Development and validation of the AFSymp™: an atrial fibrillation-specific measure of patient-reported symptoms.

BACKGROUND: Patients with atrial fibrillation (AF) can be severely incapacitated by symptoms, but validated symptom measures are lacking. The aim of this study was to develop an AF-specific symptom questionnaire (AFSymp™). METHODS: Following a literature review, qualitative interviews with 91 patients (United States [US], n = 30; United Kingdom [UK], n = 16; France, n = 15; Germany, n = 15; Japan, n = 15) with paroxysmal, persistent, and permanent AF were conducted to identify emergent concepts and to develop the items and response options for the AFSymp™. Clinical experts (n = 21) in the US, the UK, France, Germany, and Japan provided feedback on the most clinically relevant symptoms via an email survey. Cognitive interviews with 30 patients were conducted to evaluate content validity. A prospective, observational, psychometric evaluation study (n = 313) consisting of two study visits was performed at 32 sites across the US. RESULTS: After item reduction, the AFSymp™ consisted of 11 items with a 1-week recall period. Exploratory and confirmatory factor analysis resulted in three subscales (heart symptoms, tiredness, chest discomfort) and two items: dizziness and shortness of breath. Internal consistency was strong across subscales (Cronbach's α 0.82-0.91). The test-retest reliability of items and subscales was acceptable (intra-class correlation [ICC] 0.58-0.78). The reproducibility of the single global score was strong (ICC 0.78). The construct and known-groups validity was acceptable. CONCLUSION: The AFSymp™ demonstrates evidence of reliability and validity as a comprehensive measure of AF symptoms that can be used to assess patient outcomes in clinical and research settings. More research is needed to evaluate the instrument's responsiveness.

Development and validation of the living with pulmonary hypertension questionnaire in pulmonary arterial hypertension patients.

BACKGROUND: The Living with Pulmonary Hypertension questionnaire (LPH) was adapted from the Minnesota Living with Heart Failure Questionnaire for use in patients with pulmonary arterial hypertension (PAH). Study objectives were to confirm the face and content validity, to assess the structure and psychometric properties, and provide guidance for the interpretation of the LPH. METHODS: A qualitative interview study was conducted with PAH patients in the US (n=12), Germany (n=14) and France (n=12) to evaluate the face and content validity of the LPH. Psychometric validation was performed using blinded data from a double blind, Phase III, clinical trial (n=196). Validation analyses were performed on baseline and week 12 (visit 6/last visit) data and included evaluation of: item response distributions, quality of completion, construct validity, reliability, clinical validity and responsiveness. Analyses to provide an estimation of the Minimal Important Difference (MID) for the LPH scores were performed. RESULTS: Cognitive debriefing interviews with 38 PAH patients indicated that the most commonly reported PAH symptoms and impacts are covered by LPH items. Patients found the LPH questionnaire relevant and comprehensive to their experience. Some suggestions were made to enhance the face validity of the LPH. The content validity of the questionnaire was supported. Results of the psychometric validation analyses (n=190) indicated that the LPH Emotional and Physical scores met the criteria for convergent and discriminant validity; for the total score all but two items met the test for item convergent validity. Internal consistency reliability was demonstrated by Cronbach's alpha values of >0.70 for all LPH scores. The LPH Physical and Total scores discriminated between World Health Organisation (WHO) Functional classes and 6 Minute walk test distances, indicating clinical validity and were also responsive to change in clinical severity, as measured by change in WHO functional class and Borg CR 10 Scale. Further investigation is required to confirm the responsiveness of the Emotional score. Estimation of MID using distribution-based methods indicated a change of 3 points for the sub-scales and 7 for the total score to be clinically meaningful. CONCLUSION: The LPH is a valid and reliable instrument that meets FDA criteria.

Content validity of the PedsQL™ 3.2 Diabetes Module in newly diagnosed patients with Type 1 diabetes mellitus ages 8-45.

OBJECTIVES: The content validity of the 28-item PedsQL™ 3.0 Diabetes Module has not been established in research on pediatric and adult patients with newly diagnosed Type 1 diabetes across a broad age range. This study aimed to document the content validity of three age-specific versions (8-12 years, 13-18 years, and 18-45 years) of the PedsQL™ Diabetes Module in a population of newly diagnosed patients with Type 1 diabetes. METHODS: The study included in-depth interviews with 31 newly diagnosed patients with Type 1 diabetes between the ages of 8 and 45 years, as well as 14 parents and/or caregivers of child and teenage patients between the ages of 8 and 18 years of age; grounded theory data collection and analysis methods; and review by clinical and measurement experts. RESULTS: Following the initial round of interviews, revisions reflecting patient feedback were made to the Child and Teen versions of the Diabetes Module, and an Adult version of the Diabetes Module was drafted. Cognitive interviews of the modified versions of the Diabetes Module were conducted with an additional sample of 11 patients. The results of these interviews support the content validity of the modified 33-item PedsQL™ 3.2 Diabetes Module for pediatric and adult patients, including interpretability, comprehensiveness, and relevance suitable for all patients with Type 1 Diabetes. CONCLUSIONS: Qualitative methods support the content validity of the modified PedsQL™ 3.2 Diabetes Module in pediatric and adult patients. It is recommended that the PedsQL™ 3.2 Diabetes Module replaces version 3.0 and is suitable for measuring patient-reported outcomes in all patients with newly diagnosed, stable, or long-standing diabetes in clinical research and practice.

Patients' experience of asthma control and clinical guidelines: perspectives from a qualitative study.

BACKGROUND: Clinical guidelines consider the concept of 'asthma control' as the primary goal of asthma treatment. This study aimed to explore patients' views of concepts that are important for understanding and evaluating asthma control. METHODS: Patients with mild to severe asthma in four countries completed the Asthma Control Questionnaire (ACQ) and discussed their experiences in focus groups. Clinicians evaluated patients' levels of asthma control based on Global Initiative for Asthma (GINA) guidelines. Clinician- and questionnaire-based ratings of asthma control were compared. Thematic analysis was used to identify key concepts from focus group transcripts. RESULTS: The sample consisted of 55 patients. Classification of asthma control, based on the ACQ, was consistent with clinician rating in 28 cases (51%). In focus groups, patients discussed concepts related to symptoms, asthma attacks (exacerbations), activity limitations, panic/fear, tiredness, sleep disturbances (nocturnal awakening and difficulty falling asleep), and rescue medication use when describing asthma control. Clinical guidelines also focus on symptoms, activity limitations, rescue medication use, and exacerbations but, in addition include lung function parameters. Guidelines do not take into account asthma-related panic/fear or tiredness and sleep disturbances beyond nocturnal awakening. CONCLUSION: The results of this study suggest that patients' understanding of asthma control extends beyond the usual clinical manifestation of respiratory symptoms and lung function. This may have implications for clinical practice, for setting and achieving the goals of asthma control as well as for evaluation of treatments for asthma from the patients' perspective.

The impact of spina bifida on caregivers.

INTRODUCTION: Neural tube defects (NTDs) are the second most common birth defects. Spina bifida (SB) and anencephaly make up approximately 90% of total NTDs. Given the number of infants born with an NTD each year, anyone who provides unpaid care for the child (especially caregivers) is affected. This literature review explores the humanistic burden on caregivers of people with SB, specifically myelomeningocele. METHODS: A search using PubMed, PsycINFO, and Embase was performed to find studies from 1976 to 2010. Interpretative phenomenological analysis was performed on qualitative data and relevant extracts from the data were collated to form master themes. RESULTS: A total of 168 abstracts met the inclusion and exclusion criteria. Of these, 25 articles related to caregivers of individuals with SB. Four master themes emerged: initial diagnosis, living with an individual with SB, social support, and coping. Different aspects of caregivers' lives were found to be affected by caring for a child with SB, including activities of daily living, work impact, time consumption, parental responsibilities, confidence, feelings and emotions, mental health, stress, social impact, psychological adjustment, and relationships. CONCLUSION: NTDs, such as SB, present a multitude of issues to caregivers. Issues that affect caregivers of individuals with SB must be addressed in order to reduce the considerable burden that SB places on the caregiver. Continued and enhanced support from health services and patient advocacy groups is needed. For example, providing additional information, support, and empathy can help parents prepare themselves for dealing with the needs of a child with SB over their lifetime.

Development and validation of the impact of dry eye on everyday life (IDEEL) questionnaire, a patient-reported outcomes (PRO) measure for the assessment of the burden of dry eye on patients.

OBJECTIVE: To develop and validate a comprehensive patient-reported outcomes instrument focusing on the impact of dry eye on everyday life (IDEEL). METHODS: Development and validation of the IDEEL occurred in four phases: 1) focus groups with 45 dry eye patients to develop a draft instrument, 2) item generation, 3) pilot study to assess content validity in 16 patients and 4) psychometric validation in 210 subjects: 130 with non-Sjögren's keratoconjunctivitis sicca, 32 with Sjögren's syndrome and 48 controls, and subsequent item reduction. RESULTS: Focus groups identified symptoms and the associated bother, the impact of dry eye on daily life and the patients' satisfaction with their treatment as the central concepts in patients' experience of dry eye. Qualitative analysis indicated that saturation was achieved for these concepts and yielded an initial 112-item draft instrument. Patients understood the questionnaire and found the items to be relevant indicating content validity. Patient input, item descriptive statistics and factor analysis identified 55 items that could be deleted. The final 57-item IDEEL assesses dry eye impact constituting 3 modules: dry eye symptom-bother, dry eye impact on daily life comprising impact on daily activities, emotional impact, impact on work, and dry eye treatment satisfaction comprising satisfaction with treatment effectiveness and treatment-related bother/inconvenience. The psychometric analysis results indicated that the IDEEL met the criteria for item discriminant validity, internal consistency reliability, test-retest reliability and floor/ceiling effects. As expected, the correlations between IDEEL and the Dry Eye Questionnaire (a habitual symptom questionnaire) were higher than between IDEEL and Short-Form-36 and EuroQoL-5D, indicating concurrent validity. CONCLUSION: The IDEEL is a reliable, valid and comprehensive questionnaire relevant to issues that are specific to dry eye patients, and meets current FDA patient-reported outcomes guidelines. The use of this questionnaire will provide assessment of the impact of dry eye on patient dry eye-related quality of life, impact of treatment on patient outcomes in clinical trials, and may aid in treatment effectiveness evaluation.

Pediatric restless legs syndrome: analysis of symptom descriptions and drawings.

The specific aims of this study were to collect and analyze detailed symptom descriptions from patients with pediatric restless legs syndrome, ages 6 to 17 years, as well as assess symptom impact and the usefulness of drawings. Trained qualitative interviewers conducted face-to-face audio-recorded interviews of children and adolescents who met criteria for definite restless legs syndrome. Thirty-three patients in 3 age groups used 16 different categories of descriptors for restless legs sensations, with a mean of 3 or more categories used per patient in each age group. "Need to move/kick," "pain/hurts," "uncomfortable/cannot get comfortable," and "like bugs or ants/crawling" were the most common descriptors. Two-thirds reported daytime sensations, and nearly half had arm involvement. They described impact on sleep, cognitive function, and affect. Drawings provided useful diagnostic information. These detailed empirical data will be useful in clinical practice, as well as in the development of formal diagnostic tools and severity measures.

Development of the Pediatric Restless Legs Syndrome Severity Scale (P-RLS-SS): a patient-reported outcome measure of pediatric RLS symptoms and impact.

OBJECTIVE: To develop a questionnaire to measure Pediatric Restless Legs Syndrome (P-RLS) symptoms and impact for use in clinical research. METHODS: Questionnaire items were developed based on open-ended, qualitative interviews of 33 children and adolescents diagnosed with definite RLS (ages 6-17 years) and their parents. The draft questionnaire was then tested through cognitive debriefing interviews with 21 of the same children/adolescents and 15 of their parents. This involved the children and parents answering the draft items and then interviewing them about the child's ability to understand and interpret the questionnaire. Expert clinicians provided clinical guidance throughout. RESULTS: Draft severity questions were generated to measure the four-symptom and four-impact domains identified from the concept elicitation interviews: RLS sensations, move/rub due to RLS, relief from move/rub, pain, and impact of RLS on sleep, awake activities, emotions, and tiredness. RLS descriptions, symptoms, and impact were compared between those who had comorbid attention-deficit/hyperactivity disorder and those who did not. Revisions to several questions were made based on the cognitive debriefing interviews and expert clinician review, resulting in a severity scale with 17 morning and 24 evening items. Caution regarding self-administration in children ages 6-8 years is recommended. To complement the child/adolescent measures, a separate parent questionnaire was also developed. CONCLUSIONS: The P-RLS-SS was constructed based on detailed input from children and adolescents with RLS, their parents, and clinical experts, thus providing a scale with strong content validity that is intended to be comprehensive, clinically relevant, and important to patients. Validation of this scale is recommended.

PRO development: rigorous qualitative research as the crucial foundation.

Recently published articles have described criteria to assess qualitative research in the health field in general, but very few articles have delineated qualitative methods to be used in the development of Patient-Reported Outcomes (PROs). In fact, how PROs are developed with subject input through focus groups and interviews has been given relatively short shrift in the PRO literature when compared to the plethora of quantitative articles on the psychometric properties of PROs. If documented at all, most PRO validation articles give little for the reader to evaluate the content validity of the measures and the credibility and trustworthiness of the methods used to develop them. Increasingly, however, scientists and authorities want to be assured that PRO items and scales have meaning and relevance to subjects. This article was developed by an international, interdisciplinary group of psychologists, psychometricians, regulatory experts, a physician, and a sociologist. It presents rigorous and appropriate qualitative research methods for developing PROs with content validity. The approach described combines an overarching phenomenological theoretical framework with grounded theory data collection and analysis methods to yield PRO items and scales that have content validity.

Using qualitative methods to inform the trade-off between content validity and consistency in utility assessment: the example of type 2 diabetes and Alzheimer's disease.

BACKGROUND: Key stakeholders regard generic utility instruments as suitable tools to inform health technology assessment decision-making regarding allocation of resources across competing interventions. These instruments require a 'descriptor', a 'valuation' and a 'perspective' of the economic evaluation. There are various approaches that can be taken for each of these, offering a potential lack of consistency between instruments (a basic requirement for comparisons across diseases). The 'reference method' has been proposed as a way to address the limitations of the Quality-Adjusted Life Year (QALY). However, the degree to which generic measures can assess patients' specific experiences with their disease would remain unresolved. This has been neglected in the discussions on methods development and its impact on the QALY values obtained and resulting cost per QALY estimate underestimated. This study explored the content of utility instruments relevant to type 2 diabetes and Alzheimer's disease (AD) as examples, and the role of qualitative research in informing the trade-off between content coverage and consistency. METHOD: A literature review was performed to identify qualitative and quantitative studies regarding patients' experiences with type 2 diabetes or AD, and associated treatments. Conceptual models for each indication were developed. Generic- and disease-specific instruments were mapped to the conceptual models. RESULTS: Findings showed that published descriptions of relevant concepts important to patients with type 2 diabetes or AD are available for consideration in deciding on the most comprehensive approach to utility assessment. While the 15-dimensional health related quality of life measure (15D) seemed the most comprehensive measure for both diseases, the Health Utilities Index 3 (HUI 3) seemed to have the least coverage for type 2 diabetes and the EuroQol-5 Dimensions (EQ-5D) for AD. Furthermore, some of the utility instruments contained items that could not be mapped onto either of the proposed conceptual models. CONCLUSIONS: Content of the utility measure has a significant impact on the treatment effects that can be observed. This varies from one disease to the next and as such contributes to lack of consistency in observable utility effects and incremental utility scores. This observation appears to have been omitted from the method development considerations such as reference methods. As a result, we recommend that patients' perspectives obtained via qualitative methods are taken into consideration in the ongoing methods development in health state descriptions for generic utility instruments. Also, as a more immediate contribution to improving decision making, we propose that a content map of the chosen utility measure with patient-reported domains be provided as standard reporting in utility measurement in order to improve the transparency of the trade-offs in relation to patient relevance and consistency.

Alzheimer's disease treatment: assessing caregiver preferences for mode of treatment delivery.

INTRODUCTION: Management of patients with Alzheimer's Disease (AD) can exert a substantial burden upon caregivers. As new modes of treatment administration are developed, it is important to assess caregiver satisfaction and preference in a standardized manner. This study describes the development of the Alzheimer's Disease Caregiver Preference Questionnaire (ADCPQ) to assess AD caregivers' satisfaction with and preference for patch or capsule treatments in AD patients. METHODS: Twenty-five published articles (1987-2002) were reviewed to identify potential ADCPQ domains. Three caregiver focus groups (n=24) were conducted to develop a first draft of the questionnaire. After evaluating the acceptance of ADCPQ to caregivers through in-depth interviews (n=10), its psychometric properties were assessed using data from 986 patients enrolled in a multicenter, randomized, double-blind, four-arm, placebo- and active-controlled, 24-week trial. RESULTS: Focus groups indicated that caregivers expressed dissatisfaction with current AD treatment routines including limitations related to: efficacy, administration schedule, number of pills, adherence to treatment, side effects, and taking pills. In-depth interviews with caregivers found the ADCPQ to be comprehensible with an acceptable layout. The resultant ADCPQ comprises three modules: A) baseline, 11 items assessing treatment expectations; B) week 8, 33 items on satisfaction and preferences with treatment options; C) week 24, 10 items assessing overall opinions of treatment options. Missing data per item was low (

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.

Patient experiences with oily skin: the qualitative development of content for two new patient reported outcome questionnaires.

OBJECTIVE: To develop the content for two new patient reported outcome (PRO) measures to: a) assess the severity of symptoms; and b) the impact of facial skin oiliness on emotional wellbeing using qualitative data from face to face, and internet focus groups in Germany and the US. METHODS: Using input from initial treatment satisfaction focus groups (n = 42), a review of relevant literature and expert clinicians (n = 3), a discussion guide was developed to guide qualitative inquiry using Internet focus groups (IFGs). IFGs were conducted with German (n = 26) and US (n = 28) sufferers of oily skin. Questionnaire items were generated using coded transcript data from the focus groups. Cognitive debriefing was conducted online with 42 participants and face to face with an additional five participants to assess the comprehension of the items. RESULTS: There were equal numbers of male and female participants; mean age was 35.4 (SD 9.3) years. On average, participants had had oily skin for 15.2 years, and 74% (n = 40) reported having mild-moderate acne. Participants reported using visual, tactile and sensory (feel without touching their face) methods to evaluate the severity of facial oiliness. Oily facial skin had both an emotional and social impact, and was associated with feelings of unattractiveness, self-consciousness, embarrassment, irritation and frustration. Items were generated for a measure of oily skin severity (Oily Skin Self-Assessment Scale) and a measure of the impact of oily skin on emotional well-being (Oily Skin Impact Scale). Cognitive debriefing resulted in minor changes to the draft items and confirmed their face and content validity. CONCLUSION: The research provides insight into the experience of having oily skin and illustrates significant difficulties associated with the condition. Item content was developed for early versions of two PRO measures of the symptoms and emotional impact of oily facial skin. The psychometric validation of these measures reported elsewhere.

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 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.

Identifying the clinical domains of fibromyalgia: contributions from clinician and patient Delphi exercises.

OBJECTIVE: In evaluating the effectiveness of fibromyalgia (FM) therapies, it is important to assess the impact of those therapies on the full array of domains considered important by both clinicians and patients. The objective of this research was to identify and prioritize the key clinically relevant and important domains impacted by FM that should be evaluated by outcome assessment instruments used in FM clinical trials, and to approach consensus among clinicians and patients on the priority of those domains to be assessed in clinical care and research. METHODS: Group consensus was achieved using the Delphi method, a structured process of consensus building via questionnaires together with systematic and controlled opinion feedback. The Delphi exercises involved 23 clinicians with expertise in FM and 100 patients with FM as defined by American College of Rheumatology criteria. RESULTS: The Delphi exercise revealed that the domains ranked most highly by patients were similar to the domain rankings by clinicians. Pain was consistently ranked highest by both panels. Fatigue, impact on sleep, health-related quality of life, comorbid depression, and cognitive difficulty were also ranked highly. Stiffness was ranked highly by patients but not clinicians. In contrast, side effects was important to clinicians but was not identified as important in the patient Delphi exercise. CONCLUSION: The clinician and patient Delphi exercises identified and ranked key domains that need to be assessed in FM research. Based on these results, a conceptual framework for measuring patient-reported outcomes is proposed.

Patient-reported outcomes of deferasirox (Exjade, ICL670) versus deferoxamine in sickle cell disease patients with transfusional hemosiderosis. Substudy of a randomized open-label phase II trial.

BACKGROUND/AIMS: There is increasing evidence demonstrating the value of transfusions in sickle cell disease (SCD). However, resultant iron overload can be life threatening if untreated. Chelation therapy with deferoxamine requires parenteral infusions that can negatively impact quality of life and adherence to treatment. METHODS: As part of a phase II trial, SCD patient-reported outcomes were evaluated. One hundred and ninety-five patients were randomized (2:1) to receive oral deferasirox (5-30 mg/kg/day) or deferoxamine (20-50 mg/kg, 5 days per week); 121 had previously received deferoxamine. RESULTS: At each time point, significantly more patients who had previously received deferoxamine were 'satisfied/very satisfied' with deferasirox, or found treatment to be 'convenient/very convenient' compared with deferoxamine (p < 0.001). In these patients, fewer hours were lost from daily activities with deferasirox than deferoxamine treatment. Most patients (77%) preferred deferasirox, and more were willing to continue taking deferasirox than deferoxamine at end-of-study (84 vs. 11%, respectively). CONCLUSIONS: Patients with SCD are therefore more satisfied with deferasirox, which has a lower impact on daily activities than deferoxamine. Given the high levels of satisfaction, it is likely that quality of life will be improved. These results also suggest that treatment adherence with deferasirox may be better than with deferoxamine, which should lead to improved long-term outcomes.

Development and validation of the WEll-being and Satisfaction of CAREgivers of Children with Diabetes Questionnaire (WE-CARE).

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

Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with beta-thalassemia.

BACKGROUND: Iron chelation therapy (ICT) with deferoxamine (DFO), the current standard for the treatment of iron overload in patients with transfusion-dependent disorders such as beta-thalassemia, requires regular subcutaneous or intravenous infusions. This can lead to reduced quality of life and poor adherence, resulting in increased morbidity and mortality in iron-overloaded patients with beta-thalassemia. Deferasirox is an orally administered iron chelator that has been approved for use in the United States, Switzerland, and other countries. OBJECTIVE: This analysis was conducted to compare patient-reported outcomes (PROs) during receipt of DFO infusions or once-daily oral therapy with deferasirox (ICL670). METHODS: PROs were prospectively evaluated as part of a randomized, Phase III study comparing the efficacy and safety profile of DFO 20 to 60 mg/kg per day with those of deferasirox 5 to 30 mg/kg per day in patients (age > or =2 years) with beta-thalassemia who were receiving regular transfusions and had a liver iron concentration of > or =2 mg/g dry weight. PRO questionnaires were completed by patients or a parent or legal guardian at baseline, week 4, week 24, and end of study (EOS). Patients assessed their level of satisfaction with study treatment (very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied) and rated its convenience (very convenient, convenient, neutral, inconvenient, or very inconvenient). Time lost from normal activities due to ICT in the previous 4 weeks was recorded using a single global assessment. At week 4, patients who had previous experience with DFO were asked to indicate their preference for treatment (ICT received before the study, ICT received during the study, no preference, or no response) and the reason for that preference. At EOS, all patients were asked if they would be willing to continue using the ICT they had received during the study. All study analyses were performed in all patients who received at least 1 dose of study medication. RESULTS: Five hundred eighty-six patients (304 females, 282 males; age range, 2-53 years) received treatment with DFO (n = 290) or deferasirox (n = 296). Significantly more patients treated with deferasirox reported being very satisfied or satisfied with treatment compared with those treated with DFO (week 4: 92.0% vs 50.4%, respectively; week 24: 89.6% vs 44.0%; EOS: 85.1% vs 38.7%; all, P < 0.001). At the same time points, the majority of those treated with deferasirox reported that treatment was very convenient or convenient compared with those treated with DFO (95.5% vs 21.3%, 91.7% vs 17.4%, and 92.7% vs 11.3%, respectively; all, P < 0.001). Among patients who had previously taken DFO and were randomized to receive deferasirox during the study, 96.9% reported a preference for deferasirox over DFO. At EOS, the proportion of patients indicating a willingness to continue study therapy was significantly greater in those receiving deferasirox than in those receiving DFO (85.8% vs 13.8%; P < 0.001). CONCLUSIONS: In this study, patient-reported satisfaction and convenience were significantly higher for the once-daily, oral ICT deferasirox than for DFO infusions. Among patients who had received DFO before the study, the majority indicated a preference for deferasirox over DFO. Most patients receiving deferasirox indicated that they would be willing to continue taking it. These results suggest that deferasirox had a positive impact on patients' daily lives.

The impact of iron overload and its treatment on quality of life: results from a literature review.

BACKGROUND: To assess the literature for the impact of iron overload and infusion Iron Chelation Therapy (ICT) on patients' quality of life (QoL), and the availability of QoL instruments for patients undergoing infusion ICT. Also, to obtain patients' experiences of having iron overload and receiving infusion ICT, and experts' clinical opinions about the impact of treatment on patients' lives. METHODS: A search of studies published between 1966 and 2004 was conducted using Medline and the Health Economic Evaluation Database (HEED). Qualitative results from patient and expert interviews were analysed. Hand searching of relevant conference abstracts completed the search. RESULTS: Few studies measuring the impact of ICT with deferoxamine (DFO) on patients QoL were located (n = 15). QoL domains affected included: depression; fatigue; dyspnoea; physical functioning; psychological distress; decrease in QoL during hospitalization. One theme in all articles was that oral ICT should improve QoL. No iron overload or ICT-specific QoL instruments were located in the articles. Interviews revealed that the impact of ICT on patients with thalassemia, sickle cell disease, and myelodysplastic syndromes is high. CONCLUSION: A limited number of studies assessed the impact of ICT or iron overload on QoL. All literature suggested a need for easily administered, efficacious and well tolerated oral iron overload treatments, given the impact of current ICT on adherence. Poor adherence to ICT was documented to negatively impact survival. Further research is warranted to continue the qualitative and quantitative study of QoL using validated instruments in patients receiving ICT to further understanding the issues and improve patients QoL.