Validation of the post sleep questionnaire for assessing subjects with restless legs syndrome: results from two double-blind, multicenter, placebo-controlled clinical trials

<p>Abstract</p> <p>Background</p> <p>Because of the subjective nature of Restless Legs Syndrome (RLS) symptoms and the impact of these symptoms on sleep, patient-reported outcomes (PROs) play a prominent role as study endpoints in clinical trials investigating RLS treatments. The objective of this study was to validate a new measure, the Post Sleep Questionnaire (PSQ), to assess sleep dysfunction in subjects with moderate-to-severe RLS symptoms.</p> <p>Methods</p> <p>Pooled data were analyzed from two 12-week, randomized, placebo-controlled trials of gabapentin enacarbil (N = 540). At baseline and Week 12, subjects completed the PSQ and other validated health surveys: IRLS Rating Scale, Clinical Global Impression of Improvement (CGI-I), Profile of Mood States (POMS), Medical Outcomes Study Scale-Sleep (MOS-Sleep), and RLS-Quality of Life (RLSQoL). Pooled data were used <it>post hoc </it>to examine the convergent, divergent, known-group validity and the responsiveness of the PSQ.</p> <p>Results</p> <p>Convergent validity was demonstrated by significant correlations between baseline PSQ items and total scores of IRLS, POMS, RLSQoL, and the MOS-Sleep Scale (p ≤ 0.007 each). Divergent validity was demonstrated through the lack of significant correlations between PSQ items and demographic characteristics. Correlations (p < 0.0001) between RLS severity groups and PSQ items demonstrated known-group validity. Mean changes in investigator- and subject-rated CGI-I scores for each PSQ item (p < 0.0001) demonstrated the PSQ's responsiveness to patient change as reported by their care provider.</p> <p>Conclusions</p> <p>Although these analyses were potentially limited by the use of clinical trial data and not prospective data from a study conducted solely for validation purposes, the PSQ demonstrated robust psychometric properties and is a valid instrument for assessing sleep and sleep improvements in subjects with moderate-to-severe RLS symptoms.</p> <p>Trial Registration</p> <p>This study analyzed data from two registered trials, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00298623">NCT00298623</a> and <a href="http://www.clinicaltrials.gov/ct2/show/NCT00365352">NCT00365352</a>.</p

What is the Impact of the Analysis Method Used for Health State Utility Values on QALYs in Oncology? A Simulation Study Comparing Progression-Based and Time-to-Death Approaches

Background: Health state utility values (‘utilities’) are an integral part of health technology assessment. Though traditionally categorised by disease status in oncology (i.e. progression), several recent assessments have adopted values calculated according to the time that measures were recorded before death. We conducted a simulation study to understand the limitations of each approach, with a focus on mismatches between the way utilities are generated, and analysed. Methods: Survival times were simulated based on published literature, with permutations of three utility generation mechanisms (UGMs) and utility analysis methods (UAMs): (1) progression based, (2) time-to-death based, and (3) a ‘combination approach’. For each analysis quality-adjusted life-years (QALYs) were estimated. Goodness of fit was assessed via percentage mean error (%ME) and mean absolute error (%MAE). Scenario analyses were performed varying individual parameters, with complex scenarios mimicking published studies. The statistical code is provided for transparency and to aid future work in the area. Results: %ME and %MAE were lowest when the correct analysis form was specified (i.e. UGM and UAM aligned). Underestimates were produced when a time-to-death element was present in the UGM but not included in the UAM, while the ‘combined’ UAM produced overestimates irrespective of the UGM. Scenario analysis demonstrated the importance of the volume of available data beyond the initial time period, for example follow-up. Conclusions: We show that the use of an incorrectly or over-specified UAM can result in substantial bias in the estimation of utilities. We present a flowchart to highlight the issues that may be faced

nonprogression with avelumab treatment associated with gains in quality of life in metastatic merkel cell carcinoma

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comparative effectiveness of avelumab versus chemotherapy in merkel cell carcinoma innovative use of patient insights

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Validation of an abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) among patients on antihypertensive medications

<p>Abstract</p> <p>Background</p> <p>The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) Version 1.4 is a reliable and valid instrument to assess patients' satisfaction with medication, providing scores on four scales – side effects, effectiveness, convenience and global satisfaction. In naturalistic studies, administering the TSQM with the side effects domain could provoke the physician to assess the presence or absence of adverse events in a way that is clinically atypical, carrying the potential to interfere with routine medical care. As a result, an abbreviated 9-item TSQM (TSQM-9), derived from the TSQM Version 1.4 but without the five items of the side effects domain was created. In this study, an interactive voice response system (IVRS)-administered TSQM-9 was psychometrically evaluated among patients taking antihypertensive medication.</p> <p>Methods</p> <p>A total of 3,387 subjects were invited to participate in the study from an online panel who self-reported taking a prescribed antihypertensive medication. The subjects were asked to complete the IVRS-administered TSQM-9 at the start of the study, along with the modified Morisky scale, and again within 7 to 14 days. Standard psychometric analyses were conducted; including Cronbach's alpha, intraclass correlation coefficients, structural equation modeling, Spearman correlation coefficients and analysis of covariance (ANCOVA).</p> <p>Results</p> <p>A total of 396 subjects completed all the study procedures. Approximately 50% subjects were male with a good racial/ethnic mix: 58.3% white, 18.9% black, 17.7% Hispanic and 5.1% either Asian or other. There was evidence of construct validity of the TSQM-9 based on the structural equation modeling findings of the observed data fitting the Decisional Balance Model of Treatment Satisfaction even without the side effects domain. TSQM-9 domains had high internal consistency as evident from Cronbach's alpha values of 0.84 and greater. TSQM-9 domains also demonstrated good test-retest reliability with high intraclass correlation coefficients exceeding 0.70. As expected, the TSQM-9 domains were able to differentiate between individuals who were low, medium and high compliers of medication, with moderate to high effect sizes. There was evidence of convergent validity with significant correlations with the medication adherence scale.</p> <p>Conclusion</p> <p>The IVRS-administered TSQM-9 was found to be a reliable and valid measure to assess treatment satisfaction in naturalistic study designs, in which there is potential that the administration of the side effects domain of the TSQM would interfere with routine clinical care.</p

Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma

Background: Response rates are primary endpoints in many oncology trials; however, correlation with overall survival (OS) is not uniform across cancer types, treatments, or lines of therapy. This study explored the association between objective response (OR) and OS in patients with chemotherapy-refractory metastatic Merkel cell carcinoma who received avelumab (anti-PD-L1). Methods: Eighty-eight patients enrolled in JAVELIN Merkel 200 (part A; NCT02155647) received i.v. avelumab 10&nbsp;mg/kg every 2&nbsp;weeks until confirmed progression, unacceptable toxicity, or withdrawal. Using conditional landmark analyses, we compared OS in patients with and without confirmed OR (RECIST v1.1). We applied a Cox model that included OR as a time-varying covariate and adjusted for age, visceral disease, and number of previous therapies. Results: Twenty-nine patients had confirmed OR; 20 by study week 7 and 7 more between study weeks 7 and 13. Survival probabilities 18 months after treatment initiation were 90% [95% confidence interval (CI) 65.6-97.4] in patients with OR at week 7 and 26.2% (95% CI 15.7-37.8) in patients without OR but who were alive at week 7. Median OS was not reached in patients with OR and was 8.8 months (95% CI 6.4-12.9) in patients without. Similar results were observed for the week 13 landmark. The adjusted Cox model showed OR was associated with a 95% risk reduction of death [hazard ratio 0.052 (95% CI 0.018-0.152)] compared with a nonresponse. Conclusions: Patients with OR by 7 or 13&nbsp;weeks had significantly longer OS than patients without, confirming that early OR is an endpoint of major importance

Prevalence of dementia and medication use patterns among Indiana Medicaid beneficiaries

This study was undertaken to estimate the prevalence of dementia among Indiana Medicaid beneficiaries in 2003 and to examine patterns of medication use among patients with dementia. The study developed and validated criteria to identify patients with dementia from medical claims data. The use of dementia-indicated drugs, antipsychotic drugs and anticholinergic drugs among patients with dementia in 2003 was assessed. The study also assessed associations between use of dementia-indicated drugs with sociodemographic characteristics, health care utilization and expenditures among patients with dementia. A combination of retrospective data and primary expert panel survey data was used for addressing the research questions. The retrospective data used were the Indiana Medicaid eligibility and claim files for the period July 1, 2001 to December 31, 2003. A total of 26 ICD codes were rated as specific for diagnosis of dementia by expert panel members from 47 ICD codes that were identified from literature for identifying patients with dementia. The prevalence of dementia was 11 percent among individuals age 50 years or older and 14 percent among individuals age 60 years or older. This represented a 2.5 times to 3.5 times increase in prevalence of dementia compared to studies in Medicaid populations approximately 10 years earlier. The use of dementiaindicated drugs among patients with dementia was low at 34.4 percent compared to the use of antipsychotic drugs (50.4%) and anticholinergic drugs (60.8%). Change in number of hospitalizations was 0.21 lower among dementia-indicated drug users compared to dementia-indicated drug non-users. Dementia-indicated drug users also had 49 percent lower risk of hospitalization compared to patients with dementia that did not use dementia-indicated drugs. After adjusting for multiple covariates, dementia-indicated drug users had $98 lower change in outpatient expenditures,$171 lower change in physician-related expenditures, $614 higher change in nursing home expenditures and$697 higher change in prescription drug expenditures compared to dementia-indicated drug non-users. However, there were no significant differences in the adjusted change in total expenditures between dementia-indicated drug users and dementia-indicated drug non-users. The study findings indicate that the use of dementia-indicated drugs among patients with dementia living in community setting is recommended on account of better clinical outcomes with no significant change in total expenditures associated with their use