An instrument assessing satisfaction with iron chelation therapy: Psychometric testing from an open-label clinical trial.

INTRODUCTION: The Satisfaction with Iron Chelation Therapy (SICT) instrument was developed based on a literature review, in-depth patient and clinician interviews, and cognitive debriefing interviews. An, open-label, single arm, multicenter trial evaluating the efficacy and safety of deferasirox in patients diagnosed with transfusion-dependent iron overload, provided an opportunity to assess the psychometric measurement properties of the instrument. METHODS: Psychometric analyses were performed using data at baseline from 273 patients with a range of transfusion-dependent iron overload conditions who were participating in a multinational study. Responsiveness was further evaluated for all patients who also had subsequent satisfaction domain scores collected at week 4. RESULTS: Baseline SICT domain scores had acceptable floor and ceiling effects and internal consistency reliability (Cronbach's alpha: 0.75-0.85). Item discriminant and item convergent validity were both excellent although one item in each analysis did not meet the specified criterion. Small to moderate correlations were observed between SICT and Short Form 36 Health Survey (SF-36) domain scores. Patients with the highest levels of serum ferritin at baseline (>3100 ng/mL) were the least satisfied about the Perceived Effectiveness of ICT and vice versa. Satisfaction improved in all patients, although there were no clear differences observed between groups of patients defined according to changes in serum ferritin levels from baseline to week 4 (stable, improved, or worsened). CONCLUSIONS: The SICT domains are reliable and valid. Further testing using a more specific criterion (such as assessing patient global ratings of change in satisfaction domains that correspond to the SICT domains) could help to establish with greater confidence the responsiveness of the instrument.

Psychometric evaluation of the Diabetes Symptom Checklist-Revised (DSC-R)--a measure of symptom distress.

OBJECTIVE: To assess the psychometric validity, reliability, responsiveness, and minimal important differences of the Diabetes Symptoms Checklist-Revised (DSC-R), a widely used patient-reported outcome measure of diabetes symptom distress. RESEARCH DESIGN AND METHODS: Psychometric validity of the DSC-R was assessed using blinded data from a large-scale trial of approximately 4000 type 2 diabetes patients. Confirmatory factorial analysis (CFA) and multitrait analysis were used to examine the construct validity of the structure of DSC-R. DSC-R internal consistency, discriminative validity, and responsiveness were also assessed. Distribution and anchor-based methods were used to estimate minimal important differences for DSC-R domains. RESULTS: Mean age of the sample was 56 years, 42% were female, 88% were Caucasian. Patients had a mean body mass index (BMI) of 32.2 and mean glucose-fasting level of 151.7 md/dl. CFA and multitrait analysis indicated that the scoring of the DSC-R has acceptable construct validity. Item-scale correlations ranged from 0.44 to 0.78. Cronbach's alpha coefficients ranged from 0.69 to 0.87. At baseline, DSC-R scores were higher among patients with higher BMI scores (P < 0.0001), supporting the discriminative validity of the DSC-R. Minimal important difference estimates ranged from 0.39 to 0.60 points when using distribution methods and from 0.00 to 0.33 when estimated using anchor-based methods. CONCLUSIONS: The DSC-R demonstrated excellent psychometric properties when tested in a large-scale diabetes clinical trial. Responsiveness and test-retest reliability of the DSC-R warrant further evaluation.

Corrected and uncorrected near and distance vision with ReSTOR compared to monofocal intraocular lens implantation after cataract surgery: a pooled analysis.

BACKGROUND/AIM: To evaluate distance and near vision-related benefit after implantation of ReSTOR multifocal intraocular lenses (IOLs) following cataract surgery. METHODS: Two prospective open-labeled nonrandomized studies were pooled. Patients' perception of benefit was assessed with the TyPE, administered at baseline and after each eye surgery. RESULTS: A total of 499 patients received ReSTOR IOLs, and 173 received monofocal IOLs. The distance vision of monofocal and ReSTOR patients improved equally with and without glasses. A greater improvement in near vision without glasses was reported by ReSTOR-implanted patients as early as after the 1st eye surgery (p < 0.0001). More ReSTOR patients than monofocal patients reported independence from glasses after the 1st eye surgery (64 vs. 52%; p = 0.0002). This difference had increased after the 2nd eye surgery (85 vs. 51%; p < 0.0001). CONCLUSIONS: The improvement in near vision without glasses was significantly more evident in ReSTOR patients, allowing the majority of them to be free of glasses.

Satisfaction and adherence in patients with iron overload receiving iron chelation therapy as assessed by a newly developed patient instrument.

OBJECTIVES: This study assesses satisfaction with iron chelation therapy (ICT) based on a reliable and valid instrument, and explores the relationship between satisfaction and adherence to ICT. METHODS: Patients in the USA and UK completed a new "Satisfaction with ICT" (SICT) instrument consisting of 28 items, three pertaining to adherence. Simple and multivariate regression analyses assessed the relationship between satisfaction with different aspects of ICT and adherence. RESULTS: First assessments of the SICT instrument indicate its validity and reliability. Recommended thresholds for internal consistency, convergent validity, discriminant validity, and floor and ceiling effects were met. A number of variables were identified in the simple linear regression analyses as significant predictors of "never thinking about stopping ICT," a proxy for adherence. These significant variables were entered into the multivariate model to assess the combined factor effects, explaining 42% of the total variance of "never thinking about stopping ICT." A significant and positive relationship was demonstrated between "never thinking about stopping ICT" and age (P = 0.04), Perceived Effectiveness of ICT (P = 0.003), low Burden of ICT (P = 0.002), and low Side Effects of ICT (P = 0.01). CONCLUSIONS: The SICT is a reliable and valid instrument which will be useful in ICT clinical trials. Furthermore, the administration of ICT by slow subcutaneous infusion negatively impacts on satisfaction with ICT which was shown to be a determinant of adherence. This points to the need for new more convenient and less burdensome oral iron chelators to increase adherence, and ultimately to improve patient outcomes.

Iron chelation therapy: clinical effectiveness, economic burden and quality of life in patients with iron overload.

INTRODUCTION: This study of UK patients examines clinical, health-related quality of life (HRQOL) and economic outcomes associated with iron chelation therapy (ICT). Desferrioxamine (DFO) (Desferal; Novartis, Switzerland) and Deferiprone (Ferriprox; Apotex, Canada) are ICTs used to treat iron overload. DFO requires 8-to 12-hour infusions a minimum of five times per week. Deferiprone is administered in an oral daily regimen. Although pharmacologically efficacious, clinical effectiveness of ICT within the real-world setting is yet to be fully elucidated. METHODS: A naturalistic cohort study of 60 patients (beta-thalassaemia, n=40; sickle cell disease, n=14; myelodysplastic syndromes, n=6; 63% female) receiving ICT in four UK treatment centres was conducted. Serum ferritin level data were abstracted from medical charts. Compliance, HRQOL, satisfaction and resource utilisation data were collected from interviews. Maximum ICT costs were estimated using the resource utilisation data associated with DFO. RESULTS: Mean serum ferritin levels, generally, remained elevated despite ICT. Compliance was suboptimal and HRQOL scores were lower than population norms. The total estimated mean weighted annual per-patient cost of DFO treatment was approximately pound19,000. DFO-related equipment, DFO drug, and home healthcare were estimated to account for 43%, 19% and 24% of costs, respectively. Other more minor components of total annual costs were for in-patient infusions, ICT home delivery services and monitoring costs. CONCLUSION: Generally, patients are not achieving target serum ferritin thresholds despite chronic treatment for iron overload. ICT appears to negatively impact HRQOL; compliance with ICT is poor; and, in the case of DFO, treatment costs well exceed the cost of DFO alone. These results suggest that current ICT in the real-world setting is suboptimal with respect to various clinical, HRQOL and economic outcomes.

Patient-reported benefit of ReSTOR multi-focal intraocular lenses after cataract surgery: results of principal component analysis on clinical trial data.

BACKGROUND: Restoration of functional distance and near vision independently of additional correction remains a goal for cataract surgery. ReSTOR, a new multi-focal intraocular lens (IOL) addresses this issue with an improvement in both distance and near vision, often without need for glasses. This analysis attempted to discuss the patient-reported benefit of ReSTOR using a full but organised representation of data. METHODS: Two non-randomised, open-label clinical trials conducted in Europe and the United-States were conducted to compare the efficacy of ReSTOR to AcrySof mono-focal IOLs. A total of 710 patients in need of bilateral cataract extraction were included in the pooled study. The TyPE, a patient questionnaire, was fully completed by 672 of them before and after each eye surgery. The TyPE, composed of 67 items measuring overall visual functioning in both conditions (with and without wearing glasses), evaluates limitations, troubles and satisfaction in distance and near vision. A principal component analysis (PCA) of the TyPE questionnaire was performed on pooled data from baseline and post-surgery observations in order to fully represent the change in the TyPE data over time. ReSTOR and mono-focal groups were used as illustrative variables. The coordinates of the first 2 factors were compared between visits and between IOLs (ReSTOR vs. mono-focal), using paired t-tests and t-tests, respectively. RESULTS: The first factor of the PCA explained 55% of the variance and represented 'visual functioning and patient satisfaction'. The second factor explained 6% of the variance and was interpreted as 'independence from glasses'. An overall difference in factorial coordinates in both factors was seen between baseline and the first eye surgery, and between the first and the second eye surgery. No difference between ReSTOR and mono-focal IOL groups was observed at baseline. After surgery, ReSTOR treated-patients had higher coordinates on both "visual functioning and satisfaction" and "independence from glasses" factors. Findings observed on the factorial plan were supported by statistical comparisons of factorial coordinates. CONCLUSION: Both mono-focal and ReSTOR-implanted patients improved their visual functioning after bilateral cataract surgery. Moreover, ReSTOR patients reported an additional benefit in independence from glasses as well as in visual functioning and patient satisfaction.

Patient-reported outcomes helped predict survival in multiple myeloma using partial least squares analysis.

OBJECTIVE: The prognostic value of Patient-Reported Outcomes (PRO) in predicting mortality during treatment of multiple myeloma (MM) patients was assessed using partial least square (PLS) regression, a statistical method that is well-adapted for highly correlated data. STUDY DESIGN AND SETTING: Four PRO measures, The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, the EORTC QLQ-MY24, the FACIT-Fatigue scale, and the FACT/GOG-Ntx scale, were administered during a trial designed to evaluate the efficacy and safety of bortezomib (VELCADE 1.3mg/m(2)) in MM patients (N=202). Clinical and PRO data were analyzed for predictive value by univariate and multivariate logistic regression methods and then by PLS regression. RESULTS: Fifteen baseline PRO parameters were significant in predicting mortality during treatment when univariate logistic regression was used. In contrast, only two variables were retained in the multivariate analysis, as correlated variables were excluded from the model. Using PLS regression, 14 of the 21 PRO predictors were significant in predicting mortality. Clinical and PRO data used together increased the predictive power of all models compared to clinical data alone. CONCLUSION: The prognostic value of PRO was established and was more informative using PLS regression. PLS regression may therefore be a valuable method for analyzing PRO data.

Descriptive and prognostic value of patient-reported outcomes: the bortezomib experience in relapsed and refractory multiple myeloma.

PURPOSE: Bortezomib, a boronic acid dipeptide, has been recently introduced as a new approach to treating multiple myeloma (MM). The goal of this work was to evaluate the added value of patient-reported outcomes (PRO) in the interpretation of bortezomib clinical trial outcomes. PATIENTS AND METHODS: Two hundred two patients with relapsed, refractory MM were treated with bortezomib as part of the SUMMIT (Study of Uncontrolled Multiple Myeloma Managed with Proteasome Inhibition Therapy) study. Patients were administered the following four PRO measures at several time points: the European Organisation for Research and Treatment of Cancer (EORTC) core Quality of Life Questionnaire (QLQ-C30) and the myeloma-specific module (QLQ-MY24), the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale, and the Functional Assessment of Cancer Therapy (FACT)/Gynecologic Oncology Group (GOG) Neurotoxicity (Ntx) scale. Minimal important difference (MID) thresholds were used to define patients as improved, stable, or worsened. A survival analysis was conducted to assess the predictive power of PRO data. RESULTS: For the total population, there was a positive change between baseline and best end point. Consistent with the clinical responses, change in PRO scores showed statistically significant differences between response groups with PRO improvement in patients with complete response (CR) or partial response (PR), mostly stable scores in patients with minor response or no change, and deterioration in most scores for patients with progressive disease. Change in scores for neuropathy-related symptoms was reasonably stable. In contrast, fatigue scores significantly improved for patients with CR or PR. When various MID thresholds were applied, the proportion of improved patients exceeded 35% for several domains within all change group definitions. Moreover, survival analysis results demonstrated the additional prognostic information PRO data can provide to supplement clinical data. CONCLUSION: This study demonstrated the complementary value for PRO assessments in further interpreting clinical response, the impact of adverse effects, and patient prognosis in clinical trials.

Psychometric Validation of the National Eye Institute Visual Function Questionnaire - 25 (NEI VFQ-25) French version: in a population of patients treated for ocular hypertension and glaucoma.

OBJECTIVE: Physicians need reliable, valid and sensitive questionnaires to assess QOL related to glaucoma or ocular hypertension. This article presents the psychometric properties of the French version of the National Eye Institute Visual Function Questionnaire - 25 (NEI VFQ-25). METHODS: A mail survey was sent to 20000 households. The survey identified 581 residents with glaucoma or ocular hypertension. Of these a random sample (n = 204) took part in a telephone survey during which the NEI VFQ-25 was completed by eligible patients (those taking at least one topical treatment for glaucoma or ocular hypertension on the day of the interview). Multi-trait analysis was performed to assess the construct validity of the questionnaire. Internal consistency reliability was assessed using Cronbach's alpha and the average inter-item correlation. Known groups validity was assessed by comparing patients grouped by duration of glaucoma, adjusted for age and gender. RESULTS: One hundred and seventy-three patients participated in the survey. Analysis of convergent validity showed that all of the items in each scale correlated above 0.40 with their own scale except for the 'driving' scale. The success rate of the discriminant validity ranged from 57.1% to 100% except for the 'driving' scale, which was 7.1%. Cronbach's alpha coefficients were all above 0.70 except the 'driving' score. Participants with glaucoma for less than 20 years consistently had better 'global', 'near vision', 'distant vision', 'driving', 'social function' and 'peripheral vision' scores than those with disease of 20+ years duration, indicating better QOL in patients with a shorter disease duration. CONCLUSION: The NEI VFQ-25 is a validated instrument to measure vision-targeted QOL in French populations with glaucoma.

Bet-Hedging Diapause Strategies in Stochastic Environments.

In many insect species, adult emergence spreads over several years because of the existence of prolonged diapause in certain individuals. From stochastic models, we show that diversified bet-hedging strategies (mixed strategies with emergence after 1 or 2 yr) are more fit than simple diapause strategy (emergence after 1 yr) or fixed prolonged diapause strategy (emergence after 2 yr) in isolated chestnut weevil populations. This conclusion applies to a large range of survival rates in prolonged diapause and is insensitive to initial conditions, magnitude of temporal autocorrelation, distribution of demographic parameters, and quoted values of population size limitation. However, the shape of the fitness distribution as a function of prolonged diapause frequency changes greatly in the absence of population size limitation. Whatever the survival rate during prolonged diapause, we find that there is no genotypic advantage to extending diapause for all chestnut weevil larvae to more than 1 yr. Our models predict selection of bet-hedging strategies over a large range of prolonged diapause frequencies. This result is consistent with the existence of several mixed strategies in a population. Emergences after 3 yr are not crucial for selection or for the dynamics of mixed strategies in the chestnut weevil.