Background: To evaluate the psychometric properties of the newly developed seven-item Irritable Bowel Syndrome – Diarrhea predominant (IBS-D) Daily Symptom Diary and four-item Event Log using phase II clinical trial safety and efficacy data in patients with IBS-D. This instrument measures diarrhea (stool frequency and stool consistency), abdominal pain related to IBS-D (stomach pain, abdominal pain, abdominal cramps), immediate need to have a bowel movement (immediate need and accident occurrence), bloating, pressure, gas, and incomplete evacuation. Methods: Psychometric properties and responsiveness of the instrument were evaluated in a clinical trial population [ClinicalTrials.gov identifier: NCT01494233]. Results: A total of 434 patients were included in the analyses. Significant differences were found among severity groups (p < 0.01) defined by IBS Patient Global Impression of Severity (PGI-S) and IBS Patient Global Impression of Change (PGI-C). Severity scores for each Diary and Event Log item score and five-item, four-item, and three-item summary scores were calculated. Between-group differences in changes over time were significant for all summary scores in groups stratified by changes in PGI-S (p < 0.05), two of six Diary items, and three of four Event Log items; a one-grade change in PGI-S was considered a meaningful difference with mean change scores on all Diary items −0.13 to −0.86 [standard deviation (SD) 0.79–1.39]. Similarly, for patients who reported being ‘slightly improved’ (considered a clinically meaningful difference) on the PGI-C, mean change scores on Diary items ranged from −0.45 to −1.55 (SD 0.69–1.39). All estimates of clinically important change for each item and all summary scores were small and should be considered preliminary. These results are aligned with the previous standalone psychometric study regarding reliability and validity tests. Conclusions: These analyses provide evidence of the psychometric properties of the IBS-D Daily Symptom Diary and Event Log in a clinical trial population.

PURPOSE:Diarrhea-predominant irritable bowel syndrome (IBS-D) can considerably impact patients' lives. Patient-reported symptoms are crucial in understanding the diagnosis and progression of IBS-D. This study psychometrically evaluates the newly developed IBS-D Daily Symptom Diary and Symptom Event Log (hereafter, "Event Log") according to US regulatory recommendations.METHODS:A US-based observational field study was conducted to understand cross-sectional psychometric properties of the IBS-D Daily Symptom Diary and Event Log. Analyses included item descriptive statistics, item-to-item correlations, reliability, and construct validity.RESULTS:The IBS-D Daily Symptom Diary and Event Log had no items with excessive missing data. With the exception of two items ("frequency of gas" and "accidents"), moderate to high inter-item correlations were observed among all items of the IBS-D Daily Symptom Diary and Event Log (day 1 range 0.67-0.90). Item scores demonstrated reliability, with the exception of the "frequency of gas" and "accidents" items of the Diary and "incomplete evacuation" item of the Event Log. The pattern of correlations of the IBS-D Daily Symptom Diary and Event Log item scores with generic and disease-specific measures was as expected, moderate for similar constructs and low for dissimilar constructs, supporting construct validity. Known-groups methods showed statistically significant differences and monotonic trends in each of the IBS-D Daily Symptom Diary item scores among groups defined by patients' IBS-D severity ratings ("none"/"mild," "moderate," or "severe"/"very severe"), supporting construct validity.CONCLUSIONS:Initial psychometric results support the reliability and validity of the items of the IBS-D Daily Symptom Diary and Event Log.

Fatigue is a common symptom of chronic hepatitis C virus (cHCV) infection and a common side effect of interferon-based treatment for cHCV. This study provides confirmatory evidence of the reliability and validity of the Fatigue Severity Scale (FSS) to document fatigue in cHCV research and identifies values that indicate clinically important differences in FSS to aid in interpreting fatigue in cHCV clinical trials.

Fatigue is a common symptom of chronic hepatitis C virus (HCV) infection and a frequent side-effect of peginterferon/ribavirin (PR) therapy for HCV. This study evaluated the impact of adding the oral HCV NS3/4A protease inhibitor simeprevir to PR on patient-reported fatigue and health status among patients with chronic HCV genotype 1 infection enrolled in the Phase IIb PILLAR and ASPIRE trials [NCT00882908; NCT00980330].

There is no widely accepted validated scale to assess the comprehensive symptom burden and severity of neurogenic orthostatic hypotension (NOH). The Orthostatic Hypotension Questionnaire (OHQ) was developed, with two components: the six-item symptoms assessment scale and a four-item daily activity scale to assess the burden of symptoms. Validation analyses were then performed on the two scales and a composite score of the OHQ.

Recently published articles have described criteria to assess qualitative research in the health field in general, but very few articles have delineated qualitative methods to be used in the development of Patient-Reported Outcomes (PROs). In fact, how PROs are developed with subject input through focus groups and interviews has been given relatively short shrift in the PRO literature when compared to the plethora of quantitative articles on the psychometric properties of PROs. If documented at all, most PRO validation articles give little for the reader to evaluate the content validity of the measures and the credibility and trustworthiness of the methods used to develop them. Increasingly, however, scientists and authorities want to be assured that PRO items and scales have meaning and relevance to subjects. This article was developed by an international, interdisciplinary group of psychologists, psychometricians, regulatory experts, a physician, and a sociologist. It presents rigorous and appropriate qualitative research methods for developing PROs with content validity. The approach described combines an overarching phenomenological theoretical framework with grounded theory data collection and analysis methods to yield PRO items and scales that have content validity.

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.

Abstract Objectives: Chronic insomnia and depression are often associated. Measuring the impact on quality of life associated with changes in sleep in co-treatment of insomnia and depression requires a valid and reliable patient reported outcome (PRO) instrument. This study aimed to assess the validity of the Sleep Impact Scale (SIS), a sleep-specific PRO instrument, in a population comorbid with Major Depressive Disorder (MDD) and insomnia to support its use in clinical or clinical trial applications. Research design and methods: Data from 379 subjects enrolled in a 27 week US, multi-center, phase IV, randomized, double-blind, parallel group, placebo-controlled trial of zolpidem tartrate extended-release taken in combination with escitalopram vs. placebo combined with escitalopram were pooled across treatment groups. Results from multi-trait analyses, tests of internal consistency and test–retest reliability, concurrent validity, known-groups validity, responsiveness, and thresholds for minimal important difference (MID) were examined. Results: Mean baseline scores on the SIS ranged from 22.85 (±13.41) on Satisfaction with Sleep to 43.49 (±21.12) on Mental Fatigue, reflecting impairments due to sleep problems. The SIS was found to be internally consistent (α ≥ 0.70 for all domains) and have good construct validity. The item–domain correlations were ≥0.52 with no instance of an item correlating more highly with a domain other than its own. There were some floor and no ceiling effects. The test–retest reliability of the SIS domains ranged between 0.68 and 0.83. Clinical validity assessed through known groups methods was supported. The SIS was responsive to changes on all domains. Preliminary estimates of minimum important difference (MID) were obtained to interpret changes in SIS domains. Limitations: Limitations include the need for further qualitative research on content validity and the lack of a patient global assessment of change. Conclusions: This study yielded adequate evidence of the validity of the SIS for use in clinical trials and research on MDD patients with comorbid insomnia.

Abstract Abstract 1881 Poster Board I-904 Introduction: The impact of multiple myeloma treatment on patient-reported health-related quality of life (HRQoL) merits careful evaluation since treatment effect and toxicity may impact HRQoL. Previously, the positive impact of achieving CR in the VISTA study on HRQoL had been reported at the fourth cycle after CR onset. The aim of this study was to describe the rate of patients who experienced a sustained HRQoL improvement after best response and the overall HRQoL impact of best response. Patients and Methods: The VISTA trial was a randomized, open-label, multicenter study designed to compare the efficacy and safety of VMP to melphalan/prednisone (MP) in subjects with previously untreated multiple myeloma who were ineligible for transplantation. Patients were followed over a 9-cycle period (54 weeks) and for a post-treatment follow-up phase. Response to therapy was defined according to the European Group for Blood and Marrow Transplantation criteria. The European Organization for Research on Treatment of Cancer (EORTC) QLQ-C30, a HRQoL questionnaire commonly used in multiple myeloma, was administered at screening, day 1 of each cycle during the treatment phase, and every 8 weeks until progression during follow-up. A sustained HRQoL improvement was defined as a change in score of at least 5 points (Dubois et al, JCO 2006; 24:976–82) for at least 2 consecutive cycles after best response (Complete Response [CR], Partial Response [PR] or Minimal Response [MR]). The rate of sustained improvement and the time to sustained improvement were calculated in the population of patients who were followed for at least 2 cycles after best response (n=363). Treatment groups were compared using a log-rank test. Cox proportional hazard models were applied to explore the effect of covariates (type of best response, score at baseline, score at best response) on the chance of sustained improvement in each EORTC QLQ-C30 score. Results: Mean and median age of study patients was 72 and 71 years, respectively; 51% were female, mean and median KPS was 80. All EORTC domain scores were similar at baseline across the study arms. Worse health was reported in all domains with VMP arm at best tumor response onset. However, after best response onset, patients in the VMP arm had a higher sustained HRQoL improvement rate than those in the MP arm in 14 of the 15 EORTC QLQ-C30 scores. VMP patients had a slightly lower sustained response rate only in Cognitive Functioning: 27% vs 28%, respectively. VMP patients were more likely than MP patients to experience a statistically significant sustained response in three QLQ-C30 domains according to the log-rank test: Nausea/Vomiting (p=0.0095), Appetite Loss (p=0.0170), and Diarrhea (p=0.0082). The differences for Nausea and Diarrhea remained significant in the Cox models when adjusted for baseline score, score at best response, and type of response (CR, PR or MR). VMP patients also had a higher rate of sustained response over MP patients for Global Health (49% vs 40%), Pain (40% vs 32%), and Insomnia (32% vs 24%). However, these differences were not statistically significant. Conclusions: Patients treated with VMP more frequently experienced a sustained HRQoL improvement in most of the EORTC QLQ-C30 domains than patients in the MP arm after best tumor response. In particular, the likelihood of a sustained improvement in Nausea and Diarrhea was significantly higher in VMP patients, independent of the type of response and the respective symptom score at baseline and at time of best response. Although the incidences of nausea and diarrhea were higher in the VMP arm at best response onset, these data suggest that HRQoL decrements reported by patients begin to improve with best response onset. Further analysis is planned. Disclosures: Dhawan: Janssen Cilag: Employment, Equity Ownership. Robinson:Johnson & Johnson: Employment, Equity Ownership, Research Funding. Meunier:Mapi Values: Employment. Regnault:Mapi Values: Employment. Rosa:Mapi Values: Employment. Cakana:Janssen Cilag: Employment, Equity Ownership. van de Velde:Johnson & Johnson: Employment, Equity Ownership. Richardson:Millennium Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Keryx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. San Miguel:Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; OrthoBiotech: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.