Visual activities of daily living survey for retinitis pigmentosa.

PURPOSE: To gauge the value of low-vision-specific function and activities of daily living measures (LVFAM) in the assessment of Patient Reported Outcomes (PRO) of Retinitis Pigmentosa (RP). STUDY DESIGN: Prospective observation study. METHODS: The May-July 2023 Visual activities of daily living (ADL) Survey of the low-vision-specific function and activities of daily living measure (LVFAM) was conducted on 15 RP patients attending our Ophthalmology outpatient clinic. We used the better corrected visual acuity, and the better Mean Deviation (MD) values of the central 10 degrees of Humphrey's visual field as macular sensitivity, and examined the total scores after Rasch Analysis for each of the low-vision-specific function of Daily Living (LVFDL) and the low-vision-specific activities of Daily Living (LVADL) among LVFAM, as well as the relationship between the items. RESULTS: Age 26-78 (mean 60.8), 5 men and 10 women, corrected visual acuity of 0.01-1.0 (mean 0.45) in the better eye, macular sensitivity of 3.47-40.00 (mean 18.60) dB, mean 52.2 for LVFDL and 66.4 for LVADL. The correlations were positive for visual acuity and LVFDL and LVADL, and negative for macular sensitivity, LVFDL and LVADL. In addition, four items were scored 0 by at least 5 (33%) of the LVFDL respondents, and two items were scored 1 by at least 5 (33%) of the LVADL respondents, suggesting that the results differed by question items. CONCLUSION: The LVFAM was useful not only for the total score but also for each question item in the development strategy of PROs in RP with no treatment.

Patient-Reported Outcome Measures Used on Patients With Anterior Cruciate Ligament Injury.

Patient-reported knee-related rating scores and scales are widely used in reporting the clinical outcomes of anterior cruciate ligament (ACL) surgery. Understanding the psychometric properties of such measures is vital to recognizing the limitations that such measures may confer. The aim of this study was to review the available evidence as to the psychometric properties of patient-reported outcome measures (PROMs) used in ACL surgery. Eleven studies were identified, the majority being prospective cohort studies. Eight English, ACL-specific patient-reported outcome measures were identified and evaluated: Lysholm score, Tegner Activity Scale (TAS), Cincinnati score, ACL-Quality of Life (QOL) score, International Knee Documentation Committee (IKDC) Subjective Knee Form (SKF), Knee Injury and Osteoarthritis Outcome Score (KOOS)-ACL score, and ACL-Return to Sport Injury (RSI) scale. Only the Lysholm score, ACL-QOL, IKDC SKF, and ACL-RSI were evaluated for internal consistency, having an acceptable Cronbach's α (α>0.70). Most of the scoring systems were assessed for test-retest reliability, with four of them (Lysholm score, TAS, Cincinnati score, and IKDC SKF) having acceptable intraclass correlation coefficient (ICC) values (ICC > 0.70). Criterion validity was assessed for most measures with a good correlation with the IKDC. Effect sizes and standardized response means were large for three instruments that measured responsiveness (Lysholm score, TAS, and Cincinnati score) and moderate for one (ACL-QOL). Evidence is stronger and more robust for the Lysholm score, TAS, ACL-QOL, and IKDC SKF. However, there is variation in their psychometric properties as well as the aspect of knee-related health they are assessing. Hence, none can be universally applicable to all patients with ACL injuries. Recognizing these parameters is vital when choosing which instrument to use in reporting the outcomes of ACL injury or ACL surgery studies.

Measurement properties of the Iranian version of the breast cancer perception scale (BCPS) according to the COSMIN checklist.

BACKGROUND: Breast cancer is a prevalent cancer characterized by its aggressive nature and potential to cause mortality among women. The rising mortality rates and women's inadequate perception of the disease's severity in developing countries highlight the importance of screening using conventional methods and reliable scales. Since the validity and reliability of the breast cancer perception scale (BCPS) have not been established in the Iranian context. Therefore, this study aimed to determine the measurement properties of the BCPS in women residing in Tabriz, Iran. METHODS: The present study comprised a cross-sectional design, encompassing a sample of 372 Iranian women. The participants were selected through a multi-stage cluster random sampling technique conducted over a period spanning from November 2022 to February 2023. The measurement properties of the Iranian version of BCPS were assessed following the guidelines outlined in the COSMIN checklist. This involved conducting various steps, including the translation process, reliability testing (internal consistency, test-retest reliability, and measurement error), and methodological tests for validity (content validity, face validity, construct validity, and hypothesis testing). The study also investigated the factors of responsiveness and interpretability. The presence of floor and ceiling effects was assessed. RESULTS: The internal consistency of the scale was assessed using Cronbach's alpha, yielding a satisfactory value of 0.68. Additionally, McDonald's omega (95% CI) was computed, resulting in a value of 0.70 (0.66 to 0.74). Furthermore, the test-retest reliability was evaluated, revealing a high intraclass correlation coefficient (ICC) of 0.97 (95% CI: 0.94 to 0.99). The CVI, CVR, and impact scores of the BCPS were determined to be 0.98, 0.95, and 3.70, respectively, indicating favorable levels of content and face validity. To assess construct validity, an examination of the Exploratory Factor Analysis (EFA) was conducted on a set of 24 items. This analysis revealed the presence of six distinct factors, which collectively accounted for 52% of the cumulative variance. The fit indices of the validity model (CFI = 0.91, NFI = 0.96, RFI = 0.94, TLI = 0.90, χ2/df = 2.03, RMSEA = 0.055 and SRMR = 0.055) were confirmed during the confirmatory factor analysis (CFA). The overall score of BCPS exhibited a ceiling effect of 0.3%. The floor effect observed in the overall score (BCPS) was found to be 0.5%. Concerning the validation of the hypothesis, Spearman's correlation coefficient of 0.55 was obtained between the BCPS and the QLICP-BR V2.0. This correlation value signifies a statistically significant association. Furthermore, it is worth noting that the minimum important change (MIC) of 3.92 exhibited a higher value compared to the smallest detectable change (SDC) of 3.70, thus suggesting a satisfactory level of response. CONCLUSIONS: The obtained findings suggest that the Iranian version of the BCPS demonstrates satisfactory psychometric properties for assessing the perception of breast cancer among Iranian women. Furthermore, it exhibits favorable responsiveness to clinical variations. Consequently, it can serve as a screening instrument for healthcare professionals to comprehend breast cancer and as a reliable tool in research endeavors.

Long-term patient-reported outcomes among patients undergoing revascularization vs medical therapy for intermittent claudication.

OBJECTIVE: Society for Vascular Surgery guidelines recommend revascularization for patients with intermittent claudication (IC) if it can improve patient function and quality of life. However, it is still unclear if patients with IC achieve a significant functional benefit from surgery compared with medical management alone. This study examines the relationship between IC treatment modality (operative vs nonoperative optimal medical management) and patient-reported outcomes for physical function (PROMIS-PF) and satisfaction in social roles and activities (PROMIS-SA). METHODS: We identified patients with IC who presented for index evaluation in a vascular surgery clinic at an academic medical center between 2016 and 2021. Patients were stratified based on whether they underwent a revascularization procedure during follow-up vs continued nonoperative management with medication and recommended exercise therapy. We used linear mixed-effect models to assess the relationship between treatment modality and PROMIS-PF, PROMIS-SA, and ankle-brachial index (ABI) over time, clustering among repeat patient observations. Models were adjusted for age, sex, diabetes, Charlson Comorbidity Index, Clinical Frailty Score, tobacco use, and index ABI. RESULTS: A total of 225 patients with IC were identified, of which 40% (n = 89) underwent revascularization procedures (42% bypass; 58% peripheral vascular intervention) and 60% (n = 136) continued nonoperative management. Patients were followed up to 6.9 years, with an average follow-up of 5.2 ± 1.6 years. Patients who underwent revascularization were more likely to be clinically frail (P = .03), have a lower index ABI (0.55 ± 0.24 vs 0.72 ± 0.28; P < .001), and lower baseline PROMIS-PF score (36.72 ± 8.2 vs 40.40 ± 6.73; P = .01). There were no differences in patient demographics or medications between treatment groups. Examining patient-reported outcome trends over time; there were no significant differences in PROMIS-PF between groups, trends over time, or group differences over time after adjusting for covariates (P = .07, P = .13, and P =.08, respectively). However, all patients with IC significantly increased their PROMIS-SA over time (adjusted P = .019), with patients managed nonoperatively more likely to have an improvement in PROMIS-SA over time than those who underwent revascularization (adjusted P = .045). CONCLUSIONS: Patient-reported outcomes associated with functional status and satisfaction in activities are similar for patients with IC for up to 7 years, irrespective of whether they undergo treatment with revascularization or continue nonoperative management. These findings support conservative long-term management for patients with IC.

From patient-reported outcomes (PROs) to family-reported outcomes (FROs): Acceptability and perceived usefulness of routine screening in cancer care.

OBJECTIVES: To explore the acceptability of screening for family-reported outcomes (FROs) among cancer caregivers (unpaid family members or friends who provide support to patients with cancer) and identify from their perspective the key components of a FRO screening program. METHODS: Using a qualitative descriptive design, semi-structured interviews were undertaken with 23 adult caregivers of people with cancer between 2020 and 2021. Interview questions focused on acceptability of FRO screening, types of FROs, timing/frequency of screening, preferred resources following screening, and communication of FROs to patients and clinicians. Participants were recruited in Canada. Interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis and constant comparison. RESULTS: Almost all caregivers welcomed FRO screening in usual care and viewed it as an avenue toward obtaining more resources. Other potential benefits of FRO screening included increased self-reflection and role acknowledgment. Caregivers prioritized screening for emotional symptoms, and most preferred that the results be shared with the patient's treating team rather than their primary care provider. Caregivers did not want results to be shared with patients, instead favoring learning how best to discuss results with patients. Many spoke of a "one stop shop" containing all relevant information on caring for the patient (first) and for themselves (second). Opinions regarding timing and frequency of FRO screening differed. Periodic administration of FRO measures, with each one not exceeding 20 minutes, was deemed appropriate. SIGNIFICANCE OF RESULTS: This study extends the concept of patient-reported outcome measures to caregivers, and findings can be used to guide the development of FRO screening programs.

Flexible approaches to eCOA administration in clinical trials: The site perspective.

The Critical Path Institute convened the Support Flexible Approaches to PRO Data Collection project as part of the eCOA: Getting Better Together Initiative which was instigated to identify and address common challenges and drive positive change with eCOA implementation in clinical trials. The project aimed to identify clinical trial stakeholders' concerns related to electronic PRO (ePRO) implementation and propose areas of improvement via simplification and flexibility. One workstream focused on patient-/site-centric approaches for simplification and surveyed representatives of clinical sites and site monitors for their perspectives. A semi-structured questionnaire was developed and distributed via snowball sampling to site professionals and clinical research associates (CRAs) that had ePRO experience who had been identified via representative groups or sponsor-led site networks. Responses were received from various site roles across a range of global regions; the largest contribution was from the United States. Topics raised included helpdesk capabilities, technical concerns, device types, and user interfaces among others and are discussed further in this paper. The feedback derived from the questionnaire provided the basis for concrete ideas that sponsors should consider incorporating into protocol design for participant visits, technology use, devices, and methods of back-up data collection.

Incorporating patient-reported outcome data into a predictive calculator for allogeneic hematopoietic cell transplantation recipients.

BACKGROUND: The Center for International Blood and Marrow Transplant Research (CIBMTR) provides a 1-year overall survival calculator to estimate outcomes for individual patients before they undergo allogeneic hematopoietic cell transplantation (HCT) to inform risk. The calculator considers pre-HCT clinical and demographic characteristics, but not patient-reported outcomes (PROs). Because pre-HCT PRO scores have been associated with post-HCT outcomes, the authors hypothesized that adding PRO scores to the calculator would enhance its predictive power. METHODS: Clinical data were obtained from the CIBMTR and the Blood and Marrow Transplant Clinical Trials Network. The PRO measures used were the 36-Item Short Form Survey (SF-36) and the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation. One thousand thirty-three adult patients were included. RESULTS: When adjusted for clinical characteristics, the SF-36 physical component score was significantly predictive of 1-year survival (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.81-0.95; p = .0015), whereas the mental component score was not (HR, 1.02; 95% CI, 0.95-1.10; p = 0.6396). The baseline single general health question on the SF-36 was also significantly associated with mortality (HR, 1.91 for those reporting fair/poor health vs. good, very good, or excellent health; 95% CI, 1.33-2.76; p = .0005). The addition of PRO scores to the calculator did not result in a significant change in the model's predictive ability. Self-reported pre-HCT scores were strongly predictive of self-reported health status (odds ratio, 3.35; 95% CI, 1.66-6.75; p = .0007) and quality of life (odds ratio, 3.24; 95% CI, 1.93-5.41; p < .0001) after HCT. CONCLUSIONS: The authors confirmed the significant, independent association of pre-HCT PRO scores with overall survival, although adding PRO scores to the survival calculator did not improve its performance. They also demonstrated that a single general health question was as accurate as the full measure for predicting survival, an important finding that may reduce respondent burden and promote its inclusion in routine clinical practice. Validation of these findings should be performed.

Assessing asthma symptoms in children: qualitative research supporting the development of the Pediatric Asthma Diary-Child (PAD-C) and Pediatric Asthma Diary-Observer (PAD-O).

BACKGROUND: Pediatric asthma has been identified by regulators, clinicians, clinical trial sponsors, and caregivers as an area in need of novel fit-for-purpose clinical outcome assessments (COAs) developed in accordance with the U.S. Food and Drug Administration's (FDA's) regulatory guidance for evaluating clinical benefit in treatment trials. To address this gap, the Patient-Reported Outcome (PRO) Consortium's Pediatric Asthma Working Group has continued development of 2 COAs to assess asthma signs and symptoms in pediatric asthma clinical trials to support efficacy endpoints: a PRO measure, the Pediatric Asthma Diary-Child (PAD-C) for children 8-11 years old (y.o.) and an observer-reported outcome measure, the Pediatric Asthma Diary-Observer (PAD-O) for caregivers of children 4-11 y.o. This qualitative research aimed to generate evidence regarding the content validity of the PAD-C and PAD-O. METHODS: Semi-structured combined concept elicitation and cognitive interviews were conducted with a diverse sample of U.S. participants (15 children 8-11 y.o. and 30 caregivers of children 4-11 y.o.). All children had clinician-diagnosed mild to severe asthma. Interviews explored the experience of pediatric asthma and assessed the understanding and relevance of both measures. Interviews were conducted across 3 iterative rounds to allow for modifications. RESULTS: Concept elicitation findings demonstrated that the core sign/symptom and impact concepts assessed in the PAD-C (cough, hard to breathe, out of breath, wheezing, chest tightness, and nighttime awakenings/symptoms) and PAD-O (cough, difficulty breathing, short of breath, wheezing, and nighttime awakenings/signs) correspond to those most frequently reported by participants; concept saturation was achieved. All PAD-C and PAD-O instructions and core items were well understood and considered relevant by most participants. Feedback from participants, the Pediatric Asthma Working Group, advisory panel, and FDA supported modifications to the measures, including addition of 1 new item to both measures and removal of 1 caregiver item. CONCLUSIONS: Findings provide strong support for the content validity of both measures. The cross-sectional measurement properties of both measures and their user experience and feasibility in electronic format will be assessed in a future quantitative pilot study with qualitative exit interviews, intended to support the reliability, construct validity, final content, and, ultimately, FDA qualification of the measures.

Pediatric asthma is one of the most common chronic diseases in children. However, there are problems of underdiagnosis, poor disease management, and undertreatment for many pediatric asthma patients, pressuring healthcare systems worldwide. Evaluating asthma symptoms is an important part of the development of treatments for pediatric asthma. However, there are few clinical outcome assessments (COAs) developed in line with regulatory guidance to directly assess symptom severity and evaluate the benefit of new treatments in children with asthma. In this study, we continued the development of the Pediatric Asthma Diary­Child (PAD-C) and the Pediatric Asthma Diary­Observer (PAD-O), according to regulatory guidance, to assess asthma signs and symptoms in children 4 through 11 years old and address this unmet need. The study aimed to explore the experience of pediatric asthma and assess how well-understood and relevant the measures are. Three rounds of qualitative interviews were conducted with 15 children 8 through 11 years old and 30 caregivers of children 4 through 11 years old with asthma. Results show that both measures are well-understood and assess the relevant and important aspects of pediatric asthma reported by children and caregivers. Findings provide evidence supporting the PAD-C and PAD-O as measures of symptom severity and their future use in pediatric asthma treatment trials. Further research is underway to evaluate their measurement properties and assess the user experience and feasibility of electronic completion, to ultimately support the PAD-C and PAD-O in an ongoing COA qualification process by the United States Food and Drug Administration.

Psychometric Validation of the Perception of Injection (PIN) Questionnaire Using Data From Two Phase III, Open-Label, Active-Controlled, Non-Inferiority Studies in People Living With HIV.

INTRODUCTION: Currently, there are no patient-reported outcome tools specifically validated for use in people living with human immunodeficiency virus (PLHIV) to measure treatment injection acceptance and experience. The Perception of Injection (PIN) questionnaire was modified with consent from the Vaccinees' Perception of Injection (VAPI), a validated instrument developed by Sanofi Pasteur. The objective of developing the PIN was to provide information on participant experience with injectable therapies, including acceptance of pain, injection-site reactions, and tolerability following injections in PLHIV. METHODS: This post hoc analysis used data from participants who received the long-acting intramuscular cabotegravir plus rilpivirine combination treatment every 4 weeks, as part of the ATLAS (NCT02951052) and FLAIR (NCT02938520) studies, to evaluate the psychometric properties of the PIN questionnaire. RESULTS: These findings support the reliability, validity, and responsiveness to change for the PIN questionnaire in PLHIV. CONCLUSION: As a clinical trial endpoint, the PIN questionnaire could provide valuable evidence around the acceptance and experience of injections in PLHIV which could have implications for treatment adherence in this population. TRIAL REGISTRATION: ATLAS (NCT02951052); 1 November, 2016. FLAIR (NCT02938520); 19 October, 2016.

Identification of sources of DIF using covariates in patient-reported outcome measures: a simulation study comparing two approaches based on Rasch family models.

When analyzing patient-reported outcome (PRO) data, sources of differential item functioning (DIF) can be multiple and there may be more than one covariate of interest. Hence, it could be of great interest to disentangle their effects. Yet, in the literature on PRO measures, there are many studies where DIF detection is applied separately and independently for each covariate under examination. With such an approach, the covariates under investigation are not introduced together in the analysis, preventing from simultaneously studying their potential DIF effects on the questionnaire items. One issue, among others, is that it may lead to the detection of false-positive effects when covariates are correlated. To overcome this issue, we developed two new algorithms (namely ROSALI-DIF FORWARD and ROSALI-DIF BACKWARD). Our aim was to obtain an iterative item-by-item DIF detection method based on Rasch family models that enable to adjust group comparisons for DIF in presence of two binary covariates. Both algorithms were evaluated through a simulation study under various conditions aiming to be representative of health research contexts. The performance of the algorithms was assessed using: (i) the rates of false and correct detection of DIF, (ii) the DIF size and form recovery, and (iii) the bias in the latent variable level estimation. We compared the performance of the ROSALI-DIF algorithms to the one of another approach based on likelihood penalization. For both algorithms, the rate of false detection of DIF was close to 5%. The DIF size and form influenced the rates of correct detection of DIF. Rates of correct detection was higher with increasing DIF size. Besides, the algorithm fairly identified homogeneous differences in the item threshold parameters, but had more difficulties identifying non-homogeneous differences. Over all, the ROSALI-DIF algorithms performed better than the penalized likelihood approach. Integrating several covariates during the DIF detection process may allow a better assessment and understanding of DIF. This study provides valuable insights regarding the performance of different approaches that could be undertaken to fulfill this aim.

Measuring dengue illness intensity: Development and content validity of the dengue virus daily diary (DENV-DD).

BACKGROUND: Dengue is the most prevalent arboviral infection causing an estimated 50-60 million cases of febrile illness globally per year, exacting considerable disease burden. Few instruments exist to assess the patient illness experience, with most based on healthcare provider assessment, lacking standardization in timepoints and symptom assessment. This study aimed to evaluate the content validity of the novel 'Dengue Virus Daily Diary (DENV-DD)', designed to measure symptom intensity and disease burden within outpatient infant to adult populations. METHODS: The Dengue Illness Index Report Card was used as a foundation to create the DENV-DD, consisting of patient- and observer-reported outcome (PRO/ObsRO) instruments. In two South American dengue-endemic communities, qualitative combined concept elicitation and cognitive debriefing interviews were conducted among individuals and caregivers of children with symptomatic laboratory-confirmed dengue. Interviews were conducted across two rounds allowing DENV-DD modifications. A small-scale quantitative assessment of the DENV-DD was also conducted with data from an independent Dengue Human Infection Model (DHIM) to generate early evidence of feasibility of DENV-DD completion, instrument performance and insight into the sign/symptom trajectory over the course of illness. RESULTS: Forty-eight participants were interviewed (20 adults, 20 older children/adolescents with their caregivers, 8 caregivers of younger children). A wide spectrum of signs/symptoms lasting 3-15 days were reported with fever, headache, body ache/pain, loss of appetite, and body weakness each reported by > 70% participants. DENV-DD instructions, items and response scales were understood, and items were considered relevant across ages. DHIM data supported feasibility of DENV-DD completion. CONCLUSIONS: Findings demonstrate content validity of the DENV-DD (PRO/ObsRO instruments) in dengue-endemic populations. Psychometric and cultural validity studies are ongoing to support use of the DENV-DD in clinical studies.

Dengue is the most common viral infection transmitted to humans by mosquitos, and affects an estimated 50­60 million individuals globally per year. However, there are few resources for understanding and capturing the patient experience of dengue throughout illness. Most research studies are based on healthcare provider assessment, which lack consistency in terms of assessment time points and the signs/symptoms assessed. The 'Dengue Illness Index Report Card (DII-RC)' was used as a foundation to create the new 'Dengue Virus Daily Diary (DENV-DD)' to better capture the patient experience of symptom intensity and dengue disease burden for the duration of illness. Forty-eight individuals and caregivers of younger children from Peru and Ecuador who recently had symptomatic dengue were interviewed to understand the patient experience over the time of illness and to test whether the DENV-DD is understood by patients and caregivers and includes all relevant and important signs/symptoms and health-related quality of life impacts. Nine individuals with active dengue infection also completed the DENV-DD daily for 28-days as part of a clinical study. We found that > 70% of patients experienced fever, headache, body ache/pain, loss of appetite and body weakness. The DENV-DD instructions, questions and response option(s) were well understood, feasible to complete and the concepts assessed by the DENV-DD were relevant to the dengue experience. Our study adds to the understanding of the dengue illness experience and supports the DENV-DD for use in future dengue studies as an assessment of signs/symptoms throughout the duration of illness.

Establishing clinically meaningful within-individual improvement thresholds for eight patient-reported outcome measures in people with relapsing-remitting multiple sclerosis.

BACKGROUND: As disease-modifying therapies do not reverse the course of multiple sclerosis (MS), assessment of therapeutic success involves documenting patient-reported outcomes (PROs) concerning health-related quality of life, disease and treatment-related symptoms, and the impact of symptoms on function. Interpreting PRO data involves going beyond statistical significance to calculate within-patient meaningful change scores. These thresholds are needed for each PRO in order to fully interpret the PRO data. This analysis of PRO data from the PROMiS AUBAGIO study, which utilized 8 PRO instruments in teriflunomide-treated relapsing-remitting MS (RRMS) patients, was designed to estimate clinically meaningful within-individual improvement thresholds in the same manner, for 8 PRO instruments. RESULTS: The analytical approach followed a triangulation exercise that considered results from anchor- and distribution-based methods and graphical representations of empirical cumulative distribution functions in PRO scores in groups defined by anchor variables. Data from 8 PRO instruments (MSIS-29 v2, FSMC, MSPS, MSNQ, TSQM v1.4, PDDS, HRPQ-MS v2, and HADS) were assessed from 434 RRMS patients. For MSIS-29 v2, FSMC, MSPS, and MSNQ total scores, available anchor variables enabled both anchor- and distribution-based methods to be applied. For instruments with no appropriate anchor available, distribution-based methods were applied. A recommended value for meaningful within-individual improvement was defined by comparing mean change in PRO scores between participants showing improvement of one or two categories in the anchor variable or those showing no change. A "lower bound" estimate was calculated using distribution-based methods. An improvement greater than the lower-bound estimate was considered "clinically meaningful". CONCLUSION: This analysis produced estimates for assessing meaningful within-individual improvements for 8 PRO instruments used in MS studies. These estimates should be useful for interpreting scores and communicating study results and should facilitate decision-making by regulatory and healthcare authorities where these 8 PROs are commonly employed.

Patient-Reported Outcome Measures in Liver and Gastrointestinal Cancer Randomized Controlled Trials.

OBJECTIVE: For many years, outcomes such as mortality and morbidity were the standard for evaluating oncological treatment effectiveness. With the introduction of patient-reported outcome measures (PROMs), the focus shifted from a mere extension of a patient's life or release from disease to the improvement of a multilayered concept of health, decisively affecting life satisfaction. In this study, we deal with the topic of PROMs in liver and gastrointestinal randomized controlled trials. RESULTS: The final database included 43 papers reporting results of randomized controlled trials (RCTs) for liver or gastrointestinal cancer interventions where one of the primary or secondary outcomes was a health-related quality of life measure. The most often used PROM was the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30) for both liver cancer and gastrointestinal cancer (in 62% of gastrointestinal cancer studies and 57% of liver cancer studies). For the gastrointestinal cancer group, the QLQ-STO22, a cancer-specific extension of the QLQ-C30, was the second most commonly used PROM. In liver cancer, the generic PROM Short Form 36 and the EORTC QLQ-HCC18, a cancer-specific extension of the QLQ-C30, were the second most commonly used PROMs. CONCLUSION: We found that RCTs often do not include comprehensive quality-of-life measures. When quality of life is part of an RCT, it is often only a secondary outcome. For a holistic view of the patient, a stronger integration and weighting of patient-reported outcomes in RCTs would be desirable.

Do clinical trials prepare to fail by failing to prepare? An examination of MS trials and recommendations for patient-reported outcome measure selection.

BACKGROUND: Many clinical trials use patient-reported outcome (PRO) measures, which can influence treatment decision-making, drug approval and label claims. Given that many PRO measure options exist, and there are conceptual and contextual complexities with PRO measurement, we aimed to evaluate how and why specific PRO measures have been selected for pivotal multiple sclerosis (MS) clinical trials. Specifically, we aimed to identify the reasons documented for PRO measure selection in contemporary phase III MS disease-modifying treatment (DMT) clinical trials. METHODS: We searched for phase III clinical trials of MS DMTs published between 2015 and 2021 and evaluated trial protocols, or primary publications where available, for PRO measure selection information. Specifically, we examined study documents for their clarification of clinical concepts measured, definitions of concepts measured, explanations of which PRO measures were considered, why specific PRO measures were chosen, and trade-offs in PRO measure selection. RESULTS: We identified 1705 abstracts containing 61 unique phase III MS DMT clinical trials. We obtained and examined 27/61 trial protocols. Six protocols were excluded: four contained no mention of PRO measures and two contained redacted sections preventing adequate assessment, leaving 21 protocols for assessment. For the remaining 34 trials (61-27), we retrieved 31 primary publications; 15 primary publications mentioned the use of a PRO measure. None of the 36 clinical trials that mentioned the use of PRO measures (21 protocols and 15 primary publications) documented clear PRO or clinical outcome assessment (COA) measurement strategies, provided clear justifications for PRO selection, or reasons why specific PRO measures were selected when alternatives existed. CONCLUSION: PRO measure selection for clinical trials is not evidence-based or underpinned by structured systematic approaches. This represents a critical area for study design improvement as PRO measure results directly affect patient care, PRO measurement has conceptual and contextual complexities, and there is a wide range of options when selecting a PRO measure. We recommend trial designers use formal approaches for PRO measure selection to ensure PRO measurement-based decisions are optimised. We provide a simple, logical, five-stage approach for PRO measure selection in clinical trials.

Prevalence and burden of atopic dermatitis involving the head, neck, face, and hand: A cross sectional study from the TARGET-DERM AD cohort.

BACKGROUND: Atopic dermatitis (AD) is severely burdensome, and there has been poor characterization of any differences in impact based on the area affected. OBJECTIVE: To estimate the prevalence and HRQoL impact of head/face/neck/hand (HFNH) involvement among patients with moderate-to-severe atopic dermatitis. METHODS: All TARGET-DERM AD registry patients with moderate/severe Investigator Global Assessment (vIGA-AD) were assessed using the Patient Oriented SCORing Atopic Dermatitis, Patient Oriented Eczema Measure (POEM) and the (Children's) Dermatology Life Quality Index ((C)DLQI). RESULTS: 541 participants met the criteria (75.0% adults) and 84% (N = 453) reported HFNH involvement. HFNH and non-HFNH involved participants had similar characteristics; 55.2% female and 46.9% White. Compared to the non-HFNH involved, the involved had severe vIGA-AD (28.5% vs 16.3%, P = .02) and higher median body surface area affected (15% vs 10%, P ≤ .01) and were twice as likely to have higher (C)DLQI and POEM scores. LIMITATIONS: This was an analysis of real-world and patient reported outcome data. CONCLUSION: Real-world HFNH involved AD patients were associated with significantly worse quality of life, POEM/(C)DLQI, and more severe disease. Detailed assessments of specific areas affected by AD are needed to personalize treatment.

Tenosynovial Giant Cell Tumor Observational Platform Project (TOPP) Registry: A 2-Year Analysis of Patient-Reported Outcomes and Treatment Strategies.

BACKGROUND: The Tenosynovial giant cell tumor Observational Platform Project (TOPP) registry is an international prospective study that -previously described the impact of diffuse-type tenosynovial giant cell tumour (D-TGCT) on patient-reported outcomes (PROs) from a baseline snapshot. This analysis describes the impact of D-TGCT at 2-year follow-up based on treatment strategies. MATERIAL AND METHODS: TOPP was conducted at 12 sites (EU: 10; US: 2). Captured PRO measurements assessed at baseline, 1-year, and 2-year follow-ups were Brief Pain Inventory (BPI), Pain Interference, BPI Pain Severity, Worst Pain, EQ-5D-5L, Worst Stiffness, and -Patient-Reported Outcomes Measurement Information System. Treatment interventions were no current/planned treatment (Off-Treatment) and systemic treatment/surgery (On-Treatment). RESULTS: A total of 176 patients (mean age: 43.5 years) were included in the full analysis set. For patients without active treatment strategy -(Off-Treatment) at baseline (n = 79), BPI Pain Interference (1.00 vs. 2.86) and BPI Pain Severity scores (1.50 vs. 3.00) were numerically favorable in patients remaining Off-Treatment compared with those who switched to an active treatment strategy at year 1. From 1-year to 2-year -follow-ups, patients who remained Off-Treatment had better BPI Pain Interference (0.57 vs. 2.57) and Worst Pain (2.0 vs. 4.5) scores compared with patients who switched to an alternative treatment strategy. In addition, EQ-5D VAS scores (80.0 vs. 65.0) were higher in patients who remained -Off-Treatment between 1-year and 2-year follow-ups compared with patients who changed treatment strategy. For patients receiving systemic treatment at baseline, numerically favorable scores were seen in patients remaining on systemic therapy at 1-year follow-up: BPI Pain Interference (2.79 vs. 5.93), BPI Pain Severity (3.63 vs. 6.38), Worst Pain (4.5 vs. 7.5), and Worst Stiffness (4.0 vs. 7.5). From 1-year to 2-year follow-up, EQ-5D VAS scores (77.5 vs. 65.0) were higher in patients who changed from systemic treatment to a different treatment strategy. CONCLUSION: These findings highlight the impact D-TGCT has on patient quality of life, and how treatment strategies may be influenced by these outcome measures. (ClinicalTrials.gov number: NCT02948088).

Health-Related Quality of Life as Assessed by the EQ-5D-5L Predicts Outcomes of Patients Treated with Azacitidine-A Prospective Cohort Study by the AGMT.

In this prospective study (NCT01595295), 272 patients treated with azacitidine completed 1456 EuroQol 5-Dimension (EQ-5D) questionnaires. Linear mixed-effect modelling was used to incorporate longitudinal data. When compared with a matched reference population, myeloid patients reported more pronounced restrictions in usual activities (+28%, p < 0.0001), anxiety/depression (+21%, p < 0.0001), selfcare (+18%, p < 0.0001) and mobility (+15%, p < 0.0001), as well as lower mean EQ-5D-5L indices (0.81 vs. 0.88, p < 0.0001), and lower self-rated health on the EuroQol Visual Analogue Scale (EQ-VAS) (64 vs. 72%, p < 0.0001). After multivariate-adjustment, (i) the EQ-5D-5L index assessed at azacitidine start the predicted time with clinical benefit (TCB) (9.6 vs. 6.6 months; p = 0.0258; HR = 1.43), time to next treatment (TTNT) (12.8 vs. 9.8 months; p = 0.0332; HR = 1.42) and overall survival (OS) (17.9 vs. 12.9 months; p = 0.0143; HR = 1.52); (ii) Level Sum Score (LSS) predicted azacitidine response (p = 0.0160; OR = 0.451) and the EQ-5D-5L index showed a trend (p = 0.0627; OR = 0.522); (iii) up to 1432 longitudinally assessed EQ-5D-5L response/clinical parameter pairs revealed significant associations of EQ-5D-5L response parameters with haemoglobin level, transfusion dependence and hematologic improvement. Significant increases of the likelihood ratios were observed after addition of LSS, EQ-VAS or EQ-5D-5L-index to the International Prognostic Scoring System (IPSS) or the revised IPSS (R-IPSS), indicating that they provide added value to these scores.

The Amblyopia Quality of Life (AmbQoL): Development and Content Validation of a Novel Health-Related Quality of Life Instrument for Use in Adult and Pediatric Amblyopia Populations.

INTRODUCTION: Amblyopia is a neurodevelopmental vision disorder, characterized by poor vision in one or both eyes. Given the lack of existing clinical outcome assessments (COA) considered fit-for-purpose for amblyopia clinical trials, this study developed new COAs to assess amblyopia symptoms and health-related quality of life (HRQoL) impacts in adult and pediatric amblyopia populations that conform with best practice standards and regulatory guidelines. METHODS: Findings from a targeted qualitative literature review informed the development of three versions of the new Amblyopia Quality of Life Questionnaire (AmbQoL): a patient-reported outcome measure (PRO) for individuals aged 13 years and older, a PRO for children aged 9-12 years, and an observer-reported outcome measure (ObsRO) for caregivers of children aged 4-8 years. Qualitative interviews were conducted with the target populations, and with ophthalmologists experienced in treating amblyopia patients to evaluate the content validity for further development of the AmbQoL. A translatability assessment was conducted to ensure cultural appropriateness and usability across multiple languages. Feedback from Food and Drug Administration (FDA) was also sought on the instruments, and clinical experts provided input at key stages. RESULTS: Interviews were conducted with 112 patients/caregivers and ten ophthalmologists from the USA, France, and Germany. The instructions, items, and response options were well understood across all AmbQoL versions. Feedback from the patients, caregivers, ophthalmologists, the translatability assessment, the FDA, and the expert clinicians informed minor wording modifications to enhance clarity and translatability. Some items were removed due to low relevance. The study resulted in a 23-item adult/adolescent PRO, 24-item child PRO, and 12-item ObsRO, each employing a 7-day recall period. CONCLUSION: Each AmbQoL version has documented support for its face and content validity for use in amblyopia populations aged ≥ 4 years. Further research is necessary to evaluate the psychometric measurement properties of the AmbQoL instruments to enable their use in amblyopia treatment trials.

Validation of the Spanish Acute Cystitis Symptoms Score (ACSS) in native Spanish-speaking women of Europe and Latin America.

INTRODUCTION AND OBJECTIVES: The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for clinical diagnostics and patient-reported outcome (PRO), which may assess the symptoms and the effect on the quality of life in women with acute cystitis (AC). The current study aimed to create a validated Spanish version of the ACSS questionnaire. MATERIAL AND METHODS: The process of linguistic validation of the Spanish version of the ACSS consisted of the independent forward and backward translations, revision and reconciliation, and cognitive assessment. Clinical evaluation of the study version of the ACSS was carried out in clinics in Spain and Latin America. Statistical tests included the calculation of Cronbach's α, split-half reliability, specificity, sensitivity, diagnostic odds ratio, positive and negative likelihood ratio, and area under the receiver-operating characteristic curve (AUC). RESULTS: The study was performed on 132 patients [age (mean;SD) 45.0;17.8 years] with AC and 55 controls (44.5;12.2 years). Cronbach's α of the ACSS was 0.86, and the split-half reliability was 0.82. The summary scores of the ACSS domains were significantly higher in patients than in controls, 16.0 and 2.0 (p < 0.001), respectively. The predefined cut-off point of ≥6 for a summary score of the "Typical" domain resulted in a specificity of 83.6% and a sensitivity of 99.2% for the Spanish version of the ACSS. AUC was 0.91 [0.85; 0.97]. CONCLUSIONS: The validated Spanish ACSS questionnaire evaluates the symptoms and clinical outcomes of patients with AC. It can be used as a patient's self-diagnosis of AC, as a PRO measure tool, and help to rule out other pathologies in patients with voiding syndrome.