Measuring Frailty Using Patient-Reported Outcomes (PRO) Data: A Feasibility Study in Patients with Multiple Myeloma.

PURPOSE: The objective of this retrospective study was to determine the feasibility of measuring frailty using patient responses to relevant EORTC QLQ-C30 items as proxy criteria for the Fried Frailty Phenotype, in a cohort of patients with Relapsed/Refractory Multiple Myeloma (RRMM). METHODS: Data were pooled from nine Phase III randomized clinical trials submitted to the FDA for regulatory review between 2010 and 2021, for the treatment of RRMM. Baseline EORTC QLQ-C30 responses were used to derive a patient-reported frailty phenotype (PRFP), based on the Fried definition of frailty. PRFP was assessed for internal consistency reliability, structural validity, and known groups validity. RESULTS: This study demonstrated the feasibility of adapting patient responses to relevant EORTC QLQ-C30 items to serve as proxy Fried frailty criteria. Selected items were well correlated with one another and PRFP as a whole demonstrated adequate internal consistency reliability and structural validity. Known groups analysis demonstrated that PRFP could be used to detect distinct comorbidity levels and distinguish between different functional profiles, with frail patients reporting more difficulty in walking about, washing/dressing, and doing usual activities, as compared to their pre-frail and fit counterparts. Among the 4928 patients included in this study, PRFP classified 2729 (55.4%) patients as fit, 1209 (24.5%) as pre-frail, and 990 (20.1%) as frail. CONCLUSION: Constructing a frailty scale from existing PRO items commonly collected in cancer trials may be a patient-centric and practical approach to measuring frailty. Additional psychometric evaluation and research is warranted to further explore the utility of such an approach.

Floor and ceiling effects in the EORTC QLQ-C30 Physical Functioning Subscale among patients with advanced or metastatic breast cancer.

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 Physical Functioning subscale is a widely used patient-reported outcome measure that quantifies cancer patients' physical functioning. Strong floor/ceiling effects can affect a scale's sensitivity to change. The aim of this study was to characterize floor/ceiling effects of the physical functioning domain in patients with advanced/metastatic breast cancer enrolled in commercial clinical trials and a community-based trial. METHODS: The clinical trial cohort comprised patients from 5 registrational trials submitted to the Food and Drug Administration for review (2010-2017). The community cohort comprised a subgroup of patients from the Alliance Patient Reported Outcomes to Enhance Cancer Treatment (PRO-TECT) trial. The distribution of patient responses to Physical Functioning items and the summed score were assessed at the baseline and 3-month follow-up for both cohorts. Descriptive statistics were used to determine floor/ceiling effects at the item and scale levels. RESULTS: The clinical trial cohort and the community cohort consisted of 2407 and 178 patients, respectively. Twenty-four percent or more of the respondents reported "not at all" for having trouble/needing help with each Physical Functioning item across both cohorts and measurement time points. Fourteen to twenty percent of the patients scored perfectly (100 of 100) on the Physical Functioning subscale summary measure (where higher scores indicated better physical functioning) across both cohorts and time points. CONCLUSIONS: Minor floor effects and notable ceiling effects were found at the item and scale levels of the Physical Functioning subscale, regardless of cohort, and this creates some uncertainty about its ability to detect changes in physical functioning among high-functioning patients. Investigators may consider adding additional high-functioning items from the EORTC's item library to more accurately describe the impact of anticancer treatment on patients' physical functioning.

An exploration of the mental health and well-being of postgraduates in pharmacy and pharmaceutical science programs.

BACKGROUND: Postgraduate students enrolled at colleges and schools of pharmacy are at an increased risk of experiencing difficulties with mental health and well-being; however, there is minimal work exploring mental health and well-being among postgraduates in pharmacy and pharmaceutical science programs. OBJECTIVES: (1) to explore the current mental health and well-being of pharmacy postgraduates, (2) to identify factors that promote and hinder mental well-being at the individual and organizational levels, and (3) to explore perspectives regarding organizational priorities, resources, and support tools that may improve the mental health and well-being of postgraduates in pharmacy and pharmaceutical science programs. METHODS: This study conducted a cross-sectional survey of postgraduates in pharmacy and pharmaceutical science programs. Surveys were distributed electronically via the American Pharmacists Association's (APhA) broadcast e-mail system to postgraduate members and through the professional networks of APhA Academy of Pharmaceutical Research and Science (APhA-APRS) Postgraduate Advisory Committee members. The survey had 3 sections: demographics, current mental health and well-being status, and barriers and facilitators to mental health and well-being. Descriptive statistics and frequencies were generated for quantitative survey responses. Open-ended responses were categorized and presented with each question. RESULTS: Fifty-one responses were analyzed. The sample had a mean age of 29.0 ± 6.6 years, included 58.8% women or womxn, and most were in doctoral programs (58.8%) for 2.3 ± 2.7 years in various disciplines. There were 27.5% of respondents categorized as having flourishing mental health and 7.8% with languishing mental health. Factors such as practicing self-care or engaging in hobbies (94.1% for each) were most commonly rated as having a positive impact on well-being, and societal racism and discrimination (66.7%) was most commonly reported as having a negative effect on well-being. Top priorities for postgraduates included work-life balance, career prospects, meaningful relationships, and financial concerns. CONCLUSION: There are a number of organizational and institutional priorities that may improve pharmacy and pharmaceutical science graduate students' mental health and well-being.

Reprint of: Examining Medicare Part D Medication Therapy Management program in the context of mental health.

OBJECTIVES: To describe and compare the delivery of medication therapy management (MTM) between Medicare beneficiaries with and without mental health conditions. DESIGN: Nationally representative cross-sectional study that used a 20% random sample of 2014 Medicare Parts A, B, and D data merged with a 100% sample of 2014 MTM data. SETTING AND PARTICIPANTS: Medicare beneficiaries continuously enrolled in Parts A, B, and D in 2014 were included in this study. Comprehensive medication review (CMR) use and MTM delivery were examined among a subset of 825,003 MTM-enrolled beneficiaries. OUTCOME MEASURES: Predisposing, enabling, and need characteristics were selected on the basis of the Andersen Behavioral Model of Health Services Use. Descriptive, bivariable, and multivariable logistic regression statistics were used to determine associations between beneficiary characteristics and MTM delivery. RESULTS: A total of 3,016,620 (43%) and 3,997,105 beneficiaries (57%) were categorized into mental health and nonmental health cohorts, respectively. MTM enrollment in the mental health cohort was significantly higher than that in the nonmental health cohort (17.4% vs. 7.5%, P < 0.001). However, once enrolled, a greater proportion of beneficiaries in the nonmental health cohort received CMRs (19.3% vs. 17.7%, P < 0.001). Patients in the mental health cohort were more likely to have hospitalization (22% vs. 9.2%, P < 0.001) or emergency department visit (25.2% vs. 11.5%, P < 0.001) and used more medications in 2014 (16 % vs. 12%, P < 0.001). The proportion of patients in the mental health cohort receiving a CMR in 2014 that had at least 1 medication-related problem (MRP) identified and resolved was higher than that of patients in the nonmental health cohort (24.8% vs. 20.6%, P < 0.001). CONCLUSION: Although patients with mental health conditions are more often enrolled into MTM, they are less likely to receive a CMR once enrolled. Given that this population has higher medical complexity and a higher MRP burden following a CMR, opportunities exist for pharmacists to enhance MTM delivery in this population.

Examining Medicare Part D Medication Therapy Management program in the context of mental health.

OBJECTIVES: To describe and compare the delivery of medication therapy management (MTM) between Medicare beneficiaries with and without mental health conditions. DESIGN: Nationally representative cross-sectional study that used a 20% random sample of 2014 Medicare Parts A, B, and D data merged with a 100% sample of 2014 MTM data. SETTING AND PARTICIPANTS: Medicare beneficiaries continuously enrolled in Parts A, B, and D in 2014 were included in this study. Comprehensive medication review (CMR) use and MTM delivery were examined among a subset of 825,003 MTM-enrolled beneficiaries. OUTCOME MEASURES: Predisposing, enabling, and need characteristics were selected on the basis of the Andersen Behavioral Model of Health Services Use. Descriptive, bivariable, and multivariable logistic regression statistics were used to determine associations between beneficiary characteristics and MTM delivery. RESULTS: A total of 3,016,620 (43%) and 3,997,105 beneficiaries (57%) were categorized into mental health and nonmental health cohorts, respectively. MTM enrollment in the mental health cohort was significantly higher than that in the nonmental health cohort (17.4% vs. 7.5%, P < 0.001). However, once enrolled, a greater proportion of beneficiaries in the nonmental health cohort received CMRs (19.3% vs. 17.7%, P < 0.001). Patients in the mental health cohort were more likely to have hospitalization (22% vs. 9.2%, P < 0.001) or emergency department visit (25.2% vs. 11.5%, P < 0.001) and used more medications in 2014 (16 % vs. 12%, P < 0.001). The proportion of patients in the mental health cohort receiving a CMR in 2014 that had at least 1 medication-related problem (MRP) identified and resolved was higher than that of patients in the nonmental health cohort (24.8% vs. 20.6%, P < 0.001). CONCLUSION: Although patients with mental health conditions are more often enrolled into MTM, they are less likely to receive a CMR once enrolled. Given that this population has higher medical complexity and a higher MRP burden following a CMR, opportunities exist for pharmacists to enhance MTM delivery in this population.

Patient-reported frailty phenotype (PRFP) vs. International Myeloma Working Group frailty index (IMWG FI) proxy: A comparison between two approaches to measuring frailty.

INTRODUCTION: Frailty assessments may help to identify patients at highest risk for treatment-related toxicity, early treatment discontinuation due to toxicity, and death in Multiple Myeloma. We aimed to compare the patient-reported frailty phenotype (PRFP) and a modified version of the International Myeloma Working Group frailty index (IMWG FI) in terms of their strengths, limitations, and classification of frailty in a cohort of patients with relapsed/refractory multiple myeloma (RRMM). MATERIALS AND METHODS: Data were pooled from six RRMM Phase 3 randomized clinical trials submitted to the Food and Drug Administration for regulatory review between 2010 and 2021. Patients were classified as fit, intermediate fit/pre-frail, or frail using both PRFP and the IMWG FI proxy. Agreement between the two approaches in classification of patient frailty was assessed using weighted Cohen's kappa. A contingency table and Venn diagram were generated to analyze overlap in categorization of patient frailty across the different severity groups. Descriptive statistics were used to summarize and compare the clinical and demographic characteristics of patients categorized as frail by PRFP vs. IMWG FI proxy. RESULTS: Of the 2,750 patients included in this analysis, IMWG FI proxy classified 16.4% (452) patients as frail, 28.1% (772) as intermediate fit/pre-frail, and 55.5% (1,526) as fit. Meanwhile, PRFP classified 21.7% (597) of patients as frail, 24.5% (675) as intermediate fit/pre-frail, and 53.8% (1478) as fit. Fair agreement was observed between PRFP and IMWG FI proxy (weighted Cohen's Kappa = 0.34 [0.31-0.37]). On average, patients who were categorized as frail by IMWG FI proxy were older and had higher Charlson Comorbidity Index scores than patients classified as frail by PRFP. In contrast, patients who were classified as frail by PRFP had worse EORTC QLQ-C30 Physical Functioning subscale summary scores as compared to patients in the IMWG FI proxy frail group (median score of 40 vs. 47 out of 100). DISCUSSION: Our analysis found fair concordance between IMWG FI proxy and PRFP. This demonstrates that while both frailty models measure the same underlying construct, the variables that constitute each approach may result in differing frailty categorizations for the same patient. Further prospective studies are needed to establish and compare the predictive and prognostic abilities of the different frailty indices in MM.

High rifaximin out-of-pocket costs are associated with decreased treatment retention among patients with hepatic encephalopathy.

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) is associated with significant morbidity and mortality for those with cirrhosis. Despite the known benefits of rifaximin use for HE, treatment retention remains low. This study aimed to evaluate the impact of out-of-pocket (OOP) rifaximin cost on treatment retention among commercially insured patients in the United States. METHODS: Adult patients with cirrhosis and HE were identified from the IBM MarketScan claims database. Those who began rifaximin treatment between January 1, 2011, and December 1, 2021 were included. Regression models were used to analyze the relationship between patients' 30-day OOP rifaximin cost and rifaximin retention (≥80% eligible days with rifaximin supply) at 180, 360, and 540 days. Models were controlled for patient demographic and clinical characteristics including age, sex, comorbid conditions, Charlson comorbidity index (CCI), and lactulose use. RESULTS: A total of 6839 adult patients were included. Most patients were between 55 and 64 years (57.1%), male (60.4%), and living in urban settings (84.6%). Treatment retention was low for all time periods; retention rates for rifaximin were 42%, 25%, and 16% at 180, 360, and 540 days, respectively. In multivariable analysis, 30-day OOP costs of ≥ $150 were associated with a decreased likelihood of rifaximin retention at 180, 360, and 540 days [relative risk (RR) = 0.67, RR = 0.62, and R = 0.60, respectively]. Younger age was associated with reduced treatment retention for all time periods. Metastatic cancer and depression were associated with reduced treatment retention at 180 days (RR = 0.70 and RR = 0.87, respectively). CONCLUSIONS: Rates of rifaximin treatment retention are low despite the known benefits of rifaximin use for breakthrough HE. High 30-day OOP cost is associated with reduced rifaximin treatment retention.

Patient-Reported Outcomes in Pediatric Cancer Registration Trials: A US Food and Drug Administration Perspective.

Pediatric patient-reported outcome (PRO) data can help inform the US Food and Drug Administration's (FDA's) benefit-risk assessment of cancer therapeutics by quantifying symptom and functional outcomes from the patient's perspective.This study assessed use of PROs in commercial pediatric oncology trials submitted to the FDA for regulatory review. FDA databases were searched to identify pediatric oncology product applications approved between 1997 and 2020. Sponsor-submitted documents were reviewed to determine whether PRO data were collected, which instruments were used, and the quality of collected data (ie, sample size, completion rates, and use of fit-for-purpose instruments). The role of PROs in each trial (endpoint hierarchy) was also recorded in addition to whether any PRO endpoints were included in product labeling.We reviewed 17 pediatric oncology applications, 4 of which included PRO data: denosumab, tisagenlecleucel, larotrectinib, and selumetinib. In these 4 instances, PROs served as exploratory endpoints and were not incorporated in product labeling. Trials that collected PRO data were phase II or phase I/II single-arm studies with sample sizes of 28 to 88 patients. Symptomatic adverse events (AEs) were characterized using clinician-reported Common Terminology Criteria for Adverse Events (CTCAE) without additional patient self-report.PROs were infrequently used in pediatric cancer registration trials. When PROs were used, PRO data were limited by lack of a clear research objective and corresponding prospective statistical analysis plan. Contemporary PRO symptom libraries, such as the National Cancer Institute's Pediatric PRO-CTCAE, may provide an opportunity to better evaluate the occurrence and impact of symptomatic AEs, from the patient's perspective, in pediatric oncology trials.

Maternal ADHD and Perinatal Prescription Stimulant Use.

OBJECTIVE: To describe patterns and predictors of perinatal prescription stimulant use. METHODS: We used MarketScan® commercial claims data (2013-2018) and a repeated cross-sectional study design to assess perinatal use of prescription stimulants. Clinical/demographic characteristics were compared across cohorts of women who continued versus discontinued stimulant treatment at various stages of pregnancy. Associations were tested for significance using chi-square tests (categorical variables) and independent t-tests (continuous variables). RESULTS: Out of 612,001 pregnancies, 15,413 involved pre-pregnancy stimulant use. Of these, stimulant treatment was discontinued prior to conception in 6,416 (42%), discontinued during trimester 1 in 5,977 (39%), and continued into later trimesters in 3,020 (19%). Compared with pregnancies involving stimulant discontinuation prior to conception, those that continued into pregnancy occurred in women who were older (29.9 vs. 28.9 years) and had more severe ADHD (3.1 vs. 1.8 ADHD-related billing claims). CONCLUSIONS: There is considerable heterogeneity in the management of ADHD during pregnancy.