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Introduction: Niacin is underutilised because of flushing. Lack of a quantitative tool to assess niacin-induced flushing has precluded the objective evaluation of flushing associated with extended-release (ER) niacin formulations. We developed the Flushing Symptom Questionnaire((c)) (FSQ), a quantitative tool to assess patient-reported flushing, and assessed its ability to characterise ER niacin-induced flushing.Methods: This study focused on the responses to one question in the FSQ, the Global Flushing Severity Score (GFSS), reported on a 0-10 scale (none = 0, mild = 1-3, moderate = 4-6, severe = 7-9 and extreme = 10) to assess flushing during ER niacin initiation (week 1) and maintenance (weeks 2-8).Results: Flushing severity with ER niacin was greatest during week 1 and remained greater than placebo for the study duration. During weeks 2-8, 40% of patients on ER niacin vs. 8% of those on placebo had > 1 day/week with 'moderate or greater' GFSS.Conclusions: In conclusion, the GFSS component of the FSQ was a sensitive and responsive quantitative measure of ER niacin-induced flushing that will aid in the objective comparison of novel strategies intended to improve tolerability and adherence to niacin, an agent proven to reduce cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: Niacin is currently the most effective approved agent for raising high-density lipoprotein cholesterol. However, niacin-induced cutaneous flushing (redness, warmth, tingling and/or itching) significantly limits patient acceptance. To further characterize flushing, a patient-reported Flushing Symptom Questionnaire (FSQ) was developed and validated.Methods: The FSQ was validated in an 8-week, randomized, double-blind, placebo-controlled trial of extended-release (ER) niacin and placebo. The primary flushing endpoint of the study was based on the single Global Flushing Severity Score (GFSS), an item within the FSQ, which assesses overall flushing severity on a 0-10 discretized analog scale.Results: A total of 175 patients were randomized to one of four treatment groups (sequences of placebo and ER niacin [given as niacin (NIASPAN) 1 g (N1) and 2g (N2)]. Test-retest reliability and reproducibility coefficients for the single-item GFSS were all above 0.75. Construct validity was supported by moderate to strong correlations (r > 0.5) with other FSQ items. All FSQ item scores and specifically the GFSS discriminated between treatment groups and demonstrated expected relationships with predefined known groups. The GFSS demonstrated high responsiveness in patients who switched from ER niacin to placebo. The ability of the GFSS and GFBS to discriminate changes in flushing symptoms in patients who increased drug dose was less than expected possibly due to accommodation to the flushing effects of niacin over time; differential drop-out due to flushing; and/or FSQ items not being sensitive enough to detect a change that was present.Conclusions: The FSQ items and specifically the Global Flushing Severity Score (GFSS), are reliable and valid measures to assess niacin-induced flushing. [ABSTRACT FROM AUTHOR]

Background: In the KEYNOTE-590 study, first-line pembrolizumab plus chemotherapy provided statistically significant improvement in overall survival, progression-free survival, and objective response rate compared with chemotherapy, with a manageable safety profile in patients with advanced esophageal cancer. Prespecified health-related quality-of-life (HRQoL) outcomes are reported., Materials and Methods: Change from baseline to week 18 in the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) global health status/QoL (GHS/QoL) and QLQ-Esophageal cancer module (OES18) dysphagia, pain, and reflux scales were evaluated., Results: The HRQoL analysis included 730 patients who received treatment and completed ≥1 HRQoL assessment. Least squares mean (LSM) change from baseline to week 18 was similar between treatment groups for QLQ-C30 GHS/QoL and physical functioning and QLQ-OES18 reflux scales. The QLQ-OES18 dysphagia (LSM difference, -5.54; 95% CI, -10.93 to -0.16) and pain (LSM difference, -2.94; 95% CI, -5.86 to -0.02) scales favored pembrolizumab plus chemotherapy over placebo plus chemotherapy. Median time to confirmed deterioration (TTD) was similar between treatment groups for QLQ-C30 GHS/QoL and physical functioning and QLQ-OES18 dysphagia and reflux scales. Compared with chemotherapy, pembrolizumab plus chemotherapy prolonged median TTD, as seen on the QLQ-OES18 pain scale (HR, 0.69; 95% CI, 0.51 to 0.95)., Conclusion: The use of pembrolizumab plus chemotherapy maintained HRQoL at week 18 relative to baseline and was comparable with placebo plus chemotherapy. These HRQoL results together with published reports of efficacy, support the use of pembrolizumab plus chemotherapy as first-line therapy for advanced/metastatic esophageal cancer., Clinicaltrials.gov Id: NCT03189719., (© The Author(s) 2024. Published by Oxford University Press.)

Objectives: To understand industry practices and challenges when submitting patient experience data (PED) for regulatory decisions by the US Food and Drug Administration (FDA)., Methods: A two-part online survey related to collection, submission, and use of PED by FDA in regulatory decision-making (part 1) and a best-worst exercise for prioritizing potential PED initiatives (part 2) was completed by industry and contract research organization (CRO) members with ≥ 2 years of recent experience with patient-reported outcome (PRO), natural history study (NHS), or patient preference (PP) data; and direct experience with FDA filings including PED., Results: A total of 50 eligible respondents (84% industry) completed part 1 of the survey, among which 46 completed part 2. Respondents mostly had PRO (86%) and PP (50%) experience. All indicated that FDA meetings should have a standing agenda item to discuss PED. Most (78%) reported meetings should occur before pivotal trials. A common challenge was justifying inclusion without knowing if and how data will be used. Most agreed that FDA and industry should co-develop the PED table in the FDA clinical review (74%), and the table should report reason(s) for not using PED (96%) in regulatory decision-making. Most important efforts to advance PED use in decision-making were a dedicated meeting pathway and expanded FDA guidance (51% each)., Conclusions: FDA has policy targets expanding PED use, but challenges remain regarding pathways for PED submission and transparency in regulatory decision-making. Alignment on the use of existing meeting opportunities to discuss PED, co-development of the PED table, and expanded guidance are encouraged., (© 2023. Merck & Co., Inc., Rahway, NJ, USA and its affiliates and Tommi Tervonen, Cecilia Jimenez-Moreno, Bennet Levitan, Montse Soriano Gabarró, Cynthia Girman, Brett Hauber.)

Background: Despite a number of respiratory syncytial virus (RSV) vaccine candidates being tested in clinical trials, disease-specific, self-reported instruments assessing symptom severity of RSV infection from the perspective of adult patients are still needed. The RSV Infection, Intensity and Impact Questionnaire (RSV-iiiQ) was adapted from the Influenza Intensity and Impact Questionnaire (FluiiQ™). This study evaluated some measurement properties of the RSV-iiiQ., Methods: Data were collected in a web-based survey over two consecutive days. Participants completed the RSV-iiiQ, the Patient Global Impression of Severity, Sheehan Disability Scale, Patient Global Impression of Change, EQ-5D-5L, and a demographic questionnaire. Test-retest reliability, internal consistency, construct validity, and responsiveness of the RSV-iiiQ scales were assessed., Results: 111 adults with RSV were enrolled and self-reported a variety of symptoms across the range of disease severity via a web-based platform. The RSV-iiiQ scales demonstrated satisfactory test-retest reliability, construct validity, and discriminating ability. One-factor confirmatory factor analyses confirmed that each of the four scales was sufficiently unidimensional, and internal consistencies indicated that the computation of RSV-iiiQ scale scores was plausible. Correlation-based analyses provided support for the construct validity of the RSV-iiiQ scores, and known groups analyses supported discriminating ability. Estimates of responsiveness of the scale scores were also satisfactory., Conclusions: RSV infection is highly symptomatic and causes significant disease burden, and self-report instruments assessing symptom severity and impact are important for evaluation of new treatments. This study describes the preliminary psychometric properties of the RSV-iiiQ and indicates this tool may be useful for the assessment of the severity of symptoms and impact of acute RSV infection in adults. The findings also indicated two items, Runny nose and Ear pain, may be unnecessary and should be revisited using item response theory analysis with a larger sample size., (© 2024. Merck & Co., Inc., Rahway, NJ, USA and its affiliates and Richard H. Osborne.)

Introduction: KEYNOTE-394 showed pembrolizumab significantly improved overall survival, progression-free survival, and objective response rate with manageable safety versus placebo for patients from Asia with previously treated advanced hepatocellular carcinoma. We present results on health-related quality of life (HRQoL)., Methods: HRQoL was evaluated using the EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EuroQol-5D-3L (EQ-5D-3L) questionnaires. Key HRQoL endpoints were least squares mean (LSM) score changes from baseline to week 12 and time to deterioration (TTD) for EORTC QLQ-C30 global health status (GHS)/QoL. p values were one-sided and nominal without adjustment for multiplicity., Results: The HRQoL population included patients randomly assigned to pembrolizumab ( n = 298) and placebo ( n = 152). From baseline to week 12, a greater decline in EORTC QLQ-C30 GHS/QoL score was observed with placebo (LSM, -8.4; 95% CI: -11.7 to -5.1) versus pembrolizumab (-4.0; 95% CI: -6.4 to -1.6; difference vs. placebo: 4.4; 95% CI: 0.5-8.4; nominal p = 0.0142). Similarly, a greater decline in the EQ-5D-3L visual analog scale score was observed with placebo (-6.9; 95% CI: -9.4 to -4.5) versus pembrolizumab (-2.7; 95% CI: -4.5 to -1.0; difference vs. placebo: 4.2; 95% CI: 1.2-7.2; nominal p = 0.0030). TTD in EORTC QLQ-C30 GHS/QoL score was similar between arms (hazard ratio, 0.85; 95% CI: 0.58-1.25; nominal p = 0.1993)., Conclusion: Patients receiving placebo showed a greater decline in HRQoL than those receiving pembrolizumab. Combined with efficacy and safety data from KEYNOTE-394 and the global KEYNOTE-240 and KEYNOTE-224 trials, our data support the clinically meaningful benefit and manageable tolerability of pembrolizumab as second-line therapy for patients with advanced hepatocellular carcinoma., Competing Interests: Shukui Qin, Weijia Fang, Shuangyan Ou, Feng Zhang, Kin Chung Lee, Hye Jin Choi, Jiandong Tong, Min Tao, Aibing Xu, Ashley Cheng, Chang-Hsien Lu, Chang-Fang Chiu, Mohamed Ibrahim Abdul Wahid, and Zhendong Chen report no conflicts of interest. Ho Yeong Lim reports serving in an advisory role for Bayer, Eisai, AstraZeneca, Roche, and Ipsen. Zhenggang Ren reports serving in a consulting or advisory role for AstraZeneca, Merck Sharp & Dohme, and Roche. Shital Kamble and Josephine M. Norquist are full-time employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and hold stock in Merck & Co., Inc., Rahway, NJ, USA. Wenyan Zhong and Chen Li are full-time employees of MSD China. The idea for this study originated with the study sponsor, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Molnupiravir is an orally administered antiviral authorized for COVID-19 treatment in adults at high risk of progression to severe disease. Here, we report secondary and post hoc analyses of participants' self-reported symptoms in the MOVe-OUT trial, which evaluated molnupiravir initiated within 5 days of symptom onset in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed COVID-19., Methods: Eligible participants completed a 15-item symptom diary daily from day 1 (randomization) through day 29, rating symptom severity as "none," "mild," "moderate," or "severe"; loss of smell and loss of taste were rated as "yes" or "no." Time to sustained symptom resolution/improvement was defined as the number of days from randomization to the first of 3 consecutive days of reduced severity, without subsequent relapse. Time to symptom progression was defined as the number of days from randomization to the first of 2 consecutive days of worsening severity. The Kaplan-Meier method was used to estimate event rates at various time points. The Cox proportional hazards model was used to estimate the hazard ratio between molnupiravir and placebo., Results: For most targeted COVID-19 symptoms, sustained resolution/improvement was more likely, and progression was less likely, in the molnupiravir versus placebo group through day 29. When evaluating 5 distinctive symptoms of COVID-19, molnupiravir participants had a shorter median time to first resolution (18 vs 20 d) and first alleviation (13 vs 15 d) of symptoms compared with placebo., Conclusions: Molnupiravir treatment in at-risk, unvaccinated patients resulted in improved clinical outcomes for most participant-reported COVID-19 symptoms compared with placebo. Clinical Trials Registration. ClinicalTrials.gov: NCT04575597., Competing Interests: Potential conflicts of interest. Y. G., A. P., M. G. J., Y. Z., Y. Z., A. W.-D., M. B., A. P., C. D. A., and J. M. N. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, and may own and/or hold stock options in Merck & Co, Inc, Rahway, NJ, USA. J. D. was an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, at the time of study conduct and holds stock and/or stock options in Merck & Co, Inc, Rahway, NJ, USA. A. Puenpatom also reports travel support from Merck & Co., Inc., Rahway, NJ, USA. A. W. holds stock and/or stock options in Carbon Health Technologies, Inc, and CurieAI for advisory work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: In the KEYNOTE-158 study (NCT02628067), pembrolizumab showed a high objective response rate and durable clinical benefit for patients with previously treated, unresectable/metastatic microsatellite instability-high (MSI-H)/mismatch repair‒deficient (dMMR) non-colorectal solid tumours. We present health-related quality of life (HRQoL) results from the MSI-H/dMMR population (cohort K)., Patients and Methods: Eligible patients had previously treated MSI-H/dMMR advanced non-colorectal solid tumours, measurable disease per RECIST v1.1, and ECOG performance status ≤1. Patients received pembrolizumab 200 mg Q3W for 35 cycles (2 years). The EORTC Quality of Life Questionnaire (QLQ-C30) and EQ-5D-3L were administered at baseline, at regular intervals throughout treatment, and 30 days after treatment discontinuation. Prespecified analyses (exploratory endpoints) included the magnitude of change from baseline to post-baseline timepoints in all patients and by the best overall response for QLQ-C30 global health status (GHS)/QoL, QLQ-C30 functional/symptom scales/items, and EQ-5D-3L visual analogue scale (VAS) score., Results: At data cutoff (October 5, 2020), 351 patients were enrolled, of whom 311 and 315 completed baseline QLQ-C30 and EQ-5D-3L questionnaires, respectively. QLQ-C30 GHS/QoL scores improved from baseline to week 9 (mean [95% CI] change, 3.07 [0.19-5.94]), then remained stable or improved by week 111, with greater improvements observed in patients with a best response of complete response (CR) or partial response (PR) (10.85 [6.36-15.35]). Patients with CR/PR showed improvements in physical (5.58 [1.91-9.25]), role (9.88 [3.80-15.97]), emotional (5.62 [1.56-9.68]), and social (8.33 [2.70-13.97]) functioning, and stable cognitive functioning (1.74 [-1.45 to 4.94])., Conclusions: Pembrolizumab generally improved or preserved HRQoL in patients with previously treated MSI-H/dMMR advanced non-colorectal solid tumours., Competing Interests: Conflict of Interest Statement The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests. Michele Maio: study funding to the institution from Merck Sharp & Dohme LLC, and Merck & Co., Inc., Rahway, NJ, USA, to support study conduct; honoraria for serving as a speaker from MSD, Roche, Bristol Myers Squibb (BMS), Sanofi, AstraZeneca, Amgen, Pierre Fabre, Eli Lilly, GlaxoSmithKline (GSK), Sciclone, Alfasigma, and Merck Serono; personal fees for advisory boards from Merck Sharp & Dohme LLC, Roche, BMS, Incyte, AstraZeneca, Amgen, Pierre Fabre, Eli Lilly, Sanofi, GSK, Alfasigma, and Merck Serono; stockholder in Epigen Therapeutics and Theravance. Mayur M. Amonkar: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Owns stock in Merck & Co., Inc., Rahway, NJ, USA. Josephine M. Norquist: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Owns stock in Merck & Co., Inc., Rahway, NJ, USA. Paolo A. Ascierto: research funding from Bristol Myers Squibb, Roche-Genentech, Array, and Sanofi; personal fees for advisory/consultant role for Bristol Myers Squibb, Roche-Genentech, MSD, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, MedImmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Nektar, Italfarmaco, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, and Seagen; personal fees for travel support from MSD; unpaid consultant for Takis. Ludmila Manzyuk: nothing to disclose. Daniel Motola-Kuba: research funding from Roche/Genentech, Novartis, Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Eli Lilly, AstraZeneca, and MSD. Nicolas Penel: study funding to the institution from MSD to support study conduct; research funding to the institution from Bayer-HealthCare. Philippe A. Cassier: research funding from Roche/Genentech, Novartis, Amgen, Bristol Myers Squibb, Blueprint Medicines, GlaxoSmithKline, Janssen, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, MSD, Celgene, AbbVie, Toray Industries, Transgene, Innate Pharma, and Loxo; personal fees from Roche/Genentech, Novartis, Amgen, Merck Serono, and AstraZeneca; nonfinancial support from Roche/Genentech, Novartis, AstraZeneca, MSD, and Plexxikon; travel accommodations from NETRIS Pharma. Giovanni Mendonca Bariani: research funding from mAbxience, MSD, and Bristol Myers Squibb; advisory role for Libbs. Ana De Jesus Acosta: research funding from AstraZeneca, Merck & Co., Inc., Rahway, NJ, USA; consulting for Merck & Co., Inc., Rahway, NJ, USA. Toshihiko Doi: honoraria from AbbVie, Astellas Pharma, Bristol Myers Squibb Japan, Oncolys BioPharma, Ono Pharmaceutical, and Taiho Pharmaceutical; consulting or advisory role for AbbVie, Amgen, Bayer, Boehringer Ingelheim, Daiichi Sankyo, MSD, Novartis, Otsuka, Rakuten Medical, Sumitomo Dainippon, Taiho Pharmaceutical, and Takeda; research funding to the institution from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Lilly Japan, Merck Serono, MSD, Novartis, Pfizer, Quintiles, Sumitomo Group, and Taiho Pharmaceutical. Federico Longo: honoraria from Amgen, Bayer, Bristol Myers Squibb, Celgene, Ferrer, Lilly, Merck, MSD, Roche, Sanofi, and SERVIER; consulting or advisory role for Amgen, Bayer, Bristol Myers Squibb, Lilly, MSD, Roche, and SERVIER; travel expenses from Amgen, Bayer, Bristol Myers Squibb, Celgene, Ferrer, Lilly, Merck, MSD, Roche, Sanofi, and SERVIER. Wilson H. Miller, Jr.: consulting role for Bristol Myers Squibb, Merck & Co., Inc., Rahway, NJ, USA, Roche, Novartis, Amgen, GSK, Mylan, and EMD Serono; honoraria from BMS, Merck, Roche, GSK, Novartis, Amgen, Mylan, and EMD Serono; grants to the institution from Merck, CIHR, CRS, Terry Fox Research Institute, Samuel Waxman Cancer Research Foundation, and CCSRI; current or past (within the prior two years) investigator in clinical trials for BMS, Novartis, GSK, Roche, AstraZeneca, Methylgene, MedImmune, Bayer, Amgen Merck, Incyte, Pfizer, Sanofi, Array, MiMic, Ocellaris Pharma, Astellas, and Alkermes. Do-Youn Oh: consultant or advisory board member for AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, Bristol Myers Squibb/Celgene, BeiGene, Basilea, and Turning Point; research grant from AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, and Handok. Maya Gottfried: nothing to disclose. Ruixue Wang: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Owns stock in Merck & Co., Inc., Rahway, NJ, USA. Kevin Norwood: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Owns stock in Merck & Co., Inc., Rahway, NJ, USA. Aurelien Marabelle: funding to institution during the conduct of the study from MSD; honorarium from MSD and Sanofi; research grants from Foundation MSD Avenir, Sanofi, and Bristol Myers Squibb; personal fees for speakers bureau from Bristol Myers Squibb, Sanofi, and MSD., (Copyright © 2022 Merck Sharp & Dohme LLC., a subsidiary Merck & Co., Inc, The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: Clinically important thresholds in patient-reported outcomes measures like the Kansas City Cardiomyopathy Questionnaire (KCCQ) have not been defined for patients with heart failure and preserved ejection fraction (HFpEF). The aim of this study was to estimate meaningful thresholds for improvement or worsening in the KCCQ physical limitation score (PLS) in patients with HFpEF., Methods and Results: In this pre-specified analysis from VITALITY-HFpEF, anchor- and distribution-based approaches were used to estimate thresholds for improvement or worsening in the KCCQ-PLS using Patient Global Impression of Change (PGIC) as an anchor. The KCCQ-PLS contains six elements, with each increment in response resulting in a change of 4.17 points when converted to a 0-100 scale. The mean change in KCCQ-PLS from baseline to week 12 was calculated for each PGIC group to estimate a meaningful within-patient change. Of 789 patients enrolled, 698 had complete KCCQ-PLS and PGIC data at week 12. The mean (± standard deviation) changes in KCCQ-PLS corresponding to PGIC changes of 'a little better', 'better', and 'much better' were 5.7 ± 18.6, 11.6 ± 19.3, and 18.4 ± 25.3 points, respectively. The scores of patients who responded 'a little better' (n = 177) overlapped substantially with those who reported 'no change' (n = 193; mean change 2.8 ± 18.9). The mean change in KCCQ-PLS for patients responding 'a little worse' (n = 32) was -2.6 ± 18.0 points. The threshold for meaningful within-patient change in KCCQ-PLS based on distribution-based analyses was 12.3 points. Using area under the curve (AUC) analyses of KCCQ-PLS, the sensitivity and specificity of a 4.17-point change were 0.61 and 0.57, for an 8.33-point change they were 0.49 and 0.64, and for a 12.5-point change they were 0.44 and 0.72 for being at least a little better on the PGIC (AUC = 0.54)., Conclusion: In the VITALITY-HFpEF trial, a change in KCCQ-PLS of ≥8.33 points (corresponding to an improvement in ≥2 response categories of KCCQ-PLS) may represent the minimal clinically important difference for improvement and a change of ≤ -4.17 points (corresponding to a worsening in ≥1 response category of KCCQ-PLS) may suggest deterioration in patients with HFpEF., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: The NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ) was developed to assess NSCLC symptom severity in accordance with Food and Drug Administration evidentiary expectations leading to Food and Drug Administration qualification in 2018. This study evaluated the NSCLC-SAQ's measurement properties within a clinical trial., Methods: The KEYNOTE-598 phase 3 study of participants with stage IV metastatic NSCLC with programmed death-ligand 1 tumor proportion score greater than or equal to 50% was used to assess the NSCLC-SAQ's reliability, construct validity, responsiveness, and estimate clinically meaningful within-person change. Other patient-reported outcome measures included patient global impression items of severity and change in lung cancer symptoms, and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 and lung cancer module, LC13., Results: Participants (N = 560) were mostly men (70%), had a mean age of 64 years, and had Eastern Cooperative Oncology Group performance status of 1 (64%) or 0 (36%). Internal consistency at baseline (Cronbach's α = 0.74) and test-retest reliability after 3 weeks (intraclass correlation coefficient = 0.79) were satisfactory. NSCLC-SAQ items, domains, and total score correlated moderately to highly with patient-reported outcome measures capturing similar content, and the total score differentiated among patient global impression of severity groups ( p < 0.001). The total score detected improvement over time and the estimated clinically meaningful within-person change threshold for improvement ranged from three to five points on the 0 to 20 scale. Few participants exhibited symptom worsening (n = 38), limiting inferences in this group., Conclusions: The NSCLC-SAQ was found to be reliable, valid, responsive, and interpretable for assessing symptom improvement in NSCLC. Further evaluation is recommended in trial participants whose symptoms worsen over time., (© 2022 The Authors.)

Background: In the primary analysis population (i.e., PD-L1 combined positive score [CPS] ≥ 1) of the phase 3 KEYNOTE-061 study (NCT02370498), pembrolizumab did not significantly prolong overall survival or progression-free survival. Pembrolizumab had a favorable safety profile in the all-patient population. We present results of prespecified health-related quality of life (HRQoL) analyses., Methods: HRQoL was measured using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), EORTC QLQ gastric cancer questionnaire (QLQ-STO22), and EuroQol 5-dimension, 3-level questionnaire (EQ-5D-3L). Data were analyzed from patients who received ≥ 1 dose of study treatment and who completed ≥ 1 HRQoL assessment. Key analyses included baseline to week 12 least-squares mean (LSM) change in global health status (GHS)/QoL, functional/symptom subscales, and time to deterioration (TTD; ≥ 10-point decrease from baseline) for specific subscales., Results: The HRQoL population included 371 patients (pembrolizumab, n = 188; paclitaxel, n = 183). Compliance and completion rates for all 3 questionnaires were similar in both groups at baseline and week 12. There was no difference in LSM change between groups (- 3.54; 95% CI - 8.92 to 1.84) in GHS/QoL at week 12. LSM change from baseline to week 12 for most QLQ-C30, QLQ-STO22, and EQ-5D-3L subscales indicated some worsening of QoL in both groups. TTD for GHS/QoL, nausea/vomiting, and appetite loss subscales in QLQ-C30 and the pain subscales in QLQ-STO22 were similar between treatment groups., Conclusions: In this population with advanced gastric and GEJ cancer receiving second-line treatment, HRQoL was similar in patients receiving pembrolizumab and those receiving paclitaxel., Clinical Trial Registry and Number: ClinicalTrials.gov, NCT02370498., (© 2021. The Author(s).)

Background: In the randomised phase III KEYNOTE-062 study, pembrolizumab was non-inferior to chemotherapy for overall survival in patients with programmed death-ligand 1 (PD-L1)-positive [combined positive score (CPS) ≥1] advanced gastric/gastroesophageal junction (GEJ) cancer. We present findings of prespecified health-related quality-of-life (HRQOL) analyses for pembrolizumab versus chemotherapy in this population., Materials and Methods: HRQOL, a secondary endpoint, was measured in patients who received ≥1 dose of study treatment and completed ≥1 HRQOL questionnaire [European Organisation for the Research and Treatment of Cancer (EORTC) 30-question quality-of-life (QLQ-C30), EORTC 22-question quality-of-life gastric-cancer-specific module (QLQ-STO22)]. Least squares mean (LSM) change (baseline to week 18) in global health status/quality of life (GHS/QOL; EORTC QLQ-C30) and time to deterioration (TTD) in GHS/QOL, nausea/vomiting and appetite loss scores (EORTC QLQ-C30) and abdominal pain/discomfort scores (EORTC QLQ-STO22) were evaluated., Results: The HRQOL population comprised 495 patients with CPS ≥1 (pembrolizumab, 252; chemotherapy, 243). Compliance rates at week 18 were similar for pembrolizumab and chemotherapy (EORTC QLQ-C30, 87.9% and 81.9%; EORTC QLQ-STO22, 87.9% and 81.3%, respectively). There was no between-arm difference in LSM score change in GHS/QOL [-0.16; 95% confidence interval (CI) -5.01 to 4.69; P = 0.948]. The LSM score change for most subscales showed comparable worsening in both arms. TTD for GHS/QOL [hazard ratio (HR), 0.96; 95% CI, 0.67-1.38; P = 0.826], appetite loss (HR, 0.83; 95% CI, 0.58-1.20; P = 0.314) and pain (HR, 1.22; 95% CI, 0.78-1.91; P = 0.381) were similar between arms. Longer TTD was observed for pembrolizumab versus chemotherapy for nausea/vomiting (HR, 0.61; 95% CI, 0.44-0.85; P = 0.003)., Conclusions: HRQOL was maintained with first-line treatment with pembrolizumab in patients with PD-L1-positive advanced gastric/GEJ cancer and was similar between pembrolizumab and chemotherapy in this population., Competing Interests: Disclosure EVC reports advisory/consultancy fees from Array, AstraZeneca, Bayer, BioPharma, Bristol Myers Squibb, Celgene, Halozyme, Lilly, Merck KGaA, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Novartis, Roche and Servier; and researching grant/funding (institution) from Amgen, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Ipsen, Lilly, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA., Merck KGaA, Novartis, Roche and Servier. AV is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Y-JB reports consulting/advisory role for Astellas, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Daichii-Sankyo, Eli Lilly, Genentech/Roche, Genexine, Green Cross, Hanmi, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono, Novartis, Samyang Biopharmaceuticals and Taiho; and grants (to the institution for clinical trials) from Astellas, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Boehringer Ingelheim, Boston Biomedical, CKD Pharma, Curis, Daiichi Sankyo, Eli Lilly, Five Prime, Genentech/Roche, Genexine, Green Cross, GSK, MacroGenics, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono, Novartis, Ono, Pfizer, Taiho and Takeda. CSF reports consulting role for Agios, Amylin Pharmaceuticals, Bain Capital, CytomX Therapeutics, Daiichi Sankyo, Eli Lilly, Entrinsic Health, EvolveImmune Therapeutics, Genentech, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Taiho and Unum Therapeutics. He also serves as a director for CytomX Therapeutics and owns unexercised stock options for CytomX and Entrinsic Health. He is a co-founder of EvolveImmune Therapeutics and has equity in this private company. KS reports grants and personal fees from Astellas Pharma, Eli Lilly and Company, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Ono Pharmaceutical and Taiho Pharmaceutical; personal fees from AbbVie, Bristol Myers Squibb, GlaxoSmithKline, Novartis, Pfizer Inc., Takeda Pharmaceuticals and Yakult; and grants from Chugai Pharma, Daiichi Sankyo, Dainippon Sumitomo Pharma and Medi Science. YYJ reports advisory fees from Bristol Myers Squibb, Lilly, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono and Pfizer; and research expenses from Amgen, Bayer, Boehringer Ingelheim, Genentech, Lilly and Roche. VS reports research funding from Bristol Myers Squibb, EMD-Serono and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. SSt reports advisory/consultancy role for Bayer, Bristol Myers Squibb, Exelixis, Genentech, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and QED. JMN is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. UK is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. SSh is an employee and a stockholder of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. MA reports scientific consultancy role for Bristol Myers Squibb, Lilly, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Servier; and honoraria for speaking for Bristol Myers Squibb, Lilly, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Servier. All other authors have declared no conflicts of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Background: In the KEYNOTE-177 study, pembrolizumab monotherapy provided statistically significant and clinically meaningful improvements in progression-free survival versus chemotherapy as first-line treatment in patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. To further support the efficacy and safety findings of the KEYNOTE-177 study, results of the health-related quality of life (HRQOL) analyses are reported here., Methods: KEYNOTE-177 is an open-label, randomised, phase 3 trial being done at 192 cancer centres in 23 countries, in patients aged 18 years and older with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and who had not received previous systemic therapy for metastatic disease. Eligible patients were randomly assigned (1:1) centrally by use of interactive voice response or integrated web response technology to receive pembrolizumab 200 mg intravenously every 3 weeks or investigator's choice chemotherapy (mFOLFOX6 [leucovorin, fluorouracil, and oxaliplatin] or FOLFIRI [leucovorin, fluorouracil, and irinotecan] intravenously every 2 weeks with or without intravenous bevacizumab or cetuximab). Patients and investigators were not masked to treatment assignment. The primary endpoints were progression-free survival (previously reported) and overall survival (data to be reported at the time of the final analysis). HRQOL outcomes were evaluated as prespecified exploratory endpoints. The analysis population comprised all randomly assigned patients who received at least one dose of study treatment and completed at least one HRQOL assessment. HRQOL outcomes were mean change from baseline to prespecified week 18 in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29) scale and item scores, and in the EuroQoL 5 Dimensions 3 Levels (EQ-5D-3L) visual analogue scale and health utility scores; the proportion of patients with improved, stable, or deteriorated scores from baseline to prespecified week 18 in EORTC QLQ-C30 scales and items; and time to deterioration in EORTC QLQ-C30 global health status/quality of life (GHS/QOL), physical functioning, social functioning, and fatigue scores and EORTC QLQ-CR29 urinary incontinence scores. The threshold for a small and clinically meaningful mean difference in EORTC QLQ-C30 score was 5-8 points. This study is registered with ClinicalTrials.gov, NCT02563002 and is ongoing; recruitment is closed., Findings: Between Feb 11, 2016, and Feb 19, 2018, 307 patients were enrolled and randomly assigned to receive pembrolizumab (n=153) or chemotherapy (n=154). The HRQOL analysis population comprised 294 patients (152 receiving pembrolizumab and 142 receiving chemotherapy). As of Feb 19, 2020, median time from randomisation to data cutoff was 32·4 months (IQR 27·7-37·8). Least squares mean (LSM) change from baseline to prespecified week 18 showed a clinically meaningful improvement in EORTC QLQ-C30 GHS/QOL scores with pembrolizumab versus chemotherapy (between-group LSM difference 8·96 [95% CI 4·24-13·69]; two-sided nominal p=0·0002). Median time to deterioration was longer with pembrolizumab versus chemotherapy for GHS/QOL (hazard ratio 0·61 [95% CI 0·38-0·98]; one-sided nominal p=0·019), physical functioning (0·50 [95% CI 0·32-0·81]; one-sided nominal p=0·0016), social functioning (0·53 [95% CI 0·32-0·87]; one-sided nominal p=0·0050), and fatigue scores (0·48 [95% CI 0·33-0·69]; one-sided nominal p<0·0001)., Interpretation: Pembrolizumab monotherapy led to clinically meaningful improvements in HRQOL compared with chemotherapy in patients with previously untreated microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. These data, along with the previously reported clinical benefits, support pembrolizumab as a first-line treatment option for this population., Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA., Competing Interests: Declaration of interests TA reports consulting or advisory roles, or both, and received honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, Chugai, Clovis Oncology, GlaxoSmithKline, Gritstone Oncology, HalioDx, Pierre Fabre, Roche/Ventana, Sanofi, Servier, Tesaro and Merck Sharp & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA (MSD); travel, accommodations, and expenses from Roche/Ventana, Bristol Myers Squibb, and MSD; speaker bureau fees from Bristol Myers Squibb and Servier; and research funding from MSD. TA also reports participation in the scientific committee of the ARCAD foundation and GERCOR group as non-renumerated activities. MA is an employee of Merck Sharp & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA, and is a shareholder in Merck & Co, Kenilworth, NJ, USA. JMN is an employee of Merck Sharp & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ USA, and may own stock or hold stock options, or both, in the Company. K-KS reports honoraria from Bristol Myers Squibb, Guardant Health, Innovent Biologics, Merck KGaA, Roche, and Servier; consulting or advisory roles, or both, for Roche; research grants or funding, or both, from Amgen, Bristol Myers Squibb, Gilead, Merck KGaA, Roche, and MSD; and travel, accommodations, and expenses from Merck KGaA, Innovent Biologics, and MSD. TWK reports research grants or funding, or both, from Merck Serono, AstraZeneca, and Pfizer. BVJ reports research grants or funding, or both, from MSD. LHJ reports research grants or funding, or both, to his institution from 2cureX, Incyte, Bristol Myers Squibb, and MSD. CJAP reports advisory roles for Nordic Pharma. DS declares no competing interests. RG-C has provided scientific advice, attended speakers bureau, or received honoraria from AAA, Advanz Pharma, Bayer, Bristol Myers Squibb, HMP, Ipsen, Merck & Co, Midatech Pharma, Novartis, PharmaMar, Pfizer, Pierre Fabre, Roche, Sanofi, Servier, and MSD; and has received support to his institution for the conduct of clinical trials or for molecular diagnostic platforms from ARMO Biosciences, AstraZeneca, Pfizer, Novartis, Ipsen, Roche, Pharmacyclics, Boston Biomedicals, Merck & Co, Amgen, Sanofi, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Sysmex, Gilead Sciences, Servier, Adacap, VCN, Lilly, Pharmamar, and MSD. RG-C also reports financial support from Pfizer and Bristol Myers Squibb to an investigator-initiated trial evaluating axitinib in neuroendocrine tumours and nivolumab in neuroendocrine carcinomas. RG-C also reports being a member of the Executive Committee of the Spanish Neuroendocrine Tumor Cooperative Group (GETNE), the Executive Committee of the European Society of Neuroendocrine Tumors (ENETS), the Scientific Advisory Group for Oncology (SAG-O) of the European Medicines Agency (EMA; 2008–17), EORTC, ASCO, ESMO, SEOM, TTD, GEMCAD; and is a global PI of a clinical trial of Axitinib (Pfizer) in neuroendocrine tumours and a clinical trial of nivolumab (Bristol Myers Squibb) and chemotherapy in neuroendocrine carcinomas. IS reports advisory or consultancy, or both, roles for Ipsen, Pfizer, Syrtex, Amgen, and Pharmamar; and speaker bureau fees from AAA, Sanofi, and Novartis. CDLF reports advisory or consultancy, or both, roles for Roche, Pierre Fabre, Oncologie, Eisai, Bayer, and MSD; and travel, accommodations, and expenses from Amgen, Eisai, Bristol Myers Squibb, and Roche. FR reports honoraria; advisory or consultancy roles, or both; research grants or funding, or both; travel, accommodations, and expenses from Roche, Merck-Serono, Sanofi, Bristol Myers Squibb, Servier, Lilly, Amgen, Bayer, Celgene, and MSD. EE reports personal financial interests, honoraria, advisory roles, travel grants, and research grants from Hoffman-La Roche, Sanofi, Aventis, Amgen, Merck Serono, Servier, Array Pharmaceuticals, Bristol Myers Squibb, and MSD; and institutional financial interests and honoraria from Hoffman-La Roche, Sanofi Aventis, Amgen, Merck Serono, Boehringer Ingelheim, AbbVie, Array Pharmaceuticals, Pierre Fabre, Novartis, Bristol Myers Squibb, GlaxoSmithKline, MedImmune, and MSD. LAD is a member of the board of directors of Personal Genome Diagnostics and Jounce Therapeutics. LAD is a compensated consultant to PGDx, 4Paws (PetDx), Innovatus CP, Se'er, Kinnate, and Neophore. LAD is an uncompensated consultant to Merck & Co. LAD has received research support for clinical trials from Merck & Co. LAD is an inventor of multiple licensed patents related to technology for circulating tumour DNA analyses and mismatch repair deficiency for diagnosis and therapy from Johns Hopkins University. Some of these licenses and relationships are associated with equity or royalty payments directly to Johns Hopkins and LAD. LAD holds equity in Personal Genome Diagnostics, Jounce Therapeutics, Thrive Earlier Detection, Se'er, Kinnate and Neophore. LAD's spouse holds equity in Amgen. The terms of all these arrangements are being managed by Johns Hopkins and Memorial Sloan Kettering in accordance with their conflict of interest policies. TY reports research funding from Novartis Pharma, MSD, Sumitomo Dainippon Pharma, Chugai Pharmaceutical, Sanofi, Daichi Sankyo, Parexel International, Ono Pharmaceutical, and GlaxoSmithKline. EVC reports advisory board roles for Array, AstraZeneca, Bayer, Biocartis, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Halozyme, GlaxoSmithKline, Incyte, Ipsen, Lilly, Merck KGaA, Novartis, Pierre Fabre, Roche, Servier, Sirtex, Taiho, and MSD; and research funding from Bayer, Boehringer Ingelheim, Celgene, Ipsen, Lilly, Merck KGaA, Novartis, Roche, Servier, and MSD. PY is an employee of MSD China Holding. MF is an employee of Merck Sharp & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ USA, who may own stock or hold stock options, or both in the Company. DTL reports advisory board roles for MSD and Bristol Myers Squibb; research funding from MSD, Bristol Myers Squibb, Aduro Biotech, Curegenix, Medivir, and Nouscom; honoraria from MSD; and is an inventor of licensed intellectual property from Johns Hopkins University., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Health-related quality of life (HRQoL) is an important outcome measure and prognostic indicator in hepatocellular carcinoma (HCC). KEYNOTE-240 (NCT02702401) assessed the efficacy and safety of pembrolizumab plus best supportive care (BSC) versus placebo plus BSC in patients with HCC who previously received sorafenib. This study presents the results of a prespecified exploratory analysis of patient-reported outcomes., Methods: Patients completed the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and its HCC supplement (EORTC QLQ-HCC18) electronically at baseline; at weeks 2, 3, 4, 6, 9, 12, and 18; and then every 9 weeks until 1 year or end of treatment, and at the 30-day safety follow-up visit., Results: The HRQoL population included 271 and 127 patients randomly assigned to pembrolizumab and placebo, respectively. From baseline to week 12, changes in both scores were similar between pembrolizumab and placebo; global health status/QoL scores were stable. The proportions of patients who improved, remained stable, or deteriorated across all functional domain and symptom scores were generally similar between pembrolizumab and placebo. Time to deterioration was similar between the 2 arms based on the prespecified analysis of EORTC QLQ-HCC18 domains of abdominal swelling, fatigue, and pain., Conclusion: Pembrolizumab preserved HRQoL during treatment for advanced HCC. Combined with efficacy and safety results from KEYNOTE-240, these findings support a positive benefit/risk profile for pembrolizumab in a second-line treatment setting for patients with HCC who previously received sorafenib., (© 2020 American Cancer Society.)

Purpose: The objective of this study was to evaluate the psychometric properties of the Dysmenorrhea Daily Diary (DysDD), an electronic patient-reported outcome, in a sample of 355 women with primary dysmenorrhea enrolled in a phase IIb, multicenter, randomized, partially blinded, placebo-controlled trial for treatment of dysmenorrhea., Methods: Subjects completed the DysDD over three menstrual cycles, one pre-treatment baseline cycle and two treatment cycles. The DysDD was administered alongside the Menstrual Distress Questionnaire (MDQ), the Short-Form 36 Version 2.0 (SF-36v2), and a Global Assessment of Change (GAC). Item response distributions, test-retest reliability, concurrent and known groups validity, responsiveness, and minimally important difference (MID) were evaluated for the DysDD., Results: As expected, item response distributions varied throughout the menstrual period for all items, with the response scales fully utilized. Within-cycle test-retest reliability was adequate (weighted kappa: 0.5-0.7), although between-cycle test-retest was poor (weighted kappa: 0.1-0.5), most likely due to the highly variable nature of dysmenorrhea between cycles rather than limitations of the measure. Correlations with the MDQ and SF-36v2 were low-moderate, but in the predicted direction, supporting concurrent validity. There were significant differences in DysDD scores across severity groups based on pain medication use. The DysDD was responsive to changes in patients' dysmenorrhea with significantly different changes in scores between change groups (p < 0.0001). MID analyses suggest changes on the DysDD 0-10 pelvic pain score of three points can be considered clinically meaningful., Conclusions: Overall, findings indicate that the DysDD has acceptable reliability and is a valid and responsive instrument for assessing dysmenorrhea.

In 2014, the European Medicines Agency (EMA) released for comment a draft reflection paper on the use of patient-reported outcome (PRO) measures in oncology studies. A twelve-member International Society for Quality of Life Research (ISOQOL) taskforce was convened to coordinate the ISOQOL response. Twenty-one ISOQOL members provided detailed comments and suggestions on the paper: 81 % from academia and 19 % from industry. Taskforce members consolidated and further refined these comments and shared the recommendations with the wider ISOQOL membership. A final response was submitted to the EMA in November 2014. The impending publication of the EMA reflection paper presents a valuable opportunity for ISOQOL to comment on the current direction of EMA PRO guidance and strategy. The EMA paper, although focused on cancer, could serve as a model for using PROs in other conditions, as it provides a useful update surrounding some of the design issues common to all trial research including PRO endpoints. However, we believe there are a number of additional areas in need of greater consideration. The purpose of this commentary is therefore to highlight the strengths of this timely and potentially useful document, but also to outline areas that may warrant further discussion.

Purpose: Dysmenorrhea refers to the experience of pelvic pain/cramps experienced by women around or during menstruation. A literature review indicated that no existing patient-reported outcome measure was adequate to support labeling claims in dysmenorrhea. Therefore, this study aimed to develop a new measure that could be used as a primary end point in dysmenorrhea clinical trials., Methods: Open-ended interviews were conducted with 52 dysmenorrhea patients, including a subset of 12 women with a comorbid pelvic pain condition (PPC). Verbatim transcripts were analyzed thematically. The findings were used to generate draft items for an electronic diary (eDiary). A further 24 dysmenorrhea patients pilot-tested the eDiary for 1-5 weeks and completed cognitive interviews to assess content validity. Revisions to the eDiary were implemented based on the findings., Results: In the first set of interviews, 51 women (98 %) spontaneously reported pain/cramps in or around the pelvic region (abdomen, lower back, legs/upper thighs, and vaginal area). Pain experiences reported were similar across dysmenorrhea and dysmenorrhea plus PPC subgroups, except that the pelvic pain among PPC patients occurred throughout the month, not only during menstruation. All participants described the detrimental impact of dysmenorrhea on health-related quality of life., Conclusions: The eDiary was conceptually comprehensive and easy to complete/understand during cognitive debriefing. The resulting nine-item diary included assessment of: menstrual bleeding severity; pain severity; use of analgesics; impact on work/school, physical activities, social and leisure activities, and sleep. Psychometric validation is ongoing and will assess the reliability, validity, and responsiveness of the eDiary as a comprehensive dysmenorrhea assessment.

Background: Niacin has lipid-modifying efficacy and cardiovascular benefit, but is underutilised because of niacin-induced flushing (NIF). This real-world, prospective, observational study characterised the severity and impact of NIF symptoms among participants who were newly prescribed extended-release (ER) niacin., Methods: Participants were surveyed daily during week 1 of therapy, at weeks 5, 9, 13, and at months 7, 10 and 13. Surveys included the Flushing Symptom Questionnaire (FSQ), which includes the Global Flushing Severity Score (GFSS) question, the Flushing Impact Questionnaire (FIQ) and the Treatment Satisfaction Questionnaire for Medication (TSQM)., Results: Overall, 306 participants were enrolled. During week 1, 30.0% of participants reported a maximum GFSS ≥ 4 (moderate or greater). Mean FIQ domain scores increased with increasing flushing severity, primarily driven by the Irritation/Frustration domain. By week 13, only 2.5% of participants had attained a 2 g ER niacin dose. By month 13, 43.5% (n = 133) had discontinued ER niacin. At discontinuation, only 3.1% of participants had attained the 2 g dose. Over half of the participants who discontinued experienced flushing symptoms: 82% reported moderate to extreme flushing (GFSS ≥ 4), and 68% reported severe to extreme flushing (GFSS ≥ 7). Participants who discontinued and had flushing side effects reported high degrees of impact in the FIQ Irritation/Frustration domain, and high dissatisfaction as a result of side effects, as measured by the TSQM., Conclusion: In a real-world setting, NIF side effects were bothersome and had an impact on the continuation of therapy., (© 2013 John Wiley & Sons Ltd.)

Purpose: Interpretation guidelines are needed for patient-reported outcome (PRO) measures' change scores to evaluate efficacy of an intervention and to communicate PRO results to regulators, patients, physicians, and providers. The 2009 Food and Drug Administration (FDA) Guidance for Industry Patient-Reported Outcomes (PRO) Measures: Use in Medical Product Development to Support Labeling Claims (hereafter referred to as the final FDA PRO Guidance) provides some recommendations for the interpretation of change in PRO scores as evidence of treatment efficacy., Methods: This article reviews the evolution of the methods and the terminology used to describe and aid in the communication of meaningful PRO change score thresholds., Results: Anchor- and distribution-based methods have played important roles, and the FDA has recently stressed the importance of cross-sectional patient global assessments of concept as anchor-based methods for estimation of the responder definition, which describes an individual-level treatment benefit. The final FDA PRO Guidance proposes the cumulative distribution function (CDF) of responses as a useful method to depict the effect of treatments across the study population., Conclusions: While CDFs serve an important role, they should not be a replacement for the careful investigation of a PRO's relevant responder definition using anchor-based methods and providing stakeholders with a relevant threshold for the interpretation of change over time.

The Adult/Adolescent Vaccination Report Card (VRC) was developed and validated by Merck in 1998 for use in vaccine clinical trials to collect information from trial subjects on complaints for both local and systemic events after vaccination. This short report describes the revision to the original validated VRC in order to align with the guidelines outlined in the 2007 FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Since the VRC elicits trial subjects' self-reports of any adverse experiences (AE) occurring post vaccination, it was important that subsequent modifications of the VRC retained the original user-friendly characteristics while gathering the appropriate information to align with the FDA Guidance. A convenience sample of 15 participants (71% females, 87% white and mean (SD) age 45 (13) years was recruited to obtain feedback in order to revise the Adult/Adolescent VRC. Based on the feedback received, the following were slightly revised: ruler for the measurements of local systemic reactions, severity ratings, and general instructions. The revised VRC is currently being used in Merck vaccine clinical trials.

Purpose: Understand the choice of recall period for PRO measures based on intended use, characteristics of the disease, treatment, and attributes of studies., Methods: Current practice and considerations were reviewed within several disease areas (overactive bladder, menopausal hot flashes, niacin-induced flushing, osteoarthritis pain, irritable bowel symptoms, benign prostatic hyperplasia, and alopecia)., Results: Rationales were identified for using different recall periods, including event-driven (immediate), daily, up to weekly, and longer than weekly. This work demonstrates that (1) recall depends on what the PRO measure captures, its intended use, and attributes of the disease and study; (2) within the same disease area, recall can vary depending on the concept or phenomenon of interest; (3) recall must consider patient burden and their ability to easily and accurately recall the information requested; and (4) recall must be consistent with the duration of the trial and the scheduled clinic visits., Conclusions: Shorter recall periods may underestimate symptom burden when symptoms have diurnal or day-to-day fluctuation and may place undue burden on patients. On the other hand, recall intervals that are too long may either over- or underestimate the health state. Therefore, appropriate criteria should be considered given attributes of the disease when selecting an adequate recall period.

Objective: Clinical trials of new agents to reduce the severity and impact of influenza require accurate assessment of the effect of influenza infection. Because there are limited high-quality adult influenza Patient Reported Outcomes (PRO) measures, the aim was to develop and validate a simple but comprehensive questionnaire for epidemiological research and clinical trials., Methods: Construct and item generation was guided by the literature, concept mapping, focus groups, and interviews with individuals with laboratory-confirmed influenza and expert physicians. Items were administered to 311 people with influenza-like illness (ILI) across 25 US sites. Analyses included classic psychometrics, structural equation modeling (SEM), and Rasch analyses., Results: Concept mapping generated 149 concepts covering the influenza experience and clustered into symptoms and impact on daily activities, emotions, and others. Items were drafted using simplicity and brevity criteria. Eleven symptoms from the literature underwent review by physicians and patients, and two were removed and one added. The symptoms domain factored into systemic and respiratory symptoms, whereas the impact domains were unidimensional. All domains displayed good internal consistency (Cronbach α ≥ 0.8) except the three-item respiratory domain (α = 0.48). A five-factor SEM indicated excellent fit where systemic, respiratory, and daily activities domains differentiated patients with ILI or confirmed influenza. All scales were responsive over time., Conclusions: Patient and clinician consultations resulted in an influenza PRO measure with high validity and good overall evidence of reliability and responsiveness. The Influenza Intensity and Impact Questionnaire (FluiiQ™) will improve the evaluation of existing and future agents designed to prevent or control influenza infection by increasing the breadth and depth of measurement in this field., (Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objective: To understand migraine postdrome by directly interviewing migraine patients with postdrome symptoms. To document these symptoms, as well as impacts, as a prelude to developing a postdrome migraine questionnaire., Background: Migraine attacks are traditionally divided into 4 phases. Of these, the postdrome is the least studied, and no patient-reported outcomes to assess symptoms and impacts of this migraine phase have been published., Methods: Qualitative concept elicitation focus groups were conducted with 34 patients in 3 geographically diverse US cities to elicit the symptoms and burden of migraine postdrome. Data elicited from focus groups were coded using Atlas.ti software to facilitate identification of concepts and terminologies of migraine postdrome. A draft questionnaire was developed based on the symptoms and impacts of migraine postdrome described by patients. Cognitive debriefing interviews were conducted with 15 patients in Connecticut and Chicago to confirm content validity, relevance, and comprehension., Results: Patients defined the onset of postdrome as when they no longer experienced the migraine pain. Postdrome was often described as "[being] or [feeling] wiped out" and "headache hangover." The symptoms most frequently reported by the patients who participated in the focus groups and included in the draft post-migraine questionnaire were: tiredness, difficulty concentrating, weakness, dizziness, lightheadedness, and decreased energy. Patients also reported decreased activity level as a result of experiencing postdrome symptoms. Postdrome symptoms were reported to impact the ability to work, to affect family interactions and social life, and to cause cognitive impairment. A preliminary questionnaire measuring severity and duration of symptoms and severity of impacts of the post-migraine experience, with an 11-point (0 to 10) response scale, was developed. This preliminary questionnaire was tested for content validity, relevance, and comprehension using cognitive debriefing interviews. All patients reported that the questionnaire was relevant to their condition. Irrelevant and redundant items such as body tension and annoyance were eliminated., Conclusions: Migraine postdrome is debilitating for those who experience it. Concept elicitation and cognitive debriefing research support the relevance of the items in the post-migraine questionnaire. Future research will provide evidence of the post-migraine questionnaire's psychometric properties and interpretation guidelines., (© 2010 American Headache Society.)

Scoring the severity of a diabetic foot wound infection may help assess the severity, determine the type and urgency of antibiotic and surgical treatment needed, and predict clinical outcomes. We developed a 10-item diabetic foot infection wound score (results could range from 3 to 49 [least to most severe]) incorporating semi-quantitative grading of both wound measurements and various infection parameters. Using data from a prospective diabetic foot infection antibiotic trial (SIDESTEP), we evaluated the score's accuracy in predicting outcome, analyzed its components and tested it for consistency, construct, and validity. Wound scores for 371 patients significantly correlated with the clinical response; it was favorable at the follow-up assessment in 94.8% with a baseline score 19. Scores demonstrated good internal consistency (Cronbach's alpha >0.70 to <0.95). Patients with more severe wounds had higher scores, supporting construct validity. Excluding scores for wound discharge (purulent and nonpurulent), leaving an eight-item score, provided better measurement statistics. This easily performed wound score appears to be a reliable, valid, and useful tool for predicting clinical outcomes. Further validation studies in different patient populations should refine the items included.

Background: The literature on changes in health-related quality of life (HRQOL) in weight loss studies is inconsistent, and few studies use more than one type of measure. The purpose of the current study was to compare one-year changes in HRQOL as a function of weight change using three different measures: a weight-related measure (Impact of Weight on Quality of Life-Lite [IWQOL-Lite)]) and two generic measures (SF-36; EQ-5D)., Methods: Data were obtained from 926 participants (mean Body Mass Index (BMI) (kg/m(2)) = 35.4; 84% female; mean age = 49.5 years) in a placebo-controlled randomized trial for weight loss. At baseline and one-year, participants completed all three HRQOL measures. HRQOL was compared across weight change categories (> or = 5% and 0-4.9% gain, 0-4.9%, 5.0-9.9% and > or = 10% loss), using effect sizes., Results: The weight-related measure of HRQOL exhibited greater improvements with one-year weight loss than either of the generic instruments, with effect sizes ranging from 0.24 to 0.62 for 5-9.9% weight reductions and 0.44 to 0.95 for > or = 10% reductions. IWQOL-Lite Self-Esteem also showed a small improvement with weight gain. Changes in the two generic measures of HRQOL were inconsistent with each other, and in the case of the SF-36, variable across domains. For participants gaining > or = 5% of weight, the greatest reductions in HRQOL occurred with respect to SF-36 Mental Health, MCS, and Vitality, with effect sizes of -0.82, -0.70, and -0.63 respectively., Conclusion: This study found differences between weight-related and generic measures of health-related quality of life in a one-year weight loss trial, reflecting the potential value of using more than one measure in a trial. Although weight loss was generally associated with improved IWQOL-Lite, physical SF-36 subscale and EQ-5D scores, a small amount of weight gain was associated with a slight improvement on weight-specific HRQOL and almost no change on the EQ-5D, suggesting the need for further research to more fully study these relationships. We believe our findings have relevance for weight loss patients and obesity clinicians/researchers in informing them of likely HRQOL outcomes associated with varying amounts of weight loss or gain.

Objective: To study the frequency of normal serum urate (SU) levels during acute gout in the largest studies of acute gout treatment to date., Methods: Data collected from 2 randomized controlled clinical trials assessing the efficacy of etoricoxib or indomethacin for 7 days in acute gout were used to assess SU levels during acute gouty attacks. Efficacy was similar with both agents, so both groups were combined for analysis., Results: A total of 339 patients were enrolled in the 2 studies; 94% were male; mean age was 50.5 years. At baseline, 14% of patients had a "true" normal SU (

Treatment with niacin effectively improves multiple lipid parameters and cardiovascular outcomes. Widespread use of niacin, however, is limited by flushing, which is mediated primarily by prostaglandin D2 (PGD2). Laropiprant is a selective PGD2 receptor 1 (DP1) antagonist that reduces objective measures of niacin-induced flushing symptoms upon initiation of therapy and with more chronic use. Results from early dosing and formulation studies have culminated in the development of a combination extended-release (ER) niacin/laropiprant tablet aimed at providing the beneficial lipid-modifying effects of niacin, while reducing niacin-induced flushing. The improvement in the tolerability of niacin with ER niacin/laropiprant allows niacin dosing to initiate directly at 1 g and rapidly advance to a 2-g target dose. ER niacin/laropiprant generally is tolerated well and represents a new treatment option for dyslipidemia that offers the potential for more patients to receive the lipid-modifying and cardiovascular benefits of niacin.

The aim of this study was to validate the nighttime symptoms score (NSS), which incorporates individual scores for difficulty going to sleep and nighttime awakening caused by nasal symptoms and nasal congestion on awakening, as a clinically relevant measure of allergic rhinitis (AR). Fifty-five general season AR (SAR) symptom items were generated by interviews with 14 patients with symptomatic SAR without concomitant asthma for use in an Importance Rating Questionnaire (IRQ). A second group of patients (n = 83) with symptomatic AR without asthma rated the importance of each item on the IRQ. Correlation coefficients were calculated to examine the relationships between the six sleep quality questions on the IRQ and the other AR symptoms and between the symptom questions of the NSS, the Daytime Nasal Symptoms Score (DNSS), and the individual domains of the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ). The majority (94%) of patients with active AR reported some degree of symptoms relating to sleep quality. The six sleep quality items on the IRQ were selected by 71-84% of patients. The sleep quality items were more highly correlated with each other (r = 0.48-0.85) than with the four items of the DNSS (r = 0.01-0.42). There was a moderate-to-strong correlation of the RQLQ sleep domain with the two sleep questions of the NSS (r = 0.44-0.57). The individual symptom questions of the NSS and the DNSS were only moderately correlated with each other. Sleep quality questions measure aspects of SAR that are not captured by daytime SAR symptoms. The results show that the NSS is a valid and relevant clinical measure of the impact of nighttime sleep disturbance on AR patients.

Acute respiratory syncytial virus (RSV)-induced bronchiolitis is often associated with continuing respiratory symptoms following hospitalization. To date, there is no validated objective measure to evaluate symptoms of RSV-induced bronchiolitis. We report on the reliability, validity, and responsiveness of the bronchiolitis caregiver diary (BCD) of symptoms and healthcare utilization associated with postacute RSV. The BCD measures four symptoms (daytime cough, wheeze, trouble breathing, and nighttime cough), healthcare utilization, and rescue medication for worsening of lung symptoms. Data from the 4-week treatment period of the reported prospective, placebo-controlled trial of montelukast for treatment of postacute RSV were used to assess reliability (internal consistency and test-retest), construct validity (cross-sectional and longitudinal correlations), discriminant validity (known-groups analyses), and responsiveness. The primary outcome of this study was the percentage of symptom-free days (SFD). The secondary outcome was a composite symptom score (CSS; average of daytime cough, wheezing, and trouble breathing). Cronbach's alpha of 0.85 indicated that the four symptoms were internally consistent, supporting a unidimensional scale structure. Test-retest reliabilities for the percentage of SFD and CSS were above the recommended cut point of 0.70. Cross-sectional and longitudinal correlations were sizeable and statistically significant, demonstrating construct validity. Hypothesized known-group differences were statistically significant in the appropriate direction. Responsiveness analyses indicated moderate effect sizes for percentage of SFD. In conclusion, the BCD provides a valid, reliable, and responsive tool for the assessment of symptoms of postacute RSV-induced bronchiolitis, capable of measuring moderate effect sizes, and demonstrating responsiveness to therapy., (Copyright 2005 Wiley-Liss, Inc.)

This paper uses the standard error of measurement (SEM) and the standard error of the difference (S(diff)) in relation to data on individuals with amyotrophic lateral sclerosis (ALS) to calculate the minimum change scores required by statistical criteria for each dimension of the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40). Data collected from a longitudinal study was used to evaluate the usefulness of SEM and S(diff) criteria and to compare these criteria with an anchor-based approach in determining meaningful change. Questionnaires were completed on two occasions, 3 months apart. 764 questionnaires were returned. Questionnaires included the ALSAQ-40 and dimension specific transition items. The ALSAQ-40 is a disease specific health-related quality of life instrument for use in studies of patients with ALS or other motor neuron diseases. For all dimensions of the ALSAQ-40 the patterns of SEMs were similar over time. The results suggest that, for example, six points change on a 0-100 transformed scoring of the physical mobility dimension may be considered on distributional grounds a minimum meaningful change. The demonstrated consistency of SEMs for the dimensions of the ALSAQ-40 is empirical evidence of the theoretically claimed advantage of this measure of sample independence, and supports use of this distributional approach to calculate meaningful change.

The purpose of this study was to examine whether there are advantages in terms of outcome assessment of using Rasch methods of scoring the 12-item Oxford Hip Score (OHS) questionnaire over conventionally Likert scores. As part of a prospective cohort study of total hip replacements in five former regions of England the OHS was sent to patients pre-operatively, at 3 months and 1 year post-operatively. Post-operative data was collected on over 5000 cases. Based on the level of satisfaction with surgery, patients were divided into satisfied and dissatisfied. Analyses were performed to test the relative precision (RP) of Rasch scoring vs. conventionally Likert scores in discriminating the groups experiencing different level of satisfaction. Considerable gains in precision were achieved with Rasch scoring methods when groups were compared 3 and 12 months post-operatively. The results from the current study suggest that in some situations there may be substantial gains in measuring health related outcomes using Rasch-based scoring methods.

Objectives: To explore sociodemographic and health status factors associated with waiting times both for first outpatient appointment and for total hip replacement surgery (THR)., Methods: A survey of THR in five former English regions was conducted between September 1996 and October 1997. Every patient listed for THR was asked to fill out a questionnaire preoperatively. This questionnaire included the 12-item Oxford Hip Score (OHS) questionnaire and two questions on the length of time patients waited for an outpatient appointment and subsequently for their operation., Results: From multiple logistic regression analyses, region, private vs. public sector, housing tenure and preoperative OHS were all independently associated with a waiting time for an outpatient appointment for > 3 months. Region, housing tenure and gender were also independently associated with a wait of >or= 6 months on the surgical waiting list., Conclusions: A large proportion of patients had long waiting times both for an outpatient appointment and while on a surgical waiting list. There were significant differences in waiting time according to social, geographical and health care system factors. Patients with a worse pain and disability at surgery waited longer for an outpatient appointment. The longer patient waited, the worse was their pain and disability, suggesting that patients were not prioritized by these criteria. Benefits of prioritizing should be tested.

Background and Objective: To be useful, results from health-related quality of life (HRQoL) measures must be interpretable. The objective of this article is to examine statistical (distributional) approaches to interpretability. The standard error of measurement (SEM) and the standard error of the difference (S(diff)) are used in data on individuals with Parkinson's disease to calculate the minimum change scores required to be statistically meaningful for each dimension of an instrument to assess HRQoL in Parkinson's disease, the PDQ-39., Methods: Data was collected from both a community and a clinic study; in both studies the PDQ-39 was administered at baseline and follow-up., Results: The patterns of SEMs and S(diff)s were similar both across time periods and between samples, for all dimensions except Social Support., Conclusions: The results suggest that, for example, six points change on a 0-100 transformed scoring of the Mobility dimension may be considered on distributional grounds a minimum meaningful change. The demonstrated consistency across occasions and types of sample of SEMs and S(diff) for the majority of the dimensions of the PDQ-39, is evidence of the theoretically claimed advantage of this measure of sample independence, and supports use of this distributional approach to minimum meaningful change.

Objectives: To compare alternative Rasch-based approaches to the assessment of change over time through the example of an outcome measure used in total hip replacement surgery., Subjects: Preoperative data were collected on 1424 patients receiving total hip replacement surgery; 1221 (86%) were sent follow-up questionnaires 1 year after surgery., Measures: The 12-item Oxford Hip Score (OHS) questionnaire administered preoperatively and 1-year postoperatively., Methods: Subscales of the OHS for pain and functional impairment were examined for unidimensionality and item invariance. Two criteria were used to examine Rasch-based measurement of the 2 subscales. Advantages of Rasch measurement were examined in terms of whether it produced improved discrimination of outcomes of patients (1) undergoing different levels of complexity of surgery; and (2) reporting different retrospective judgments of the success of their surgery. Using the method of relative precision in relation to groups of patients distinguished in these 2 ways, change scores using Likert scoring methods were compared with 2 Rasch scoring methods: (1) separate analyses of the 2 time points; and (2) a common scale analysis obtained by stacking patients from the 2 time points., Results: Less evidence for item invariance over time was found for the pain subscale. Other evidence supported treating subscales as unidimensional. Whichever Rasch scoring method was used, some gains in precision over standard Likert scoring were obtained in discriminating between groups of patients., Conclusions: The evidence from the current study suggests that there may be some gains in sensitivity to change of outcome measures from different Rasch-based scoring approaches.

Objectives: To determine which factors are predictive of physical and mental health one year after a first measurement of health status in amyotrophic lateral sclerosis (ALS) patients., Methods: The Physical Component Summary (PCS) score and the Mental Component Summary (MCS) score of the SF-36 were used as the main outcome measures in patients enrolled in the European ALS Health Profile Study (ALS-HPS). Correlation and stepwise regression procedures were used to determine the relationship between patients' physical and mental health status at follow-up with baseline measures., Results: A total of 1118 patients were recruited into the ALS-HPS, of which 918 (82.11%) returned fully or partially completed baseline and follow-up surveys. PCS scores declined over time. No significant changes were reported for the MCS scores over time for patients with ALS. Baseline scores were found to be significant predictors of patients' health status over time., Conclusions: Overall, patients' physical health status at the time of recruitment was the major predictor of the physical health status at both first and second follow-up time assessments. The same relationship was found between baseline and follow-up mental health status. The study also confirms the appropriateness of the use of the SF-36 in ALS patients.

Objectives: To use statistical procedures, operationalising what is known as item response theory (IRT), to assess the unidimensionality of the 40 item Amyotrophic Lateral Sclerosis Assessment Questionnaire, and consequently to develop a single index figure from the measure. A secondary objective is to compare scores gained on the ALSAQ-40 with a five item short form (the ALSAQ-5)., Methods: Postal survey of patients diagnosed with motor neurone disease (MND) on the MND Associations database. Copies of the ALSAQ-40 and, nested within it, the ALSAQ-5 were completed on two occasions. At time one, the survey contained the ALSAQ-40 and demographic questions. In addition, patients were asked to indicate if they were willing to take part in the follow up. Those who agreed to do so were sent another copy of the questionnaire after a period of three months. Respondents were also asked to indicate how much change they had experienced since baseline on each of the five domains of the questionnaire. Rasch analysis, a form of IRT methodology, was used to determine if the 40 items in the ALSAQ-40 tapped an underlying "latent trait", and were consequently measuring a unidimensional construct. The results from the ALSAQ-40 single index were then compared with those gained from the ALSAQ-5., Results: Analyses indicated that, at both baseline and follow up, all items on the ALSAQ-40 fitted the Rasch model. Consequently the 40 items were summed to create a single index. Results on this instrument were compared with those gained by summing the five items of the ALSAQ-5. Results on the instruments were found to be highly correlated., Conclusions: Evidence from the analyses suggests that 40 item ALSAQ does contain a unidimensional scale, and can, therefore be summed to create a single index. Furthermore the ALSAQ-5 closely replicates the results of the patient measure.

We examined whether there are advantages in terms of outcome assessment of using Rasch methods of scoring the 12-item Oxford Hip Score questionnaire over conventionally summed scores. Data were collected on patients receiving total hip replacement surgery. Three patient groups were created according to surgery type: primary, revision, and re-revision; two groups were created according to satisfaction with surgery: very satisfied and dissatisfied. Analyses were performed to test the relative precision (RP) of Rasch scoring versus conventionally summed scores in discriminating the groups experiencing different types of surgery and level of satisfaction. At the 1-year follow-up, RP ratios favored the Rasch scoring method in both tests of discrimination. Considerable gains in precision were achieved with Rasch scoring methods when groups were compared in a cross-sectional way. Alternative approaches to scoring questionnaires should be investigated to better assess comparisons over time.

This paper examines the sensitivity to change over time of the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40). Individuals' health status change was assessed by means of the Rasch-based Reliable Change Index (RCI) for ALSAQ-40 questionnaires completed on two occasions, three months apart. In addition, at follow-up respondents indicated how much change they had experienced since baseline via dimension-specific self reported transition questions. 764 individuals returned questionnaires at baseline and follow-up. For all dimensions, of respondents defined by the RCI as worse, a majority rated themselves as worse. However, on two dimensions over 60% of the respondents who rated themselves as being worse were defined as unchanged by the RCI. As with effect size smaller RCI cut-off points might be needed for subjects with ALS. This study confirms that the ALSAQ-40 is a valid and responsive disease specific health related quality of life instrument for use in studies of patients with ALS or other motor neuron diseases.