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OBJECTIVES: To estimate the preferences of patients with asthma and asthma-treating clinicians for attributes of biologic treatments, to compare patients' and clinicians' preferences, and to better understand the reasons for their preferences. METHODS: Adults with moderate-to-severe asthma and clinicians who treat asthma in the US completed a cross-sectional, online survey including a discrete choice experiment (DCE) that consisted of seven attributes spanning treatment efficacy, risk and convenience. Marginal utilities were estimated using a mixed logit model, and relative attribute importance scores calculated. Clinicians were also asked about the value of biomarker agnostic biologic treatments. The survey was followed by qualitative interviews targeting a sub-sample of survey participants, in which the rationale behind their survey responses was discussed. RESULTS: In the DCE, both patients and clinicians placed the most importance on exacerbation and hospitalization rate reduction, and risk of injection site reaction. Patients valued location of administration more than clinicians. Rationale for individual-level preferences varied, with patients and clinicians reporting their preference depended on event frequency and anticipated quality of life impacts. Clinicians mentioned compliance and financial impacts, while patients mentioned personal experience, particularly around site reactions. Most patients and clinicians would value a biomarker agnostic asthma treatment. CONCLUSIONS: Asthma treatment preferences are largely driven by treatment efficacy and minimizing the risk of site reactions, although preferences differ between patients and clinicians across other attributes, highlighting the need for shared decision-making and individualized care.
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Introduction: Long COVID affects health-related quality of life (HRQoL). Here, we investigate the extent to which symptoms experienced during the acute phase of COVID-19 are significant predictors of the presence of long COVID at 12 weeks. Methods: Post-hoc analysis of COMET-ICE trial data, which assessed sotrovimab vs. placebo for treatment of mild-to-moderate COVID-19 among high-risk patients. Patient-reported outcome measures were completed during the trial, including the inFLUenza Patient-Reported Outcome Plus (FLU-PRO Plus), the 12-Item Short Form (SF-12) Hybrid questionnaire, and the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI:GH). COVID-19 symptoms and impacts (measured by the FLU-PRO Plus) and HRQoL (measured by SF-12 Hybrid and WPAI:GH) were compared between the acute phase (Days 1-21 and 29) and long-COVID phase (at Week 12) among patients with and without long COVID based on COMET-ICE data. Subgroups experiencing long COVID were derived using "All," "Returning," and "Persisting" symptomatic definitions. Long-COVID predictors were identified using a multivariate logistic regression model; odds ratios (ORs) and 95% CIs were calculated. Results: Long-COVID subgroups had significantly higher baseline scores for most FLU-PRO Plus domains and Total Score compared with the non-long-COVID group. WPAI:GH and SF-12 Hybrid scores generally showed significantly more impairment for the long-COVID subgroups at baseline and Week 12 vs. the non-long-COVID group. In the univariate analyses, all FLU-PRO Plus domains were significant predictors of long COVID (all p < 0.05), with the exception of the Sense domain. Older age increased the risk of long COVID (OR 1.02, 95% CI 1.00-1.04, p < 0.05). Non-White patients were significantly less likely to have long COVID by the Returning and Persisting definitions vs. White patients (all p < 0.05). In the multivariate analysis, higher scores for the Nose domain (ORs 3.39-5.60, all p < 0.01) and having COPD (ORs 3.75-6.34, all p < 0.05) were significant long-COVID predictors. Conclusion: Patients who progressed to long COVID had higher symptom severity during the acute disease phase and showed significantly greater negative impact on HRQoL over an extended time period from initial infection through at least the subsequent 3 months. The FLU-PRO Plus Nose domain and having COPD were significant predictors of long COVID.
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COVID-19 , Calidad de Vida , Humanos , COVID-19/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Anciano , SARS-CoV-2 , Adulto , Encuestas y Cuestionarios , Medición de Resultados Informados por el Paciente , Síndrome Post Agudo de COVID-19 , Tratamiento Farmacológico de COVID-19RESUMEN
Introduction: Newer treatment options for relapsed/refractory multiple myeloma (RRMM) with efficacy and safety profiles that differ from traditional therapies have facilitated personalized management strategies to optimize patient outcomes. In the context of such personalized management, understanding how treatment characteristics influence patients' preferences is essential. This study assessed patients' preferences for RRMM treatment attributes and determined trade-offs between potential benefits, administration procedures, and adverse effects. Methods: Patients' preferences were evaluated using a discrete choice experiment (DCE). Patients with RRMM who reported failing two lines of anti-myeloma treatment (immunomodulatory agent and a proteasome inhibitor [PI]) or ≥ 3 lines (including ≥1 PI, immunomodulatory agent, or anti-CD38 monoclonal antibody), were recruited across the US, UK, Italy, Germany, France, and Spain. DCE attributes and levels were identified using a targeted literature review, a review of clinical data for relevant RRMM treatments, qualitative patient interviews, and input from clinical and myeloma patient experts. The DCE was administered within an online survey from February-June 2022. Preference data were analyzed using an error-component logit model and willingness to make trade-offs for potential benefits, and relative attribute importance scores were calculated. Results: Overall, 296 patients from the US (n = 100), UK (n = 49), Italy (n = 45), Germany (n = 43), France (n = 39), and Spain (n = 20) participated in the DCE. Mean (standard deviation) age was 63.8 (8.0) years, 84% had a caregiver, and patients had a median of 3 (range: 2-8) prior lines of therapy. Efficacy attributes most influenced patients' preferences, with increasing overall response rate (25-85%) and overall survival (6 months to 2 years) contributing to ~50% of treatment decision-making. Administration procedures were also considered important to patients. Avoiding individual side effects was considered relatively less important, with patients willing to tolerate increases in side effects for gains in efficacy. Patient characteristics such as rate of disease progression, sociodemographics, or clinical characteristics also influenced treatment preferences. Conclusion: Patients with RRMM were willing to tolerate increased risk of side effects for higher efficacy. Preferences and risk tolerance varied between patients, with preference patterns differing by certain patient characteristics. This highlights the importance of shared decision-making for optimal treatment selection and patient outcomes.
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PURPOSE: The Impact of Weight on Self-perception Questionnaire (IW-SP) is a three-item patient-reported outcome measure (PROM) instrument assessing the impact of body weight on self-perception. To date no published threshold for meaningful change exists. The objective of this study was to estimate the minimal important change (MIC) for the IW-SP among people with type 2 diabetes. METHODS: Responder analyses were conducted using anchor- and distribution-based approaches with existing clinical trial data (SURPASS-2). As SURPASS-2 did not include a priori anchors, a set of alternative exploratory anchors were identified based on the MICs and items from two conceptually related measures used in the trial as well as percent change in body weight. Exploratory anchors with change estimates that were sufficiently related to change in IW-SP (r ≥ 0.30) and were not redundant with other anchors were retained for the MIC analyses. The analyses were conducted in two stages (estimation = 2/3 of sample) to derive initial IW-SP MIC estimates, and a subsequent confirmation stage (remaining 1/3 of sample). RESULTS: While the most conceptually related anchors and items performed best in responsiveness analyses, all anchors resulted in a similar estimate of minimal meaningful change for the IW-SP total score: a 1-point change in raw units (1-5-point scale), corresponding to a 25-point change for transformed scores (0-100 scale). Distribution-based analyses supported these MIC estimates. Results were similar across both stages for all analyses. CONCLUSION: The MIC for the IW-SP for patients with T2D is a 25-point change on the transformed score.
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Diabetes Mellitus Tipo 2 , Humanos , Calidad de Vida/psicología , Encuestas y Cuestionarios , Peso Corporal , AutoimagenRESUMEN
Purpose: To quantify the preferences of people with type 2 diabetes (T2D) for treatment attributes of a glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist (RA) versus an injectable GLP-1 RA medication profile. Patients and Methods: Injection-naive people taking oral medications for T2D in the US and UK completed a web survey including a discrete choice experiment to quantify patients' preferences for five treatment attributes: delivery system, frequency of nausea, frequency of hypoglycemia, HbA1c reduction, and weight reduction. Attributes and levels were based on head-to-head clinical trial data of tirzepatide 5mg, 10mg, and 15mg versus semaglutide 1mg. Preference data were analyzed separately by country using multinomial mixed logit (MXL) models. MXL parameters were used to estimate the predicted preference for each tirzepatide dose versus semaglutide 1mg. Direct preferences for each dose of tirzepatide versus semaglutide 1mg were elicited. Results: Participants (N=620) in the US (N=301) and UK (N=319) were 50.8% and 50.5% female with mean ages of 60.7 years and 58.9 years, respectively. The order and magnitude of relative attribute importance (RAI) scores differed between countries. HbA1c reduction (26.3%) had the greatest impact on US participants' preferences, and hypoglycemia (32.8%) did among UK participants. Attribute-level marginal utility results indicated preferences for greater HbA1c improvements, the single-use pre-filled pen, lower hypoglycemia, greater weight reductions, and lower frequency of nausea. Assuming the availability of only tirzepatide or semaglutide 1mg, the predicted preference for tirzepatide (5, 10, and 15mg) in the US is 95.6% (vs 4.4% for semaglutide 1mg) and in the UK was 86.3% (vs 13.7% for semaglutide 1mg). Conclusion: HbA1c reduction, frequency of hypoglycemia, and weight reduction are key drivers of preferences among people with T2D when considering medication options. Overall, people with T2D are likely to prefer the tirzepatide over the semaglutide 1mg medication profiles.
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PURPOSE: A well-defined and reliable patient-reported outcome instrument for COVID-19 is important for assessing symptom severity and supporting research studies. The InFLUenza Patient-Reported Outcome (FLU-PRO) instrument has been expanded to include loss of taste and smell in the FLU-PRO Plus, to comprehensively cover COVID-19 symptoms. Our studies were designed to evaluate and validate the FLU-PRO Plus among patients with COVID-19. METHODS: Two studies were conducted: (1) a qualitative, non-interventional, cross-sectional study of patients with COVID-19 involving hybrid concept elicitation and cognitive debriefing interviews; (2) a psychometric evaluation of the measurement properties of FLU-PRO Plus, using data from COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial-Intent to Care Early). RESULTS: In the qualitative interviews (n = 30), all 34 items of the FLU-PRO Plus were considered relevant to COVID-19, and participants determined the questionnaire was easily understood, well written, and comprehensive. In the psychometric evaluation (n = 845), the internal consistency reliability of FLU-PRO Plus total score was 0.94, ranging from 0.71 to 0.90 for domain scores. Reproducibility (Day 20-21) was 0.83 for total score, with domain scores of 0.67-0.89. Confirmatory factor analysis with the novel smell/taste domain demonstrated an acceptable fit to the data. CONCLUSION: The content, reliability, validity, and responsiveness of the FLU-PRO Plus in the COVID-19 population were supported. Our results suggest that FLU-PRO Plus is a content- and psychometrically-valid, fit-for-purpose measure which is easily understood by patients. FLU-PRO Plus is a suitable PRO measure for evaluating symptoms of COVID-19 and treatment benefit directly from the patient perspective. TRIAL REGISTRATION: ClinicalTrials.Gov: NCT04545060, September 10, 2020; retrospectively registered.
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COVID-19 , Gripe Humana , Humanos , Reproducibilidad de los Resultados , Psicometría , Estudios Transversales , Calidad de Vida/psicología , Medición de Resultados Informados por el Paciente , Encuestas y CuestionariosRESUMEN
BACKGROUND: Conventional injectable glucagon (IG) and nasal glucagon (NG), both having similar efficacy, are two options for the emergency treatment of severe hypoglycemia in Spain. This study elicited the effect of changes in key attributes on preferences for NG and IG medication profiles of people with diabetes and caregivers in Spain. METHODS: The relative attribute importance (RAI) that participants placed on glucagon preparation, preparation and administration time, delivery method, recovery time, device size, storage temperature, and headache risk was estimated from an online discrete choice experiment. In addition, patients and caregivers were presented with NG and IG profiles that included rates of successful administration; the proportion of participants choosing each profile was summarized. RESULTS: The analysis included 276 adults with diabetes (65% type 1) and 270 caregivers (49% type 1). Overall mean age was 40 years; 51% were female. The most important attributes were storage temperature (RAI [95% confidence interval] = 27.3% [22.9-32.2]) and delivery method (17.4% [13.1-21.9]). Headache risk (16.2% [11.8-20.7]), time to prepare and administer (14.5% [10.1-18.8]), glucagon preparation (11.4% [6.8-15.8]), recovery time (8.9% [4.3-13.3]), and device size (4.3% [0.3-8.8]) were also relevant. When comparing medication profiles, significantly more participants (78%) preferred NG over IG profiles (P < .001). CONCLUSION: Adults with diabetes and caregivers prefer a glucagon treatment with a higher rate of successful administration, wider storage temperature, and nasal delivery method, when efficacy is similar. Participants favored NG over conventional IG as a rescue medication for severe hypoglycemia. This information may help decision-making by payers and treatment discussions between health care professionals and patients.
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Diabetes Mellitus , Hipoglucemia , Adulto , Humanos , Femenino , Masculino , Glucagón/uso terapéutico , Administración Intranasal , Cuidadores , España , Temperatura , Diabetes Mellitus/tratamiento farmacológico , Hipoglucemia/tratamiento farmacológico , Cefalea/tratamiento farmacológicoRESUMEN
BACKGROUND: The double-blind, randomized, placebo-controlled phase 3 study of orally administered PLX3397 in patients with pigmented villonodular synovitis or giant cell tumor of the tendon sheath (ENLIVEN) showed that pexidartinib provides a robust objective tumor response in adults with tenosynovial giant cell tumors (TGCT) not amenable to improvement with surgery. Based on these results, in 2019, pexidartinib received accelerated approval in the United States in this population as a breakthrough therapy under an orphan drug designation. However, the ability of pexidartinib to relieve pain in ENLIVEN was not fully detailed, and the relationship between pain relief and objective tumor response was not described. QUESTIONS/PURPOSES: (1) What level of pain relief was achieved by pexidartinib treatment in ENLIVEN? (2) How was pain relief related to objective tumor responses? (3) How durable was pain relief? METHODS: The current study included planned primary and exploratory assessments of patient-assessed worst pain at the site of the tumor in the ENLIVEN trial. ENLIVEN was a phase 3 randomized, placebo-controlled clinical trial in which adults with TGCT not amenable to improvement with surgery received pexidartinib or placebo for 24 weeks, after which eligible patients could receive open-label pexidartinib. Of 174 patients assessed for eligibility, 121 were randomized (50% [60] to placebo, 50% [61] to pexidartinib), and 120 were given either placebo or pexidartinib (59 received placebo and 61 received pexidartinib) and were included in an intent-to-treat analysis. Fifty-nine percent (71 of 120) of the overall treated population was female, and 88% (106 of 120) were White. Mean age was 45 ± 13 years. Tumors were mostly in the lower extremities (92% [110 of 120]), most commonly in the knee (61% [73 of 120]) and ankle (18% [21 of 120]). As a secondary outcome, patients scored worst pain at the site of the tumor in the past 24 hours on an 11-point numeric rating scale (NRS). The primary definition of a pain response was a decrease of at least 30% in the weekly mean worst-pain NRS score and increase of less than 30% in narcotic analgesic use between baseline and week 25. Planned exploratory assessments of pain included the frequency of a pain response using alternative thresholds, including a decrease in worst-pain NRS score of 50% or more and a decrease of at least 2 points (minimum clinically important difference [MCID]), the magnitude of pain reduction between baseline and week 25, correlation between worst-pain NRS score and tumor shrinkage by RECIST 1.1 criteria, and the durability of the pain response during the open-label extension. Pain responses during the randomized portion of the trial were compared according to intention-to-treat analysis, with a one-sided threshold of p < 0.025 to reduce the risk of false-positive results. Pain assessment was complete for 59% (35 of 59) of patients in the placebo group and 54% (33 of 61) of patients in the pexidartinib group. Demographic and disease characteristics did not differ between the two treatment groups. RESULTS: A difference in the primary assessment of a pain response was not detected between pexidartinib and placebo (response percentage 31% [19 of 61] [95% CI 21% to 44%] versus 15% [9 of 59] [95% CI 8% to 27%]; one-sided p = 0.03). In the exploratory analyses, pexidartinib provided a modest improvement in pain (response percentage 26% [16 of 61] [95% CI 17% to 38%] versus 10% [6 of 59] [95% CI 5% to 20%]; one-sided p = 0.02 using the 50% threshold and 31% [19 of 61] [95% CI 21% to 44%] versus 14% [8 of 59] [95% CI 7% to 25%]; one-sided p = 0.02 using the MCID threshold). The least-squares mean change in the weekly mean worst-pain NRS score between baseline and week 25 was larger in patients treated with pexidartinib than placebo (-2.5 [95% CI -3.0 to -1.9] versus -0.3 [95% CI -0.9 to 0.3]; p < 0.001), although the mean difference between the two groups (-2.2 [95% CI -3.0 to -1.4]) was just over the MCID. Improvement in the weekly mean worst-pain NRS score correlated with the reduction in tumor size (r = 0.44; p < 0.001) and tumor volume score (r = 0.61; p < 0.001). For patients in the open-label extension, the change in the worst-pain NRS score from baseline was similar to the change at the end of the randomized portion and just above the MCID (mean -2.7 ± 2.2 after 25 weeks and -3.3 ± 1.7 after 50 weeks of receiving pexidartinib). CONCLUSION: Based on the current study, a modest reduction in pain, just larger than the MCID, may be an added benefit of pexidartinib in these patients, although the findings are insufficient to justify the routine use of pexidartinib for pain relief. LEVEL OF EVIDENCE: Level II, therapeutic study.
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Tumor de Células Gigantes de las Vainas Tendinosas , Adulto , Humanos , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Aminopiridinas , Dolor , Método Doble CiegoRESUMEN
Purpose: To understand the perspectives of people with type 2 diabetes (T2D) on safely reaching near normoglycemia, defined as a glycated hemoglobin A1c (HbA1c) value of <6%. HbA1c indicates the average blood sugar level over the past few months. Patients and Methods: This cross-sectional online quantitative survey of people with T2D asked about the current impacts of T2D, the anticipated benefits of safely achieving near normoglycemia among participants with a current HbA1c ≥6%, or the actual benefits of safely achieving near normoglycemia among participants who had an HbA1c <6%. Participants reported on specific areas of psychological/emotional impact of T2D and the psychological/emotional benefits of achieving near normoglycemia. Results: Participants (N = 1000; United States = 500 and United Kingdom = 500) were 53.1% male and had a mean age of 62.9 years (SD = 13.3). The majority reported that the current HbA1c ≥6% (81.2%) and 49.2% had been diagnosed more than 10 years ago. The vast majority of participants (>90%) indicated that achieving near normoglycemia was meaningful, with 95% of the participants indicating that achieving near normoglycemia would be of somewhat or extreme importance to them. In total, 93.8% of participants with a current HbA1c ≥6% and 80.3% of those with a current HbA1c <6% anticipated/reported having experienced improvements as a result of achieving near normoglycemia. Among those who experienced or anticipated positive psychological/emotional impacts (n = 247), the most commonly reported impacts included less worry about future diabetes-related complications (79.8%), feeling in control over one's life (72.9%), and overall health-related quality of life (59.9%). Conclusion: Achieving near normoglycemia is both meaningful and important to the majority of people with T2D, including both those who have and those who have not experienced reaching near normoglycemia. A wide range of specific impacts, including psychological/emotional concepts, are experienced by people with T2D, many of which may be improved through achieving near normoglycemia.
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INTRODUCTION: Alopecia areata (AA) is an autoimmune disease characterized by hair loss. Patients with AA experience a range of social and emotional impacts, and the lack of effective treatments and multiple affected locations can deepen the burden of illness. The objective of the current study was to assess health-related quality of life (HRQL) among patients with AA, and to evaluate the relationship between patient-reported AA severity, HRQL and treatment patterns. METHODS: A web survey was completed by participants recruited through the National Alopecia Areata Foundation. The survey included questions on disease characteristics, burden and impact (evaluated by the Skindex-16 for AA and items on work/school and sexual relationships), healthcare utilization and treatment experience. Analyses were conducted for the overall sample and by key subgroups, including AA severity and disease duration. RESULTS: A total of 1327 participants with AA completed the survey. The mean age was 39.7 [standard deviation (SD) 12.3] years and 58.4% were female. On average, participants had experienced signs and symptoms of AA for 11.5 years (SD 12.5) and were diagnosed by a healthcare provider (HCP) 10.5 (SD 12.2) years ago. Participants reported a range of severity of current scalp hair loss, including 0% (2.6%), 1-20% (39.8%), 21-49% (26.2%), 50-94% (10.2%) and 95-100% (21.3%). Participants reporting 95-100% of scalp hair missing were less likely to be currently seeing an HCP and to currently be on treatments for AA. There was a non-linear relationship between HRQL and current AA severity. Participants with 1-20% to 50-94% of current scalp hair missing reported higher symptom, functioning and emotional impacts due to AA than participants with 0% missing scalp hair and/or 95-100% missing scalp hair. Similar findings were observed for current eyebrow and eyelash severity, except for emotional impacts. CONCLUSION: Severity of AA plays an important role in understanding the burden of illness and healthcare patterns of people living with AA.
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OBJECTIVE: To evaluate the content validity and psychometric properties of the Activity Impairment in Migraine Diary (AIM-D). BACKGROUND: Measuring treatment effects on migraine impairment requires a psychometrically sound patient-reported outcome (PRO) measure developed consistent with U.S. Food and Drug Administration guidance. METHODS: The AIM-D was created from concepts that emerged during qualitative interviews with five clinicians experienced in treating migraine and concept elicitation (CE) interviews with 40 adults with episodic migraine (EM) or chronic migraine (CM). The initial version was refined based on three waves of cognitive interviews with 38 adults with EM or CM and input from a panel of clinical and measurement experts. The AIM-D was psychometrically evaluated using data from 316 adults with EM or CM who participated in a 13-week prospective observational study. Study participants completed PRO assessments including the AIM-D and a daily headache diary. Exploratory and confirmatory factor analysis were used to determine the factor structure. The reliability, validity, and responsiveness of the AIM-D were assessed. Additional PRO measures including the Patient Global Impression - Severity (PGI-S), Migraine Specific Quality of Life Questionnaire, Version 2.1 Role Function-Restrictive domain, and Headache Impact Test were used for psychometric evaluation of the AIM-D. RESULTS: Based on CE interviews with adults with migraine and input from an expert panel, activity impairment was identified as the target in the preliminary conceptual framework, which had two domains: performance of daily activities (PDAs) and physical impairment (PI). Revision of the draft AIM-D through multiple rounds of cognitive interviews and expert panel meetings resulted in a content valid 11-item version. Exploratory factor analysis supported both one- and two-domain structures for the AIM-D, which were further supported by confirmatory factor analysis (factor loadings all >0.90). The AIM-D domains (PDA and PI) and total score showed high internal consistency reliability (Cronbach's alpha 0.95-0.97), acceptable test-retest reliability for weekly average scores (intraclass correlation coefficient >0.60 for participants with no change in PGI-S between baseline and week 2), and good convergent and known-groups validity. There was evidence of responsiveness based on changes in PGI-S score and monthly migraine days. CONCLUSION: The AIM-D is a content valid and psychometrically sound measure designed to evaluate activity impairment and is suitable for use in clinical trials of preventive treatments for EM or CM.
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Trastornos Migrañosos/diagnóstico , Trastornos Migrañosos/tratamiento farmacológico , Medición de Resultados Informados por el Paciente , Psicometría/normas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría/instrumentación , Psicometría/métodos , Investigación Cualitativa , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
PURPOSE: To assess the response to pexidartinib treatment in six cohorts of adult patients with advanced, incurable solid tumors associated with colony-stimulating factor 1 receptor (CSF1R) and/or KIT proto-oncogene receptor tyrosine kinase activity. PATIENTS AND METHODS: From this two-part phase I, multicenter study, pexidartinib, a small-molecule tyrosine kinase inhibitor that targets CSF1R, KIT, and FMS-like tyrosine kinase 3 (FLT3), was evaluated in six adult patient cohorts (part 2, extension) with advanced solid tumors associated with dysregulated CSF1R. Adverse events, pharmacokinetics, and tumor responses were assessed for all patients; patients with tenosynovial giant cell tumor (TGCT) were also evaluated for tumor volume score (TVS) and patient-reported outcomes (PRO). CSF1 transcripts and gene expression were explored in TGCT biopsies. RESULTS: Ninety-one patients were treated: TGCT patients (n = 39) had a median treatment duration of 511 days, while other solid tumor patients (n = 52) had a median treatment duration of 56 days. TGCT patients had response rates of 62% (RECIST 1.1) and 56% (TVS) for the full analysis set. PRO assessments for pain showed improvement in patient symptoms, and 76% (19/25) of TGCT tissue biopsy specimens showed evidence of abnormal CSF1 transcripts. Pexidartinib treatment of TGCT resulted in tumor regression and symptomatic benefit in most patients. Pexidartinib toxicity was manageable over the entire study. CONCLUSIONS: These results offer insight into outcome patterns in cancers whose biology suggests use of a CSF1R inhibitor. Pexidartinib results in tumor regression in TGCT patients, providing prolonged control with an acceptable safety profile.
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Tumor de Células Gigantes de las Vainas Tendinosas , Pirroles , Adulto , Aminopiridinas/efectos adversos , Tumor de Células Gigantes de las Vainas Tendinosas/metabolismo , Tumor de Células Gigantes de las Vainas Tendinosas/patología , Humanos , Inhibidores de Proteínas Quinasas/efectos adversos , Pirroles/farmacologíaRESUMEN
Background and purpose - The ENLIVEN trial showed that, after 25 weeks, pexidartinib statistically significantly reduced tumor size more than placebo in patients with symptomatic, advanced tenosynovial giant cell tumor (TGCT) for whom surgery was not recommended. Here, we detail the effect of pexidartinib on patient-reported physical function and stiffness in ENLIVEN.Patients and methods - This was a planned analysis of patient-reported outcome data from ENLIVEN, a double-blinded, randomized phase 3 trial of adults with symptomatic, advanced TGCT treated with pexidartinib or placebo. Physical function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS)-physical function (PF), and worst stiffness was assessed using a numerical rating scale (NRS). A mixed model for repeated measures was used to compare changes in PROMIS-PF and worst stiffness NRS scores from baseline to week 25 between treatment groups. Response rates for the PROMIS-PF and worst stiffness NRS at week 25 were calculated based on threshold estimates from reliable change index and anchor-based methods.Results - Between baseline and week 25, greater improvements in physical function and stiffness were experienced by patients receiving pexidartinib than patients receiving placebo (change in PROMIS-PF = 4.1 [95% confidence interval (CI) 1.8-6.3] vs. -0.9 [CI -3.0 to 1.2]; change in worst stiffness NRS = -2.5 [CI -3.0 to -1.9] vs. -0.3 [CI -0.9 to 0.3]). Patients receiving pexidartinib had higher response rates than patients receiving placebo for meaningful improvements in physical function and stiffness. Improvements were sustained after 50 weeks of pexidartinib treatment.Interpretation - Pexidartinib treatment provided sustained, meaningful improvements in physical function and stiffness for patients with symptomatic, advanced TGCT.
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Aminopiridinas/uso terapéutico , Tumor de Células Gigantes de las Vainas Tendinosas/tratamiento farmacológico , Tumor de Células Gigantes de las Vainas Tendinosas/fisiopatología , Medición de Resultados Informados por el Paciente , Pirroles/uso terapéutico , Adulto , Método Doble Ciego , Femenino , Humanos , Extremidad Inferior , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The Kingdom of Saudi Arabia (KSA) has the second highest prevalence of type 2 diabetes mellitus (T2DM) in the Middle East. There is a paucity of research on the experiences and treatment preferences of patients with T2DM in KSA. This study explored Saudi patients' health-related quality of life, eating habits, experiences during Ramadan, and preference between two glucagon-like peptide-1 receptor agonist (GLP-1 RA) treatment devices. METHODS: A cross-sectional, observational study was conducted in three cities in KSA. Participants completed sociodemographic and clinical forms, EQ-5D-5L, Impact of Weight on Self-Perceptions, and a diabetes treatment survey. Participants also viewed instructional videos on GLP-1 RA injection devices and indicated their device preference. RESULTS: Of the 310 participants, 53% were male. The mean age was 43 years (range: 30.0-75.0), duration since diabetes diagnosis was 6.3 years (range: 0.2-27.1), the most commonly reported last HbA1c level was between ≥7.1% and 8% (45%). The mean EQ-5D-5L index score was 0.90, with some participants reporting problems with pain/discomfort (34.5%) and usual activities (33.2%). Patients reported a low-to-moderate impact of weight on self-perception. In preparation for Ramadan, participants sought physician advice on diabetes management (37%) and/or increased checks of their blood glucose (37%). After watching the videos, 89% (n=277) of participants indicated a device preference, with significantly more preferring the dulaglutide device (n=186, 67%) over the semaglutide device (n=91, 33%) (p<0.0001). CONCLUSION: This study indicates that T2DM has a significant social, emotional, and behavioral impact on the lives of patients in KSA.
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PURPOSE: The purpose of this study was to evaluate the psychometric properties of the PROMIS-Physical Function (PF) and Worst Stiffness Numeric Rating Scale (NRS) among patients with tenosynovial giant cell tumors (TGCT). METHODS: Measurement properties of the customized lower extremity (LE) and upper extremity (UE) PROMIS-PF scales and Worst Stiffness NRS were assessed using data from the Phase 3 ENLIVEN trial (n = 120). Anchor- and distribution-based analyses were utilized to derive a responder threshold for meaningful change over time. The Patient Global Rating of Concept (PGRC)-Physical Functioning and Patient Global Impression of Change (PGIC)-Stiffness served as anchors. Responsiveness and responder threshold analyses were from baseline to week 25. RESULTS: Cronbach's alpha values for internal consistency reliability were 0.93 and 0.91 for the PROMIS-PF LE and UE, respectively. Test-retest reliability intra-class correlation coefficients were > 0.75 for both instruments. Convergent validity for both instruments was supported by moderate to strong correlations (≥0.30) with the Brief Pain Inventory and EQ-5D. Known-groups validity was established between subgroups stratified by pain level (p < 0.05). Responsiveness was supported by evaluating change scores among different levels of change in PGRC-Physical Functioning and PGIC-Stiffness (overall F values < 0.001). Triangulation of responder definition analyses resulted in a threshold of ≥3 for the PROMIS-PF and ≥ 1 for the Worst Stiffness NRS. CONCLUSION: This study is the first to establish the psychometric properties of patient-reported outcome measures in TGCT. The evidence demonstrates that the PROMIS-PF and Worst Stiffness NRS have good reliability, validity, and responsiveness, and provides guidance for the interpretation of meaningful change.
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PURPOSE: To determine important symptoms and functional effects of venous malformations (VMs) to assess the content validity of commonly used patient-reported outcome (PRO) measures for use with VM patients. METHODS: This cross-sectional, qualitative study involved cognitive interviews with participants with VM aged ≥ 14 years. From February to June 2016, 11 participants (8 female) with a mean (± standard deviation) age of 31 ± 15 years were recruited from three clinical sites. The following subgroups were evaluated: 5 adults (aged ≥ 18) with trunk/extremity VMs; 3 adolescents (aged 14-17) with trunk/extremity VMs; and 3 adults with head/neck VMs. We evaluated the content validity of the Worst Pain Numeric Rating Scale (NRS), Patient-Reported Outcomes Measurement Information System (PROMIS®) Pain Interference 8-item short form, and PROMIS Physical Function 8-item short form. RESULTS: The most common participant-reported VM symptoms were swelling (n = 10), skin discoloration (n = 8), acute episodic pain (n = 8), chronic pain (n = 7), numbness (n = 7), and tingling/burning (n = 6). Participants reported that VMs affected their physical function (n = 10), appearance (n = 10), relationships/social activities (n = 7), and emotional health (n = 3). The Worst Pain NRS and PROMIS Pain Interference measures were relevant to all participants' VM experience. Only adults with head/neck VMs found the PROMIS Physical Function measure to be irrelevant. The assessed PRO measures did not address several symptoms commonly reported by VM patients (swelling, skin discoloration, numbness, and appearance). CONCLUSION: These results suggest that several VM symptoms are not assessed fully by commonly used PRO measures, and that the relevance of functional limitation questions may vary by VM location.
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Malformaciones Arteriovenosas/psicología , Medición de Resultados Informados por el Paciente , Calidad de Vida/psicología , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor/patología , Dimensión del Dolor/métodos , Investigación Cualitativa , Escleroterapia/métodos , Adulto JovenRESUMEN
OBJECTIVE: Despite the increased availability of biologic treatments indicated for severe asthma, patient and physician preferences for these medications remains largely unknown. The purpose of this study was to understand perceptions of biologic therapies, barriers to care with biologic medications, and preferences for biologic therapy attributes. METHODS: This mixed-methods study involved quantitative surveys and qualitative telephone interviews with patients and physicians from the United States. Participants described preferences for relevant attributes, and barriers to use of biologic medications. Participants rated, ranked, and indicated importance of preferences for different levels of key attributes including: mode of administration, administration setting, dosing frequency, number of injections, and time to onset of effect. Other attributes unique to each group were also included. RESULTS: A total of 47 patients and 25 physicians participated. Patients ranked out-of-pocket costs, mode of administration, time to onset of efficacy, and administration setting as the most important attributes. Physicians ranked mode of administration, time to onset of efficacy, dosing frequency, and insurance reimbursement/access as most important. Both groups expressed preferences for less frequent administrations (Q8W over Q4W or Q2W) (all P<0.01) and subcutaneous (SC) over intravenous injection (both P<0.0001). Key patient barriers to biologic medications include location of treatment, administration time, scheduling, cost/insurance coverage, number of injections, and mode of administration. Physicians identified patient candidacy, convincing patients, administration setting, mode of administration, cost, and administrative burden as key barriers to initiating therapy; and efficacy, speed of onset, convenience of administration, cost, and patient compliance as barriers to staying on therapy. CONCLUSIONS: Patients and physicians expressed strong preferences for less frequent dosing, SC administration, and faster onset. Cost/insurance coverage and convenience issues were key barriers to use. Increased awareness and understanding of preferences and barriers may be useful in facilitating physician-patient conversations with the goal of individualizing treatment.
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BACKGROUND: Tenosynovial giant cell tumour (TGCT), a rare, locally aggressive neoplasm, overexpresses colony-stimulating factor 1 (CSF1). Surgery is standard with no approved systemic therapy. We aimed to evaluate pexidartinib, a CSF1 receptor inhibitor, in patients with TGCT to provide them with a viable systemic treatment option, especially in cases that are not amenable to surgical resection. METHODS: This phase 3 randomised trial had two parts. Part one was a double-blind study in which patients with symptomatic, advanced TGCT for whom surgery was not recommended were randomly assigned via an integrated web response system (1:1) to the pexidartinib or placebo group. Individuals in the pexidartinib group received a loading dose of 1000 mg pexidartinib per day orally (400 mg morning; 600 mg evening) for the first 2 weeks, followed by 800 mg per day (400 mg twice a day) for 22 weeks. Part two was an open-label study of pexidartinib for all patients. The primary endpoint, assessed in all intention-to-treat patients, was overall response at week 25, and was centrally reviewed by RECIST, version 1.1. Safety was analysed in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02371369. FINDINGS: Between May 11, 2015, and Sept 30, 2016, of 174 patients assessed for eligibility, 120 patients were randomly assigned to, and received, pexidartinib (n=61) or placebo (n=59). There were 11 dropouts in the placebo group and nine in the pexidartinib group. Emergence of mixed or cholestatic hepatotoxicity caused the data monitoring committee to stop enrolment six patients short of target. The proportion of patients who achieved overall response was higher for pexidartinib than placebo at week 25 by RECIST (24 [39%] of 61 vs none of 59; absolute difference 39% [95% CI 27-53]; p<0·0001). Serious adverse events occurred in eight (13%) of 61 patients in the pexidartinib group and one (2%) of 59 patients in the placebo group. Hair colour changes (67%), fatigue (54%), aspartate aminotransferase increase (39%), nausea (38%), alanine aminotransferase increase (28%), and dysgeusia (25%) were the most frequent pexidartinib-associated adverse events. Three patients given pexidartinib had aminotransferase elevations three or more times the upper limit of normal with total bilirubin and alkaline phosphatase two or more times the upper limit of normal indicative of mixed or cholestatic hepatotoxicity, one lasting 7 months and confirmed by biopsy. INTERPRETATION: Pexidartinib is the first systemic therapy to show a robust tumour response in TGCT with improved patient symptoms and functional outcomes; mixed or cholestatic hepatotoxicity is an identified risk. Pexidartinib could be considered as a potential treatment for TGCT associated with severe morbidity or functional limitations in cases not amenable to improvement with surgery. FUNDING: Daiichi Sankyo.
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Antineoplásicos/administración & dosificación , Tumor de Células Gigantes de las Vainas Tendinosas/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Adulto , Anciano , Antineoplásicos/efectos adversos , Método Doble Ciego , Femenino , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/efectos adversos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Tenosynovial giant cell tumor (TGCT), a rare, locally aggressive neoplasm of the synovium of joints and tendon sheaths, is associated with joint destruction, pain and swelling. Impacts on physical function (PF) vary depending on tumor size and location. The aim of this study was to identify relevant items, and demonstrate the content validity of custom measures of lower extremity PF from the Patient-Reported Outcomes Measurement Information System Physical Function Physical Function (PROMIS-PF) item bank among patients with TGCT. METHODS: Patients were recruited for qualitative research interviews to identify predominant TGCT symptoms and impacts. Patients completed a checklist to evaluate the relevance of each PROMIS-PF item. The publicly available PROMIS-PF item response theory (IRT) parameters were used to select items representing the range of the latent PF trait. RESULTS: Participants (n = 20) were 75% female, mean age 42.5 years. TGCTs were located in the knee (n = 15), hip (n = 3), and ankle (n = 2). Fifty-four PROMIS-PF items were identified as relevant by ≥20% of the participants. PF concepts discussed by participants during the qualitative interviews were also used to select relevant items. Selected items (n = 13) were used to create a physical function subscale specific to lower extremity tumors. CONCLUSIONS: We describe a novel method of combining qualitative research and IRT-based item information to select a relevant and content valid subset of PROMIS-PF items to assess heterogeneous impacts on PF in TGCT, a rare disease population.
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PURPOSE: Comprehensive (qualitative and quantitative) assessments of the 12-item functional assessment of anorexia/cachexia therapy (FAACT) anorexia/cachexia subscale (A/CS) and relevant subscales were undertaken for use in constructing potential endpoints in clinical trials of non-small cell lung cancer (NSCLC) with involuntary weight loss. METHODS: Eleven participants (≥ 18 years) from six clinical sites with a diagnosis of stage III unresectable or stage IV NSCLC and involuntary weight loss (either ≥ 5% body weight loss within six months prior to screening or screening BMI < 20 kg/m2) were interviewed to evaluate the content validity of the A/CS domain. A psychometric evaluation was conducted on the A/CS domain, and symptoms and concerns subscales, using data from previously completed phase III clinical trials (ROMANA1 [N = 474] and ROMANA2 [N = 488]). RESULTS: Anorexia-related symptoms were highly relevant to participants and had important impacts on their lives including energy levels, and physical, social, and psychological functioning. The majority of participants endorsed the A/CS domain items and found them to be easily understood, relevant, and comprehensive. Confirmatory factor analyses established that the A/CS symptoms and concerns subscales provided an acceptable fit as single factor models in ROMANA1 and ROMANA2. Reliability, validity, and responsiveness were established for the 12item A/CS domain, 5item anorexia symptoms subscale, and 4-item anorexia concerns subscale. CONCLUSIONS: These scales have good content validity, favorable psychometric properties, and can be used for characterizing the effect of treatment on anorexia symptoms and/or anorexia-related concerns in patients with NSCLC.