BackgroundThe FROM-16 is a generic family quality of life (QoL) instrument that measures the QoL impact of patients’ disease on their family members/partners. The study aimed to assess the responsiveness of FROM-16 to change and determine Minimal Important Change (MIC).MethodsResponsiveness and MIC for FROM-16 were assessed prospectively with patients and their family members recruited from outpatient departments of the University Hospital Wales and University Hospital Llandough, Cardiff, United Kingdom. Patients completed the EQ-5D-3L and a global severity question (GSQ) online at baseline and at 3-month follow-up. Family members completed FROM-16 at baseline and a Global Rating of Change (GRC) in addition to FROM-16 at follow-up. Responsiveness was assessed using the distribution-based (effect size-ES, standardized response mean -SRM) and anchor-based (area under the receiver operating characteristics curve ROC-AUC) approaches and by testing hypotheses on expected correlation strength between FROM-16 change score and patient assessment tools (GSQ and EQ-5D). Cohen’s criteria were used for assessing ES. The AUC ≥ 0.7 was considered a good measure of responsiveness. MIC was calculated using anchor-based (ROC analysis and adjusted predictive modelling) and distribution methods based on standard deviation (SD) and standard error of the measurement (SEM).ResultsEighty-three patients with 15 different health conditions and their relatives completed baseline and follow-up questionnaires and were included in the responsiveness analysis. The mean FROM-16 change over 3 months = 1.43 (SD = 4.98). The mean patient EQ-5D change over 3 months = −0.059 (SD = 0.14). The responsiveness analysis showed that the FROM-16 was responsive to change (ES = 0.2, SRM = 0.3; p < 0.01). The ES and SRM of FROM-16 change score ranged from small (ES = 0.2; SRM = 0.3) for the distribution-based method to large (ES = 0.8, SRM = 0.85) for anchor-based methods. The AUC value was above 0.7, indicating good responsiveness. There was a significant positive correlation between the FROM-16 change scores and the patient’s disease severity change scores (p < 0.001). The MIC analysis was based on data from 100 family members of 100 patients. The MIC value of 4 was suggested for FROM-16.ConclusionsThe results of this study confirm the longitudinal validity of FROM-16 which refers to the degree to which an instrument is able to measure change in the construct to be measured. The results yield a MIC value of 4 for FROM-16. These psychometric attributes of the FROM-16 instrument are useful in both clinical research as well as clinical practice.

In this hypothesis-generating analysis, we examined whether longitudinal changes in patient-reported outcomes (PROs), such as symptoms, over time would be prognostic for progression-free survival (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL) who were newly treated with obinutuzumab (G) in combination with CHOP (G-CHOP) or rituximab (R) with CHOP (R-CHOP), in the GOYA Phase 3 trial (NCT01287741). Our results show that from the study baseline to cycle 3 day 1, every 1-point increase (worsening) in fever symptoms was associated with a 41% higher risk of death (hazard ratio [HR], 1.41; P = 0.01). Every 1-point increase (worsening) in lumps or swelling symptoms was associated with a 27% higher risk of disease progression or death (PFS events) (HR, 1.27; P = 0.01) and a 29% higher risk of death (OS events) (HR, 1.29; P = 0.02). No significant associations were observed between survival and changes in other symptoms, such as itching. Our study suggests that changes in some PROs are related to survival in DLBCL patients.Supplementary InformationThe online version contains supplementary material available at 10.1186/s41687-024-00708-w.

PurposeMost patient-reported outcome (PROs) used in thrombosis research and clinical practice are delivered using technology like online questionnaires. However, only few have undergone formal electronic adaptation from paper to digital versions, threatening the validity and reliability of the PROs. The present study aimed to perform an electronic adaption and cross-cultural translation of two PROs measuring health-related quality of life in a Danish cohort of patients with venous thrombosis (VTE), specifically the VEINES-QoL/Sym questionnaire and the PEmb-QoL questionnaire.MethodsThe electronic adaption and cross-cultural translation processes followed the international guidelines recommended by ISPOR. The migration of the questionnaires from paper to electronic versions was conducted in the Research Electronic Data Capture (REDCap). Following approval of the electronically adapted and translated versions, a pretest of the questionnaires was performed by cognitive interviewing patients with VTE recruited from a hospital setting.ResultsNine men and ten women between the age of 19 and 73 years participated in cognitive interviews. The questionnaires were successfully adapted from paper to electronic versions, and during the migration process only a few modifications to the content and format were made. Most comments were related to technicalities, e.g. touch functions and checkboxes. The cross-cultural translation of both questionnaires was satisfactory, as only minor rephrasing was required.ConclusionsThe original and Danish version of VEINES-QoL/Sym and PEmb-QoL were successfully adapted into electronic versions and are ready to share for REDCap users. Furthermore, the Danish versions of the two questionnaires have shown satisfactory face validity.

BackgroundPresbyopia is an age-related condition that causes a decreased ability to focus on nearby objects. Multifocal contact lenses are commonly used to address this issue. However, there seems to be a notable dissatisfaction among multifocal contact lens wearers. The absence of a reliable instrument to measure the patient’s perspective, despite the widespread use of this method, highlights the need for further research in this area.ObjectiveThe objective of this study is to develop an item-bank integrating all domains necessary to assess the patient’s perspective on multifocal contact lens performance, offering a comprehensive measure. The item-bank will ensure a high level of content validity, be self-administered, and will initially be available in Spanish. The aim of this tool is to serve as a valuable resource for research and optometric clinics, facilitating the follow-up of patients with presbyopia who wear multifocal contact lenses or those who are newly starting to use them.MethodologyThe MCL-PRO item bank, followed a systematic and step-wise inductive approach to gather information, following the recommendations outlined in the COSMIN guidelines and similar studies. The process involved the following steps: (1) Literature review and relevant existing items identification (2) Social media review, (3) Semi-structured focus groups, (4) performing qualitative analysis, (5) refining and revising the items, and (6) generating the content of the item bank.ResultsA total of 575 items were included in the item-bank hosted under 8 different domains that were found to be important for presbyopic population: visual symptoms (213), activity limitation (111), ocular symptoms (135), convenience (36), emotional well-being (33), general symptoms (16), cognitive issues (21) and economic issues (10).ConclusionThe item-bank created has followed standardised methodology for its development and encloses all the aspects for MCL performance evaluation from patients perspective.

BackgroundThe construct validity and interpretation of the Patient-Reported Outcome Measurement Information System (PROMIS®) Physical Function short form 20a (PF20a) questionnaire were evaluated for patients with late-onset Pompe disease (LOPD), a rare, autosomal recessive, progressive neuromuscular disorder treatable by enzyme replacement therapy (ERT).MethodsIn the phase 3 PROPEL study, adults with LOPD underwent testing of physical functioning and had PRO measurements at baseline and at weeks 12, 26, 38, and 52 while receiving experimental or standard-of-care ERT. All patients were pooled for analyses, without comparisons between treatment groups. Associations and correlations between PROMIS PF20a scores and the 6-minute walk distance (6MWD), % predicted forced vital capacity (FVC), manual muscle test (MMT) of the lower extremities, Gait, Stairs, Gowers’ maneuver, Chair (GSGC) score, and Rasch-built Pompe-specific Activity (R-PAct) scale were evaluated by calculating regression coefficients in linear regression models and Pearson correlation coefficients (R); patients’ age, sex, race, ERT prior to study, body mass index, and study treatment were included as covariables. The minimal clinically important difference (MCID) of PROMIS PF20a was determined using distribution- and anchor-based methods.Results123 patients received at least 1 dose of ERT. In multivariable analyses, PROMIS PF20a scores had strong correlations with R-PAct scores (R = 0.83 at baseline and R = 0.67 when evaluating changes between baseline and 52 weeks) and moderate correlations with the 6MWD (R = 0.57 at baseline and R = 0.48 when evaluating changes between baseline and 52 weeks). Moderate correlations were also observed between PROMIS PF20a and MMT (R = 0.54), GSGC (R=-0.51), and FVC (R = 0.48) at baseline. In multivariable linear regression models, associations were significant between PROMIS PF20a and 6MWD (P = 0.0006), MMT (P = 0.0034), GSGC (P = 0.0278), and R-PAct (P < 0.0001) at baseline, between PROMIS PF20a and 6MWD (P < 0.0001), FVC (P = 0.0490), and R-PAct (P < 0.0001) when combining all measurements, and between PF20a and 6MWD (P = 0.0016) and R-PAct (P = 0.0001) when evaluating changes in scores between baseline and 52 weeks. The anchor-based and distribution-based MCID for a clinically important improvement for PROMIS PF20a were 2.4 and 4.2, respectively.ConclusionsPROMIS PF20a has validity as an instrument both to measure and to longitudinally follow physical function in patients with LOPD.Trial registrationClinicalTrials.gov, NCT03729362. Registered 2 November 2018, https://www.clinicaltrials.gov/search?term=NCT03729362.

Cardiovascular diseases (CVD) represent the world's leading cause of death. Health-related quality of life (HRQoL) is a widely applied concept of patients' perceived health and is directly linked to CVD morbidity, mortality, and re-hospitalization rates. Cardiac rehabilitation (CR) improves both cardiovascular outcomes and HRQoL. Regrettably, CR is still underutilized, especially in subgroups like women and elderly patients. The aim of our study was to investigate the predictive potential of sex and age on change of HRQoL throughout outpatient CR. 497 patients of outpatient CR were retrospectively assessed from August 2015 to September 2019 at the University Hospital Zurich. A final sample of 153 individuals with full HRQoL data both at CR entry and discharge was analyzed. HRQoL was measured using the 36-Item Short Form Survey (SF-36) with its physical (PCS) and mental (MCS) component scale. In two-factorial analyses of variance, we analyzed sex- and age-specific changes in HRQoL scores throughout CR, adjusting for psychosocial and clinical characteristics. Age was grouped into participants over and under the age of 65. In both sexes, mean scores of physical HRQoL improved significantly during CR (p <.001), while mean scores of mental HRQoL improved significantly in men only (p =.003). Women under the age of 65 had significantly greater physical HRQoL improvements throughout CR, compared with men under 65 (p =.043) and women over 65 years of age (p =.014). Sex and age did not predict changes in mental HRQoL throughout CR. Younger women in particular benefit from CR with regard to their physical HRQoL. Among older participants, women report equal improvements of physical HRQoL than men. Our results indicate that sex- and age-related aspects of HRQoL outcomes should be considered in CR.

BackgroundTo assess quality of life and unmet needs after stroke, patient-reported outcome measures (PROMs) have gained increasing attention. However, patients’ perspectives on assessing PROMs remain unclear, potentially hindering implementation into clinical practice. Therefore, this study explored patients’ preferences on assessing PROMs after ischemic stroke.MethodsA paper-based questionnaire was sent to stroke survivors treated at the Department of Neurology, University of Leipzig, Germany. Health-related quality of life (HRQoL, EQ-5D-5L) and preferences regarding different aspects of data collection to assess PROMs were investigated and linked to socio-demographic and medical characteristics.Results158 persons were contacted and 80 replies were subsequently analyzed. Mean age was 70.16 years and mean HRQoL was 68.79 (visual analogue scale with a theoretical maximum of 100). Participants showed positive attitudes towards PROMs as they saw potential to improve care of other patients (n = 66/79; 83.54%) or to improve their own situation (n = 53/74; 71.62%). Participants preferred an annual interview after stroke (n = 39/80; 48.75%) and would preferably spend 15–30 min (n = 41/79; 51.90%) to answer a written survey (n = 69/80; 86.25%). The initially treating clinic was preferred as initiator of such surveys (n = 43/79; 54.43%). Stratification revealed that participants with more than 1 h of daily digital media usage preferred email as way of communication.ConclusionsFor the first time, this study showed individual preferences on assessing PROMs after ischemic stroke, focusing on the way, time interval, duration, and initiation site of surveys. These insights might help to successfully implement PROMs after stroke and subsequently detect unmet needs and deficits in stroke care.

BackgroundErythropoietic protoporphyria is a rare, inherited disorder presenting in early childhood with severe, painful phototoxicity. EPP has significant impacts on health-related quality of life, though there is variable disease severity. Accurately capturing how much time individuals with EPP can spend outdoors before they develop symptoms is critical to understanding HRQoL and measuring therapeutic response. Therefore, the goal of this study was to develop a comprehensive and content valid sun exposure diary to assess the efficacy of new therapies in individuals with EPP.MethodsQualitative interviews were conducted with adult and adolescent EPP participants, as well as five clinical experts, to obtain their input on the content of an existing sun exposure diary. Revisions to the diary were made based on evidence generated in cognitive debriefing interviews analyzed in eight consecutive groups of EPP participant.ResultsInterviews were conducted with 17 adults and 6 adolescents with EPP. The average age of adults was 40 years and of adolescents was 14 years. Clinical experts thought the original diary needed clarification on the description of symptoms, how time outdoors was captured, and the distinction between direct vs. indirect sunlight. Participants with EPP also noted these items needed revision, and that the distinction between prodromal symptoms and full reaction symptoms should be clarified. In the final diary version, participants with EPP found most items to be clear and easy to complete/think about. Seventy-six percent of participants (13/17) asked thought the diary was easy to complete. The remainder thought the majority of the diary was easy to complete with the exception of select questions.ConclusionsEvaluating a new treatment for EPP requires accurately capturing time in sunlight and symptoms in this unique disorder. The newly developed sun exposure diary is content valid and can be used to assess important aspects of symptoms and daily life and therefore evaluate clinically meaningful therapeutic response.

BackgroundThe Dysphagia Symptom Questionnaire (DSQ) is a patient-reported outcome measure that assesses the frequency and severity of dysphagia in patients with eosinophilic esophagitis (EoE); however, it has only been validated for use in patients with EoE aged 11–40 years. This study examined the content validity of the DSQ and its usability on an electronic handheld device in children aged 7–10 years with EoE.MethodsIn this qualitative, observational cohort study, participants were recruited to partake in two rounds of interviews. During visit 1, a cognitive interview examined EoE-associated concepts and the appropriateness of the DSQ for assessing dysphagia. Participants completed the DSQ daily for 2 weeks, and DSQ scores were calculated. After 2 weeks, a second interview assessed the usability of the DSQ on the electronic device and the burden associated with completing it daily.ResultsOverall, 16 participants were included (aged 7–8 years: n = 8; aged 9–10 years: n = 8); most were male (75%) and white (81%), and the mean (standard deviation [SD]) age was 8.4 (1.3) years. The most commonly reported EoE-associated concept was ‘trouble with swallowing’ (63% [10/16]). Most participants reported that the questions were ‘easy to complete’ and ‘relevant to someone with EoE and dysphagia’. Overall, participants reported understanding the questions and associated responses; however, further probing demonstrated inconsistent comprehension. Key challenging concepts included ‘solid food’, ‘trouble swallowing’, ‘vomit’, and ‘relief’; some participants also reported difficulty differentiating between pain levels (31% [4/13]). Most caregivers reported that their child had experienced dysphagia (94% [15/16]); however, mean (SD) DSQ scores over the study period were low (7.3 [7.4]), suggesting infrequent and mild dysphagia, or a lack of comprehension of the questions. Most participants reported that completing the DSQ on the electronic device was easy (93% [14/15]) and they would be willing to complete it for longer than 2 weeks (73% [11/15]).ConclusionsDifficulties with comprehension and comprehensiveness suggest that the DSQ may not be sufficiently comprehensive for use in all patients in this population, and wording/phrasing changes are required before use in a clinical trial setting.

Ensuring that cognitive assessments are fit for purpose is critical in the evaluation of the clinical benefit of new therapeutic interventions. Although guidelines for Clinical Outcome Assessments (COA) are available, performance outcome (PerfO) assessments, and in particular those assessing cognition (Cog-PerfOs) are more complex and have additional requirements that need to be considered. I outline three areas where further discussion around validation methods for Cog-PerfOs and best practices is warranted: (1) content validity (2) ecological validity, and (3) construct validity in multinational contexts. I conclude with a discussion of several potential avenues for the improvement of validation of Cog-PerfOs used to evaluate the efficacy of medical products that target cognitive symptomatology. These include the involvement of cognitive psychologists in establishing content validity of Cog-PerfOs, evaluating the congruence of laypeople’s and expert understanding of cognitive concepts, supplementing qualitative with quantitative evidence when establishing content validity, demonstrating ecological validity, and ensuring normative data are available in multinational contexts.