Psychometric Properties of the Asthma Symptom Index in Patients with Severe Asthma.

BACKGROUND: Evaluation of symptoms is essential in asthma clinical research. Daily symptom diaries require once- or twice-daily recording, making them less suited to real-world use. A modified version of the established Asthma Symptom Utility Index (ASUI) that includes symptom attributes (Asthma Symptom Index [ASI]) was developed as a less-burdensome measure of asthma symptoms. OBJECTIVE: To evaluate the ASI and replicate ASUI psychometric properties, including validity, reliability, responsiveness, and minimal clinically important difference (MCID) estimation in patients ≥12 years of age with severe asthma. METHODS: Patients from a randomized trial (MUSCA [n = 497]) and a cross-sectional study (IDEAL [n = 721]) were analyzed post hoc. Demographic information, spirometry, ASI and ASUI scores, and other patient-reported outcome measures such as Asthma Control Questionnaire (ACQ-5) and St George's Respiratory Questionnaire (SGRQ) at baseline and during follow-up (MUSCA only) were obtained. RESULTS: Internal consistency reliability and test-retest reliability were considered good (>0.70 [Cronbach's alpha] and 0.87-0.90 [intraclass correlation]). ASI/ASUI scores correlated strongly with ACQ-5 and SGRQ scores (spearman correlation [rs] magnitude: 0.67-0.85). ASI and ASUI scores differed for asthma control (defined by ACQ-5) and lung function (% predicted forced expiratory volume in 1 second). Changes in ASI and ASUI scores from baseline to week 4 and week 12 had high correlations with changes in ACQ-5 (rs magnitude: 0.57-0.69). MCIDs ranged from -0.42 to -0.26 (ASI) and 0.07 to 0.11 (ASUI). CONCLUSION: Findings show the good reliability, validity, and responsiveness of the ASI, indicating potential value for real-world symptom assessment in severe asthma.

TX-001HR is associated with a clinically meaningful effect on severity of moderate to severe vasomotor symptoms in the REPLENISH trial.

OBJECTIVE: The aim of the study was to evaluate the clinically meaningful effect of oral TX-001HR (17ß-estradiol [E2]/progesterone [P4]) capsules on hot flushes severity (vasomotor symptoms [VMS] severity scale) using the patient-reported Clinical Global Impression (CGI). METHODS: REPLENISH (NCT01942668) was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial that evaluated TX-001HR in postmenopausal women (40-65 y) with a uterus. Those with frequent moderate to severe hot flushes (≥7/d or ≥50/wk) were randomized in a VMS substudy to daily E2/P4 (1/100, 0.5/100, 0.5/50, or 0.25/50 mg/mg), or placebo. Patients rated VMS severity from 1 (mild) to 3 (severe) and symptom improvements with the CGI. CGI results were an anchor in a nonparametric discriminant analysis to define clinically important differences (CIDs) and minimal CID in VMS severity at weeks 4 and 12. RESULTS: In the VMS substudy (n = 726), determined CID and minimal CID severity thresholds were reductions of 0.525 and 0.350 points at week 4, respectively, and 0.775 and 0.225 points at week 12. Significantly more women taking the two highest E2/P4 doses (1/100 and 0.5/100) versus placebo met CID severity thresholds at weeks 4 (40% and 44% vs 17%; P < 0.05) and 12 (56% and 48% vs 29%; P < 0.05). CONCLUSION: REPLENISH trial data demonstrated that E2/P4 1/100 and 0.5/100 provided clinically meaningful improvements in hot flushes severity in postmenopausal women. In conjunction with previously demonstrated clinically meaningful VMS frequency improvements, these data support oral E2/P4 1/100 and 0.5/100 for postmenopausal women with a uterus seeking treatment for moderate to severe VMS.

Evaluation of clinical meaningfulness of estrogen plus progesterone oral capsule (TX-001HR) on moderate to severe vasomotor symptoms.

OBJECTIVE: The aim of this study was to determine the clinical meaningfulness of TX-001HR in reducing moderate to severe vasomotor symptoms (VMS) in menopausal women with a uterus. METHODS: In the REPLENISH study (NCT01942668), women with moderate to severe hot flushes (≥7/d or ≥50/wk) were enrolled in a VMS substudy and randomized to four doses of daily TX-001HR (17ß-estradiol/progesterone) or placebo. Participants assessed improvement of their VMS by the Clinical Global Impression and the Menopause-Specific Quality of Life (MENQOL) questionnaire, which were used to define clinical responders, clinically important differences (CIDs) or minimal CID (MCID) in VMS frequency. Response thresholds were determined by nonparametric discriminant analyses utilizing bootstrapping methods. RESULTS: In the modified intent-to-treat VMS substudy population (n = 726), statistically significantly more Clinical Global Impression-based clinical responders were observed with TX-001HR than placebo for MCID (weekly reduction of ≥25 moderate to severe VMS: 82-88% vs 69%; all, P < 0.05) and CID (weekly reduction of ≥39 VMS: 68%-73% vs 52%; all, P < 0.05) at week 12. Week 4 results were similar. For Menopause Quality of Life-based analysis, significantly more clinical responders were observed with TX-001HR than placebo for MCID (weekly reduction of ≥34 VMS: 74%-81% vs 55%; all, P < 0.01) and CID (weekly reduction of ≥44 VMS: 61%-69% vs 42%; all, P < 0.01) at week 12. CONCLUSIONS: TX-001HR provided clinically meaningful improvements (as measured by 2 different methods), in addition to statistically significant reductions, in menopausal VMS frequency. TX-001HR may provide a new option, as a single oral capsule of estradiol and progesterone (identical to the hormones naturally occurring in women) for the treatment of moderate to severe VMS in menopausal women with a uterus.

A cost-effectiveness clinical decision analysis model for treatment of Schizophrenia.

BACKGROUND: Schizophrenia afflicts approximately 0.7% of Mexican citizens during their lifetime. This study explored whether the difference in clinical efficacy and safety between atypical antipsychotics and conventional neuroleptics results in decreases in use and cost of medical services in Mexico, offsetting the higher price of atypical antipsychotics. METHODS: A U.S. decision analytic Markov model was adapted for use in Mexico to determine cost-effectiveness of treatments and outcomes that Mexican patients with schizophrenia may experience over a 5-year period when treated with olanzapine, haloperidol, or risperidone. Model parameter estimates were based on clinical trial data, published medical literature, and where needed, clinician judgment. Direct medical costs were incorporated into the model and outcomes were estimated using lack of relapse and clinical outcomes based on the Brief Psychiatric Rating Scale (BPRS) as effectiveness indicators. All costs are reported in Mexican pesos. RESULTS: Over a 5-year period, the cost of treating schizophrenia ranged from 196,620 pesos per patient initiating therapy with haloperidol to 226,670 pesos per patient beginning therapy with risperidone. Olanzapine was estimated to have slightly better non-relapse and BPRS-based effectiveness outcomes, but comparative total medical costs compared to risperidone. Patients receiving olanzapine experienced 13 and 2% fewer relapses compared with patients on haloperidol and risperidone, respectively. The 5-year incremental cost-effectiveness ratio of olanzapine compared with haloperidol was 52,740 pesos per improved patient, BPRS-based outcome and 212,540 pesos per avoided relapse. Sensitivity analyses indicated the model was sensitive only to changes in drug costs. CONCLUSIONS: Compared with haloperidol, olanzapine therapy results in improved symptoms, fewer relapses, and is cost-effective, even with conservative values for key model parameters. Olanzapine results in slightly improved patient outcomes and comparable costs compared with risperidone.