An instrument for measuring health-related quality of life in patients with Deep Venous Thrombosis (DVT): development and validation of Deep Venous Thrombosis Quality of Life (DVTQOL) questionnaire

BACKGROUND: Few studies have evaluated patient-reported outcomes in connection with a primary event of deep venous thrombosis, partly due to a lack of disease-specific measures. The aim here was to develop a disease-specific health-related quality of life (HRQL) measure, the deep venous thrombosis quality of life questionnaire (DVTQOL), for patients with recent exposition and treatment of proximal deep venous thrombosis. METHODS: A total of 121 consecutive outpatients (50 % males; mean age 61.2 ± 14 years) treated with warfarin (Waran(®)) for symptomatic proximal deep venous thrombosis were included in the study. Patients completed the SF-36, EQ-5D and the pilot version of the DVTQOL. RESULTS: Items having: high ceiling and floor effect, items with lower factor loadings than 0.50 and items loading in several factors were removed from the pilot version of DVTQOL. In addition, overlapping and redundant items identified by the Rasch analysis were excluded. The final DVTQOL questionnaire consists of 29 items composing six dimensions depicting problems with: emotional distress; symptoms (e.g. pain, swollen ankles, cramp, bruising); limitation in physical activity; hassle with coagulation monitoring; sleep disturbance; and dietary problems. The internal consistency reliability was high (alpha value ranged from 0.79 to 0.93). The relevant domains of the SF-36 and EQ-5D significantly correlated with DVTQOL, thereby confirming its construct validity. CONCLUSIONS: The DVTQOL is a short and user-friendly instrument with good reliability and validity. Its test-retest reliability and responsiveness to change in clinical trials, however, must be explored

Reliability and validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire in dyspepsia: A six-country study

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Incorporating development of a patient-reported outcome instrument in a clinical drug development program: examples from a heart failure program.

BackgroundPatient-reported outcome (PRO) measures can be used to support label claims if they adhere to US Food & Drug Administration guidance. The process of developing a new PRO measure is expensive and time-consuming. We report the results of qualitative studies to develop new PRO measures for use in clinical trials of omecamtiv mecarbil (a selective, small molecule activator of cardiac myosin) for patients with heart failure (HF), as well as the lessons learned from the development process.MethodsConcept elicitation focus groups and individual interviews were conducted with patients with HF to identify concepts for the instrument. Cognitive interviews with HF patients were used to confirm that no essential concepts were missing and to assess patient comprehension of the instrument and items.ResultsDuring concept elicitation, the most frequently reported HF symptoms were shortness of breath, tiredness, fluid retention, fatigue, dizziness/light-headedness, swelling, weight fluctuation, and trouble sleeping. Two measures were developed based on the concepts: the Heart Failure Symptom Diary (HF-SD) and the Heart Failure Impact Scale (HFIS). Findings from cognitive interviews suggested that the items in the HF-SD and HFIS were relevant and well understood by patients. Multiple iterations of concept elicitation and cognitive interviews were needed based on FDA request for a broader patient population in the qualitative study. Lessons learned from the omecamtiv mecarbil PRO/clinical development program are discussed, including challenges of qualitative studies, patient recruitment, expected and actual timelines, cost, and engagement with various stakeholders.ConclusionDevelopment of a new PRO measure to support a label claim requires significant investment and early planning, as demonstrated by the omecamtiv mecarbil program

The Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) Questionnaire: item reduction and further validation

The adsorption of blood proteins, serum albumin (BSA), immunoglobulin G (IgG) and fibrinogen (FGN), onto model SiO2 planar surfaces coated with poly-l-lysine/heparin multilayers (PLL/HEP) has been investigated by means of ellipsometry and quartz crystal microbalance with dissipation. Aiming at the development of low fouling coatings, this study has been focused on the effects that the number of layers and the type of polyelectrolyte present on the topmost layer have on the adsorption of these proteins. The three proteins interact with PLL-ended coatings whereas HEP-ended coatings prevent the adsorption of both BSA and IgG and induce a decrease in the adsorbed amount of FGN, down to 0.4 mg/m2 for three bilayers, as the number of PLL/HEP bilayers increases. These results suggest that heparin-ended multilayers prevent protein adsorption, which is an indicative of good blood compatibility. As a consequence we propose that PLL/HEP coatings could be used for the development of vascular medical devices

Application of latent growth and growth mixture modeling to identify and characterize differential responders to treatment for COPD

AbstractObjectiveTo explore the utility of applying growth mixture models (GMMs) in secondary analyses of clinical trials to identify sources of variability in data reported by patients with COPD.MethodsAnalyses were performed on data from two 6-month clinical trials comparing indacaterol and open-label tiotropium or blinded salmeterol and the first six months of a 12-month trial comparing indacaterol and blinded formoterol. Latent growth model (LGM) analyses were conducted to explore the response of the SGRQ Symptoms score from baseline to six months and GMM analyses were evaluated as a method to identify latent classes of differential responders.ResultsVariability in SGRQ Symptom scores was found suggesting subsets of patients with differential response to treatment. GMM analyses found subsets of non-responders in all trials. When the responders were analyzed separately from non-responders, there were increased treatment effects (e.g., symptoms score improvement over six months for whole groups: indacaterol=8–12 units, tiotropium=7 units, salmeterol=9 units, formoterol=11 units. Responder subgroup improvement: indacaterol=9–21 units, tiotropium=7 units, salmeterol=10 units, formoterol=20 units). Responders had significantly different baseline SGRQ Symptom scores, smoking history, age, and mMRC dyspnea scores than non-responders.ConclusionsPatients with COPD represent a heterogeneous population in terms of their reporting of symptoms and response to treatment. GMM analyses are able to identify sub-groups of responders and non-responders. Application of this methodology could be of value on other endpoints in COPD and in other disease areas

The Reflux Disease Questionnaire: a measure for assessment of treatment response in clinical trials

© 2008 Shaw et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Psychometric validation of the German translation of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire in patients with reflux disease

BACKGROUND: Symptoms of heartburn has an impact on health-related quality of life (HRQL). When a questionnaire is translated into a new language, a linguistic validation is necessary but not sufficient unless the psychometric characteristics have been verified. The aim is to document the psychometric characteristics of the German translation of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire. METHODS: 142 patients with symptoms of heartburn (Age: M = 47.5, ± 14.6; Males = 44.4%) completed the German translation of GSRS, the QOLRAD, the Short-Form-36 (SF-36) and the Hospital Anxiety and Depression (HAD) scale. RESULTS: The internal consistency reliability of GSRS ranged from 0.53–0.91 and of QOLRAD from 0.90–0.94, respectively. The test-retest reliability of GSRS ranged from 0.49–0.73 and of QOLRAD from 0.70–0.84. The relevant domains of the GSRS and QOLRAD domain scores significantly correlated. GSRS domains of Abdominal Pain and Constipation correlated (negatively) with most of the domains of the SF-36. The relevant QOLRAD domains significantly correlated with all SF-36 domains. CONCLUSIONS: The psychometric characteristics of the German translation of GSRS and QOLRAD were found to be good, with satisfactory reliability and validity. The reliability of the GSRS Abdominal Pain domain was moderate

The Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) Questionnaire: item reduction and further validation

PurposeThe Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) Questionnaire is a patient and parent-completed disease-specific instrument used in Hunter syndrome (mucopolysaccharidosis II), a rare paediatric progressive multi-systemic lysosomal storage disease. The objective of this study was to shorten the number of items of the Questionnaire to reduce response burden while maintaining its content validity.MethodsData collected in a clinical trial were used. An iterative process helped identifying redundant or low performing items based on content validity and psychometric properties. Validation on the retained items was assessed using patients and parent’s responses in terms of reliability, validity and responsiveness.ResultsThe HS-FOCUS was completed by 49 patients and 84 parents. Items were mainly removed owing to high floor effects, high inter-item correlations (>0.80) or inadequate content. The shortened patient and parent versions (18 and 21 items) each contained five function domains. Internal consistency and test–retest reliability were >0.70 for most domains, except Breathing and School/work. Concurrent validity was demonstrated by significant correlations (>0.30) with similar concepts of previously validated measures. Significant differences were found in all domain scores across levels of disability.ConclusionsThe shortened HS-FOCUS is a reliable, valid and responsive measure, where burden in answering the Questionnaire was reduced without compromising its validity

Felodipine-Metoprolol Combination Tablet: Maintained Health-Related Quality of Life in the Presence of Substantial Blood Pressure Reduction

Background: Most treated hypertensive patients do not achieve adequate blood pressure (BP) control. Initiating therapy with two drugs has been suggested when BP is >20/10 mm Hg above goal. To ensure patients' compliance, such treatment needs to be well tolerated and must not compromise health-related quality of life (HRQL). The primary objective of this study was to compare the effects on HRQL of initiating treatment with felodipine + metoprolol (F+M) fixed combination tablets, or enalapril (E), or placebo (P). Methods: A total of 947 patients of both sexes with primary hypertension (diastolic BP 95 to 110 mm Hg), aged 20 to 70 years, participated in this randomized, double-blind, parallel group, 12-week, multicenter trial. Treatment was initiated with F+M 5 + 50 mg, or E 10 mg, or P. Doses were doubled after 4 or 8 weeks if diastolic BP was >90 mm Hg. The HRQL was measured at baseline and at the last visit using two validated questionnaires: the Psychological General Well-being Index (PGWB) and the Subjective Symptom Assessment Profile (SSA-P). Office BP was measured at trough, that is, 24 h after the previous dose. Results: The HRQL was high at baseline and generally well maintained during the study. For example, the mean (SD) PGWB total score was 104 (16) at baseline and 105 (16) at 12 weeks in all three treatment groups. The BP reductions after F+M (18/14 mm Hg) and E (12/9 mm Hg) were significantly greater than after P (7/7 mm Hg), and the reduction after F+M was significantly greater than after E. Conclusions: The HRQL is maintained in the presence of substantial BP reduction during antihypertensive treatment with F+M fixed combination tablets. Am J Hypertens 2005;18:1313-1319 © 2005 American Journal of Hypertension, Lt

The impact of illness in patients with moderate to severe gastro-esophageal reflux disease

BACKGROUND: Gastro-esophageal reflux disease (GERD) is a common disease. It impairs health related quality of life (HRQL). However, the impact on utility scores and work productivity in patients with moderate to severe GERD is not well known. METHODS: We analyzed data from 217 patients with moderate to severe GERD (mean age 50, SD 13.7) across 17 Canadian centers. Patients completed three utility instruments – the standard gamble (SG), the feeling thermometer (FT), and the Health Utilities Index 3 (HUI 3) – and several HRQL instruments, including Quality of Life in Reflux and Dyspepsia (QOLRAD) and the Medical Outcomes Short Form-36 (SF-36). All patients received a proton pump inhibitor, esomeprazole 40 mg daily, for four to six weeks. RESULTS: The mean scores on a scale from 0 (dead) to 1 (full health) obtained for the FT, SG, and HUI 3 were 0.67 (95% CI, 0.64 to 0.70), 0.76 (95% CI, 0.75 to 0.80), and 0.80 (95% CI, 0.77 to 0.82) respectively. The mean scores on the SF-36 were lower than the previously reported Canadian and US general population mean scores and work productivity was impaired. CONCLUSION: GERD has significant impact on utility scores, HRQL, and work productivity in patients with moderate to severe disease. Furthermore, the FT and HUI 3 provide more valid measurements of HRQL in GERD than the SG. After treatment with esomeprazole, patients showed improved HRQL