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.

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 (

Comparing the discriminative validity of two generic and one disease-specific health-related quality of life measures in a sample of patients with dry eye.

OBJECTIVE: The purpose of this study was to compare the discriminative properties of two generic health-related quality of life (QoL) instruments (SF-36 and EQ-5D) and a newly developed disease-specific patient-reported outcomes instrument (Impact of Dry Eye on Everyday Life (IDEEL)) to distinguish between different levels of dry eye severity. METHODS: Assessment of 210 people: 130 with non-Sjogren's Keratoconjunctivitis Sicca (non-SS KCS), 32 with Sjögren's Syndrome (SS) and 48 controls; comparison of SF-36, EQ-5D, and IDEEL age-adjusted data by dry eye severity levels. Severity was assessed based on diagnosis (non-SS KCS, SS, control), patient-report (none, very mild, mild, moderate, severe, extremely severe) and clinician-report (none, mild, moderate, severe). RESULTS: Discriminative validity results were consistent for all instruments. Significant differences between severity levels were found with most SF-36 scales (P < 0.05), all EQ-5D scales (P < 0.05), and all IDEEL scales (P < 0.0001), except for Treatment Satisfaction. IDEEL scales consistently outperformed the generic QoL measures regardless of the severity criterion used. Most SF-36 scales outperformed the EQ-5D QoL scale, but the EQ-5D visual analog scale outperformed the SF-36 scales, except for General Health Perceptions. CONCLUSIONS: The disease-specific IDEEL scales are better able to discriminate between severity levels than the majority of the generic QoL scales. Preliminary evidence demonstrates that the IDEEL will be sensitive to QoL changes over time, although further testing in controlled longitudinal studies is needed.

The relative burden of dry eye in patients' lives: comparisons to a U.S. normative sample.

PURPOSE: To assess the relative burden of dry eye in daily life by comparing Short Form-36 (SF-36) responses from individuals with and without dry eye against U.S. norms. METHODS: Assessment of 210 people, 130 with non-Sjogren's keratoconjunctivitis sicca (non-SS KCS), 32 with Sjogren's Syndrome (SS), and 48 control subjects. The study population data and published normative SF-36 data were compared. Dry eye severity was assessed by recruited severity (control, non-SS KCS, SS), patient self-report (none, very mild/mild, moderate, severe/extremely severe), and clinician-report (none, mild, moderate, severe). Age- and gender-matched norms were compared with all defined severity groups. RESULTS: Compared with the norms, control subjects scored higher on all SF-36 scales. Effect size (ES) ranged from 0.15 to 0.52. Non-SS KCS patients had lower Role-Physical (ES=-0.07), Bodily Pain (ES=-0.08), and Vitality (ES=-0.11) scores, indicating more dry eye impact on those areas versus the norm. All SF-36 scale scores except Mental Health (ES=0.12) were lower in the SS group than the adjusted norm (ES range: -0.16 to -0.99). Regardless of severity classification, mild patients consistently had lower Role-Physical and Bodily Pain scores than the norm, suggesting impact on daily roles (ES < 0.2). Patients with moderately severe disease also experienced less vitality and poorer general health. The group with severe disease scored lower than the norm across all domains (ES range: -0.14 to -0.91) except Role-Emotional (ES=0.13) and Mental Health (ES=0.23). CONCLUSIONS: These results indicate dry eye's negative impact on everyday life, particularly in daily activities. Further research using disease-specific measures to examine dry eye's impact is underway.

Development and validation of the Pain Treatment Satisfaction Scale (PTSS): a patient satisfaction questionnaire for use in patients with chronic or acute pain.

The purpose of this study was to develop and validate a measure of patient satisfaction for patients receiving treatment for either acute or chronic pain: the Pain Treatment Satisfaction Scale (PTSS). Development of the initial questionnaire included a comprehensive literature review and interviews with patients, physicians and nurses in the United States, Italy and France. After initial items were created, psychometric validation was run on responses from 111 acute pain and 89 chronic pain patients in the United States. Analyses included principal components factor analysis tests of reliability, clinical validity and confounding. The hypothesized structure of the questionnaire was supported by statistical analyses, and seven overlapping or inconsistent items were removed. The multi-item domains of the final PTSS included 39 items grouped in five dimensions: information (5 items); medical care (8 items); impact of current pain medication (8 items); satisfaction with pain medication which included the two subscales medication characteristics (3 items) and efficacy (3 items); and side effects (12 items). Internal consistency reliability coefficients were good (ranging from 0.83 to 0.92). The test-retest reliability coefficients (ranging from 0.67 to 0.81) were good for all dimensions except medication characteristics (0.55). All dimensions except medical care discriminated well according to pain severity. The satisfaction with efficacy dimension, hypothesized to change in the acute pain population, indicated good preliminary responsiveness properties (effect size 0.37; P<0.001). The PTSS is a valid, comprehensive instrument to assess satisfaction with treatment of pain based on independent modules that have demonstrated satisfactory psychometric performance.

The relationship between habitual patient-reported symptoms and clinical signs among patients with dry eye of varying severity.

PURPOSE: To investigate symptom profiles and clinical signs in subjects with dry eye and normal subjects in a cross-sectional multicenter study. METHODS: Subjects aged 35 to 65 were recruited according to dry eye diagnostic codes and telephone interview and completed the Dry Eye Questionnaire 2001, among others, and underwent dry eye clinical tests. RESULTS: Subjects (122) included 28 control subjects (C), 73 with non-Sjögren's keratoconjunctivitis sicca (non-SS KCS) and 21 with Sjögren's syndrome (SS). Subjects with SS or non-SS KCS reported discomfort and dryness most frequently and that many symptoms worsened over the day and were quite bothersome. Groups were significantly different in corneal fluorescein staining, conjunctival lissamine green staining, Schirmer 1 tear test, and tear break-up time (TBUT; chi2 and Kruskal-Wallis, P<0.0001). Statistically significant, but moderate, correlations were found between the frequency and evening intensity of dryness and discomfort and TBUT, Schirmer's tear test, overall corneal fluorescein staining, and temporal lissamine green conjunctival staining (Spearman r=0.31-0.45, P<0.01). Symptoms were moderately to highly correlated with the clinician's global grading of severity and highly correlated to patient's self-assessment of severity (r=0.46-0.86, P<0.0001), whereas signs showed lower correlations (r=0.22-0.46, P<0.0001). CONCLUSIONS: Subjects with SS or non-SS KCS reported frequent and intense ocular surface symptoms in the evening, some of which correlated moderately with clinical test results. The global clinician grade of dry eye correlated more highly with patient symptoms than did clinical signs, suggesting that patient symptoms influence dry eye diagnosis and grading of dry eye more than clinical test results.

Short-term exposure to low-dose ritonavir impairs clearance and enhances adverse effects of trazodone.

Antiretroviral agents may participate in drug interactions that influence the efficacy and toxicity of other antiretrovirals, as well as pharmacologic treatments of coincident or complicating diseases. The viral protease inhibitor, ritonavir, may cause drug interactions by inhibiting the activity of cytochrome P450-3A (CYP3A) isoforms. In a single-dose, blinded, four-way crossover study, 10 healthy volunteer subjects received 50 mg of trazodone hydrochloride or matching placebo concurrent with low-dose ritonavir (four doses of 200 mg each) or with placebo. Compared to the control condition, ritonavir significantly reduced apparent oral clearance of trazodone (155 +/- 23 vs. 75 +/- 12 ml/min, p < 0.001), prolonged elimination half-life (6.7 +/- 0.7 vs. 14.9 +/- 3.9 h, p < 0.05), and increased peak plasma concentrations (842 +/- 64 vs. 1125 +/- 111 ng/ml, p < 0.05) (mean +/- SE). Coadministration of trazodone with ritonavir increased sedation, fatigue, and performance impairment compared to trazodone plus placebo; differences reached significance only for the digitsymbol substitution test. Three subjects experienced nausea, dizziness, or hypotension when trazodone was given with ritonavir; 1 of these subjects also experienced syncope. Thus short-term low-dose administration of ritonavir impairs oral clearance of trazodone and increases the occurrence of adverse reactions. The findings are consistent with impairment of CYP3A-mediated trazodone metabolism by ritonavir.

Measurement strategies for indirect costs in economic evaluations.

Considerable research has been undertaken on the different methods for valuing work absences and productivity losses (e.g., human capital vs. friction costing). However, investigation related to the best way to capture this information directly from trial participants or through surveys has been inadequate. The collection of information that may be used in providing estimates of indirect costs is problematic for a number of reasons such as the presence of poor questionnaire design, a lack of psychometric testing and accessible validating data and the potential for recall errors. In this review, the measurement methods of lost time for work activities are examined. Issues in the validity of existing instruments and recall periods are explored. Based on a review of the literature, the relevance of generic and specific methods of measuring work losses are assessed.