Is there an additional health-related quality of life (HRQL) benefit with abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) beyond that mediated by clinical endpoints?

9617 Background: HRQL was evaluated as part of COU-AA-301, a randomized phase 3 trial of AA + prednisone (P) vs placebo + P in mCRPC patients (pts) post-docetaxel, where AA + P demonstrated significant benefits over P in numerous HRQL measures. Here we report post hoc analyses investigating the role of disease progression (px) in mediating the HRQL benefits of AA. Methods: Intensity of pain and fatigue and their interference with daily activities were assessed with the BPI-SF and BFI questionnaires and multiple domains of HRQL with the FACT-P questionnaire. Mediation analyses were conducted using a series of 3 models (Baron &amp; Kenny J Pers Soc Psychol 1986), to assess whether presence and timing of disease px mediated treatment effects of AA + P vs P on HRQL changes: in Model 1, HRQL (i.e. the outcome variable) is predicted by treatment, in Model 2, px (i.e. the mediator variable) is predicted by treatment, and in Model 3, HRQL is predicted by both treatment and px. Three different disease px indicators (ie, PSA px, radiographic px, and a composite px variable) were used. Results: Treatment predicted the change in FACT-P total score from baseline (Model 1; p = 0.011). Treatment (as sole predictor) was significantly (p ≤ 0.001) predictive of both PSA px and radiographic px (Model 2). Some of the treatment benefit of AA + P on the FACT-P total score was not explained as the result of the effect of treatment on PSA and radiographic px (Model 3; p = 0.030). In Model 3, pts with late (&gt; 250 d post-randomization) or no px had better FACT-P scores than those with early px for PSA px (p = 0.019, no px; p = 0.008, late px) and radiographic px (p = 0.054, no px; p = 0.017, late px). Models evaluating the mediating role of the composite px variable showed the same pattern of results. Identical sets of mediation analyses conducted for the BPI and BFI also exhibited very similar outcomes. Conclusions: In post-docetaxel mCRPC pts, the benefits of AA to HRQL appear to be related to both treatment assignment and the mediating effects of disease px. HRQL end points expand understanding of treatment benefit beyond clinical disease px end points. Clinical trial information: NCT00638690. </jats:p

A new tool for monitoring asthma outcomes: the ITG Asthma Short Form

BACKGROUND: Asthma treatment has broadened from managing clinical markers to incorporate factors that are most meaningful to patients, collectively called health-related quality of life (HQL). OBJECTIVE: To develop an asthma-specific HQL tool, meeting demands for brevity, usefulness and measurement precision. METHODS: The 20-item Sydney Asthma Quality of Life Questionnaire (AQLQ) and six additional items were studied using factor analysis, reliability and validity tests among asthma patients 14 and older. RESULTS: The 15-item Integrated Therapeutics Group Asthma Short Form (ITG-ASF) retains the validity of the AQLQ with improved scaling properties and interpretability. The ITG-ASF yields 6 scores: Symptom-Free Index, Functioning with Asthma, Psychosocial Impact of Asthma, Asthma Energy and Asthma-Confidence in Health and a Total. All items correlated 0.40 or higher with their hypothesized scales and passed discriminant validity tests, with scaling success rates from 75 to 100%. Reliability exceeded the minimum of 0.70 for group comparisons. Ceiling and floor effects were acceptable. Scales were valid in relation to changes in asthma severity and lung function. The best predictor of asthma severity (National Asthma Education and Prevention Program (NAEPP) staging) was the Symptom-Free Index. A Spanish translation is available, Chinese-American is forthcoming. The reading grade level is 4.8. CONCLUSIONS: Development of the ITG-ASF was a data-driven process maximizing measurement precision and breadth while minimizing burden. The ITG-ASF is a brief, comprehensive and empirically valid tool that complements traditional markers of the outcomes of asthma care

Effect of abiraterone acetate (AA) on patient-reported pain in metastatic castration-resistant prostate cancer (mCRPC) post-docetaxel: Results of longitudinal sensitivity analyses.

9618 Background: The COU-AA-301 phase 3 trial showed that AA + prednisone (P) improved overall survival in mCRPC patients (pts) post-docetaxel. Compared with P alone, AA + P also had significant benefits on patient-reported pain. Here we describe post hoc sensitivity analyses of pain data from that trial, using different methods to compensate for the potential impact of missing data. Methods: Pts with mCRPC progressing after docetaxel-based chemotherapy were randomized 2:1 to AA + P or placebo + P. Pain intensity and interference of pain with daily activities were assessed with the Brief Pain Inventory-Short Form (BPI-SF) questionnaire at baseline, Day 15 of Cycle 1, and Day 1 of each 28-day treatment cycle thereafter until treatment discontinuation. The effect of treatment on BPI-SF scores was analyzed using repeated measure mixed-effects (RMM) models, piecewise linear mixed-effects (PWLME) models, and joint mixed-effects and log time-to-dropout (JMEL) models. RMM and PWMLE models assumed missing data (due to death, study dropout, or administrative issues) to be missing at random, the JMEL model to be missing not at random. Model results were compared between treatment arms. Results: 797 pts were randomized to AA + P, and 398 to P only. RMM model estimates suggested statistically significant (p &lt; 0.05) differences in change from baseline for pain intensity and pain interference scores in favor of AA + P at the majority of study visits through cycle 11. PWLME models yielded significantly smaller areas under the curve (AUCs) for AA + P vs P for pain intensity (p = 0.0031) and pain interference (p = 0.0006); smaller AUCs reflect better pain outcomes. Results using JMEL models were nearly identical to those with PWLME models, with AUCs for AA + P significantly smaller than for P alone for pain intensity (p = 0.0031) and pain interference (p = 0.0007). Conclusions: Using various modeling methods that assess the impact of missing data, AA + P showed superior patterns of pain outcomes over time compared with P only in mCRPC pts refractory to docetaxel. These results support the previously reported pain benefits of AA + P over P alone from the same trial. Clinical trial information: NCT00638690. </jats:p

Comparative Incidence and Health Care Costs of Medically Attended Adverse Effects among U.S. Medicaid HIV Patients on Atazanavir- or Darunavir-Based Antiretroviral Therapy

AbstractObjectivesThis is the first study to compare the incidence and health care costs of medically attended adverse effects in atazanavir- and darunavir-based antiretroviral therapy (ART) among U.S. Medicaid patients receiving routine HIV care.MethodsThis was a retrospective study using Medicaid administrative health care claims from 15 states. Subjects were HIV patients aged 18 to 64 years initiating atazanavir- or darunavir-based ART from January 1, 2003, to July 1, 2010, with continuous enrollment for 6 months before (baseline) and 6 months after (evaluation period) ART initiation and 1 or more evaluation period medical claim. Outcomes were incidence and health care costs of the following medically attended (International Classification of Diseases, Ninth Revision, Clinical Modification–coded or treated) adverse effects during the evaluation period: gastrointestinal, lipid abnormalities, diabetes/hyperglycemia, rash, and jaundice. All-cause health care costs were also determined. Patients treated with atazanavir and darunavir were propensity score matched (ratio = 3:1) by using demographic and clinical covariates. Multivariable models adjusted for covariates lacking postmatch statistical balance.ResultsPropensity-matched study sample included 1848 atazanavir- and 616 darunavir-treated patients (mean age 41 years, 50% women, 69% black). Multivariable-adjusted hazard ratios (HRs) (for darunavir, reference = atazanavir) and per-patient-per-month health care cost differences (darunavir minus atazanavir) were as follows: gastrointestinal, HR = 1.25 (P = 0.04), $43 (P = 0.13); lipid abnormalities, HR = 1.38 (P = 0.07),$3 (P = 0.88); diabetes/hyperglycemia, HR = 0.84 (P = 0.55), $13 (P = 0.69); and rash, HR = 1.11 (P = 0.23),$0 (P = 0.76); all-cause health care costs were $1086 (P<0.001). Too few instances of jaundice (11 in atazanavir and 1 in darunavir) occurred to support multivariable modeling.ConclusionsMedication tolerability can be critical to the success or failure of ART. Compared with darunavir-treated patients, atazanavir-treated patients had significantly fewer instances of medically attended gastrointestinal issues and more instances of jaundice and incurred significantly lower health care costs

Impact of changes in asthma severity on health-related quality of life in pediatric and adult asthma patients: results from the asthma outcomes monitoring system

The goals of asthma treatment have broadened beyond managing traditional clinical markers of disease severity, and now include a focus on benefits of treatment in terms that are most meaningful to patients. Measurement of both generic and disease-specific health-related quality of life (HQL) is advocated because each provides complementary information about how the condition affects everyday functioning and well-being and whether treatments have their intended effects. The purpose of this study was to determine the impact of changes in asthma severity (defined using NHLBI/NAEPP severity staging) on patient-assessed HQL. Two hundred and thirty-three pediatric asthma patients and 269 adult asthma patients were evaluated in a one-year observational study. Analyses were performed to compare the generic and asthma-specific scores for patients whose asthma severity improved, stayed the same, or worsened over one year. The asthma-specific scales are sensitive to changes in disease severity. Of the generic scales, those tapping areas of physical health are more affected than the mental/emotional scales. This confirms that HQL measures are responsive to changes in asthma severity. They complement traditional clinical markers used to evaluate changes in a patient's disease state and thus give the physician another useful tool in following the clinical progress of the child with asthma