Approaches to the Assessment of Clinical Benefit of Treatments for Conditions That Have Heterogeneous Symptoms and Impacts: Potential Applications in Rare Disease.

OBJECTIVES: Evaluating the clinical benefit of interventions for conditions with heterogeneous symptom and impact presentations is challenging. The same condition can present differently across and within individuals over time. This occurs frequently in rare diseases. The purpose of this review was to identify (1) assessment approaches used in clinical trials to address heterogeneous manifestations that could be relevant in rare disease research and (2) US Food and Drug Administration (FDA)-approved labeling claims that used these approaches. METHODS: A targeted literature review was conducted examining peer-reviewed publications and FDA-approved labeling claims from January 2002 to July 2020, focusing on claims incorporating clinical outcome assessments. Approaches were then assessed for their potential application in rare diseases. RESULTS: A total of 6 assessment approaches were identified: composite or other multicomponent endpoints, multidomain responder index, most bothersome symptom (MBS), goal attainment scaling, sliding dichotomy, and adequate relief. A total of 59 FDA-approved labeling claims associated with these approaches were identified: composite or other multicomponent endpoints (n=49), MBS (n=9), and adequate relief (n=1). A total of 10 FDA-approved labeling claims, all using multicomponent endpoints, were identified for rare diseases. CONCLUSIONS: Multicomponent, MBS, and adequate relief have been included in FDA-approved labeling claims. Multicomponent endpoints, including composite endpoints, were the most frequent way to address heterogeneous manifestations of both common and rare diseases. MBS may be acceptable to regulators, whereas multidomain responder index is unlikely to be. The goal attainment scaling and adequate relief approaches may have potential utility in rare disease trials, assuming the theoretical and statistical challenges inherent in each approach are managed.

Patient preferences and health state utilities associated with the treatment process of antiretroviral therapy for people living with HIV.

PURPOSE: People living with HIV (PLHIV) have reported challenges associated with daily oral antiretroviral therapy (ART), including missed doses, negative psychological impact, and difficulty remaining discreet while at home or traveling. Recently approved long-acting injectable (LAI) ART may help eliminate these concerns. The purpose of this study was to examine patient preferences and estimate health state utilities associated with oral and LAI treatment for ART. METHODS: Four health state vignettes were developed based on published literature, clinician interviews, and a pilot study. All vignettes included the same description of HIV, but differed in treatment regimens: (A) single daily oral tablet, (B) two daily oral tablets, (C) injections once monthly, and (D) injections every two months. PLHIV in the UK reported their preferences and valued the health states in time trade-off utility interviews. RESULTS: The sample included 201 PLHIV (83.1% male; mean age = 44.9y). The health states frequently selected as most preferable were D (n = 119; 59.2%) and A (n = 75; 37.3%). Utility differences among health states were relatively small, which is typical for treatment process utilities (mean utilities: A, 0.908; B, 0.905; C, 0.900; D, 0.910). Statistically significant differences in utility were found for one vs. two tablets and injections every month vs. every two months (p < 0.001). Participants' quotations highlight the wide range of reasons for treatment process preferences. CONCLUSIONS: Current results indicate that many PLHIV would prefer LAI ART. The reported utilities may be useful in economic modeling comparing oral vs. LAI ART.

Focused Neck Ultrasound and Lymph Node Sampling by Respiratory Physicians in Suspected Lung Cancer.

BACKGROUND: Malignant cervical lymphadenopathy in the setting of lung cancer represents N3 disease, and neck ultrasound (NUS) with sampling is described in the Royal College of Radiologists ultrasound training curriculum for the non-radiologists. This study reviews the incorporation of NUS +/- biopsy in the routine practice of a lung cancer fast-track clinic in the UK. METHODS: We retrospectively assessed 29 months of activity of a lung cancer fast-track clinic. Systematic focused NUS was conducted in suspected thoracic malignancy, sampling nodes with a ≥5-mm short axis, under real-time US using a linear probe (5-12 Mhz). Fine-needle aspirations (FNAs) with or without 18 Ga core biopsies were taken. RESULTS: Between August 2017 and December 2019, of 152 peripheral lymph nodes (LNs)/deposits sampled, 98 (64.5%) were supraclavicular fossa LNs with median [IQR] size 12 [8-18] mm. Core biopsies were performed in 54/98 (55%) patients, while all patients had FNAs. No complications occurred. The representative yield was 90/95 (94.7%) in cases with suspected cancer. No difference was seen between FNA versus core biopsy (p = 0.44). Of the 5 non-diagnostic samples, one was FNA only. The commonest diagnosis was lung cancer in 66/98 (67.3%). PDL-1 was sufficient in 35/36 tested (97.2%). ALK-FISH was successful in 24/25 (96%) cases. EGFR mutation analysis was successful in 28/31 (90.3%) cases. Median time from clinic to initial diagnosis was 7 [5-10] days. Computed tomography (CT) scans reported no significant lymphadenopathy in 18/96 (18.7%) cases, yet 10/18 (55.5%) cases were positive for malignancy. CONCLUSION: Neck nodal sampling by respiratory physicians was safe, timely, with a high diagnostic yield and suitability for molecular testing. Neck US can provide a timely diagnosis in cases that may be missed by CT alone.

Undergraduate students' perspectives of healthcare professionals' use of shared decision-making skills.

Essential for future healthcare professionals (HCPs) to delivering ethical and empathetic patient-centred care (PCC) as a team is the understanding of appropriate shared decision-making (SDM) responses when facilitating discussions with patients and family members. The purpose of this study was to evaluate undergraduate students' perspectives about HCPs' use of SDM as described in a case-study reflection assignment. An exploratory qualitative approach was used to analyse student-reflection assignments. The sample included 42 undergraduate students enrolled in an interprofessional education (IPE) course at a Midwest university based in the United States. Data consisted of student responses in a course reflection assignment that captured their perspectives about recommended SDM responses by HCPs. Student assignments were randomly selected using stratified sampling to provide representation of eight HCP roles. Analysis revealed two themes related to students' use of SDM responses. Results provide evidence supporting the tenet that through IPE, healthcare students can develop an understanding of SDM and ethical principles related to PCC.

Prophylactic radiotherapy for the prevention of procedure-tract metastases after surgical and large-bore pleural procedures in malignant pleural mesothelioma (SMART): a multicentre, open-label, phase 3, randomised controlled trial.

BACKGROUND: The use of prophylactic radiotherapy to prevent procedure-tract metastases (PTMs) in malignant pleural mesothelioma remains controversial, and clinical practice varies worldwide. We aimed to compare prophylactic radiotherapy with deferred radiotherapy (given only when a PTM developed) in a suitably powered trial. METHODS: We did a multicentre, open-label, phase 3, randomised controlled trial in 22 UK hospitals of patients with histocytologically proven mesothelioma who had undergone large-bore pleural interventions in the 35 days prior to recruitment. Eligible patients were randomised (1:1), using a computer-generated sequence, to receive immediate radiotherapy (21 Gy in three fractions within 42 days of the pleural intervention) or deferred radiotherapy (same dose given within 35 days of PTM diagnosis). Randomisation was minimised by histological subtype, surgical versus non-surgical procedure, and pleural procedure (indwelling pleural catheter vs other). The primary outcome was the incidence of PTM within 7 cm of the site of pleural intervention within 12 months from randomisation, assessed in the intention-to-treat population. This trial is registered with ISRCTN, number ISRCTN72767336. FINDINGS: Between Dec 23, 2011, and Aug 4, 2014, we randomised 203 patients to receive immediate radiotherapy (n=102) or deferred radiotherapy (n=101). The patients were well matched at baseline. No significant difference was seen in PTM incidence in the immediate and deferred radiotherapy groups (nine [9%] vs 16 [16%]; odds ratio 0·51 [95% CI 0·19-1·32]; p=0·14). The only serious adverse event related to a PTM or radiotherapy was development of a painful PTM within the radiotherapy field that required hospital admission for symptom control in one patient who received immediate radiotherapy. Common adverse events of immediate radiotherapy were skin toxicity (grade 1 in 50 [54%] and grade 2 in four [4%] of 92 patients vs grade 1 in three [60%] and grade 2 in two [40%] of five patients in the deferred radiotherapy group who received radiotherapy for a PTM) and tiredness or lethargy (36 [39%] in the immediate radiotherapy group vs two [40%] in the deferred radiotherapy group) within 3 months of receiving radiotherapy. INTERPRETATION: Routine use of prophylactic radiotherapy in all patients with mesothelioma after large-bore thoracic interventions is not justified. FUNDING: Research for Patient Benefit Programme from the UK National Institute for Health Research.

Using a real-life case scenario to integrate additional health professions students into an existing interprofessional team seminar.

The World Health Organization stated that the goal of interprofessional education (IPE) is to prepare students as collaboration-ready members of interprofessional care teams. Educators try to create meaningful and relevant learning experiences for multiple health professions students. A longitudinal Interprofessional Team Seminar (IPTS) course includes over 650 students from seven health professions at the professional training level. Recommendations from the National Athletic Trainers' Association (NATA) promote the inclusion of athletic training (AT) students in IPE initiatives. A new IPTS module included AT students focusing on the attributes of rapidly forming and different care teams as the patient transitions from an on-field injury, to acute care, inpatient care, and rehabilitative care, and back to activities of daily living. Qualitative review of reflections from the students assessed the impact of these IPTS modules. The intentional design of this course, focusing on behaviours of collaborative practice and supporting students to be collaboration ready, effectively introduced and highlighted profession-specific strengths and unique contributions to team-based care.

Qualitative interviews to support development of a patient-reported companion measure to the Glucocorticoid Toxicity Index.

INTRODUCTION: Glucocorticoids (GCs) are associated with multiple toxicities that have substantial impact on patients. We conducted qualitative interviews with patients to identify the toxicities that are most relevant from their perspective, with the goal of creating a patient-reported companion measure to the Glucocorticoid Toxicity Index (GTI), a clinician-facing instrument. METHODS: Thirty-one patients with recent or current GC use participated in concept elicitation interviews. Participants received GC treatment for myasthenia gravis, chronic inflammatory demyelinating polyradiculoneuropathy, vasculitis, or systemic lupus erythematosus. Transcripts were coded following a thematic analysis approach. RESULTS: Participants reported more than 100 toxicities they believed to be associated with their GC medications. Common toxicities included weight gain (87%), increased appetite (84%), insomnia/sleep problems (77%), cognitive impairment/brain fog (71%), easy bruising (68%), anxiety (65%), irritability/short temper (65%), and osteoporosis (39%). These toxicities often centered on self-esteem, neuropsychiatric effects, skin toxicities, and musculoskeletal function. They can be categorized into domains such emphasizing neuropsychiatric, metabolic/endocrine, musculoskeletal, and dermatological effects, highlighting aspects of GC toxicity that patients are uniquely positioned to appreciate and report. CONCLUSION: Our results confirm that the toxicities associated with GCs are pervasive and diverse, with substantial impact on patients' lives. These data will be used to inform the development of a patient-reported outcome measure assessing GC toxicity. This patient-reported instrument will be designed to complement the clinician-reported GTI, facilitating a more detailed understanding of the nuances of change in GC toxicity.

Health state utilities associated with weight loss: preferences of people with type 2 diabetes and obesity in Japan.

AIMS: Health state utilities associated with weight change are needed for cost-utility analyses (CUAs) examining the value of treatments for type 2 diabetes and obesity. Previous studies have estimated the utility benefits associated with various amounts of weight reduction in the US and Europe, but preferences for weight change in Asian cultures may differ from these published values. The purpose of this study was to estimate utilities associated with reductions in body weight based on preferences of individuals with type 2 diabetes and obesity in Japan. METHODS: Health state vignettes represented type 2 diabetes with respondents' own current weight and weight reductions of 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, and 20%. Utilities were elicited in time trade-off interviews with a sample of respondents in Japan with type 2 diabetes and body mass index (BMI) ≥25 kg/m2 (the cutoff for obesity in Japan). RESULTS: Analyses were conducted with data from 138 respondents (84.8% male; mean age = 58.0 years; mean BMI = 29.4 kg/m2) from all eight regions of Japan. Utility gains gradually increased with rising percentage of weight reductions ranging from 2.5% to 15%. Weight reductions of 2.5% to 15% resulted in utility increases of 0.013 to 0.048. The health state representing a 20% weight reduction yielded a wide range of preferences (mean utility increase of 0.044). Equations are recommended for estimating utility change based on any percentage of weight reduction (up to 20%) in Japanese people with type 2 diabetes and obesity. LIMITATIONS: This study was conducted in a sample with limited representation of patients with BMI >35 kg/m2 (n = 13) and relatively few women (n = 21). CONCLUSION: Results may be used to provide inputs for CUAs examining the value of treatments that are associated with weight loss in patients with type 2 diabetes and obesity in Japan.

Health State Utilities Associated with False-Positive Cancer Screening Results.

INTRODUCTION: Early cancer detection can significantly improve patient outcomes and reduce mortality rates. Novel cancer screening approaches, including multi-cancer early detection tests, have been developed. Cost-utility analyses will be needed to examine their value, and these models require health state utilities. The purpose of this study was to estimate the disutility (i.e., decrease in health state utility) associated with false-positive cancer screening results. METHODS: In composite time trade-off interviews using a 1-year time horizon, UK general population participants valued 10 health state vignettes describing cancer screening with true-negative or false-positive results. Each false-positive vignette described a common diagnostic pathway following a false-positive result suggesting lung, colorectal, breast, or pancreatic cancer. Every pathway ended with a negative result (no cancer detected). The disutility of each false positive was calculated as the difference between the true-negative and each false-positive health state, and because of the 1-year time horizon, each disutility can be interpreted as a quality-adjusted life-year decrement associated with each type of false-positive experience. RESULTS: A total of 203 participants completed interviews (49.8% male; mean age = 42.0 years). The mean (SD) utility for the health state describing a true-negative result was 0.958 (0.065). Utilities for false-positive health states ranged from 0.847 (0.145) to 0.932 (0.059). Disutilities for false positives ranged from - 0.031 to - 0.111 (- 0.041 to - 0.111 for lung cancer; - 0.079 for colorectal cancer; - 0.031 to - 0.067 for breast cancer; - 0.048 to - 0.088 for pancreatic cancer). CONCLUSION: All false-positive results were associated with a disutility. Greater disutility was associated with more invasive follow-up diagnostic procedures, longer duration of uncertainty regarding the eventual diagnosis, and perceived severity of the suspected cancer type. Utility values estimated in this study would be useful for economic modeling examining the value of cancer screening procedures.

Health state utilities associated with hyperphagia: Data for use in cost-utility models.

Objective: Rare genetic diseases of obesity typically present with hyperphagia, a pathologic desire to consume food. Cost-utility models assessing the value of treatments for these rare diseases will require health state utilities representing hyperphagia. This study estimated utilities associated with various hyperphagia severity levels. Methods: Four health state vignettes were developed using published literature and clinician input to represent various severity levels of hyperphagia. Utilities were estimated for these health states in a time trade-off elicitation study in a UK general population sample. Results: In total, 215 participants completed interviews (39.5% male; mean age 39.1 years). Mean (SD) utilities were 0.98 (0.02) for no hyperphagia, 0.91 (0.10) for mild hyperphagia, 0.70 (0.30) for moderate hyperphagia, and 0.22 (0.59) for severe hyperphagia. Mean (SD) disutilities were -0.08 (0.10) for mild, -0.28 (0.30) for moderate, and -0.77 (0.58) for severe hyperphagia. Conclusions: These data show increasing severity of hyperphagia is associated with decreased utility. Utilities associated with severe hyperphagia are similar to those of other health conditions severely impacting quality of life (QoL). These findings highlight that treatments addressing substantial QoL impacts of severe hyperphagia are needed. Utilities estimated here may be useful in cost-utility models of treatments for rare genetic diseases of obesity.

Endobronchial Ultrasound-guided Sampling of Centrally Located Intrapulmonary Tumors Provides Suitable Material for Diagnostic and Molecular Testing.

BACKGROUND: Curvilinear endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a key diagnostic and staging procedure for patients with suspected lung cancer. However, sampling centrally located intrapulmonary tumors is feasible but less well established. METHODS: We retrospectively evaluated the diagnostic utility of EBUS-TBNA in patients who underwent sampling of centrally located intrapulmonary tumors. Diagnostic accuracy, sample suitability for molecular testing, and complications were assessed. RESULTS: Between January 2015 and April 2021, 102 EBUS-TBNA procedures sampled centrally located intrapulmonary tumors in 99 patients. The median age was 70 [interquartile range, 63 to 75] years and 51% (51/99) were male. The commonest site was the right upper lobe (n=42/99; 42%). The median tumor size was 29 [interquartile range, 21 to 35] mm. The diagnostic yield was 88/102 (86%) with a false negative rate of 14% (14/102). In addition to intrapulmonary tumor sampling, lymph nodes were sampled in 65/102 procedures and 30/65(46%) were positive for lung cancer. Cancer was diagnosed in 87/99 (88%) cases. When requested, molecular testing was adequate in ≥94% of samples. Complications included minor bleeding in 6/102 (6%) with 2 requiring cold saline instillation, desaturation in 1/102 (1%), and tachycardia in 1/102(1%). One procedure was abandoned due to patient tachycardia. Delayed complications occurred in 1 patient who was hospitalized ≤7 days with pneumonia. CONCLUSION: EBUS-TBNA sampling of centrally located intrapulmonary tumors provides similar diagnostic accuracy to lymph node sampling, provides suitable material for molecular testing, and has a low complication rate.

A retrospective cohort study on COVID-19 at 2 Los Angeles hospitals: Older age, low triage oxygenation, and chronic kidney disease among the top risk factors associated with in-hospital mortality.

Los Angeles, California became a warzone of COVID-19 infections with up to one death every 10 minutes at the end of 2020. As resources thinned, and ICU beds and ventilators became scarce, physicians began agonizing over potentially rationing medical care. In this study, we conducted a retrospective cohort analysis of 7,429 confirmed COVID-19 positive patients from two community hospitals in Los Angeles, California between March 16, 2020 and June 9, 2021. We applied the Cox proportional hazards regression model to determine the risk factors most strongly associated with in-hospital mortality. Using the multivariable Cox proportional hazards model, there was a higher hazard ratio (HR) for mortality in patients who were older (age ≥60 years) [HR 2.189, 95% CI 1.991-2.407, p<0.001], had low triage oxygenation < 90% [HR 1.439, 95% CI 1.339-1.546, p<0.001], had chronic kidney disease (CKD) [HR 1.348, 95% CI 1.234-1.496, p = 0.001)], and who were obese (BMI ≥ 30 kg/m^2) [HR 1.221, 95% CI 1.155-1.340, p = 0.003)]. Overall, our study concluded that age ≥ 60 years, low triage oxygenation less than 90%, chronic kidney disease, and obesity were the top patient characteristics associated with increased mortality for both the univariate and multivariate Cox proportional hazards model analyses. Furthermore, by separating our data set into a development and validation set, we created a novel prediction tool to forecast in-hospital mortality and achieved 86% accuracy.

Health State Utilities for Adverse Events Associated with Chimeric Antigen Receptor T-Cell Therapy in Large B-Cell Lymphoma.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy provides effective treatment for large B-cell lymphoma (LBCL). Cost-utility analyses examining and comparing the value of these treatments require health state utilities representing key characteristics to differentiate among therapies. This study estimated utilities for adverse events (AEs) associated with CAR T-cell therapy, including cytokine release syndrome (CRS) and neurological events (NEs). METHODS: Health state vignettes were drafted based on literature review, AE reports from a trial of CAR T-cell therapy, and clinician input. Health states were valued in time trade-off interviews with general population participants in the UK. The first vignette described relapsed/refractory LBCL treated with CAR T-cell therapy without AEs. Five other vignettes had the same LBCL and treatment description, with the addition of an AE. Disutilities (i.e., utility decrease) associated with these AEs were calculated by subtracting the utility of the health state without AEs from those of the other health states. RESULTS: Interviews were completed with 218 participants (50% male; mean age 49 years). Mean (standard deviation [SD]) utility for CAR T-cell therapy without AEs was 0.73 (0.30). Mean (SD) disutilities associated with CRS were -0.01 (0.04) for grade 1, -0.05 (0.09) for grade 2, and -0.23 (0.24) for grade 3/4. Mean (SD) disutilities associated with NEs were -0.04 (0.07) for grade 1/2 and -0.18 (0.22) for grade 3/4. CONCLUSIONS: More severe AEs were associated with greater disutilities. Health state utilities estimated in this study may be useful in cost-effectiveness models examining the value of CAR T-cell therapy in patients with LBCL.

Time between endobronchial ultrasound needle passes as a metric to monitor progress of trainees.

BACKGROUND: Methods to assess and track progress of new endobronchial ultrasound (EBUS) operators and trainees is desirable to ensure training goals and procedural competence are achieved. Relying on the diagnostic yield or on question-based assessments alone is not sufficient. This study examined the longitudinal change in times taken between needle passes (needle pass time; NPT) during EBUS lymph node sampling as a metric to monitor progress. RESEARCH DESIGN AND METHODS: :The EBUS database of a tertiary hospital was accessed to extract data on the first 50 EBUS procedures for three trainees. The NPT was derived using PACS images that are stored to document every needle pass during an EBUS procedure and an average NPT was calculated. RESULTS: Between the three trainees, 157 procedures were carried out within the study period with 302 nodal stations sampled. The mean NPT (n = 204 stations) was 2:49 ± 0:49 mins. The mean node short axis diameter was 15.5 ± 8.7 mm. There was a negative correlation between node size and time per pass (r - 0.146, p = 0.045).The average NPT showed a negative correlation with procedure order through the first 50 procedures. Less variation between procedures was noted for the three trainees from the 30th procedure onward. On multivariate regression, NPT was significantly associated with procedure order regardless of station sampled or lymph node diameter. CONCLUSION: NPT is novel, easy, and robust metric that can potentially help ensure EBUS trainees are advancing in a given training program.

Health state utilities associated with weight loss in type 2 diabetes and obesity.

INTRODUCTION: Health state utilities associated with weight change are needed as inputs for cost-utility analyses (CUAs) examining the value of treatments for obesity and type 2 diabetes (T2D). Although some pharmaceutical treatments currently in development are associated with substantial weight loss, little is known about the utility impact of weight decreases greater than 10%. The purpose of this study was to estimate utilities associated with body weight decreases up to 20% based on preferences of individuals with obesity, with and without T2D. METHODS: Health state vignettes were developed to represent respondents' own current weight and weight decreases of 2.5, 5, 10, 15, and 20%. Health state utilities were elicited in time trade-off interviews in two UK locations (Edinburgh and London) with a sample of participants with obesity, with and without T2D. Mean utility increases associated with each amount of weight decrease were calculated. Regression analyses were performed to derive a method for estimating utility change associated with weight decreases. RESULTS: Analyses were conducted with data from 405 individuals with obesity (202 with T2D, 203 without T2D). Utility increases associated with various levels of weight decrease ranged from 0.011 to 0.060 in the subgroup with T2D and 0.015 to 0.077 in the subgroup without T2D. All regression models found that the percentage of weight decrease was a highly significant predictor of change in utility (p < .0001). The relationship between weight change and utility change did not appear to be linear. Equations are recommended for estimating utility change based on the natural logarithm of percentage of weight decrease. DISCUSSION: Results of this study may be used to provide inputs for CUAs examining and comparing the value of treatments that are associated with substantial amounts of weight loss in patients with obesity, with or without T2D.

A Review of Interventional Trials in Youth-Onset Type 2 Diabetes: Challenges and Opportunities.

INTRODUCTION: In recent decades, the dramatic rise of obesity among youth in the US has been accompanied by a rise in the prevalence of type 2 diabetes (T2D) in this population. This alarming trend underscores the importance of conducting trials to evaluate new therapies in children with T2D. METHODS: A targeted review of peer-reviewed literature and trials registered on www.clinicaltrials.gov was conducted in January 2021 to identify pharmaceutical interventional studies in youth with T2D. Information regarding enrollment data, study design elements, subjects' baseline characteristics, and key treatment outcomes was documented. RESULTS: Among the 16 clinical studies included in this review, only five appeared to meet projected enrollment targets in < 4 years. Although three other studies met recruitment targets, two took approximately 5 years to complete and the third took nearly 10 years. CONCLUSIONS: Despite legislation requiring evaluation of pharmaceutical treatments in pediatric populations, surprisingly few interventional studies have been conducted in children with T2D. This review highlights that recruitment challenges may be impeding the conduct and completion of interventional studies. Consequently, few pharmaceutical treatments have been proven to be effective and approved for children with T2D. Metformin and liraglutide remain the only non-insulin treatments formally approved in the US for use in this population. More clinical research is needed to support regulatory decision-making as well as treatment decisions for children with T2D in clinical settings. Sponsors and investigators will need to implement strategies for improving trial enrollment as well as work with regulatory agencies to develop novel study designs that may require fewer patients.

Measuring respiratory symptoms in moderate/severe asthma: evaluation of a respiratory symptom tool, the E-RS®: COPD in asthma populations.

BACKGROUND: Symptom constructs included in the Evaluating Respiratory Symptoms in Chronic Obstructive Pulmonary Disease (E-RS®: COPD) tool may be relevant to patients with asthma. The purpose of this study was to evaluate content validity and psychometric performance of the E-RS: COPD in moderate/severe asthma patients. METHODS: Content validity of the E-RS: COPD was evaluated in patients with moderate/severe asthma using concept elicitation and cognitive debriefing interviews. Secondary analyses using data from two clinical trials in patients with moderate/severe asthma evaluated the factor structure of the E-RS: COPD plus two supplementary items (wheeze; shortness of breath with strenuous physical activity) and assessed psychometric properties of the tool, which will be referred to as E-RS®: Asthma when used in asthma populations. RESULTS: Qualitative interviews (N = 25) achieved concept saturation for asthma respiratory symptoms. Concepts in the E-RS: COPD were relevant to patients and instructions were understood. Most patients (19/25; 76%) reported experiencing all concepts in the E-RS: COPD; no patients indicated missing symptoms. Secondary analyses of clinical trial data supported the original factor structure (RS-Total and three symptom-specific subscales). The two supplemental items did not fit with this factor structure and were not retained. RS-Total and subscale score reliability was high (internal consistency [α] > 0.70). Validity was demonstrated through significant (P < 0.0001) relationships with the St George's Respiratory Questionnaire (SGRQ) and Asthma Symptom Severity scale. E-RS: Asthma was responsive to change when evaluated using SGRQ, Patient Global Impression of Change and Asthma Quality of Life Questionnaire as anchors (P < 0.0001). Clinically meaningful change thresholds were also identified (RS-Total: - 2.0 units). CONCLUSIONS: The E-RS: Asthma is reliable and responsive for evaluating respiratory symptoms in patients with moderate/severe asthma.

Estimating health state utilities associated with a rare disease: familial chylomicronemia syndrome (FCS).

Aims: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder with no currently approved therapies. Treatments are in development, and cost-utility analyses will be needed to examine their value. These models will require health state utilities representing FCS. Therefore, the purpose of this study was to estimate utilities for FCS and an associated episode of acute pancreatitis (AP).Methods: Because it is not feasible to gather a large enough sample of patients with this extremely rare condition to complete standardized preference-based measures, vignette-based methods were used to estimate utilities. In time trade-off interviews, general population participants in the UK and Canada valued health state vignettes drafted based on literature review, clinician input, and interviews with patients. Four health states described variations of FCS. A fifth health state, describing AP, was added to one of the other health states to evaluate its impact on utility.Results: A total of 308 participants provided utility data (208 UK; 100 Canada). Mean utilities for FCS health states ranged from 0.46 to 0.83, with higher triglycerides, more severe symptoms, and a history of AP associated with lower utility values. The disutility (i.e. utility decrease) of AP ranged from -0.17 to -0.25, with variations depending on the health state to which it was added. Utility means were similar in the UK and Canada.Conclusions: The vignette-based approach is useful for estimating utilities of a rare disease. The health state utilities derived in this study would be useful in models examining cost-effectiveness of treatments for FCS.

The association of individual and facility characteristics with psychiatric hospitalization among nursing home residents.

OBJECTIVE: To examine resident and facility characteristics associated with psychiatric hospitalizations (PH) for Medicaid enrolled nursing home (NH) residents. METHODS: Participants were all Medicaid enrolled NH residents (n = 32,604) from all Medicaid certified nursing homes in Florida (n = 584) with complete data. We used individual demographic and diagnostic characteristics, as well as facility characteristics, to explore risk of psychiatric hospitalization in this dataset. RESULTS: Using generalized estimating equations, we found that younger age, male gender, poor physical health, serious mental illness, dementia, and drug use disorder were associated with risk of psychiatric hospitalization. Most notably, residents under 65 were more than three times more likely to undergo psychiatric hospitalization and dementia was associated with a three-fold increase in the risk of psychiatric hospitalization. Predictors of PH differed somewhat for younger and older residents. Among facility characteristics, greater facility size, low proportion of those paying via Medicare and high proportion of residents with serious mental illness were associated with increased risk of psychiatric hospitalization, whereas, low proportion of residents paying via Medicaid, high proportion of residents paying via Medicare, and low proportion of resident with serious mental illness were associated with reduced risk. CONCLUSIONS: Both resident and facility characteristics impact risk for psychiatric hospitalization. Attention to identified predictors may reduce risk and improve outcomes for nursing home residents.

Health state utilities associated with treatment options for acute myeloid leukemia (AML).

Aims: Acute myeloid leukemia (AML) treatment typically involves remission induction chemotherapy followed by consolidation chemotherapy. New treatments for AML have recently been introduced, including a chemotherapy formulation called CPX-351, which is administered via less time-intensive IV infusion than the standard "7 + 3" continuous infusion regimen of cytarabine plus an anthracycline. The purpose of this study was to estimate utilities that could be used in economic modeling of AML treatment. Materials and methods: In time trade-off interviews, participants from the UK general population valued 12 health states drafted based on literature and clinician interviews. To identify disutility associated with chemotherapy, two types of induction and four types of consolidation were added to an otherwise identical health state describing AML. The decrease in utility when adding these chemotherapy regimens represents the disutility of each regimen. Five additional health states were valued to estimate utilities associated with other AML treatments. Results: Two hundred participants completed interviews. Mean (SD) utilities were 0.55 (0.31) for pre-treatment AML and 0.66 (0.29) for AML in temporary remission. Adding any chemotherapy significantly decreased utility (p < 0.0001). Induction had a mean disutility of -0.11 with CPX-351 and -0.15 with 7 + 3. Mean disutility for consolidation ranged from -0.03 with outpatient CPX-351 to -0.11 with inpatient 5 + 2. Utilities are also reported for other AML treatments (e.g. transplant, low-intensity chemotherapy). Limitations: One limitation is that the differences in adverse event profiles between the treatment regimens were based on clinician opinion. Future use of CPX-351 in clinical trials or clinical settings will provide additional information on its adverse event profile. Conclusions: While all chemotherapy regimens were associated with disutility, regimens with shorter hospitalization and less time-intensive infusion were generally perceived as preferable. These utilities may be useful in cost-utility models comparing the value of AML treatments.