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Daniel Eek,1 Meaghan Krohe,2 Iyar Mazar,2 Alison Horsfield,3 Farrah Pompilus,2 Rachel Friebe,2 Alan L Shields2 1AstraZeneca, Gothenburg, Sweden; 2Adelphi Values, Boston, MA, USA; 3AstraZeneca, Macclesfield, UK Objective: The emergence of various modes of administration for cancer treatment, including oral administration, brings into focus the importance of patient preference for administration. The purpose of this research was to evaluate the administration preferences of cancer patients, specifically between oral and intravenous (IV) treatment, as well as the factors contributing to preference. Methods: A literature search was conducted in OvidSP to identify research in which the preferences of cancer patients for oral or IV treatment have been evaluated. Data were analyzed in two stages: 1) those articles that directly compared preference between modes of administration were tallied to determine explicit preference for oral or IV treatment; and 2) all attributes associated with patient preference were documented. Results: Of the 48 abstracts identified as part of the initial OvidSP search, eight articles were selected for full-text review. One article was removed following full-text review, and seven additional articles were identified through a gray literature search, yielding a total of 14 articles for evaluation. In Stage 1, 13 of the 14 articles compared preference, of which eleven articles (84.6%) reported that patients preferred oral treatment over IV, while two (15.4%) stated that cancer patients preferred IV treatment over oral. In Stage 2, the most frequently reported attributes contributing to preference included convenience, ability to receive treatment at home, treatment schedule, and side effects. Discussion: Evidence suggests that oncology patients prefer oral treatment to IV. Rationale for preference was due to a number of factors, including convenience, perception of efficacy, and past experience. Further evaluation should be conducted, given the limited data on patient preference in oncology. Keywords: oncology, patient preference, mode of administration, literature review, mode of administration, oncology, treatment

Background: Triplet or quadruplet therapies incorporating proteasome inhibitors, immunomodulators, and anti-CD38 antibodies have led to prolonged survival among patients with newly diagnosed multiple myeloma; however, most patients have a relapse. Frontline lenalidomide therapy has increased the number of patients with lenalidomide-refractory disease at the time of the first relapse., Methods: In this phase 3, randomized, open-label trial, we evaluated belantamab mafodotin, pomalidomide, and dexamethasone (BPd), as compared with pomalidomide, bortezomib, and dexamethasone (PVd), in lenalidomide-exposed patients who had relapsed or refractory myeloma after at least one line of therapy. The primary end point was progression-free survival. Disease response and safety were also assessed., Results: A total of 302 patients underwent randomization; 155 were assigned to the BPd group, and 147 to the PVd group. At a median follow-up of 21.8 months (range, <0.1 to 39.2), the 12-month estimated progression-free survival with BPd was 71% (95% confidence interval [CI], 63 to 78), as compared with 51% (95% CI, 42 to 60) with PVd (hazard ratio for disease progression or death, 0.52; 95% CI, 0.37 to 0.73; P<0.001). Data on overall survival were immature. The percentage of patients with a response to treatment (partial response or better) was 77% (95% CI, 70 to 84) in the BPd group and 72% (95% CI, 64 to 79) in the PVd group; 40% (95% CI, 32 to 48) and 16% (95% CI, 11 to 23), respectively, had a complete response or better. Grade 3 or higher adverse events occurred in 94% of the patients in the BPd group and 76% of those in the PVd group. Ocular events occurred in 89% of the patients who received BPd (grade 3 or 4 in 43%) and 30% of those who received PVd (grade 3 or 4 in 2%); ocular events in the BPd group were managed with belantamab mafodotin dose modification. Ocular events led to treatment discontinuation in 9% of the patients in the BPd group and in no patients in the PVd group., Conclusions: Among lenalidomide-exposed patients with relapsed or refractory myeloma, BPd conferred a significantly greater benefit than PVd with respect to progression-free survival, as well as deeper, more durable responses. Ocular events were common but were controllable by belantamab mafodotin dose modification. (Funded by GSK; DREAMM-8 ClinicalTrials.gov number, NCT04484623; EudraCT number, 2018-004354-21.)., (Copyright © 2024 Massachusetts Medical Society.)

Introduction: NUT (nuclear protein of the testis) carcinoma (NUTca) is a rare and aggressive cancer that is genetically hallmarked by a chromosomal abnormality in the NUT gene, and presents with tumors in the head, neck, and lungs. Currently there is no standard of care, but patients may undergo surgery, radiation, and/or chemotherapy. There is a lack of published research describing the patient experience of NUTca. The objective of this study was to develop a conceptual framework (CF) that describes patients' experience of NUTca to inform the selection of outcome measures and design of patient-centric endpoints for future clinical research., Methods: Individual, semi-structured telephone interviews were conducted with patients and caregivers of patients who have/had NUTca (caregivers interviewed due to recruitment challenges resulting from the rarity of NUTca). Participants were asked about their disease symptoms, impacts, and treatment experience. Interviews were audio-recorded, transcribed, and analyzed using inductive coding. The CF was developed through inductive categorization of concepts, sub-domains, and domains., Results: Twenty-seven interviews were completed (patients n = 10; caregivers n = 17). Participants reported systemic symptoms (e.g., fatigue) and symptoms related to the location of the tumor (e.g., nose blockage for head/neck tumor). Pain emerged as an important and bothersome symptom across tumor locations. Participants reported impacts on their daily activities (e.g., showering), emotions (e.g., preoccupation), sleep, social life (e.g., isolation), roles (e.g., caring for children), and finances. The final CF was organized into four symptom domains [systemic, location-specific (head/neck, lung), pain, and digestive] and six impact domains (daily activities, emotional, sleep, social, role, and financial)., Conclusions: This study describes the patient experience of NUTca and proposes an evidence-based CF that informs both the clinical community's understanding of the disease and selection of a patient-reported outcome (PRO) measure to assess treatment benefit in future NUTca trials., (© 2021. The Author(s).)

Purpose: Physical functioning and fatigue are key patient concerns in myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). The objective of this research was to generate supportive quantitative evidence for modular physical functioning and fatigue measures based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30) and a customized selection of 10 supplemental items from the EORTC Item Library., Methods: The 40 items were completed online cross-sectionally by 51 patients (higher risk [HR] MDS: 53%; CMML: 26%; AML: 10%). Psychometric analyses based on Rasch measurement theory (RMT) were conducted on the QLQ-C30 physical functioning and fatigue domains as well as measures combining QLQ-C30 and supplemental items. A measure of anemia-related symptoms composed of QLQ-C30 and supplemental items covering fatigue, dyspnea, and dizziness was also investigated., Results: The QLQ-C30 physical functioning and fatigue domains showed good targeting to the sample and adequate reliability, with few conceptual gaps identified. Combining the QLQ-C30 and supplemental physical functioning and fatigue items improved the conceptual coverage and the reliability of the measures. The patient-reported anemia-related symptom measure showed good measurement performance, underpinned by a clinically meaningful characterization of severity of these symptoms over a spectrum, starting with fatigue, then dyspnea, and finally dizziness (most severe)., Conclusion: The modular measurement approach of combining EORTC QLQ-C30 and Item Library offers a promising pragmatic solution to the measurement of physical functioning and fatigue, as well as anemia-related symptoms in clinical trials conducted in HR MDS, CMML, and AML., (© 2021. The Author(s).)

While open surgery has been the primary surgical approach for adult degenerative scoliosis, minimally invasive surgery (MIS) represents an alternative option and appears to be associated with reduced morbidity. Given the lack of consensus, we aimed to conduct a systematic review on available literature comparing MIS versus open surgery for adult degenerative scoliosis. PubMed, Embase, and Cochrane databases were searched through December 16, 2019, for studies that compared both MIS and open surgery in patients with degenerative scoliosis. Four cohort studies reporting on 350 patients met the inclusion criteria. In two studies, patients undergoing open surgery were younger and had more severe disease at baseline as compared with MIS. Patients who underwent MIS had less blood loss, shorter length of stay, and a reduced rate of complications and infections. Both MIS and open surgery resulted in a significant change in pain and disability scores and both approaches provided significant correction of deformity in all studies, although open surgery was associated with a greater change in pelvic incidence-lumbar lordosis mismatch (PI-LL) and sagittal vertical axis (SVA) in two and three studies, respectively. In patients with adult degenerative scoliosis undergoing surgery, both MIS and open approaches appeared to offer comparable improvements in pain and function. However, MIS was associated with better safety outcomes, while open surgery provided greater correction of spinal deformity. Further studies are needed to identify specific subset of patients who may benefit from one approach versus the other.

Background: Patient-reported outcome (PRO) instruments provide robust and effective means of evaluating patients' treatment experience; however, none adequately cover experience using self-injection devices with enhanced features, such as an electromechanical autoinjector (e-Device). The aim of this study was to develop a PRO instrument that accurately assesses patient experience of using an e-Device and to evaluate its psychometric properties., Methods: A mixed-methods approach was taken; two parallel, targeted literature reviews were conducted to identify relevant concepts and existing self-injection PRO instruments that could be adapted. Patient feedback obtained from two focus groups was used to inform initial instrument development. The pilot instrument was then administered in a multicenter, open-label, phase 3 clinical study in which patients self-injected certolizumab pegol using an e-Device, to gather evidence of its psychometric qualities. Exit interviews were conducted with a sub-sample of patients enrolled in the study to confirm the appropriateness and clarity of the items included and cognitively debrief the instrument. Confirmatory factor analysis (CFA) was conducted on all items, and each domain's internal consistency was measured using Cronbach's ɑ., Results: The literature searches identified several e-Device-specific concepts related to device features, device function, side effects/reactions/pain, confidence, and interference/convenience in daily life. Seven existing PRO instruments were identified. The Self-Injection Assessment Questionnaire (SIAQ), containing pre- and post-injection questionnaire modules, was selected as most suitable and adapted using feedback from 19 patients in the two focus groups to form the pilot Assessment of Self-Injection (ASI) questionnaire. CFA resulted in some changes to the grouping of items in the post-injection module domains following psychometric evaluation of the ASI. Internal consistency was satisfactory for all pre- and post-injection domains (ɑ > 0.8). Cognitive debriefing results from 12 patient exit interviews confirmed the ASI's appropriateness and clarity., Conclusions: The ASI was developed iteratively with patient input and was evaluated in its intended clinical context of use. Psychometric analyses indicated promising cross-sectional results; the ASI was well understood and considered relevant by patients self-injecting using the e-Device, suggesting that it could be used in real-world settings to aid with clinical decision making., Trial Registration: NCT03357471.

Background: Novel, pragmatic, patient-centered strategies are needed to ensure fit-for-purpose patient-reported outcomes (PRO) instruments in clinical trial research for rare diseases such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). The objective of the current study was to select supplemental items to add to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) to ensure content coverage of all important clinical concepts in patients with higher-risk (HR) MDS, low-blast count (LB) AML, and CMML, thus, improving the instrument's ability to detect clinically meaningful treatment benefit for this context of use., Methods: Our mixed methods approach comprised literature review, clinician consultation (n = 3), and qualitative and quantitative analysis of two stages of patient interview data (n = 14, n = 18) to select library bank items to supplement a generic cancer PRO, the EORTC QLQ-C30., Results: Unique symptom (n = 54) and impact (n = 72) concepts were organized into conceptual frameworks of treatment benefit, compared with EORTC QLQ-C30 items and conceptual gaps identified. Supplemental items (n = 13) addressing those gaps were selected from the EORTC Item Library and tested with patients. Supplemental item endorsement frequencies met World Health Organization Quality of Life criteria, suggesting good targeting and relevance for this sample. However, three supplemental items were confirmed as problematic based upon cognitive debriefing results, and expert clinical consultations. Ultimately, 10 supplemental items (n = 7 symptom; n = 3 impact) were selected for the MDS/AML/CMML context., Conclusion: Supplemental items were selected to enhance the conceptual coverage of the EORTC QLQ-C30 in the areas of fatigue, shortness of breath, and functioning.

Background: The goal of the research reported here was to understand the patient experience of living with myelofibrosis (MF) and establish content validity of the Modified Myeloproliferative Neoplasm Symptom Assessment Diary (MPN-SD)., Methods: Qualitative interviews were performed in patients with MF, including both concept elicitation and cognitive debriefing. Patients with MF were asked to spontaneously report on their signs, symptoms, and impacts of MF, as well as their understanding of the MPN-SD content, and use of the tool on an electronic platform. A supplementary literature review and meetings with MF experts were also performed., Results: Twenty-three patients with MF participated in qualitative interviews. Signs and symptoms most commonly reported by ruxolitinib-experienced patients (n = 16) were: fatigue and/or tiredness (n = 16, 100%), shortness of breath (n = 11, 69%), pain below the ribs on the left side and/or stomach pain and/or abdominal pain (n = 9, 56%), and enlarged spleen (n = 9, 56%) and for ruxolitinib-naïve patients (n = 7) were: fatigue and/or tiredness (n = 6, 86%), pain below the ribs on the left side (n = 6, 86%), enlarged spleen (n = 4, 57%), full quickly/filling up quickly (n = 4, 57%), night sweats and/or general sweats (n = 4, 57%), and itching (n = 4, 57%). Patients demonstrated that they were able to read, understand, and provide meaningful responses to the MPN-SD. The final version of the MPN-SD includes the 10 most commonly reported concepts from the MF patient interviews., Conclusions: The findings demonstrate the comprehensiveness of the MPN-SD in assessing MF symptoms in both ruxolitinib-experienced and ruxolitinib-naïve patients, while remaining easy for patients to understand and complete.

Objective: Acute intermittent porphyria is a rare metabolic disorder that affects heme synthesis. Patients with acute intermittent porphyria may experience acute debilitating neurovisceral attacks that require frequent hospitalizations and negatively impact quality of life. Although clinical aspects of acute intermittent porphyria attacks have been documented, the experience of patients is not well known, particularly for those more severely affected patients who experience frequent attacks. The aim of the present study was to qualitatively characterize the experience of patients with acute intermittent porphyria who have frequent attacks, as well as the impact of the disease on daily living., Methods: Patients with acute intermittent porphyria who experience frequent attacks were recruited and took part in 2-h qualitative one-on-one interviews with a semi-structured guide. Interviews were anonymized, transcribed, and coded. The inductive coding approach targeted textual data related to acute intermittent porphyria attack symptoms, chronic symptoms, and the impact of the disease. Saturation analysis was conducted to assess whether the research elicited an adequate account of patients' experiences., Results: In total, 19 patients with acute intermittent porphyria were interviewed (mean age 40 years; 79% female). Eighteen patients (95%) experienced both attack and chronic symptoms. Patients described attacks as the onset of unmanageable symptoms that generally lasted 3-5 days requiring hospitalization and/or treatment. Pain, nausea, and vomiting were considered key attack symptoms; pain, nausea, fatigue, and aspects of neuropathy (e.g., tingling and numbness) were considered key chronic symptoms., Conclusions: In this study population of acute intermittent porphyria with frequent attacks, most patients had symptoms during and between attacks. In these patients, acute intermittent porphyria appears to have acute exacerbations as well as chronic day-to-day manifestations, and is not just intermittent as its name implies. As a result, patients reported limitations in their ability to function across multiple domains of their lives on a regular basis and not just during acute attacks.

Background and Objective: The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported outcome instrument that quantifies the progressive loss of walking ability from the patient perspective. However, previous psychometric analyses indicated floor and ceiling effects across the multiple sclerosis severity spectrum. This study aimed to address floor effects by creating a gait module that can be used in conjunction with the MSWS-12 for better measurement of treatment benefit in the higher functioning multiple sclerosis population., Methods: We used a step-wise mixed methods study design, with relapsing-remitting multiple sclerosis patients (wave 1, n =88; wave 2, n =30), combining qualitative (concept elicitation and cognitive debriefing interviews) and quantitative (Rasch Measurement Theory) data collection and analytical techniques and consultation interviews with three neurologists specializing in multiple sclerosis., Results: Thirty-seven walking ability concepts were identified, and a five-domain conceptual framework was created. Draft items were generated and refined with patient and neurologist input. Draft items covered gait-related concepts such as dragging, shuffling, limping, tripping and falling. Rasch measurement theory psychometric analysis indicated administering MSWS-12 plus gait items improved measurement precision in targeted populations with better walking ability., Conclusion: Study findings indicate that new gait items could improve sensitivity to detect clinical change in walking ability for higher functioning multiple sclerosis patients.

Background: ABILHAND, a manual ability patient-reported outcome instrument originally developed for stroke patients, has been used in multiple sclerosis clinical trials; however, psychometric analyses indicated the measure's limited measurement range and precision in higher-functioning multiple sclerosis patients., Objective: The purpose of this study was to identify candidate items to expand the measurement range of the ABILHAND-56, thus improving its ability to detect differences in manual ability in higher-functioning multiple sclerosis patients., Methods: A step-wise mixed methods design strategy was used, comprising two waves of patient interviews, a combination of qualitative (concept elicitation and cognitive debriefing) and quantitative (Rasch measurement theory) analytic techniques, and consultation interviews with three clinical neurologists specializing in multiple sclerosis., Results: Original ABILHAND was well understood in this context of use. Eighty-two new manual ability concepts were identified. Draft supplementary items were generated and refined with patient and neurologist input. Rasch measurement theory psychometric analysis indicated supplementary items improved targeting to higher-functioning multiple sclerosis patients and measurement precision. The final pool of Early Multiple Sclerosis Manual Ability items comprises 20 items., Conclusion: The synthesis of qualitative and quantitative methods used in this study improves the ABILHAND content validity to more effectively identify manual ability changes in early multiple sclerosis and potentially help determine treatment effect in higher-functioning patients in clinical trials.

Objectives: The aim was to document, from the perspective of the empirical literature, the primary symptoms of functional dyspepsia (FD), evaluate the extent to which existing questionnaires target those symptoms, and, finally, identify any missing evidence that would impact the questionnaires' use in regulated clinical trials to assess treatment efficacy claims intended for product labeling., Methods: A literature review was conducted to identify the primary symptoms of FD and existing symptom-based FD patient-reported outcome (PRO) instruments. Following a database search, abstracts were screened and articles were retrieved for review. The primary symptoms of FD were organized into a conceptual model and the PRO instruments were evaluated for conceptual coverage as well as compared against evidentiary requirements presented in the FDA's PRO Guidance for Industry., Results: Fifty-six articles and 16 instruments assessing FD symptoms were reviewed. Concepts listed in the Rome III criteria for FD (n = 7), those assessed by existing FD instruments (n = 34), and symptoms reported by patients in published qualitative research (n = 6) were summarized in the FD conceptual model. Except for vomiting, all of the identified symptoms from the published qualitative research reports were also specified in the Rome III criteria. Only three of the 16 instruments, the Dyspepsia Symptom Severity Index (DSSI), Nepean Dyspepsia Index (NDI), and Short-Form Nepean Dyspepsia Index (SF-NDI), measure all seven FD symptoms defined by the Rome III criteria. Among these three, each utilizes a 2-week recall period and 5-point Likert-type scale, and had evidence of patient involvement in development. Despite their coverage, when these instruments were evaluated in light of regulatory expectations, several issues jeopardized their potential qualification for substantiation of a labeling claim., Conclusions: No existing PRO instruments that measured all seven symptoms adhered to the regulatory principles necessary to support product labeling. As such, the development of a new FD symptom PRO instrument is supported., Competing Interests: Compliance with Ethical Standards The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE) and were fully responsible for all aspects of manuscript development. Fiona Taylor participated in planning and executing the study, analyzing and interpreting the data, and drafting the manuscript; Catherine Foley and Farrah Pompilus participated in planning and executing the study, collecting, analyzing and interpreting the data, and drafting the manuscript; Ramon Iovin participated in collecting, analyzing, and interpreting the data and drafting the manuscript; Alan L. Shields participated in planning and executing the study, interpreting the data, and drafting the manuscript; David S. Reasner provided input on the study design and drafting of the manuscript; Robyn T. Carson, Linda S. Deal, Debra G. Silberg, and Jason Lundy provided input on the study design and manuscript. FT, CF, and ALS are employees of Adelphi Values, which received payment from the sponsors to conduct the research; RI and FP were employees of Adelphi Values at the time this research was conducted. DSR is a member of Albemarle Scientific Consulting and an employee of Ironwood Pharmaceuticals, and owns stock and stock options in Ironwood. RTC is an employee of Allergan and owns stock and stock options in Allergan. At the time of the research, LSD and DGS were employees of Shire, and have shareholdings in Shire and other pharmaceutical companies through stocks and mutual funds. JJL was an employee of the Critical Path Institute at the time this research was conducted. Any views expressed in this publication represent the personal opinions of the authors, not those of their respective employer. The authors’ respective organizations were given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.

Background: Facial lines or wrinkles are among the most visible signs of aging, and minimally invasive cosmetic procedures are becoming increasingly popular., Aims: The aim of this study was to develop and validate the Facial Line Satisfaction Questionnaire (FLSQ) for use in adults with upper facial lines (UFL)., Methods: A literature review, concept elicitation interviews (n = 33), and cognitive debriefing interviews (n = 23) of adults with UFL were conducted to develop the FLSQ. The FLSQ comprises Baseline and Follow-up versions and was field-tested with 150 subjects in a US observational study designed to assess its psychometric performance. Analyses included acceptability (item and scale distribution [i.e. missingness, floor, and ceiling effects]), reliability, and validity (including concurrent validity)., Results: In total, 69 concepts were elicited during patient interviews. Following cognitive debriefing interviews, the FLSQ-Baseline version included 11 items and the Follow-up version included 13 items. Response rates for the FLSQ were 100% and 73% at baseline and follow-up, respectively; no items had excessive missing data. Questionnaire scale scores were normally distributed. Most domain scores demonstrated good internal consistency reliability (Cronbach's α ≥ 0.70). Most items within their respective domains exhibited good convergent (item-scale correlations > 0.40) and discriminant (items had higher correlation with their hypothesized scales than other scales) validity. Concurrent validity correlation coefficients of the FLSQ domain scores with the associated concurrent measures were acceptable (range: r = 0.40-0.70). Six FLSQ items demonstrated reliability and validity as stand-alone items outside their domains., Conclusions: The FLSQ is a valid questionnaire for assessing treatment expectations, satisfaction, impact, and preference in adults with UFL., (© 2015 The Authors. Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.)