BackgroundVasomotor symptoms (VMS; hot flashes) associated with menopause have significant impacts on health-related quality of life and are a leading cause for women seeking medical attention. Patient-reported outcome (PRO) instruments are commonly used to assess treatment benefit in VMS clinical trials and must demonstrate supportive evidence of measurement properties within the context of use. This study evaluated the measurement properties of scores from the Hot Flash Daily Diary (HFDD), PROMIS Sleep Disturbance Short Form 8b (PROMIS SD SF 8b) and Menopause-Specific Quality of Life (MENQOL) for measuring treatment efficacy in VMS clinical trials.MethodsMeasurement properties of the HFDD, PROMIS SD SF 8b, and MENQOL scores were assessed using data (n = 400 participants) from a randomized, placebo-controlled, phase 3 study evaluating the efficacy and safety of elinzanetant for the treatment of VMS in postmenopausal women (OASIS 2). Analyses assessed distributional properties, reliability, validity, responsiveness, and thresholds for meaningful change.ResultsMinimal floor and ceiling effects were found across the instruments at baseline. Inter-item correlations, and confirmatory factor analysis or item-response theory supported dimensionality and scoring for the MENQOL and PROMIS SD SF 8b, respectively. Test-retest reliability between Weeks 8 and 12 was good to excellent for HFDD Frequency and Severity of moderate-to-severe hot flashes scores, PROMIS SD SF 8b T-score and MENQOL Total score (intra-class correlation coefficients 0.835–0.971). Convergent and divergent correlations with instruments assessing similar or distinct constructs were consistent with pre-specified hypotheses. Known-groups validity was supported by significant differences (p < 0.0001) between subgroups hypothesized a priori as being clinically distinct. Responsiveness was indicated by consistent and statistically significant differences (p < 0.0001) in mean changes from baseline to Week 4 and 12 between groups of participants classified as ‘improved’, ‘stable’ and ‘worsened’ (effect sizes for improvement 0.81–4.62). Triangulation of estimates from multiple anchor-based analyses derived meaningful within-individual change thresholds for the HFDD, PROMIS SD SF 8b and MENQOL scores that were likely to exceed measurement error.ConclusionsFindings provide evidence that HFDD, PROMIS SD SF 8b, and MENQOL scores are valid, reliable and responsive to change, supporting their use for assessing key efficacy endpoints in VMS clinical trials.

BackgroundElexacaftor/Tezacaftor/Ivacaftor (ETI) is a therapy approved for cystic fibrosis (CF) that has given improved clinical outcomes in patients carrying the F508del mutation. There are few published data regarding ETI’s effects on patients’ quality of life (QoL). This study aims to (fill the data gap in current literature by assessing) evaluate the long-term effects of ETI on QoL.MethodologyA prospective observational study was conducted with thirty-seven severe patients that received ETI for compassionate use (group A), 184 received it for on-label use (group B). All carried one F508del mutation. Patients were assessed using the CFQ-R (Cystic Fibrosis Questionnaire-Revised). The evaluation time-points were pre-treatment (T0), and after 12 (T1) and 24 months (T2); group A was also assessed after 36 months (T3). Twenty-five patients completed 3 years of treatment and 65 patients completed 2 years of treatment, in groups A and B respectively.ResultsAt T1, median values for almost all areas of CFQ-R statistically significant increased in group A, particularly Physical Functioning (+ 25.0), Respiratory (+ 22.2) and Health Perception (+ 22.2).The Social Functioning area statistically significant increased at T2 (+ 5.6). At T3, these improvements remained stable. At T1, all areas of CFQ-R statistically significant increased in group B, particularly the Health Perception (+ 22,2) heading. At T2, these improvements remained stable. For both groups, the changes identified at the last follow-up showed no major differences by gender, age or genetic status.ConclusionsTreatment with ETI significantly improved patients’ QoL in both groups at 12–24 months, these improvements remaining stable in patients tested at 36 months.

BackgroundMonitoring for the side effects of novel therapies using patient-reported outcomes (PROs) is critical for ensuring patient safety. Existing static patient-reported outcome measures may not provide adequate coverage of novel side effects. Item libraries provide a flexible approach to monitoring for side effects using customized item lists, but the ideal process for matching side effects to items sourced from multiple item libraries is yet to be established. We sought to develop a pragmatic process for mapping side effects to items from three major item libraries using immune checkpoint inhibitor (ICI) side effects as an example.MethodsUsing a consumer- and clinician-driven list of 36 ICI side effects, two authors independently mapped side effects to Common Terminology Criteria for Adverse Event (CTCAE) terms, and then to three item libraries: the Patient-Reported Outcome version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), the European Organisation for Research and Treatment of Cancer (EORTC) Item Library, and the Functional Assessment of Chronic Illness Therapy (FACIT) searchable library. The rates of inter-rater agreement were recorded. Following item collation from the item libraries, we devised criteria for selecting the optimal item for each side effect for inclusion in a future electronic PRO system based on guidance from the above groups.ResultsAll 36 side effects mapped to at least one CTCAE term, with eight mapping to more than one term. Twenty-three side effects mapped to at least one PRO-CTCAE term, 35 side effects mapped to at least one EORTC item, and 31 side effects mapped to at least one FACIT item. The inter-rater agreement rate was 100% (PRO-CTCAE), 83% (EORTC) and 75% (FACIT). Pre-determined criteria were applied to select the optimal item for each side effect from the three item libraries, producing a final 61-item list.ConclusionUsing ICI side effects as an example, we developed a pragmatic approach to creating customized item lists from three major item libraries to monitor for side effects of novel therapies in routine care. This process highlighted the challenges of using item libraries and priorities for future work to improve their usability.

BackgroundClinical trials for obesity have traditionally focused on weight loss and resolution of comorbidities as primary outcomes. However, secondary outcomes, such as the impact of weight reduction on patient experience, like health-related quality of life (HRQoL), have increasingly been recognized as important. Therefore, a review was conducted to determine the Clinical Outcome Assessments (COAs) and Digital Health Technologies (DHTs) used in clinical trials for obesity to assess the patient experience.MethodsTwo clinical trial databases (United States & European Union) were reviewed to identify Phase 2–4 clinical trials for obesity (2018–2023). A targeted literature review was also conducted using the OVID database to identify clinical trial for obesity publications which included COAs/DHTs (2010–2023).ResultTrials from the databases (n = 53) and publications (n = 42) were included in data extraction (N = 73). This resulted in identification of 108 COAs, the majority being patient-reported outcome (PRO) measures (n = 83), but also 24 performance outcomes (PerfO) measures, and 1 composite PRO-clinician-reported outcomes (ClinRO) measure, as well as 2 DHTs. The most frequently identified PRO measures were the Short Form 36 and the Impact of Weight on Quality of Life Lite Clinical Trials. Twenty-four PerfO measures were also identified, with the 6-minute walk test being most common. These measures were most often used to construct secondary endpoints, with physical function (PF) being the most frequently specified domain. PRO measures assessing eating-related thoughts/behaviours, physical activity, and disordered eating were also frequently included, although individual measures varied widely across trials.ConclusionReview of COAs and DHTs in registered clinical trials and publications for obesity found that PRO measures were the most common type of COA used to develop endpoints with current use of DHTs limited. Specifically, the physical function domain of multidimensional patient-reported outcome measures assessing health-related quality of life were often used to construct secondary endpoints. Further work is warranted to assess how the COAs and DHT data collected in clinical trials are viewed by regulators and payers.

BackgroundThe main objective was to evaluate the psychometric properties of the OutPatient Experience Questionnaire for Child and Adolescent Mental Health Services (OPEQ-CAMHS) among patients aged 16 and above, with a secondary objective of developing a parsimonious set of items and a short version of the instrument for this age group.MethodsA national pilot study was conducted with adolescents from outpatient CAMHS in Norway, testing a new digital, continuous measurement approach using a measurement instrument developed through a comprehensive methodological framework. The study assessed missing data, ceiling effects, factor structure, internal consistency, discriminant validity, and construct validity. A shorter version was derived from psychometric results.ResultsThe pilot study included responses from 555 (46.3%) patients. Low proportions of missing or “not applicable” responses were found for 18 of the 20 items, and all items were below the ceiling-effect criterion. Two scales emerged: “structure and process”, and “outcome”, both meeting alpha criteria. Each individual item demonstrated a stronger correlation with its expected scale than with any of the other scales. Construct validity was confirmed through associations with relevant variables expected to be associated with patient-reported experiences, including self-reported current state and well-being. The results supported a six-item short version.ConclusionsPsychometric testing confirmed data quality, internal consistency, and construct validity of OPEQ-CAMHS. The short version addresses respondent burden concerns and is now ready for broad implementation in Norwegian CAMHS and potentially in similar healthcare settings worldwide.

ObjectivesTo translate, cross-culturally adapt and validate the Serbian Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire, e.g. according to the new nomenclature Radiographic-Axial Spondyloarthritis (r-axSpA), and to relate it to disease activity and functional status domains.MethodsFour stages were accomplished: (1) Bilingual and lay panel for translation and cross-cultural adaptation (2) Cognitive debriefing interviews (assessing the language and cultural equivalence of the concepts used in the Serbian ASQoL translation) for face and content validity (3) Psychometric evaluation: (a) convergent validity by NHP as a comparator scale and (b) known group validity by correlations with disease activity and overall health status and reliability (internal consistency and test-retest reliability) (4) Independent regression analyses for relations between ASQoL and ASDAS, BASDAI, BASFI, Schober’s test, respiratory index and SPARCC were used. The statistical program SPSS (version 21; IBM, Armonk, NY, USA) was used.ResultsThe bilingual panel made a unified version of the translated documents, a lay panel confirmed the clarity of the questionnaire. Cognitive debriefing interviews with 10 patients evaluated the Serbian ASQoL as clear, precise, easy to complete. The psychometric properties with 60 randomly selected patients showed good convergent validity between ASQoL and NHP domains of pain (r = 0.79), emotional reactions (r = 0.78), physical activity (r = 0.77) and energy (r = 0.75). The internal reliability was 0.95 and 0.91 (1st and 2nd administration), respectively, and the test-retest reliability was 0.84. Regression analyses showed highly significant relationships (p < 0.001) between ASQoL and ASDAS (R²=0.403), BASDAI (R²=0.564) and BASFI (R²=0.444).ConclusionThe Serbian ASQoL demonstrated good psychometric properties and significant relationships with disease activity and functional status and is recommended for quality of life assessment in Serbian-speaking ankylosing spondylitis (radiographic axial spondyloarthritis) patients, both in clinical practice and clinical research.

BackgroundEptinezumab’s impact on self-reported work productivity in adults with migraine and 2‒4 prior preventive migraine treatment failures is not fully understood.MethodologyElectronic diaries captured monthly migraine days (MMDs) reported by patients enrolled in the randomized, double-blind, placebo-controlled DELIVER trial (NCT04418765). The migraine-specific Work Productivity and Activity Impairment questionnaire, administered at baseline and each monthly visit, was a secondary outcome of DELIVER and used to model changes from baseline in self-reported monthly hours of absenteeism (decreased work attendance) and presenteeism (reduced work efficiency while at work with a migraine) in Canada, as the base case. Path analysis illustrated eptinezumab’s impact on work productivity beyond MMDs.ResultsAs MMDs increased, monthly hours of absenteeism increased linearly while those of presenteeism increased quadratically. Best-fit models were improved after including an eptinezumab treatment effect, showing benefit over placebo after controlling for MMD frequency. Compared to placebo, patients treated with eptinezumab (pooled) had a modeled reduction from baseline of 7.2 h/month (absenteeism) (95% CI: −9.9, −4.5; P < 0.001) and 21.4 h/month (presenteeism) (95% CI: −26.3, −16.5; P < 0.001) over weeks 1‒24. Beyond MMD reductions, improvements in patient-identified most bothersome symptom (PI-MBS) and reductions in percent of severe migraine attacks contributed to eptinezumab’s effect.ConclusionsEptinezumab decreased absenteeism and presenteeism based on patient reports, with data highlighting the importance of considering the PI-MBS. The greater change from baseline than placebo in self-reported absenteeism and presenteeism was only partly explained by changes in MMDs, presenting a potential opportunity to decrease the cost of migraine in the workplace.Trial registrationClinicalTrials.gov (Identifier: NCT04418765); EudraCT (Identifier: 2019-004497-25)

BackgroundAlemtuzumab is a humanized monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Its efficacy and safety have been widely demonstrated in clinical trials, but experience from real-world cohorts is also needed to support its clinical use. Quality of life (QoL) outcomes are an important complement to the clinical benefits of treatment, offering a patient-centered perspective on how the drug contributes to general well-being. In this line we aimed to evaluate the QoL of patients treated with alemtuzumab in clinical practice.MethodsThis prospective 3-year multicenter study was carried out in adult patients diagnosed with RRMS who had started alemtuzumab according to clinical practice within 8 weeks before inclusion. The primary endpoint was the change in QoL over three years of treatment with alemtuzumab using the 29-item Multiple Sclerosis Impact Scale (MSIS-29). Secondary endpoints included changes from baseline in the 21-item Modified Fatigue Impact Scale (MFIS-21), Beck Depression Inventory (BDI-II), Symbol Digit Modalities Test (SDMT, oral version) and Work Productivity. Disability worsening was also assessed based on the Expanded Disability Status Scale (EDSS), along with the annualized relapse rate (ARR) and radiological activity.ResultsA cohort of 165 patients was analyzed (mean age 38.6 years, mean disease duration 8.5 years, mean EDSS score 3.3). MSIS-29 physical domain scores decreased significantly from baseline by a mean of 7.2 ± 1.8 points at year 1, 6.4 ± 2.2 at year 2 and 5.6 ± 2.3 at year 3 (p < 0.05 in all cases). Similarly, MSIS-29 psychological domain scores decreased significantly by a mean of 7.9 ± 2.4 points at year 1, 12.8 ± 2.9 at year 2 and 13.2 ± 3.0 at year 3 (p < 0.05 in all cases). Significant reductions from baseline were also evidenced in MFIS-21 and BDI-II scores, while SDMT scores remained unchanged. During the 3 years on alemtuzumab, the ARR was 0.15, representing an 83% reduction from the 2 years before initiation. At 3 years, 81.5% of patients were free from radiological activity and 87% were free from disability worsening.ConclusionsThese results indicate early and substantial improvements in patients’ perception of their QoL and functioning with alemtuzumab that were sustained over three years.

BackgroundPatients with multiple myeloma (MM) experience disabling symptoms that are difficult to manage and may persist after induction therapy. Monitoring disease-related and induction therapy–induced symptoms and identifying patients at greater risk for high symptom burden are unmet clinical needs. The objective of this study was to examine the trajectories of symptom severity over time and identify predictors of high symptom burden during MM induction therapy.MethodologyEligible patients with MM rated their symptoms by completing the MD Anderson Symptom Inventory MM module repeatedly during 16 weeks of induction therapy. Group-based trajectory modeling identified patient groups with persistently high-severity (versus low-severity) symptom trajectories over time. Quality of life (QOL) and affective and physical functioning status were assessed. Predictors of high symptom burden were examined by regression analysis.ResultsSixty-four MM patients participated. Most patients (89%) received bortezomib-based therapy. The five most-severe symptom trajectory groups were pain (59%), muscle weakness (46%), numbness (42%), disturbed sleep (41%), and fatigue (31%). Patients in the high-severity trajectory group for the five most-severe symptoms (31% of the sample) were more likely to have high-severity cognitive and affective symptoms. Patients in the high-severity trajectory groups for fatigue, muscle weakness, disturbed sleep, and bone aches were more likely to have high pain scores (all p < 0.05). Significant increases over time were observed in scores for pain (estimate: 0.026), numbness (0.051), muscle weakness (0.020), physical items (0.028), and affective items (0.014) (all p < 0.05). A higher baseline composite score of the five most-severe symptoms predicted worse QOL (− 6.24), and poor affective (0.80) and physical (1.10) statuses (all p < 0.01). Female sex predicted higher risk for being in the high-severity trajectory group for muscle weakness.ConclusionAlmost one-third of MM patients suffer from up to 5 moderate to severe symptoms persistently, including pain, muscle weakness, numbness, disturbed sleep, and fatigue. Importantly, these results identify a group of symptoms that should be monitored and managed as part of routine patient care during MM induction therapy and suggest that pre-therapy pain management is necessary for better symptom control.

IntroductionThe Utrecht Symptom Diary (USD) is a validated Dutch patient-reported outcome measurement (PROM) tool - based on the Edmonton Symptom Assessment System - to assess and monitor symptoms in cancer patients. The USD contains 11 items concerning frequently occurring symptoms in cancer patients (pain, sleeping problems, dry mouth, dysphagia, lack of appetite, abnormal stool, nausea, shortness of breath, fatigue, anxiety and depressed mood) and an item on overall well-being. For the outpatient USD 11 items concerning frequently occurring signs and symptoms in patients receiving chemotherapy and/or targeted therapy were added to the USD: taste alteration, oral pain, weight loss, diarrhoea, hair changes, skin problems, nail problems, eye problems, tingling, concentration problems and problems with sexuality. This current study aimed to evaluate the 11 added items on this treatment specific outpatient USD in cancer patients receiving intravenous chemotherapy and/or targeted therapy.MethodsObservational longitudinal retrospective cohort study including all adult outpatients with cancer receiving intravenous chemotherapy and/or targeted therapy in an academic hospital in the Netherlands who completed at least one outpatient USD as part of routine care (2012–2021). Relevance, comprehensiveness as well as criterion and construct validity were assessed.Results1733 patients who completed ≥ 1 outpatient USD during intravenous chemotherapy and/or targeted therapy were included for analysis. Relevance as well as comprehensiveness of the items on the outpatient USD in this patient population was shown. Criterion validation was demonstrated for all added items of the outpatient USD – except for the item on oral pain. An additional analysis showed that mouth problems were detected with both outpatient USD items oral pain and dry mouth. Construct validity was demonstrated for the items hair changes and skin and nail problems. Construct validity on eye problems was not tested due to the low number of paired outpatient USDs.ConclusionsThe treatment specific outpatient USD is a validated PROM in outpatients with cancer receiving intravenous chemotherapy and/or targeted therapy. Considering its validity in this broad group of patients, we think the treatment-specific outpatient USD is widely applicable. In addition to providing tailored supportive symptom care, the USD-data can be used to increase knowledge about symptom burden in daily practice in this population.