Psychometric Evaluation of the Diary for Irritable Bowel Syndrome Symptoms-Constipation in a Prospective Observational Study.

OBJECTIVES: To evaluate the psychometric properties of the Diary for Irritable Bowel Syndrome Symptoms-Constipation (DIBSS-C), which was developed to support primary and secondary endpoints in irritable bowel syndrome (IBS) with predominant constipation (IBS-C) clinical trials. METHODS: Observational data were collected from 108 adults with IBS-C using a smartphone-type device for 17 days. DIBSS-C data regarding bowel movements (BMs) were collected for each event (along with the Bristol Stool Form Scale); abdominal symptoms were rated each evening. Global status items and the Gastrointestinal Symptom Rating Scale-IBS were completed on day 10 and day 17 and the IBS-Symptom Severity Scale on day 17. Item-level performance, internal consistency reliability, test-retest reliability, and construct validity were evaluated. RESULTS: The Abdominal Symptoms Domain score demonstrated high internal consistency reliability (Cronbach's alpha week 1 = 0.98; week 2 = 0.96) and test-retest reliability (intraclass correlation coefficient [ICC] = 0.93). Test-retest reliability was stronger for abdominal symptoms (ICC = 0.91-0.94) than for the frequency-based BM-related outcomes (ICC = 0.54-0.66). Key construct validity hypotheses were supported by moderate to strong correlations with the corresponding Gastrointestinal Symptom Rating Scale-IBS, IBS-Symptom Severity Scale, and Bristol Stool Form Scale items. All known-groups comparisons were statistically significant for the abdominal symptom items and domain score; evidence for known-groups validity of BM-related outcomes was supportive when based on constipation severity. CONCLUSIONS: The results of this study provided key psychometric evidence for the DIBSS-C, ultimately contributing to its qualification by the US Food and Drug Administration for use in IBS-C clinical trials.

Remote-Use Applications of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised Clinical Outcome Assessment Tool: A Scoping Review.

OBJECTIVES: In 2021, the US Congress passed the Accelerating Access to Critical Therapies for Amyotrophic Lateral Sclerosis Act. The law encourages development of "tools, methods, and processes" to improve clinical trial efficiency for neurodegenerative diseases. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is an outcome measure administered during in-person clinic visits and used to support investigational studies for persons living with amyotrophic lateral sclerosis. Availability of a standardized, remote-use version of the ALSFRS-R may promote more inclusive, decentralized clinical trials. A scoping literature review was conducted to identify existing remote-use ALSFRS-R tools, synthesize feasibility and comparability of administration modes, and summarize barriers and facilitators to inform development of a standardized remote-use ALSFRS-R tool. METHODS: Included studies reported comparisons between remote and in-person, clinician-reported, ALSFRS-R administration and were published in English (2002-2022). References were identified by searching peer-reviewed and gray literature. Twelve studies met the inclusion criteria and were analyzed to compare findings within and across modes of administration. RESULTS: Remote modes of ALSFRS-R administration were categorized into 4 nonmutually exclusive categories: telephone (n = 6), videoconferencing (n = 3), computer or online platforms (n = 3), mobile applications and wearables (n = 2), and 1 unspecified telemedicine modality (n = 1). Studies comparing in-person to telephone or videoconferencing administration reported high ALSFRS-R rating correlations and nonsignificant between-mode differences. CONCLUSIONS: There is insufficient information in the ALSFRS-R literature to support remote clinician administration for collecting high quality data. Future research should engage persons living with amyotrophic lateral sclerosis, care partners, and providers to develop a standardized remote-use ALSFRS-R version.

Comparison of anchor-based methods for estimating thresholds of meaningful within-patient change using simulated PROMIS PF 20a data under various joint distribution characteristic conditions.

PURPOSE: To compare the performance of anchor-based methods for estimating thresholds of meaningful within-patient change (i.e., individual change) of clinical outcome assessments in conditions reflecting data characteristics of small- to medium-sized clinical trials. METHODS: Datasets were generated from the joint distributions of the PROMIS PF 20a T-score changes and a seven-point global change anchor measure. The 108 simulation conditions (1000 replications per condition) included combinations of three marginal distributions of T-score changes, three improvement percentages in the anchor measure, four levels of responsiveness correlations, and three sample sizes. Threshold estimation methods included mean change, median change, ROC curve, predictive modeling, half SD, and SEM. Relative bias, precision, accuracy, and measurement significance of the estimates were evaluated based on comparison with true thresholds and IRT-based individual reliable changes of PROMIS scores. Quantile regression models were applied to select and interpret effects of simulation conditions on estimation bias. RESULTS: When PROMIS T-score changes were distributed normally, the predictive modeling method performed best with 50% or more responders identified by the anchor; the mean and median methods were preferred with 30% responders. For skewed distributions, the median method and ROC method gained more advantages. Among the evaluated study conditions, the improvement percentage condition had the most obvious effects on estimation bias. CONCLUSION: To establish accurate and precise thresholds, clinical researchers are recommended to prioritize study designs with at least 50% anchor-defined responders and strongly responsive target endpoints with highly reliable scoring calibration and to select optimal anchor-based methods given the data characteristics.

Is IQWiG's 15% Threshold Universally Applicable in Assessing the Clinical Relevance of Patient-Reported Outcomes Changes? An ISPOR Special Interest Group Report.

This article discusses a recent methodological change to assess the additional benefit of drug intervention by the German Federal Joint Committee (Gemeinsamer Bundesausschuss), a key stakeholder in EUnetHTA21 (European Network for Health Technology Assessment joint consortium for future EU HTA regulation), methodological workstream. The German Federal Joint Committee (Gemeinsamer Bundesausschuss) set a universal individual response threshold at ≥ 15% of the scale range of the measurement instrument, for all patient-reported outcomes, to achieve an additional benefit rating for a given pharmaceutical intervention. This approach is originally based on a corresponding recommendation from the Institute for Quality and Efficiency in Health Care. The merits of this approach are reviewed from various perspectives, including the evidence basis, statistical and psychometric considerations, and regulatory perspectives by the ISPOR Clinical Outcomes Assessment Special Interest Group's multistakeholder group of authors (academia, contract research organizations, and industry). Particular focus is placed on the patient perspective within the Institute for Quality and Efficiency in Health Care approach. The article development incorporated feedback from ISPOR members during well-attended ISPOR US and European conference presentations and 2 formal rounds of written review. The authors concluded that the ≥ 15% response threshold is incongruent with previously defined and scientifically established thresholds and is not well-suited for universal implementation. Further scientific evidence and discussion among all stakeholders are needed, especially should this universal rule be considered in the context of future joint clinical assessments of health technologies in the European Union scheduled from 2025 onward.

Assessing test-retest reliability of patient-reported outcome measures using intraclass correlation coefficients: recommendations for selecting and documenting the analytical formula.

PURPOSE: The US Food and Drug Administration (FDA) 2009 guidance for industry on patient-reported outcome (PRO) measures describes how the Agency evaluates the psychometric properties of measures intended to support medical product labeling claims. An important psychometric property is test-retest reliability. The guidance lists intraclass correlation coefficients (ICCs) and the assessment time period as key considerations for test-retest reliability evaluations. However, the guidance does not provide recommendations regarding ICC computation, nor is there consensus within the measurement literature regarding the most appropriate ICC formula for test-retest reliability assessment. This absence of consensus emerged as an issue within Critical Path Institute's PRO Consortium. The purpose of this project was to generate thoughtful and informed recommendations regarding the most appropriate ICC formula for assessing a PRO measure's test-retest reliability. METHODS: Literature was reviewed and a preferred ICC formula was proposed. Feedback on the chosen formula was solicited from psychometricians, biostatisticians, regulators, and other scientists who have collaborated on PRO Consortium initiatives. RESULTS AND CONCLUSIONS: Feedback was carefully considered and, after further deliberation, the proposed ICC formula was confirmed. In conclusion, to assess test-retest reliability for PRO measures, the two-way mixed-effect analysis of variance model with interaction for the absolute agreement between single scores is recommended.

Secukinumab sustains early patient-reported outcome benefits through 1 year: Results from 2 phase III randomized placebo-controlled clinical trials comparing secukinumab with etanercept.

BACKGROUND: Psoriasis is a chronic condition with negative impact on patients' quality of life that most often requires lifelong effective and safe treatment. OBJECTIVE: This analysis focused on the effect of secukinumab treatment on patient-reported health-related quality of life as assessed by the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis. METHODS: The proportion of subjects achieving DLQI score 0/1 response at week 24, time to DLQI score 0/1 response, and sustained DLQI score 0/1 response up to week 52 were compared between secukinumab and etanercept. RESULTS: Of 1470 subjects, 1144 received secukinumab and 326 received etanercept. DLQI score 0/1 response rates were significantly higher for secukinumab than for etanercept at week 24. The median time to DLQI score 0/1 response was significantly shorter for secukinumab versus etanercept (12 vs 24 weeks; P < .01). The majority of secukinumab-treated subjects achieved DLQI score 0/1 response at week 24 and sustained it through week 52 along with a 90% to 100% reduction in the Psoriasis Area and Severity Index total score response. LIMITATIONS: Placebo comparisons are limited during the maintenance period because of rerandomization at week 12. CONCLUSION: Secukinumab treatment provided faster and greater sustained improvements in quality of life than etanercept over 52 weeks, consistent with greater clinical response.

Preliminary evidence on the uptake, use and benefits of the CONSORT-PRO extension.

PURPOSE: This study assessed the uptake of the CONsolidated Standards of Reporting Trials (CONSORT)-Patient-Reported Outcomes (PRO) statement; determined if use of CONSORT-PRO was associated with more complete reporting of PRO endpoints in randomised controlled trials (RCTs) and identified the extent to which high-impact journals publishing RCTs with PRO endpoints endorse CONSORT-PRO. METHODS: CONSORT-PRO citations were identified by systematically searching Medline, EMBASE and Google from 2013 (year CONSORT-PRO released) to 17 December 2015. RCTs that cited CONSORT-PRO (cases) were compared to a comparable control sample of RCTs in terms of adherence to CONSORT-PRO using t tests. General linear models assessed the relationship between CONSORT-PRO score and key, pre-specified variables. The 100 highest-impact journals that published RCTs with PRO endpoints (2014-2015) were identified via a systematic Medline search. Instructions for authors were reviewed to determine whether journals endorsed CONSORT-PRO. RESULTS: Total CONSORT-PRO scores ranged from 47 to 100% for cases and 25-96% for controls. Cases had significantly higher total CONSORT-PRO scores compared to controls: t = 2.64, p = 0.01. 'Citing CONSORT-PRO', 'journal endorsing CONSORT-PRO' and 'dedicated PRO paper' were significant predictors of higher CONSORT-PRO adherence score: R 2 = 0.48, p < 0.001. 11/100 top-ranked journals endorsed CONSORT-PRO in their instructions to authors, seven of these journals published RCTs included as cases in this study. CONCLUSION: This study demonstrated improved PRO reporting associated with journal endorsement and author use of the CONSORT-PRO extension. Despite growing awareness, more work is needed to promote appropriate use of CONSORT-PRO to improve completeness of reporting; in particular, stronger journal endorsement of CONSORT-PRO.

Treatment patterns and outcomes of Stage IIIB/IIIC melanoma in France, Germany and the UK: A retrospective and prospective observational study (MELABIS).

AIM: Real-world data on treatment patterns/outcomes in patients with advanced melanoma, while scarce, are useful for health technology assessments that govern patient access in many countries. We collected retrospective data on treatment patterns among patients in France, Germany and the UK with Stage IIIB/IIIC melanoma with macroscopic lymph node involvement, whose primary melanoma and regional lymph node metastases had been completely resected. METHODS: Patients ≥18 years were diagnosed between 1 January 2009 and 31 December 2011. Data were obtained from patients' medical records and a patient survey. RESULTS: Forty-nine centres provided data on 558 patients: 53.6% had Stage IIIB disease; 58.2% were of working age (<65 years), 22.5% reported a change in employment status due to melanoma, 8% were on long-term sick leave; and 35.1% were deceased over the study period. Overall median distant metastases-free survival was 23.4 months and median disease-free survival was 13.3 months. Hospitalisation frequency increased during distant metastatic/terminal disease phases. Adjuvant therapy was received by 7.0% (14/199) of patients in France, 2.6% (5/195) in the UK, and 33.5% (55/164) in Germany. Low-dose interferon was used more frequently than other regimens. High-dose interferon was associated with discontinuation in 28.6% and dose delay/reduction in 33.3% of patients. CONCLUSIONS: Rapid disease progression combined with increased use of healthcare resources in later phases of disease result in a high burden-of-illness for patients and healthcare providers. The use of adjuvant interferon therapy varies considerably in this population in the countries studied, highlighting the need for improved treatments for melanoma.

Using classical test theory, item response theory, and Rasch measurement theory to evaluate patient-reported outcome measures: a comparison of worked examples.

OBJECTIVE: To provide comparisons and a worked example of item- and scale-level evaluations based on three psychometric methods used in patient-reported outcome development-classical test theory (CTT), item response theory (IRT), and Rasch measurement theory (RMT)-in an analysis of the National Eye Institute Visual Functioning Questionnaire (VFQ-25). METHODS: Baseline VFQ-25 data from 240 participants with diabetic macular edema from a randomized, double-masked, multicenter clinical trial were used to evaluate the VFQ at the total score level. CTT, RMT, and IRT evaluations were conducted, and results were assessed in a head-to-head comparison. RESULTS: Results were similar across the three methods, with IRT and RMT providing more detailed diagnostic information on how to improve the scale. CTT led to the identification of two problematic items that threaten the validity of the overall scale score, sets of redundant items, and skewed response categories. IRT and RMT additionally identified poor fit for one item, many locally dependent items, poor targeting, and disordering of over half the response categories. CONCLUSIONS: Selection of a psychometric approach depends on many factors. Researchers should justify their evaluation method and consider the intended audience. If the instrument is being developed for descriptive purposes and on a restricted budget, a cursory examination of the CTT-based psychometric properties may be all that is possible. In a high-stakes situation, such as the development of a patient-reported outcome instrument for consideration in pharmaceutical labeling, however, a thorough psychometric evaluation including IRT or RMT should be considered, with final item-level decisions made on the basis of both quantitative and qualitative results.

Psychometric properties of PedsQL generic core scales for children with functional constipation in the Netherlands.

OBJECTIVES: The aim of the study was to evaluate the psychometric properties of the Dutch translation of the Pediatric Quality of Life Inventory version 4.0 Generic Core Scales (PedsQL) in children with functional constipation (FC). METHODS: The PedsQL was completed by children with FC ages 5 to 18 years and by the parents of children ages 2 to 18 years. To assess construct validity, all of the parents and children completed the PedsQL Gastrointestinal Symptoms Module (GI module) and children ages 8 to 18 years completed the defecation disorder list. Item response distributions, internal consistency reliability, patient-parent agreement, and discriminating ability were evaluated. RESULTS: Overall, 269 children were enrolled. The PedsQL showed minimal missing responses (self-report: 5.3% with >50% missing, parent report: 2.6% with >50% missing) and achieved satisfactory internal consistency for the total (self-report: α = 0.86, parent report: α = 0.88), physical health (self-report: α = 0.75, parent report α = 0.83), and psychosocial health (self-report: α = 0.80; parent report: α = 0.85) scores. Internal consistency was less convincing for those ages 5 to 7 years (α = 0.53-0.77) than for older individuals. Self-reported health-related quality of life was lower than parent reported, with the exception of children ages 5 to 7 years. Interrater reliability intraclass correlations were 0.52 to 0.61 for the overall population. Correlations among the PedsQL, GI module, and defecation disorder list were consistent with a priori hypotheses and generally supported construct validity. The PedsQL distinguished between a previously published healthy reference sample and children with FC, and between those with mild and severe symptoms (P < 0.05). CONCLUSIONS: The self-reported and proxy reported PedsQL demonstrated satisfactory measurement properties in Dutch children with FC ages 8 to 18 years. Further research is needed to establish internal consistency and validity in those ages 5 to 7 years.

Validation and Application of Thresholds to Define Meaningful Change in Vasomotor Symptoms Frequency: Analysis of Pooled SKYLIGHT 1 and 2 Data.

INTRODUCTION: Vasomotor symptoms (VMS), the characteristic symptoms of menopausal transition, are often the primary reason women seek treatment. Current treatment options for VMS include fezolinetant, a nonhormonal, selective neurokinin 3 receptor antagonist. This study aimed to define a clinically meaningful threshold for reduction of moderate-to-severe VMS in postmenopausal women treated with fezolinetant and then apply it in a responder analysis of the pooled trial data. METHODS: This analysis pooled data from two identical phase 3, double-blind, placebo-controlled studies that randomized women with moderate-to-severe VMS to once-daily fezolinetant 30 mg, 45 mg, or placebo (SKYLIGHT 1 and 2). The frequency of VMS was collected daily using an electronic diary. Patients completed the Patient Global Impression of Change in VMS (PGI-C VMS) instrument, which assessed changes in hot flushes/night sweats at weeks 4 and 12 compared with baseline using a seven-point Likert scale. VMS frequency data were anchored to PGI-C VMS data; the anchor level for meaningful within-patient change in PGI-C VMS was "moderately better." RESULTS: In the pooled population (N = 1022), the mean (standard deviation) estimated thresholds for a meaningful within-patient change in moderate-to-severe VMS frequency were - 5.73 (3.47) at week 4 and - 6.20 (5.18) at week 12. Applying the thresholds for meaningful within-patient change to responder analyses ("missing as non-responder" imputation method) indicated a favorable clinical benefit: greater proportions of responders were observed in the fezolinetant 30-mg and 45-mg groups compared with placebo at week 4 (odds ratio range 2.48-2.91; P < 0.001) and week 12 (odds ratio range 1.908-2.68; P < 0.001). CONCLUSION: PGI-C VMS is sensitive to change and correlates with VMS frequency: a reduction of approximately six VMS episodes per day from baseline to week 12 was meaningful at the individual patient level. Fezolinetant provides a meaningful clinical benefit for women with moderate-to-severe VMS associated with menopause and represents an important nonhormonal treatment option. TRIAL REGISTRATION NUMBER: NCT04003155 and NCT04003142.

ISOQOL recommends minimum standards for patient-reported outcome measures used in patient-centered outcomes and comparative effectiveness research.

PURPOSE: An essential aspect of patient-centered outcomes research (PCOR) and comparative effectiveness research (CER) is the integration of patient perspectives and experiences with clinical data to evaluate interventions. Thus, PCOR and CER require capturing patient-reported outcome (PRO) data appropriately to inform research, healthcare delivery, and policy. This initiative's goal was to identify minimum standards for the design and selection of a PRO measure for use in PCOR and CER. METHODS: We performed a literature review to find existing guidelines for the selection of PRO measures. We also conducted an online survey of the International Society for Quality of Life Research (ISOQOL) membership to solicit input on PRO standards. A standard was designated as "recommended" when >50 % respondents endorsed it as "required as a minimum standard." RESULTS: The literature review identified 387 articles. Survey response rate was 120 of 506 ISOQOL members. The respondents had an average of 15 years experience in PRO research, and 89 % felt competent or very competent providing feedback. Final recommendations for PRO measure standards included: documentation of the conceptual and measurement model; evidence for reliability, validity (content validity, construct validity, responsiveness); interpretability of scores; quality translation, and acceptable patient and investigator burden. CONCLUSION: The development of these minimum measurement standards is intended to promote the appropriate use of PRO measures to inform PCOR and CER, which in turn can improve the effectiveness and efficiency of healthcare delivery. A next step is to expand these minimum standards to identify best practices for selecting decision-relevant PRO measures.

Sphygmomanometry-evoked allodynia in chronic pain patients with and without fibromyalgia.

BACKGROUND: Fibromyalgia is a chronic pain syndrome that affects about 2% of the U.S. general population, with greater prevalence among women (3.5%) than men (0.5%). Previous research results suggest that the experience of pain (allodynia) upon sphygmomanometry may indicate the presence of fibromyalgia. OBJECTIVE: The aim of this study was to confirm these findings in patients with fibromyalgia and other chronic pain conditions and evaluate the use of sphygmomanometry as a potential screening tool for the identification of patients with fibromyalgia. METHODS: A total of 150 people participated in this multicenter, cross-sectional observational study. The study included a physician-conducted evaluation to determine if the participant met the American College of Rheumatology (ACR) 1990 diagnostic criteria for fibromyalgia. The presence of sphygmomanometry-evoked allodynia was assessed during a seated cuff pressure inflation that was repeated three times on each arm. Each site was provided a sphygmomanometer to ensure standardization, and the pressure of the cuff at the moment of pain initiation was recorded. If the patient did not indicate pain prior to 180 mmHg, then the inflation was stopped, a notation of no pain was made, and a cuff pressure of 180 mmHg was recorded. The mean of the six cuff pressure measurements was used for the analyses. Logistic regression was performed to analyze the relationship between sphygmomanometry-evoked allodynia and fibromyalgia. RESULTS: The evaluable sample was 148 (one participant had too large an arm circumference for the sphygmomanometer and another did not receive the clinician evaluation of ACR-determined fibromyalgia diagnosis). Over half of the participants were determined to have an ACR diagnosis of fibromyalgia. Of these, 71 (91%) were women and had an average age of 54 years. Of the 70 participants with no fibromyalgia diagnosis, 42 (60%) were women and also had an average age of 54 years. Sixty-one (78%) of the fibromyalgia participants, compared with 25 (36%) of those with no fibromyalgia diagnosis, reported sphygmomanometry-evoked allodynia. The participants with fibromyalgia reported pain ata lower cuff pressure compared with those without fibromyalgia (132 mmHg vs. 166 mmHg, p < .01). The logistic regression showed that sphygmomanometry-evoked allodynia predicted an ACR-determined FM diagnosis (χ(2) = 19.4, p < .01). DISCUSSION: These findings support previous research suggesting that patients who report pain upon sphygmomanometry may warrant further evaluation for the presence of fibromyalgia.

The development and initial assessment of the strategy and leadership systems capability evaluation survey.

Hospital management and leadership systems are associated with organizational success and quality care. The Strategy and Leadership Systems Capability Evaluation (CE) survey was developed by GE Healthcare to assess management and leadership systems at health care institutions, serve as a benchmark for improvement, and measure progress. To assess the psychometric properties of the 29-item CE survey, including the factor structure, scoring algorithm, reliability, and discriminant validity, an online survey was completed by 3450 employees at 15 US hospitals. Of these employees, 609 worked at a hospital where a leadership and management intervention occurred after the initial survey administration. Data were also collected on job level, number of hospital beds, hospital ownership, location, community type, and the implementation of hospital interventions. Item response frequencies showed no floor or ceiling effects and limited missing data. Interitem correlations were strong without obvious redundancies, and factor analysis suggested a unidimensional scale. The resulting scale had strong internal consistency and was able to discriminate among known groups. The CE survey was developed to evaluate management and leadership systems at health care institutions. This study provides psychometric evidence in support of the reliability, validity, and scoring structure of this survey.

Evaluating patient-reported outcome measurement comparability between paper and alternate versions, using the lung function questionnaire as an example.

OBJECTIVES: The goal of this study was to provide recommended steps to assess measurement comparability using a crossover study design and to demonstrate these steps using a short patient-reported outcome (PRO) instrument as an example. METHODS: The example PRO instrument was administered via paper, Web, interactive voice response system, and interview; a randomized crossover design was used to gather data across the multiple administration types. Participants completed the PRO instrument, demographic and health questions, and a short preference questionnaire. Evaluation included comparisons of the item-level responses and agreement, comparison of mean scale scores, score classifications, and questions designed to collect usability and administration preference. Here the authors provide a four-step evaluation guide to evaluate measurement comparability and illustrate these steps using a case-finding tool. RESULTS: In the example, item-level kappa statistics between the paper and the alternate versions ranged from good to excellent, intraclass correlation coefficient for mean scores were above 0.70, and the rate of disagreement ranged from 2% to 14%. In addition, although participants had an administration preference, they reported few difficulties with the versions they were assigned. CONCLUSIONS: The steps described in this article provide a guide for evaluating whether to combine scores across administration versions to simplify analyses and interpretation under a crossover design. The guide recommends the investigation of item-level responses, summary scores, and participant usability/preference when comparing versions, with each step providing unique information to support comprehensive evaluation and informed decisions regarding whether to combine data.

The king's foot of patient-reported outcomes: current practices and new developments for the measurement of change.

PURPOSE: Assessing change remains a challenge in patient-reported outcomes. In June 2009, a group of psychometricians, biostatisticians, and behavioral researchers from other disciplines convened as a Longitudinal Analysis of Patient-Reported Outcomes Working group as part of the Statistical and Applied Mathematical Sciences Institute Summer Psychometric program to discuss the complex issues that arise when conceptualizing and operationalizing "change" in patient-reported outcome (PRO) measures and related constructs. This white paper summarizes these issues and provides recommendations and possible paths for dealing with the complexities of measuring change. METHODS/RESULTS: This article presents and discusses issues associated with: (1) conceptualizing and operationalizing change in PRO measures; (2) modeling change using state-of-the-art statistical methods; (3) impediments to detecting true change; (4) new developments to deal with these challenges; and (5) important gaps that are fertile ground for future research. CONCLUSIONS: There was a consensus that important research still needs to be performed in order develop and refine high-quality PRO measures and statistical methods to analyze and model change in PRO constructs.

Development and psychometric evaluation of a new patient-reported outcome instrument measuring the functional impact of insomnia.

PURPOSE: The objective of this study was to develop and validate a patient-reported outcome instrument to comprehensively assess the consequences of inadequate sleep for use in insomnia-related studies. METHODS: To inform item development, relevant constructs were identified through patient focus groups, literature review, and expert input. Following a translatability assessment for United States (US) English, US Spanish, and French, the draft items were refined through iterative sets of patient interviews in the United States and France. Psychometric properties were evaluated using patient responses from a validation study including 432 participants with either a diagnosis of primary insomnia or no history of insomnia. RESULTS: Psychometric analyses supported item reduction from 38 to 26 items, yielding a unidimensional scale and preserving the original content (mood, tiredness/energy, memory/concentration, motivation, daily performance, social interaction, sexual functioning). Evidence of internal consistency (coefficient α = 0.97), convergent validity, and known-groups validity also was documented. CONCLUSIONS: The Sleep Functional Impact Scale (SFIS) is a psychometrically sound measure targeting the impact of insomnia on patient functioning. When administered with a sleep diary, this instrument has the ability to provide a more comprehensive assessment of treatment response in clinical studies.