QoL as reported by the DME patient (ClinicalTrials.gov number, NCT00605280).

Patient preferences for diabetic retinopathy health States.

PURPOSE. To develop standardized descriptions of health states that characterize vision-specific functional impacts of diabetic retinopathy (DR) according to levels of visual acuity and contrast sensitivity and to elicit preferences for these health states from persons with DR and assign weighted values to them. METHODS. Vision-specific descriptions of health states were developed based on a literature review and patient and physician interviews. The content was based on items from the National Eye Institute Visual Functioning Questionnaire (VFQ) and reflected functional impacts experienced by DR patients. Values were assigned to the range of health states, anchored by the extremes full vision and death, by using the time-tradeoff method in a sample of 98 Canadian DR patients from three clinical centers. RESULTS. The mean age of the sample was 60.4 years, and 56% were men. Mean preferences decreased from 0.98 (better-eye logMAR [Snellen equivalent] acuity, > or =20/40; worse-eye Snellen equivalent, > or =20/200) to 0.67 (Snellen equivalent visual acuity, < or =20/200, contrast sensitivity, < or =21 letters bilaterally). Preferences decreased with increasing severity of functional deficits and did not vary significantly by sex, age, VFQ quartile, or better- or worse-eye acuity. CONCLUSIONS. This is the first study that has been conducted to estimate preferences for standardized DR-specific health states, accounting for visual acuity and contrast sensitivity in both eyes. The results showed that the development and progression of DR are associated with substantial declines in preferences. In addition to the progressively greater impact from declining ETDRS visual acuity and contrast sensitivity, preference weights declined with increasing bilateral disparity. These preference values are useful for comparing the cost effectiveness of ophthalmic treatments.

Photodynamic therapy with verteporfin in age-related macular degeneration: a systematic review of efficacy, safety, treatment modifications and pharmacoeconomic properties.

Photodynamic therapy (PDT) with verteporfin has been used less comprehensively in the treatment of exudative age-related macular degeneration (AMD), and specifically of choroidal neovascularization (CNV), since the advent of antiangiogenic therapies. Recently, there has been a renewed interest in PDT as an adjunct to these and other agents in the treatment of neovascular AMD. In light of this new development and the European Medicines Evaluation Agency's (EMEA) recent labelling decision to rescind approval for the use of PDT in occult CNV lesions, the present systematic review was undertaken to revisit the evidence supporting its clinical application. Photodynamic therapy provided the first pharmacological treatment for patients suffering from subfoveal CNV, the major cause of severe vision loss in AMD. Key clinical trials evaluating efficacy and safety have examined patients with all lesion subtypes, with the primary labelled indication (i.e. lesions containing a classic component of > or = 50% ) deriving from the results of the Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study. The subsequent TAP Study Group post hoc categorization of lesions as predominantly classic is open to question, however, as it appears that the overall efficacy in this group only may have reflected the especially strong response in 100% classic lesions. Based on a subgroup analysis of the Verteporfin in Photodynamic Therapy Study, the indication for PDT subsequently was expanded in some jurisdictions, including that of the EMEA, to include occult lesions with no classic component. However, the subsequent Visudyne in Occult Study found no benefit in 100% occult lesions, resulting in the EMEA rescinding its approval for this indication.

The validation of patient-rated global assessments of treatment benefit, satisfaction, and willingness to continue--the BSW.

OBJECTIVE: This study evaluated the validity of three single-item, patient-rated, interviewer-administered, global assessments of treatment benefit, satisfaction with treatment and willingness to continue treatment, collectively referred to as the BSW. METHODS: The BSW, micturition diaries, the Overactive Bladder Questionnaire (OAB-q) and the King's Health Questionnaire (KHQ) were included in part or in total in three OAB clinical trials. Discriminant validity for full and dichotomized responses was assessed with anovas models and correlations were used to evaluate construct validity. RESULTS: The BSW demonstrated significant differences among the majority of the response levels on all measures of micturitions in all studies. The BSW also demonstrated discriminant validity with the OAB-q and the KHQ. BSW measures demonstrated significant differences among the change scores for all subscales of the OAB-q and the majority of the KHQ domains with both full and dichotomized responses. Patients who were dissatisfied with treatment and those unwilling to continue treatment also reported significantly worse OAB-q and KHQ scores compared with those who were satisfied with treatment or willing to continue treatment. BSW measures were moderately correlated with the micturition variables, moderate to strongly correlated with the OAB-q and weak to moderately with the KHQ, providing support for the construct validity of the BSW measures. CONCLUSIONS: The BSW is a useful tool to capture patients' global impressions of three key elements of treatment outcome: a perceived benefit, satisfaction with treatment, and the willingness to continue treatment, and can facilitate patient-physician communication as well as be informative to researchers.

Multinational study of reliability and validity of the King's Health Questionnaire in patients with overactive bladder.

OBJECTIVE: Overactive bladder (OAB) has substantial impact on health-related quality of life (HRQoL). The purpose of this research was to evaluate the psychometric properties of the King's Health Questionnaire (KHQ). METHODS: The KHQ (n = 1284) was administered at baseline and 12 weeks post-treatment in a multinational, double-blind, randomized clinical trial of tolterodine for treatment of OAB. Country-specific psychometric analyses of HRQoL instruments were performed. Countries demonstrating marginal psychometric properties on the KHQ were pooled with same-language countries, re-evaluated, and aggregate analysis performed on the pooled data. RESULTS: Internal consistency of the KHQ was high, item characteristics were good, most assumptions of summed scales were met, and it is externally valid and consistent. Few problems with the KHQ were noted although the performance of the personal relationships domain was complicated by the 'not applicable' response category. CONCLUSIONS: Psychometric testing supports the reliability and validity of the KHQ as an OAB-specific measure of HRQoL.

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.