Demonstrating the burden of hypoglycemia on patients' quality of life in diabetes clinical trials: measurement considerations for hypoglycemia.

OBJECTIVES: To evaluate the association between hypoglycemia and health-related quality of life (HRQoL) in the context of a clinical trial using both an objectively confirmed and a patient-reported measure of hypoglycemia. METHODS: During a phase III, double-arm, randomized study, patients completed the short form 36 health survey (SF-36), a generic HRQoL questionnaire, at baseline and at weeks 24, 52, and 104. The objectively confirmed measure of hypoglycemia was based on a combination of plasma glucose measure and presence of hypoglycemia-related symptoms. The patient-reported frequency of hypoglycemia was defined as the following item: "How often have you felt that your blood sugars have been unacceptably low recently?" The association between hypoglycemia and HRQoL was evaluated in intent-to-treat patients (N = 3059) by using repeated-measurements analyses, with SF-36 scores used as explained variables and baseline SF-36 score, age, sex, country, time, and either number of objectively confirmed hypoglycemic events (0, ≥1) or patient-reported frequency of hypoglycemia (continuous variable 0-6) as explanatory variables. RESULTS: During study duration, less than 6% of patients experienced at least one objectively confirmed hypoglycemic event and about half the patients reported unacceptably low blood sugars "none of the time." The association between the number of objectively confirmed hypoglycemic events and HRQoL was not statistically significant, while the patient-reported frequency of hypoglycemia was statistically significantly related to all SF-36 scores (P < 0.001), except physical functioning; patients reporting greater perceived frequency of hypoglycemia had worse HRQoL. CONCLUSIONS: Using a patient-reported measure of hypoglycemia in the context of a clinical trial could enable the burden of hypoglycemia for patients to be demonstrated.

Validation of the Treatment Satisfaction Questionnaire for Medication in patients with cystic fibrosis.

BACKGROUND: Our objective was to confirm the measurement properties of the Treatment Satisfaction Questionnaire with Medication (TQSM) in patients with cystic fibrosis (CF) receiving inhaled antibiotics. METHODS: The TSQM was included in the EAGER study, a clinical trial comparing a nebulized and a dry powder device for inhaled tobramycin in a CF population with chronic Pseudomonas aeruginosa (Pa) lung infection, aged 6 years and above (N=553). Reliability and validity of the questionnaire were investigated using Cronbach's α and multitrait-multimethod approach. RESULTS: The TSQM demonstrated very good reliability and construct validity: all Cronbach's α were above 0.86 and all items met the convergent and discriminant validity criteria. In multivariate regressions, higher patient satisfaction and lower perceived impact of side-effects were associated with better treatment compliance. CONCLUSIONS: The TSQM showed very good measurement properties that strongly support its use to assess satisfaction of patients with CF taking inhaled antibiotics.

Burden of anemia in patients with osteoarthritis and rheumatoid arthritis in French secondary care.

BACKGROUND: Arthritic disorders can be the cause of hospitalizations, especially among individuals 60 years and older. The objective of this study is to investigate associations between health care resource utilization in arthritis patients with and without concomitant anemia in a secondary care setting in France. METHODS: This retrospective cohort study utilized data on secondary care activity in 2001 from the Programme de Médicalisation des Systèmes d'Information database. Two cohorts were defined using ICD-10 codes: patients with an arthritis diagnosis with a concomitant diagnosis of anemia; and arthritis patients without anemia. Health care resource utilization for both populations was analyzed separately in public and private hospitals. Study outcomes were compared between the cohorts using standard bivariate and multivariable methods. RESULTS: There were 300,865 hospitalizations for patients with arthritis only, and 2,744 for those with concomitant anemia. Over 70% of patients with concomitant anemia were in public hospitals, compared with 53.5% of arthritis-only patients. Arthritis patients without anemia were younger than those with concomitant anemia (mean age 66.7 vs 74.6, public hospitals; 67.1 vs 72.2, private hospitals). Patients with concomitant anemia/arthritis only had a mean length of stay of 11.91 (SD 14.07)/8.04 (SD 9.93) days in public hospitals, and 10.68 (SD 10.16)/9.83 (SD 7.76) days in private hospitals. After adjusting for confounders, the mean (95% CI) additional length of stay for arthritis patients with concomitant anemia, compared with those with arthritis only, was 1.56 (1.14-1.98) days in public and 0.69 (0.22-1.16) days in private hospitals. Costs per hospitalization were €;480 (227-734) greater for arthritis patients with anemia in public hospitals, and €;30 (-113-52) less in private hospitals, than for arthritis-only patients. CONCLUSIONS: Arthritis patients with concomitant anemia have a longer length of stay, undergo more procedures, and have higher hospitalization costs than nonanemic arthritis patients in public hospitals in France. In private hospitals, concomitant anemia was associated with modest increases in length of stay and number of procedures; however, this did not translate into higher costs. Such evidence of anemia-related health care utilization and costs can be considered as a proxy for the clinical significance of anemia.

Measuring benefits and patients' satisfaction when glasses are not needed after cataract and presbyopia surgery: scoring and psychometric validation of the Freedom from Glasses Value Scale (FGVS).

BACKGROUND: The purpose of this study was to reduce the number of items, create a scoring method and assess the psychometric properties of the Freedom from Glasses Value Scale (FGVS), which measures benefits of freedom from glasses perceived by cataract and presbyopic patients after multifocal intraocular lens (IOL) surgery. METHODS: The 21-item FGVS, developed simultaneously in French and Spanish, was administered by phone during an observational study to 152 French and 152 Spanish patients who had undergone cataract or presbyopia surgery at least 1 year before the study. Reduction of items and creation of the scoring method employed statistical methods (principal component analysis, multitrait analysis) and content analysis. Psychometric properties (validation of the structure, internal consistency reliability, and known-group validity) of the resulting version were assessed in the pooled population and per country. RESULTS: One item was deleted and 3 were kept but not aggregated in a dimension. The other 17 items were grouped into 2 dimensions ('global evaluation', 9 items; 'advantages', 8 items) and divided into 5 sub-dimensions, with higher scores indicating higher benefit of surgery. The structure was validated (good item convergent and discriminant validity). Internal consistency reliability was good for all dimensions and sub-dimensions (Cronbach's alphas above 0.70). The FGVS was able to discriminate between patients wearing glasses or not after surgery (higher scores for patients not wearing glasses). FGVS scores were significantly higher in Spain than France; however, the measure had similar psychometric performances in both countries. CONCLUSIONS: The FGVS is a valid and reliable instrument measuring benefits of freedom from glasses perceived by cataract and presbyopic patients after multifocal IOL surgery.

Psychometric evaluation of the functional assessment of HIV Infection (FAHI) questionnaire and its usefulness in clinical trials.

PURPOSE: To evaluate psychometric properties of the Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) questionnaire, a 47-item disease-specific instrument evaluating Health-Related Quality of Life (HRQL) in human immunodeficiency virus (HIV)-infected patients. METHODS: Treatment-experienced HIV-infected patients from two clinical programmes (N = 565; N = 1,096) completed the FAHI at Baseline and after 24 weeks of treatment. Psychometric properties of the FAHI were assessed in both trial populations, including minimal important differences (MIDs) calculations. Links between HRQL assessed by FAHI Total score, and biological endpoints were explored by regression analysis and mean score comparisons. RESULTS: Cronbach's alphas ranged from 0.72 to 0.94. Most items met convergent and discriminant validity criteria. Better FAHI scores were seen for patients in earlier HIV stages. Responsiveness was demonstrated with changes in FAHI scores significantly linked to change in EQ-5D score. Depending on methods used, MIDs ranged from 3.2 to 14 for FAHI Total score. Small association was found between FAHI Total score and CD4 count and viral load (r-square < 3%). Mean changes in FAHI scores were not statistically related to viral response. CONCLUSIONS: The FAHI demonstrated acceptable psychometric properties in two independent populations. HRQL assessment enabled detection of changes in patients' health status not revealed by traditional efficacy endpoints.

Effects of etravirine versus placebo on health-related quality of life in treatment-experienced HIV patients as measured by the functional assessment of human immunodeficiency virus infection (FAHI) questionnaire in the DUET trials.

PURPOSE: To study the effects of etravirine versus placebo on the health-related quality of life (HRQL) of HIV-infected patients. METHOD: HRQL of HIV-infected patients was measured using the Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) questionnaire in two identically designed phase III clinical trials investigating efficacy and safety of etravirine as part of highly active antiretroviral therapy. Pooled analyses of covariance, adjusted for treatment group, baseline FAHI score, CD4 cell count, viral load, and enfuvirtide use helped investigate changes in FAHI scores between baseline and Week 24 in etravirine-treated (n = 599) and placebo-treated (n = 604) subjects. Responder analyses were also conducted. RESULTS: Significant improvements with etravirine treatment were observed for FAHI physical, functional, emotional, and total scores (P < .001). These improvements were greater and statistically different from those with placebo (.013

Perception and acceptance of intradermal influenza vaccination: Patient reported outcomes from phase 3 clinical trials.

An intradermal trivalent inactivated influenza vaccine administered using a microinjection system has received European marketing authorization from the European Medicine Agency. We assessed clinical trial subjects' perception of injection site reactions (ISRs) and whether ISRs affected overall acceptability of vaccination and willingness to be vaccinated in the future. A validated, self-administered, patient reported outcome questionnaire was completed 21 days after intradermal or intramuscular vaccination by elderly and non-elderly adult participants in two European randomized, controlled, open-label phase 3 trials. The questionnaire addressed: the acceptability of ISRs, effect of ISRs on arm movement or sleep, satisfaction with the injection system, and willingness to be revaccinated. Questions were answered using a 5-point Likert verbal rating scale (1 = most favourable, 5 = most unfavourable response). Mean scores were calculated per group. 5,305 questionnaires were completed and analysed (95% return rate). Mean scores were close to 1 in all cases (maximum 1.68), indicating an overall favourable opinion of the vaccination and ISRs. More than 96% of participants rated ISRs after intradermal or intramuscular vaccination as either 'totally acceptable' or 'very acceptable'. Willingness to get vaccinated the following year and satisfaction with the intradermal microinjection system or the conventional intramuscular syringe were high and were not adversely affected by ISRs. ISRs after intradermal influenza vaccine administered using a microinjection system are well accepted by the vaccinees and are generally not a cause for concern.

Scoring and psychometric properties of the Eye-Drop Satisfaction Questionnaire (EDSQ), an instrument to assess satisfaction and compliance with glaucoma treatment.

BACKGROUND: The objective of this study was to ascertain the scoring and assess the psychometric properties of the Eye-Drop Satisfaction Questionnaire (EDSQ), a 43-item Patient-Reported Outcome instrument developed to assess patients' satisfaction and compliance with glaucoma treatment. METHODS: The EDSQ was administered during an observational, retrospective study to 184 French patients treated for glaucoma. The hypothesized structure, including six dimensions (patient-clinician relationship; patient experience; patient-treatment interaction; apprehension; patient knowledge; travel), was tested by assessing the internal consistency reliability (Cronbach's alpha) and construct-related validity (item convergent and discriminant validity). As unsatisfactory results were demonstrated, another structure was defined using a principal component analysis (PCA) combined with content of items. Psychometric properties of this new structure were assessed. Scores were compared between low, moderate and high compliance profile groups defined using data collected with the Travalert electronic device. RESULTS: Analyses were performed with the 169 patients who completed at least half of the EDSQ items. The hypothesized structure showed a Cronbach's alpha lower than 0.70 for four dimensions out of six and an overall poor construct-related validity (range of item-scale correlations: 0.00-0.68). The new structure obtained with the PCA included six dimensions: concern about treatment (five items); concern about disease (two items); satisfaction with patient-clinician relationship (five items); positive beliefs (three items); treatment convenience (three items); and self-declared compliance (three items). A score ranging from 0 to 100 was calculated for each dimension, with higher scores indicating more of the attribute referred to in the dimension. Internal consistency reliability was good (Cronbach's alpha greater than 0.70 for five dimensions). The structure offered good construct-related validity (range of item-scale correlations: 0.36-0.82). Ceiling effects of 21% and 49%, were observed for the satisfaction with patient-clinician relationship and self-declared compliance scores. Patients in low compliance profile group reported the lowest score for the satisfaction with patient-clinician relationship, positive beliefs, treatment convenience and self-declared compliance dimensions, and the highest score for the concern about treatment dimension. CONCLUSIONS: The scoring of the EDSQ was developed and the questionnaire proved to have satisfactory psychometric properties. EDSQ scores showed a promising relationship to compliance profiles. The EDSQ could be used in future studies.

Application of the disease-specific Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA) questionnaire in a general population: results from a French panel study.

OBJECTIVES: To assess the psychometric properties of the disease-specific Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA) questionnaire in a general population, and collect French normative data. METHODS: A postal survey was conducted on 2900 adult panelists representative of the French population. The participants were asked to complete a questionnaire including the QoL-AGHDA and an evaluation of their overall health status (OHS). The QoL-AGHDA score ranges from 0 to 25, a lower score indicating better QoL. Psychometric properties of the QoL-AGHDA were assessed. The mean QoL-AGHDA scores were described by sex and age groups. RESULTS: The return rate was 75%. The quality of completion and internal consistency reliability were good: 95% of the respondents completed all 25 QoL-AGHDA items and Cronbach's alpha was 0.86. The QoL-AGHDA score was able to discriminate between the respondents according to their OHS (from 1.5 for excellent to 12.3 for poor OHS, P < 0.001). The mean QoL-AGHDA score was 4.6 for the overall population, 5.1 for females and 4.2 for males, and ranged from 4.8 for the youngest to 6.1 for the oldest respondents. CONCLUSIONS: The QoL-AGHDA questionnaire showed good psychometric properties when administered in the French population. French reference values were collected, completing the QoL-AGHDA normative database already available in several European countries.

Satisfactory cross-cultural validity of the ACTG symptom distress module in HIV-1-infected antiretroviral-naive patients.

BACKGROUND: Multinational clinical trials commonly include different language versions of patient-reported outcomes (PRO) instruments without considering the question of their cross-cultural validity. The inclusion of a PRO instrument, the Adult AIDS Clinical Trial Group Symptom Distress Module (SDM), in an multinational clinical trial in HIV-1 antiretroviral-naive patients offered an opportunity to explore the methods to assess cross-cultural validity of PRO instruments in the context of clinical trials. PURPOSE: To assess the cross-cultural validity of the SDM across seven cultural groups in the setting of a multinational HIV clinical trial. METHODS: Twenty-five language versions of the SDM were included in a Phase IIb/III trial comparing maraviroc with efavirenz (each in combination with zidovudine/ lamivudine) conducted in 12 countries to assess symptoms perceived by HIV-1-infected antiretroviral-naive patients. Differential item functioning (DIF) detection and the STATIS method were combined in a pragmatic approach to assess the cross-cultural validity of the SDM using pre-antiretroviral treatment data from 759 patients. RESULTS: Statistically significant DIF between cultural groups was observed for four items: fatigue; fevers; anxiety; and headache. However, examination of these items by linguists did not lead to meaningful explanations for the statistical differences. With the STATIS approach, the Bantu and European Germanic groups were the furthest from the Occidental English group. LIMITATIONS: The assessment of cross-cultural validity had to be performed on some very small samples and on data aggregated by cultural groups, which suggests the need for a cautious interpretation of the results. CONCLUSIONS: Given the heterogeneity of cultures considered, the absence of meaningful explanations for statistically significant differences between cultural groups supports the cross-cultural validity of the SDM versions included in this trial. Thus, this study demonstrated that it is feasible to conduct assessment of crosscultural validity of PRO instruments using data collected in the setting of multinational clinical trials.

Development and psychometric validation of a self-administered questionnaire assessing the acceptance of influenza vaccination: the Vaccinees' Perception of Injection (VAPI) questionnaire.

BACKGROUND: Influenza is among the most common infectious diseases. The main protection against influenza is vaccination. A self-administered questionnaire was developed and validated for use in clinical trials to assess subjects' perception and acceptance of influenza vaccination and its subsequent injection site reactions (ISR). METHODS: The VAPI questionnaire was developed based on interviews with vaccinees. The initial version was administered to subjects in international clinical trials comparing intradermal with intramuscular influenza vaccination. Item reduction and scale construction were carried out using principal component and multitrait analyses (n = 549). Psychometric validation of the final version was conducted per country (n = 5,543) and included construct and clinical validity and internal consistency reliability. All subjects gave their written informed consent before being interviewed or included in the clinical studies. RESULTS: The final questionnaire comprised 4 dimensions ("bother from ISR"; "arm movement"; "sleep"; "acceptability") grouping 16 items, and 5 individual items (anxiety before vaccination; bother from pain during vaccination; satisfaction with injection system; willingness to be vaccinated next year; anxiety about vaccination next year). Construct validity was confirmed for all scales in most of the countries. Internal consistency reliability was good for all versions (Cronbach's alpha ranging from 0.68 to 0.94), as was clinical validity: scores were positively correlated with the severity of ISR and pain. CONCLUSION: The VAPI questionnaire is a valid and reliable tool, assessing the acceptance of vaccine injection and reactions following vaccination.

Evaluation of the reliability and validity of the Medical Outcomes Study sleep scale in patients with painful diabetic peripheral neuropathy during an international clinical trial.

BACKGROUND: Sleep is an important element of functioning and well-being. The Medical Outcomes Study Sleep Scale (MOS-Sleep) includes 12 items assessing sleep disturbance, sleep adequacy, somnolence, quantity of sleep, snoring, and awakening short of breath or with a headache. A sleep problems index, grouping items from each of the former domains, is also available. This study evaluates the psychometric properties of MOS-Sleep Scale in a painful diabetic peripheral neuropathic population based on a clinical trial conducted in six countries. METHODS: Clinical data and health-related quality of life data were collected at baseline and after 12 weeks of follow-up. Overall, 396 patients were included in the analysis. Psychometric properties of the MOS-Sleep were assessed in the overall population and per country when the sample size was sufficient. Internal consistency reliability was assessed by Cronbach's alpha; the structure of the instrument was assessed by verifying item convergent and discriminant criteria; construct validity was evaluated by examining the relationships between MOS-Sleep scores and sleep interference and pain scores, and SF-36 scores; effect-sizes were used to assess the MOS-Sleep responsiveness. The study was conducted in compliance with United States Food and Drug Administration regulations for informed consent and protection of patient rights. RESULTS: Cronbach's alpha ranged from 0.71 to 0.81 for the multi-item dimensions and the sleep problems index. Item convergent and discriminant criteria were satisfied with item-scale correlations for hypothesized dimensions higher than 0.40 and tending to exceed the correlations of items with other dimensions, respectively. Taken individually, German, Polish and English language versions had good internal consistency reliability and dimension structure. Construct validity was supported with lower sleep adequacy score and greater sleep problems index scores associated with measures of sleep interference and pain scores. In addition, correlations between the SF-36 scores and the MOS-Sleep scores were low to moderate, ranging from -0.28 to -0.53. Responsiveness was supported by effect sizes > 0.80 for patients who improved according to the mean sleep interference and pain scores and clinician and patient global impression of change (p < 0.0001). CONCLUSION: The MOS-Sleep had good psychometric properties in this painful diabetic peripheral neuropathic population. TRIAL REGISTRATION: As this study was conducted from 2000 to 2002 (i.e., before the filing requirement came out), no trial registration number is available.