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Purpose: Determining if group-level differences in health outcomes are meaningful has recently been neglected in favour of determining if individuals have experienced a meaningful change. We explore interpretation of a meaningful between-group difference (MBGD) in clinical outcome assessment scores, primarily in the context of randomized clinical trials., Methods: We constructed a series of possible 'viewpoints' on how to conceptualize MBGD thresholds. Each viewpoint is discussed critically in terms of potential advantages and disadvantages, with simulated data to facilitate their consideration., Results: Five viewpoints are presented and discussed. The first considers whether thresholds for meaningful within-individual change over time can be equally applied at the group-level, which is shown to be untenable. Viewpoints 2-4 consider what would have to be observed in treatment groups to conclude a meaningful between-group difference has occurred, framed in terms of the proportion of patients perceiving that they had meaningfully improved. The final viewpoint considers an alternative framework where stakeholders are directly questioned on the meaningfulness of varying magnitudes of between-group differences. The choice of a single threshold versus general interpretative guidelines is discussed., Conclusion: There does not appear to be a single method with clear face validity for determining MBGD thresholds. Additionally, the notion that such thresholds can be purely data-driven is challenged, where a degree of subjective stakeholder judgement is likely required. Areas for future research are proposed, to move towards robust method development., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: When determining if changes on patient-reported outcome (PRO) scores in clinical trials convey a meaningful treatment benefit, statistical significance tests alone may not communicate the patient perspective. Appraising within-patient changes on PRO scores against established thresholds can determine if improvements or deteriorations experienced by individuals are meaningful. To evaluate the appropriateness of thresholds for interpreting meaningful improvements and deterioration within individuals on the European Organisation for Research and Treatment of Cancer (EORTC) 30-item core instrument (QLQ-C30) and 13-item lung cancer module (QLQ-LC13), a series of psychometric methods were applied to data from a phase III randomized controlled clinical trial in non-small cell lung cancer., Methods: Anchor-based methods of empirical cumulative distribution functions and classification statistics were employed using change scores from Baseline to Week 7 using changes on the QLQ-C30 Global Health Status item as an anchor. Distribution-based methods of one-half standard deviation and standard error of measurement identified the minimum amount of change each domain score can reliably measure., Results: While the correlations between the domain scores and the anchor item were modest in size (i.e., r ≥ 0.30 for only 5 of 24 domains), consideration of multiple methods along with the magnitude of possible step changes on the score allowed for patterns to emerge. The triangulation process planned a priori resulted in different methods being the source for different domain scores. Absolute values of the proposed thresholds ranged from 11.11 to 33.33, and all resulted in the same classifications for all EORTC domains, except QLQ-C30 Fatigue, as would the 10-point threshold that is traditionally used., Conclusion: This study confirms the appropriateness of the 10-point EORTC score threshold generally used by the field for interpreting within-patient changes, but the thresholds proposed from this study enhance interpretability by corresponding to only observable locations along the domain score scale., (© 2022. The Author(s).)

Background: The Asthma Daytime Symptom Diary (ADSD) and the Asthma Nighttime Symptom Diary (ANSD) were developed to meet the need for standardized patient-reported measures of asthma symptoms to assess treatment trial outcomes in adults and adolescents., Objective: To determine scoring and evaluate the measurement properties of the ADSD/ANSD., Methods: Adolescents (12-17 years) and adults (18+ years) with asthma completed draft 8-item electronic versions of the ADSD/ANSD for 10 days alongside the Adult Asthma Symptom Daily Scales (AASDS) and a Patient Global Impression of Severity (PGIS). Using classical and modern psychometric methods, initial analyses evaluated the performance of ADSD/ANSD items to inform scoring. Subsequent analyses evaluated the reliability and validity of ADSD/ANSD scores., Results: A demographically and clinically diverse sample (n = 130 adolescents; n = 89 adults) was recruited. Item performance was generally strong. However, items assessing chest pressure and mucus/phlegm demonstrated redundancy and poorer performance and were removed. Principal-components analysis, confirmatory factor analysis, and item response theory supported combining items to form 6-item total ADSD/ANSD scores. Internal consistency (α = 0.94-0.95) and test-retest reliability (intraclass correlation coefficient = 0.86-0.95) were strong. Strong correlations (r = 0.72-0.80) were observed between ADSD scores and AASDS items assessing asthma symptom frequency, bother, and impact on activities. Significant differences (P < .001) in mean ADSD/ANSD scores were observed between groups categorized by asthma severity (PGIS), asthma control, inhaler use, nebulizer use, activity limitations, and nighttime awakenings., Conclusions: The ADSD/ANSD items and scores demonstrated strong reliability and validity. Implementation of the measures in interventional studies will enable the evaluation of responsiveness and meaningful within-patient change., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Presbyopia is a progressive condition that reduces the eye's ability to focus on near objects with increasing age. After a systematic literature review identified no existing presbyopia-specific patient-reported outcome (PRO) instruments meeting regulatory guidance, a new PRO instrument, the Near Vision Presbyopia Task-based Questionnaire (NVPTQ), was developed., Results: To explore the patient experience with presbyopia, concept elicitation interviews were conducted with 20 presbyopic participants. The most frequently reported impacts were difficulty with reading menus/books/newspapers/magazines, reading on a cell phone/caller ID, and reading small print. Based on these results, a task-based PRO instrument (the NVPTQ) was developed instructing participants to complete four near-vision, paper-based reading tasks (book, newspaper, nutrition label, menu) under standardized settings, and subsequently assess their vision-related reading ability and associated satisfaction. The draft NVPTQ was cognitively debriefed with a sample of 20 presbyopes, which demonstrated that most participants interpreted the items as intended and endorsed the relevance of the concepts being assessed. After the qualitative research, the draft instrument was psychometrically tested using data from a Phase 2 study. Based on item-level analyses, all items in the NVPTQ demonstrated expected response option patterns and lacked substantial floor or ceiling effects. The reliability, validity, and responsiveness of the NVPTQ Performance and Satisfaction domain scores were assessed. All domains scores had large Cronbach's coefficient α values and good test-retest statistics, indicating that the scores are internally consistent and produce stable values over time. The pattern of correlations with a concurrent measure of visual functioning (National Eye Institute Visual Function Questionnaire 25) demonstrated that the NVPTQ domain scores were related to an alternative assessment of near-vision activities. The NVPTQ domain scores were able to distinguish between groups that were known to differ on the clinical outcome of uncorrected near visual acuity, supporting the construct validity of these scores. The NVPTQ domain scores showed evidence of responsiveness to change by being able to distinguish between groups defined as improved and not improved based on patient-reported and clinical outcomes., Conclusions: This research has resulted in a content-valid and psychometrically sound instrument designed to evaluate vision-related reading ability and satisfaction with vision-related reading ability., Trial Registration: ClinicalTrials.gov NCT02780115. Registered 23 May 2016, https://www.clinicaltrials.gov/ct2/show/NCT02780115?term=NCT02780115&draw=2&rank=1., (© 2021. The Author(s).)

Introduction: Presbyopia is a progressive, age-related visual condition that is characterized by reduced ability to focus on near/close objects, causing impacts on individuals' daily function and health-related quality of life. The Presbyopia Impact and Coping Questionnaire (PICQ) is a new patient-reported outcome (PRO) instrument that assesses presbyopia impact and use of coping behaviors among presbyopic individuals., Methods: To document the impacts of presbyopia and associated coping behaviors, concept elicitation (CE) interviews were conducted with 20 presbyopic participants. Results from the CE interviews were used to develop draft items for additional testing. Following item generation, the draft PICQ was cognitively debriefed with 20 participants. Data from a phase 2 controlled clinical trial were used for psychometric analyses of the PICQ. The PICQ was administered at site visits throughout a 28-day treatment period. Confirmatory factor analysis (CFA) methods were used to guide the development of the scoring algorithm. The reliability (internal consistency, test-retest), construct validity (convergent and discriminant validity, known-groups methods), and responsiveness (Guyatt's responsiveness statistic [GRS]) of the PICQ scores were evaluated. Finally, anchor-based and distribution-based methods were used to inform thresholds for interpreting meaningful within-patient change., Results: CE interviews identified the important and relevant presbyopia-related impacts and coping behaviors and 22 items were drafted and cognitively debriefed. Following minor revisions and item addition/deletion, a version of the PICQ including 23 items was subjected to psychometric testing. The analysis sample included 151 participants. The CFA established two PICQ domain scores, Coping and Impact, on 0-to-4 scales that demonstrate good model fit (root mean square error of approximation = 0.06, comparative fit index = 0.98, Tucker-Lewis index = 0.98, standardized root mean square = 0.07). Cronbach's alphas for the Coping and Impact scores were 0.89 and 0.84, respectively. Test-retest intraclass correlation coefficients were 0.77 for Coping and 0.67 for Impact. The pattern of results assessing construct validity was acceptable for the PICQ Coping and Impact scores, with the magnitude of correlations and effect sizes generally meeting a priori expectations. The corresponding GRS effect sizes for the PICQ Coping scores were -1.23 (i.e., large) for Patient Global Impression of Change (PGIC) and -0.72 (i.e., medium) for uncorrected near visual acuity (UNVA). The GRS effect sizes for the PICQ Impact scores were -0.60 (i.e., medium) for PGIC and -0.35 (i.e., small) for UNVA. Across three sets of anchor-based analyses for interpreting individual-level change, a responder threshold of -1.00 was identified for both PICQ Coping and PICQ Impact scores., Conclusions: The totality of evidence from the qualitative and quantitative research establishes that the PICQ scores produced are valid and reliable measures of presbyopia impacts and coping behaviors that are important and relevant for assessing presbyopia treatment outcomes. CLINICALTRIALS., Gov Identifier: NCT02780115; date of registration May 19, 2016., (© 2021. The Author(s).)

As patient-reported outcome (PRO) measures are being included more frequently in oncology clinical trials, regulatory and health technology assessment agencies have begun to request long-term, post-treatment PRO data to supplement traditional survival/progression endpoints. These data may be collected as part of cohort extension or registry studies to describe long-term outcomes of study participants after concluding their cancer treatment. While post-treatment PRO data may be expected to satisfy regulatory and payer expectations, significant practical barriers exist for the efficient incorporation of these data into oncology clinical trials, such as subject attrition, protocol deviations, and treatment crossover. The incorporation of post-treatment PRO assessments is a resource-intensive task requiring clear objectives for how the data will be analyzed and interpreted by both sponsors and regulators. Incorporating PRO data collection via electronic modalities (e.g., smartphone, web) may be a less expensive and more feasible option for incorporating long-term follow-up, reducing the frequency of manual study staff follow-up and expensive clinic visits. It is essential to include well-defined estimands for the statistical analysis, as well as to document limitations associated with the long-term follow-up data-collection approach. Analytical techniques will likely rely on descriptive and model-based statistics, and conclusions about treatment differences will likely be limited to preliminary findings of effectiveness (instead of efficacy). Finally, communications with health authorities and regulatory agencies regarding the LTFU study design and analysis should occur as early as possible to ensure that the PRO data to be collected offer an opportunity to properly evaluate the research question(s) of interest.

Objectives: The Diary for Irritable Bowel Syndrome Symptoms-Constipation (DIBSS-C) has been developed to assess the core signs and symptoms of irritable bowel syndrome with constipation (IBS-C). This article presents the psychometric evaluation of the DIBSS-C abdominal score., Methods: Data for these analyses are from a multicenter phase IIb study in IBS-C patients (NCT02559206). Subjects completed a number of assessments via handheld electronic diary throughout the study. The analyses used the intent-to-treat population and were blinded to randomized treatment group. The analyses evaluated the reliability, validity, and responsiveness of the DIBSS-C abdominal score; identified an appropriate scoring algorithm; and determined thresholds for interpreting clinically meaningful changes at the individual level., Results: The correlations between the DIBSS-C abdominal symptom items (ie, abdominal pain, discomfort, and bloating) were strong (>0.75). Cronbach's alpha for the abdominal symptom severity items was very strong (.94), indicating that the 3 abdominal symptom items produce a reliable score. The intraclass correlation coefficient for the abdominal score was 0.82, exceeding the threshold of 0.70 and indicating good test-retest reliability. Guyatt's responsiveness statistic values all exceeded the threshold for a large effect of 0.80, so the DIBSS-C abdominal score can be considered highly responsive to change. Triangulation across 3 sets of anchor-based analyses indicated that a threshold of -2.0 points on the abdominal score is an appropriate threshold for identifying meaningful change., Conclusions: Overall, this study provides evidence that the DIBSS-C abdominal score is valid, reliable, responsive to change, and interpretable for assessing treatment benefit in patients with IBS-C., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Purpose: Clinical outcome assessments (COAs) require evidence not only of reliability, validity, and ability to detect change, but also a definition of what constitutes a meaningful change on the instrument. The responder definition specifies the amount of change on the COA that may be interpreted as a treatment benefit and is critical for interpreting what constitutes a meaningful change on the COA scores. However, the literature that describes methods for developing and applying responder definitions can be difficult to navigate. Clear and concise guidelines regarding which methods to apply under what circumstances and how to interpret the results are lacking. This article provides a guide to the variety of available methods and issues that should be considered when establishing responder definitions for interpreting meaningful changes in COA scores., Methods: An overview is provided for selecting anchors, developing study designs, planning psychometric analyses, using psychometric results to set responder thresholds, and applying responder thresholds in demonstrating treatment efficacy., Results: There are a variety of anchor-based methods for consideration, but they all rely on a preference for strongly related and easily interpretable anchors. The benefits of applying multiple anchors and multiple analytic methods are discussed. The process of triangulation can synthesize results across multiple sources to gain confidence in a proposed responder definition. Though a link to meaningfulness from the patient's perspective is absent, distribution-based methods provide lower bound estimates of score precision and have a role in triangulation. Responder definitions are typically required within regulatory review, but their application may differ across clinical trial programs., Conclusions: By careful planning of anchor selection, study design, and psychometric methods, COA researchers can establish defensible responder thresholds that ultimately aid patients and clinicians in making informed treatment decisions.

Purpose: To pilot the newly developed Idio Scale Judgment method for estimating the amount of score change that matters to patients (i.e., change thresholds)., Methods: An online panel of 500 participants diagnosed with multiple sclerosis (MS) responded to the Neuro-QoL fatigue scale and to demographic and clinical questions. Participants compared their own fatigue to that represented by seven short form summaries (SFSs) that were located relatively close to their own fatigue levels. They judged these as representing the same, greater, or less fatigue than their own. We calculated the distances between patients' own levels of fatigue and the location of SFSs they endorsed as a change that would make a difference in daily life. These distances were used as estimates of change thresholds. Logically inconsistent judgments were tabulated and associations with clinical and demographic variables were estimated., Results: Change thresholds based on mean individual thresholds for consequential change were calculated for improvement (-3.5) and worsening (3.2). The majority of participants had no logically inconsistent judgments (69%). Having one or more reversals in judgment was not significantly associated with education or fatigue score, but was weakly associated with age, gender, and MS type and moderately associated with ratings of confidence in SFS comparisons., Conclusions: As piloted, Idio Scale Judgment had a number of design strengths. Participants made comparisons to levels of fatigue that were within range of their own, and their judgments were contextualized in personally relevant consequences. The design lends itself to collection of data in large samples allowing evaluation of the range of judgments. Some study limitations could be mitigated with modifications. We concluded that the Idio Scale Judgment has substantial promise as a new tool for estimating change thresholds.

Interpreting change in scores on patient-reported outcome instruments is a key aspect of instrument development. Without interpretation guidelines, the clinical meaning of significant improvements observed within a treatment group cannot be ascertained. While the field has contemplated this topic for several decades, there remains inconsistency in terminology, methods, and application. Careful selection of methods can result in determining when change is meaningful, but researchers must keep an open mind to the methods that best fit their study and instrument. In many cases, anchor-based methods are appropriate, but the statistical model that evaluates them should be defensible (eg, linear regression, repeated-measures modeling, logistic regression). Sometimes, researchers must entertain the use of novel methods that may be more appropriate for their planned studies and instrument (eg, standard setting, exit interviews, conjoint analysis). The selection of the method is best supported by clear, transparent communication with the regulatory agency to ensure that the method can support its goals.

By bringing data collection closer to real time and minimizing recall bias, patient diaries or event-driven logs offer substantial benefits over retrospective questionnaires for many patient-reported disease concepts. Such assessments are increasingly used to support primary and secondary endpoints in randomized controlled trials. These diaries have the potential to provide more reliable and valid assessment of patients' subjective experiences of symptoms and disease events. However, use of such diaries presents significant and unique challenges depending on the context of use. Of note, while symptom-related label claims are those most frequently granted by regulatory authorities, no guidance specific to support the development, psychometric evaluation, and interpretation of endpoints derived from patient diaries exists. This article provides an overview of key methodological, statistical, and clinical considerations for implementation of patient diaries with a regulatory perspective in mind. Approaches and solutions covered in this article include (1) techniques to establish content validity based on obtaining qualitative insights in naturalistic settings and real-life experience of diary completion, (2) demonstration of psychometric properties with respect to day-to-day variability, and (3) aggregation of data from multiple days/events to move from items to endpoints. The importance of the patients' engagement is highlighted in order to help overcome these challenges throughout all stages of diary and endpoint development and evaluation. This article can inform researchers who are developing or implementing patient diaries as clinical trial endpoints to ensure that the nuances of this mode of data collection are considered in the development of endpoints and prior to regulatory interactions.

Objective: To determine the impact of ranibizumab 0.5 mg on patient-reported visual function over 36 months in individuals with visual impairment from diabetic macular edema., Methods: RESTORE comprises a phase 3, randomized, multicenter, 12 month core study and a 24 month open-label extension study. Eyes assigned to ranibizumab in the core study received ranibizumab for 36 months; eyes assigned to laser monotherapy in the core study received ranibizumab during the extension. The primary outcome was least-squares mean change in National Eye Institute 25-item Visual Functioning Questionnaire (NEI VFQ-25) overall composite and subscale scores., Results: Of 303 core study participants, 240 (79%) entered the extension, comprising 83 (35%) participants initially assigned to ranibizumab, 83 (35%) assigned to ranibizumab plus laser combination therapy, and 74 (31%) assigned to laser monotherapy. Least-squares mean (standard error) change in NEI VFQ-25 composite score from baseline to month 12 (+5.9 [1.5]; +5.0 [1.5], for the ranibizumab and combination therapy groups, respectively) decreased by month 36 (+4.1 [1.7]; +4.0 [1.7], respectively, from baseline to month 36) following reduced injection frequency relative to the core study. At 36 months, the least-squares mean (standard error) change in the laser monotherapy group was similar to that in the ranibizumab groups (+4.1 [1.8]). Most subscale scores showed outcomes similar to that for the composite score. The greatest NEI VFQ-25 gains were consistently observed in participants for whom the study eye was the better-seeing eye., Limitations: Patients entering the extension were not randomized, and 21% of the core study participants did not enter the extension, which may have affected the results., Conclusions: Gains in patient-reported visual function at month 12 among eyes receiving ranibizumab in the core study decreased slightly by 36 months. Eyes originally receiving laser monotherapy for 12 months then ranibizumab for 24 months achieved similar gains by 36 months to eyes receiving ranibizumab for 36 months., Trial Registration: ClinicalTrials.gov: NCT00687804 and NCT00906464.

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., (Copyright © 2015. Published by Elsevier Inc.)

Rationale, Aims and Objectives: Fibromyalgia (FM) is challenging to diagnose, especially in primary care settings. The Fibromyalgia Diagnostic Screen was developed to facilitate the diagnosis of FM in clinical practice. The objectives of this study were to assess the performance of the Fibromyalgia Diagnostic Screen in primary care and specialty clinics, using the 1990 American College of Rheumatology (ACR) diagnostic criteria as the gold standard, and comparing the Fibromyalgia Diagnostic Screen with the London Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ) and the modified 2010 ACR Fibromyalgia Diagnostic Criteria (ACR-FDC)., Methods: This multicenter, cross-sectional study included 150 adult chronic pain patients who underwent a physician-administered structured history and physical exam and completed the Fibromyalgia Diagnostic Screen, the LFESSQ and the modified ACR-FDC. The analyses determined the predictive ability of the Fibromyalgia Diagnostic Screen for FM., Results: Item-level analyses provided support for the response categories and predictive ability of most of the Fibromyalgia Diagnostic Screen items. Additionally, the evaluation of the Fibromyalgia Diagnostic Screen scoring models demonstrated the greatest accuracy in predicting an FM diagnosis with a combination of patient items and clinician items that included an abbreviated tender point exam (sensitivity 0.68, specificity, 0.82). Sensitivity of the modified ACR-FDC and the LFESSQ was 0.87 and 0.86, respectively, with specificity 0.62 and 0.49, respectively., Conclusions: The Fibromyalgia Diagnostic Screen is a useful new clinical tool to aid in the evaluation of FM in clinical practice., (© 2013 John Wiley & Sons, Ltd.)

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.

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.

Objective: To assess the psychometric properties of a new patient-reported migraine instrument, the Completeness of Response Survey (CORS), which measures a comprehensive set of factors important to patients' decisions regarding the initiation and continuation of treatment., Background: Traditionally, migraine treatments and the instruments used to demonstrate their efficacy have focused on the relief of headache pain. As new treatments emerge with the potential for more complete and consistent migraine relief, more comprehensive tools are needed to demonstrate these benefits. The CORS includes 2 modules, the static CORS, which comprehensively evaluates one treatment at one time point, and the comparative CORS, which provides a more global comparison between 2 treatments at one time point. Together, the 2 modules can measure unmet treatment needs and improvements over the course of a clinical study., Methods: Data from an 8-site study comparing 147 patients' recent experiences with their current triptan therapy and 2 months of study treatment with a single-tablet formulation of sumatriptan/naproxen sodium were used to conduct a preliminary psychometric evaluation of the CORS. The study included both modules of the CORS, the Headache Impact Test, the revised Patient Perception of Migraine Questionnaire, and a migraine diary., Results: The CORS response categories in both the static and comparative modules demonstrated limited floor or ceiling effects and few missing values (<3%). Inter-item correlations, principal components analysis (component loading range: 0.62 to 0.95), and high estimates of internal consistency (alpha range: 0.88 to 0.94) for each composite score supported the structure and proposed scoring algorithm for the static module. The pattern of correlations between the CORS static and comparative items and composites with the revised Patient Perception of Migraine Questionnaire items and subscales, as well as the relationships between responses to selected static CORS items and the migraine diary, supported the construct validity of the CORS., Conclusions: The CORS is capable of demonstrating advantages of more comprehensive migraine therapies over traditional therapies, which are primarily focused on the resolution of headache pain, by addressing the frequency and speed with which the most common migraine symptoms are resolved and patients' return to normal functioning. This research shows evidence for the value and utility for the CORS static and comparative items and components, and further evaluation is underway., (© 2012 American Headache Society.)

Objectives: Existing questionnaires that assess preference and/or satisfaction with postmenopausal bone loss treatments were reviewed and determined to be inadequate for the assessment of an oral pill versus a subcutaneous injection. The Preference and Satisfaction Questionnaire (PSQ) was developed to assess preference, satisfaction, and bother with a weekly oral tablet versus a once every 6 months subcutaneous injection for treatment of postmenopausal bone loss., Methods: Questions were developed based on literature review and expert input. Content validity of the PSQ in this patient population was assessed among current or previous bisphosphonate users in group interviews, and item comprehension and readability were also evaluated. Reliability, validity, and structure of the questionnaire were assessed in two phase 3 randomized clinical trials., Results: Twenty-four women participated in cognitive interviews and found the PSQ understandable and acceptable. Subsequently, 1583 trial participants took the PSQ. Interitem correlations, ranging from 0.50 to 0.97 for preference items, 0.85 to 0.94 for pill-satisfaction items, and 0.84 to 0.92 for injection-satisfaction items, and a well-fitting confirmatory factor analysis (root mean square error of approximation 0.04, nonnormed fit index 0.99, and root mean square residual 0.08) supported the structure of the instrument. Cronbach's alpha reliability values for pill satisfaction, injection satisfaction, pill bother, and injection bother were 0.93, 0.89, 0.82, and 0.61, respectively. Discriminative validity was indicated with better satisfaction and bother scores being related to adherence and the absence of adverse events., Conclusions: The PSQ is a valid and reliable measure and may be a valuable tool to assess patient preference and satisfaction with a weekly oral tablet and 6-month subcutaneous injection for postmenopausal bone loss., (Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

In recent years, the US FDA has become more critical of instruments used to measure patient-reported outcomes (PROs) in clinical trials. To facilitate decisions related to the approval of drugs, labels and promotional claims based on PROs, the FDA created the Study Endpoints and Label Development (SEALD) group. SEALD has developed a PRO guidance related to the use of PRO measures used to support drug approvals and label claims, including recommendations for establishing thresholds for meaningful change at the individual level (i.e., defining a responder). This article examines in detail the FDA-recommended methodology for defining a responder and analyzing responder-based PRO measure results. We also present other responder analysis approaches for consideration in furthering the precision and interpretation of this methodology.

Background: : Many patient-reported outcomes (PRO) instruments are scored by averaging or summing Likert category values over all items or domains of the elicitation instrument, yielding domain-specific scores or a total score for the entire instrument., Objective: : To evaluate differences between conventional linear and preference-weighted scores for PRO instruments used in asthma, oncology, and obesity., Methods: : We estimated preference-weighted scores for all the items and response categories in the Onset-of-Effect Questionnaire (OEQ), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30, and the Impact of Weight on Quality of Life Questionnaire-Lite version (IWQOL-Lite) using choice-format conjoint analysis, known also as discrete-choice experiments., Results: : Conventional linear scoring rules can overstate the relative importance to patients of improvements in some domains and understate the relative importance of improvements in other domains., Conclusions: : Patient preference-weighted scores estimated by conjoint-analysis methods allow for non-linearities and account for the relative contribution of individual items and domains to patient well-being. Conventional linear scores and preference-weighted scores can result in different conclusions about the size of patient-reported treatment effects.