PURPOSE: To develop a patient-reported outcome measure for capturing visual and ocular symptoms before and after implantation of intraocular lenses (IOLs) for treatment of cataracts. DESIGN: Questionnaire development and validation study. METHODS: The Questionnaire for Visual Disturbances (QUVID) was developed based on a literature and instrument review; 13 clinician interviews among ophthalmologists in the United States and Europe; and 67 hybrid qualitative patient interviews among adult patients in the United States and Australia before and/or after monofocal, traditional multifocal, or trifocal IOL implantation. Assessment of the QUVID's psychometric properties was conducted via a noninterventional cross-sectional study of previously treated cataract patients in the United States, Canada, and Australia (n = 150), and assessment of ability to detect meaningful change via 2 pivotal US clinical trials among patients with trifocal or extended vision IOL compared with monofocal IOL controls (n = 457). RESULTS: The QUVID includes subitems about the bothersomeness of 7 visual symptoms: starburst, halo, glare, hazy vision, blurred vision, double vision, and dark areas. The postoperative version contains 1 item asking the respondents whether their symptoms bothered them enough to want another surgery, if the IOL was the cause. CONCLUSIONS: The QUVID was reviewed by the US Food and Drug Administration and found appropriate as a fit-for-purpose measure, demonstrating requisite evidence for content validity, construct validity, reliability, and ability to detect change. (C) 2021 The Authors. Published by Elsevier Inc.

AIMS:To present the development of the International Consultation on Incontinence Questionnaire-underactive bladder (ICIQ-UAB) as the first patient reported outcome measure for the assessment of the symptoms and impact on the health-related quality of life of UAB developed in-line with the Food and Drug Administration Guidance for Industry. METHODS:Draft items were developed following 44 semi-structured concept elicitation interviews in the UK and refined using 36 cognitive interviews. A pilot study was designed to assess the draft ICIQ-UAB's initial psychometric properties with 54 patients recruited from European hospitals. Further concept elicitation interviews were also carried out with 11 patients in the US and 10 patients in Japan. All participants had a prior urodynamic diagnosis of detrusor underactivity. RESULTS:The cognitive interviews confirmed the initial items to be understood and interpreted as intended. Pilot testing showed that both internal consistency (Cronbach's α ≥ 0.85) and test-retest reliability (stable patients; intraclass correlation coefficient ≥ 0.88) were high. The interviews in the US and Japan elicited symptoms and impacts that support previous findings in the UK and provided further insight into the experiences of patients in those countries. The developmental ICIQ-UAB was refined using the evidence from all substudies. CONCLUSIONS:The validity and reliability of the ICIQ-UAB were supported in a pilot study setting and the wider cultural applicability by the additional interviews in the US and Japan. Following further validation in future clinical trials, the developmental ICIQ-UAB is envisaged as an important tool for the monitoring of future UAB treatment strategies.

Background Metastatic melanoma is a highly aggressive cancer, often striking in the prime of life. This study provides new information directly from advanced melanoma (stage III and IV) patients on how their disease impacts their health-related quality of life (HRQL). Methods Twenty-nine in-depth, qualitative interviews were conducted with adult patients with advanced melanoma in Canada. A semi-structured interview guide was used. Interviews were transcribed verbatim and key concepts were identified using a grounded theory analytic approach. Results Many patients’ journeys began with the startling diagnosis of an invasive disease and a vastly shortened life expectancy. By the time they reached an advanced stage of melanoma, these patients’ overall functioning and quality of life had been greatly diminished by this quickly progressing cancer. The impact was described in terms of physical pain and disability, emotional distress, diminished interactions with friends and family, and burden on caregivers. Conclusion Our findings provide evidence of signs, symptoms, and functional impacts of advanced melanoma. Signs and symptoms reported (physical, mental, and social) confirm and expand on those reported in the existing clinical literature. Primary care physicians should be better trained to identify melanomas early. Oncology care teams can improve on their current approaches for helping patients navigate treatment options, with information about ancillary services to mitigate disease impacts on HRQL, such as mental health and social supports, as well as employment or financial support services.

Objectives. Using patient global impression of change (PGIC) as an anchor, an approximately 30% reduction on an 11-point numeric pain intensity rating scale (PI-NRS) is considered a clinically important difference (CID) in pain. Our objective was to define the CID for another pain measure, the worst pain severity (WPS) item of the modified Brief Pain Inventory (m-BPI). Methods. In this post hoc analysis of a double-blind, placebo-controlled, phase 2 study, 452 randomized patients with diabetic peripheral neuropathic pain (DPNP) were followed over 5 weeks, with m-BPI data collected weekly and PGIC at treatment conclusion. Receiver operating characteristic (ROC) curves (via logistic regression) were used to determine the changes in the m-BPI-WPS score that best predicted ordinal clinical improvement thresholds (i.e., “minimally improved” or better) on the PGIC. Results. Similar to the PI-NRS, a change of −3 (raw) or −33.3% from the baseline on the m-BPI-WPS optimized prediction for the “much improved” or better PGIC threshold and represents a CID. There was a high correspondence between observed and predicted PGIC categories at each PGIC threshold (ROC AUCs were 0.78–0.82). Conclusions. Worst pain on the m-BPI may be used to assess clinically important improvements in DPNP studies. Findings require validation in larger studies.

BackgroundLittle is known on the impact of emerging treatments for advanced melanoma (stages III and IV) on patients' functioning and well-being. The objective of this study was to describe the patient-reported treatment-related symptom (TRS) burden in advanced melanoma.MethodTwenty-nine in-depth, qualitative interviews were conducted among adult patients with advanced melanoma in Canada using a semi-structured interview method. Interviews were transcribed verbatim, and key concepts were identified using a grounded theory analytic approach.ResultsThe 29 patients reported 13 unique treatment journeys involving the following drug therapy categories: cytotoxic chemotherapies, CTLA-4 inhibitors, BRAF or MEK inhibitors, and PD-1 inhibitors. Patients typically underwent multiple treatment episodes over time. Common TRSs included nausea, fatigue, diarrhea or constipation, and skin rashes. Patients described these as impacting their physical functioning, ability to perform activities of daily living, social functioning, and overall quality of life.ConclusionOur findings provide a description of the patient's experience with treatment for advanced melanoma. Our sample included patients typically diagnosed in mid-life, facing an urgent sequence of medical procedures and a pharmacological treatment journey that was burdensome. There is a need for less toxic and more efficacious treatments earlier in the patient journey to alleviate the impact of advanced melanoma treatment on patients' health-related quality of life.

Purpose People chronically infected with hepatitis C virus (HCV) have diminished patient-reported outcomes (PROs). This study aimed to compare the impact of elbasvir/grazoprevir (EBR/GZR) treatment versus sofosbuvir with pegylated interferon and ribavirin (SOF/PR) on changes in PROs: 1) during the treatment period and 2) at posttreatment follow-up. Patients and methods PRO data collected during the Phase III C-EDGE Head-2-Head (H2H) open-label study was analyzed. In this trial, patients infected with HCV were randomized 1:1 to receive either EBR/GZR or SOF/PR for 12 weeks. Patients self-administered the Short Form-36 version 2 (SF-36v2®) Health Survey Acute (1-week recall) Form and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale at baseline, during treatment, and posttreatment. Between-group differences in mean change of PRO scores from baseline were estimated during the treatment period and also at the posttreatment follow-up. Effect sizes were calculated to evaluate if the detected change in mean PRO scores is clinically meaningful between groups. Results There were 255 patients (99.2% White, 54.1% female, 74.9% treatment naïve) included in the analysis. During the treatment period, significant declines in SF-36v2 scores were observed across all domains for the SOF/PR group. Compared to the SOF/PR group, the EBR/GZR group reported more improvement in scores across all SF-36v2 domain scores at the end of the treatment period. At treatment week 12, the between-group differences for 6 out of the 8 domain scores for these patients reflected at least moderate effects (effect sizes >0.5). No significant between-group differences in change in SF-36v2 scores from baseline were detected posttreatment. The decline in SF-36v2 scores observed during the treatment period for the SOF/PR group returned to near baseline scores or above posttreatment. Treatment with EBR/GZR did not impact fatigue scores, but treatment with SOF/PR led to increased fatigue scores during treatment which resolved by posttreatment follow-up week 12. Conclusion This study demonstrated that HCV treatment with EBR/GZR resulted in a significantly better PRO profile as compared to SOF/PR. PROs are an important consideration as worsening PROs experienced during treatment may negatively influence adherence and ultimately contribute to an unfavorable clinical outcome. Clinicaltrialsgov Identifier NCT02358044.

Background: To evaluate the psychometric properties of the newly developed seven-item Irritable Bowel Syndrome – Diarrhea predominant (IBS-D) Daily Symptom Diary and four-item Event Log using phase II clinical trial safety and efficacy data in patients with IBS-D. This instrument measures diarrhea (stool frequency and stool consistency), abdominal pain related to IBS-D (stomach pain, abdominal pain, abdominal cramps), immediate need to have a bowel movement (immediate need and accident occurrence), bloating, pressure, gas, and incomplete evacuation. Methods: Psychometric properties and responsiveness of the instrument were evaluated in a clinical trial population [ClinicalTrials.gov identifier: NCT01494233]. Results: A total of 434 patients were included in the analyses. Significant differences were found among severity groups (p < 0.01) defined by IBS Patient Global Impression of Severity (PGI-S) and IBS Patient Global Impression of Change (PGI-C). Severity scores for each Diary and Event Log item score and five-item, four-item, and three-item summary scores were calculated. Between-group differences in changes over time were significant for all summary scores in groups stratified by changes in PGI-S (p < 0.05), two of six Diary items, and three of four Event Log items; a one-grade change in PGI-S was considered a meaningful difference with mean change scores on all Diary items −0.13 to −0.86 [standard deviation (SD) 0.79–1.39]. Similarly, for patients who reported being ‘slightly improved’ (considered a clinically meaningful difference) on the PGI-C, mean change scores on Diary items ranged from −0.45 to −1.55 (SD 0.69–1.39). All estimates of clinically important change for each item and all summary scores were small and should be considered preliminary. These results are aligned with the previous standalone psychometric study regarding reliability and validity tests. Conclusions: These analyses provide evidence of the psychometric properties of the IBS-D Daily Symptom Diary and Event Log in a clinical trial population.

Background: Compliance, palatability, gastrointestinal (GI) symptom, and treatment satisfaction patient-and observer-reported outcome (PRO, ObsRO) measures were developed/modified for patients with transfusion-dependent anemias or myelodysplastic syndrome (MDS) requiring iron chelation therapy (ICT).Methods: This qualitative cross-sectional observational study used grounded theory data collection and analysis methods and followed PRO/ObsRO development industry guidance. Patients and caregivers of patients with transfusion-dependent anemias or MDS were individually interviewed face-to-face to cognitively debrief the Compliance, Palatability, GI Symptom Diary, and Modified Satisfaction with Iron Chelation Therapy (SICT) instruments presented electronically. Interviews were conducted in sets. Interviews began open-endedly to spontaneously elicit ICT experiences. Item modifications were debriefed during the later interviews. Interviews were audio recorded, transcribed, and coded. Data was analyzed using ATLAS. ti qualitative research software.Results: Twenty-one interviews were completed (Set 1: 5 patients, 6 caregivers; Set 2: 6 patients, 4 caregivers) in 6 US cities. Mean age was 43 years for patients and 9 years for children of caregivers. Conditions requiring ICT use across groups included transfusion-dependent anemias (85.7%) and MDS (14.3%). Concepts spontaneously reported were consistent with instruments debriefed. Interview analysis resulted in PRO and ObsRO versions of each instrument: Compliance (2 items), Palatability (4 items), GI Symptom Diary (6 items), and Modified SICT (PRO = 13, ObsRO = 17 items).Conclusion: Qualitative research data from cognitive interviews supports the content validity and relevance of the instruments developed/modified. Quantitative validation of these PRO and ObsRO measures is needed testing for validity, reliability, and responsiveness for future research use with new formulations of oral ICT.

OBJECTIVES: Despite a documented clinical need, no patient reported outcome (PRO) symptom measure meeting current regulatory requirements for clinically relevant end points is available for the evaluation of treatment benefit in diarrhea-predominant IBS (IBS-D). METHODS: Patients (N=113) with IBS-D participated in five study phases: (1) eight concept elicitation focus groups (N=34), from which a 17-item IBS-D Daily Symptom Diary and four-item IBS-D Symptom Event Log (Diary and Event Log) were developed; (2) one-on-one cognitive interviews (N=11) to assess the instrument's comprehensiveness, understandability, appropriateness, and readability; (3) four data triangulation focus groups (N=32) to confirm the concepts elicited; (4) two hybrid (concept elicitation and cognitive interview) focus groups (N=16); and (5) two iterative sets of one-on-one cognitive interviews (N=20) to further clarify the symptoms of IBS-D and debrief a revised seven-item Diary and four-item Event Log. RESULTS: Of thirty-six concepts initially identified, 22 were excluded because they were not saturated, not clinically relevant, not critical symptoms of IBS-D, considered upper GI symptoms, or too broad or vaguely defined. The remaining concepts were diarrhea, immediate need (urgency), bloating/pressure, frequency of bowel movements, cramps, abdominal/stomach pain, gas, completely emptied bowels/incomplete evacuation, accidents, bubbling in intestines (bowel sounds), rectal burning, stool consistency, rectal spasm, and pain while wiping. The final instrument included a daily diary with separate items for abdominal and stomach pain and an event log with four items completed after each bowel movement as follows: (1) a record of the bowel movement/event and an assessment of (2) severity of immediacy of need/bowel urgency, (3) incomplete evacuation, and (4) stool consistency (evaluated using the newly developed Astellas Stool Form Scale). Based on rounds of interviews and clinical input, items considered secondary or nonspecific to IBS-D (rectal burning, bubbling in intestines, spasms, and pain while wiping) were excluded. CONCLUSIONS: The IBS-D Symptom Diary and Event Log represent a rigorously developed PRO instrument for the measurement of the IBS-D symptom experience from the perspective of the patient. Its content validity has been supported, and future work should evaluate the instrument's psychometric properties.

Abstract Background Adherence to iron chelation therapy (ICT) is critical in patients with transfusion dependent anemias (TDA) (e.g., sickle cell disease [SCD], thalassemia), myelodysplastic syndromes (MDS), aplastic anemia, and myelofibrosis (MF). One of the biggest challenges is poor adherence to therapy, which in turn could cause tissue damage in vital organs such as the heart, liver, and endocrine organs, leading to end-organ dysfunction and eventually organ failure. Some causes of poor adherence to ICT therapy in the literature include inconvenience and palatability issues. The literature also suggests that satisfaction with medication impacts adherence to medication regimens, and that satisfaction is an umbrella term for specific components such as convenience, and efficacy. There is limited information on the factors that influence adherence with ICT, however, from the patient and caregiver perspective. Aim The objective of this study was to explore the factors that influence adherence with ICT from the perspective of patients and caregivers of patients through qualitative research. Methods Semi-structured interviews including an open-ended component were conducted to elicit subjects’ (patients with TDA, MDS, aplastic anemia, or MF or caregivers thereof) experiences with ICT. Institutional Review Board approval was granted and subjects were screened by clinicians to meet pre-defined inclusion and exclusion criteria. Audio recordings of the interviews were transcribed and a code book that contained definitions of all codes was developed through a consensus process. Transcripts were coded and data were analyzed using Atlas ti, a qualitative data analysis software package. Several concepts related to adherence and satisfaction were identified. Results Four interviewers conducted 11 patient and 10 caregiver interviews in 6 US cities. The children of the caregivers were not interviewed as they were below the age of nine. Eight of the eleven patients were male and three were female, aged 14 to 81 years (mean=43). Nine of the ten caregivers were female, aged 35 to 65 years (mean=48). Six of the ten children of caregivers were female and four were male, with a mean age of 8.9 years (range 1.56-16.81 years). Conditions across pediatric and adult patients included: MDS (n=3), SCD (n=13), thalassemia (n=3), MF (n=1), and aplastic anemia (n=1). Reported reasons for adherence included perceived effect on health and longevity, support from clinicians and caregivers, and an established routine for taking their treatment. Reported reasons for non-adherence included palatability related issues of taste and aftertaste, texture of the ICT formulation, solubility, side effects such as GI symptoms, and mealtime restrictions. Caregivers reported better adherence if their children had a better understanding of treatment benefit, which usually “gets better as the child gets older”; physician involvement in explaining the importance of ICT; and patients witnessing the decrease in their iron levels. Caregivers indicated that if they were satisfied with the efficacy of the ICT, their children were more likely to adhere to their medications. Coping mechanisms included modifying how the medicine was taken to change or mask the taste, aftertaste, or texture and “dose splitting” during the day. Conclusions Factors associated with adherence and non-adherence to ICT and satisfaction with current therapies identified by patients and caregivers of patients provide information and insight for clinicians to provide optimal treatment with ICT and gain better adherence. These factors can be used to develop measures of adherence, palatability, GI symptoms, and satisfaction with ICT and design interventions to improve adherence to ICT. Disclosures Bal: Novartis Pharmaceutical Corporation: Employment, Equity Ownership. Cote:Novartis Pharmaceutical Corporation: Employment, Equity Ownership. Lasch:Pharmerit International: Employment, Research Funding. Huang:Novartis Pharmaceutical Corporation: Employment, Equity Ownership.

Thyroid diseases are common and often affect quality of life (QoL). No cross-culturally validated patient-reported outcome measuring thyroid-related QoL is available. The purpose of the present study was to test the cross-cultural validity of the newly developed thyroid-related patient-reported outcome ThyPRO, using tests for differential item functioning (DIF) according to language version.

Patient-reported outcomes (PRO) instruments currently used for patients with brain metastases (BM) have not been developed with adequate patient input from the appropriate population. The objective of this study was to develop a new PRO in this population. The BASIQ was developed according to the FDA PRO Guidance. A literature review, seven expert interviews, and 19 in-depth interviews with BM patients were conducted to identify the symptoms and impacts of BM important to this population and generate an initial version of the BASIQ. Twenty face-to-face cognitive interviews (CIs) were conducted to assess the content validity of the BASIQ and to assess the understandability, relevance, wording, and importance of items and, if necessary, revise it. The initial 23-item BASIQ included a 7-item event log with a yes/no response (assessing vision, reading, nausea, numbness, needing to stay in bed, falling, fainting), 7-item daily symptom section (assessing severity of headache, memory, balance, physical weakness, dizziness, tiredness, energy) on an 11-point NRS, and a 9-item impact section (assessing speaking certain words, putting ideas into words, staying focused on a topic, walking, understanding words read/heard, following a story in a book/on TV, doing things around the house, bathing, dressing). During the CIs, most of the patients reported that the instrument was easy to understand, of adequate length and format and did not contain any difficult words. Based on the CIs, items were deleted, modified, or included as impacts rather than symptoms. A revised 18-item BASIQ used a 24-hour recall period and an 11-point NRS assessing severity. Robust qualitative methods used to identify the symptoms and impacts of patients with BM led to the development of a much needed PRO measure in BM. Additional qualitative and quantitative research is planned to further support the use of the tool in clinical research.