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Patient-reported outcome (PRO) data are critical in understanding treatments from the patient perspective in cancer clinical trials. The potential benefits and methodological approaches to the collection of PRO data after treatment discontinuation (eg, because of progressive disease or unacceptable drug toxicity) are less clear. The purpose of this article is to describe the Food and Drug Administration's Oncology Center of Excellence and the Critical Path Institute cosponsored 2-hour virtual roundtable, held in 2020, to discuss this specific issue. We summarize key points from this discussion with 16 stakeholders representing academia, clinical practice, patients, international regulatory agencies, health technology assessment bodies/payers, industry, and PRO instrument development. Stakeholders recognized that any PRO data collection after treatment discontinuation should have clearly defined objectives to ensure that data can be analyzed and reported. Data collection after discontinuation without a justification for its use wastes patients' time and effort and is unethical. • All roundtable participants agreed that it is important to understand long-term effects, from the patients' perspective, of treatments under investigation in clinical trials, which includes the period after the study treatment has ended. This information is of critical importance for regulatory, payer, clinical, and patient decision making. • To ensure the most effective use of patient-reported outcome (PRO) data collected in the period after study treatment has ended, clinical trial sponsors need to set a research question before designing the collection of the PRO data needed to answer that research question. • The patient advocates who attended this roundtable agreed that patients will complete PRO measures in this period if it is made clear why their input is valuable. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Many trials conclude "no clinically meaningful detriment" to health-related quality of life (HRQL) or function between arms, even when notable differential toxicity is observed. Mean change from baseline analyses of function or HRQL can possibly obscure important change in subgroups experiencing symptomatic toxicity. We evaluate the impact of diarrhea, a key treatment arm toxicity, on patient-reported HRQL and functioning in clinical trials submitted to US Food and Drug Administration.Methods: This study used 4 randomized, breast cancer trials (adjuvant to late-line metastatic) as case examples. Diarrhea, physical functioning (PF), and global health status and quality of life (GHS/QoL) from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 were analyzed at baseline and approximately 3 and 6 months.Results: Generally, patients reporting very much diarrhea at months 3 and 6 had worse PF (9-19 points lower) and GHS/QoL (16-19 points lower) than patients reporting no diarrhea regardless of treatment arm. In the change from baseline analysis, patients reporting very much diarrhea also experienced a greater decrease in PF (6-13 points) and GHS/QoL (6-16 points) versus patients reporting no diarrhea in both arms.Conclusions: In trials with moderate to large differences in symptomatic toxicity by arm, reporting "no meaningful difference in functioning and HRQL between arms" based on mean change from baseline analysis is insufficient and may obscure important impacts on subgroups experiencing symptomatic adverse events. Additional exploratory analyses with simple data visualizations evaluating functioning or HRQL in patient subgroups experiencing expected symptomatic toxicities can further inform the safety and tolerability of an investigational agent. [ABSTRACT FROM AUTHOR]

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. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 Physical Functioning subscale is an important tool for measuring cancer patients' physical function in global clinical trials because of its validation across multiple linguistic and cultural contexts. The addition of high‐functioning items from the EORTC item library to the Physical Functioning subscale may allow investigators to more accurately describe the impact of anticancer treatment on patients who are high functioning at the baseline. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: How frequently patient-reported outcome (PRO) data are collected in commercial cancer clinical trials after treatment discontinuation and the quality of that data are poorly understood. We reviewed treatment discontinuation follow-up PRO data collection to learn about trials collecting these data and understand data quality. The review included 4 cancer types representing potential for long- (prostate cancer), medium-/long- (breast cancer), and short-term (pancreatic cancer and hepatocellular carcinoma) follow-up owing to disease trajectory.Methods: We reviewed registration trials in US Food and Drug Administration databases between January 2010 and January 2019. Protocols were reviewed to determine whether PROs were collected and, if so, whether these included the follow-up phase. Clinical study reports were reviewed when follow-up PROs were collected to determine completion rates. Results were summarized using descriptive analyses.Results: Of the 46 trials containing PRO data, 46% had at least 1 follow-up PRO assessment. Follow-up schedules of assessment were wide ranging; the first assessment occurred between 30 days and 6 months after stopping treatment with follow-up for as long as 3 years. PRO completion rates were reported in 57% of 21 trials; at the first follow-up assessment, completion rates for the treatment arm ranged from 38% to 91% and from 41% to 100% in the control arm.Conclusions: The quality of the follow-up PRO data, based on completion rates, was variable, as was the duration of follow-up. A clear research objective should be developed for follow-up PRO data, accounting for patient burden. If PRO data are collected, monitoring should be implemented to improve completion because poor completion limits data use in the benefit-risk assessment. [ABSTRACT FROM AUTHOR]

Purpose: On August 2, 2017, the Food and Drug Administration approved ibrutinib (IMBRUVICA) for the treatment of patients with chronic graft versus host disease (cGVHD) after the failure of one or more lines of systemic therapy. The approval was based on results from a single-arm, multicenter trial that enrolled patients with refractory cGVHD. This paper describes the FDA review of patient-reported outcomes (PRO) data from Study PCYC-1129-CA and the decision to incorporate descriptive PRO data in the FDA label to support the primary clinician-reported outcome results.Methods: In this trial, the Lee Chronic GVHD Symptom Scale (LSS) was used to capture patient-reported symptom bother. The 42 patients who received treatment were included in the analysis and completed the PRO tool. Post hoc descriptive analyses were conducted to further understand the measurement properties of the LSS.Results: The analysis submitted to FDA reported that 18 patients had a ≥ 7-point improvement on the LSS overall summary score at any point during the assessment period. For 10 patients, the ≥ 7-point improvement was sustained for ≥ 2 consecutive PRO assessments. An assessment of the responder threshold suggested the threshold submitted to the FDA was reasonable and in line with clinical findings.Conclusions: Overall, study PCYC-1129-CA demonstrated favorable clinician-reported cGVHD efficacy results that were complemented by results from PRO data, supporting the FDA's positive benefit-risk assessment leading to regular approval. Limitations included the single-arm trial design, responder definition, and instrument shortcomings. These limitations were thoroughly explored through additional FDA post hoc analyses. [ABSTRACT FROM AUTHOR]

Background: Patient-reported outcomes (PROs) are commonly included in submissions to the United States Food and Drug Administration (FDA). Open-label designs are frequent in cancer trials. Between-arm differences in PRO missingness may affect results. We sought to compare PRO completion rates between study arms in randomized open-label and double-blind cancer trials.Methods: Randomized, controlled trials for oncology and malignant hematology products submitted to the FDA in fiscal years 2007-2017 were identified using internal FDA databases. Applicant study reports were reviewed to assess PRO use and reporting of completion rates. Completion rates were collected for each PRO and compared between arms. Results were summarized using descriptive statistics.Results: Ninety-six trials for anticancer products from 2007 to 2017 contained PROs. Fifty-one (53.1%) were randomized, controlled trials with useable information on PRO completion. The median completion rate for investigational arms was 89.7% (range = 33.7-100.0%) and 88.2% (range = 11.0-100.0%) for control arms. At six months, seven double-blind trials had gaps of at least 10% in at least one PRO between arms; in four trials, these gaps favored the control arm (median difference = 11.5%, range = 10.0-17.0%). For open-label trials, four trials had such gaps, all of which favored the investigational arm (median difference = 28.5%, range = 10.0-69.0%).Conclusions: Among trials that provided interpretable PRO completion information, completion rates were high. Most trials had comparable completion rates between arms. However, when large between-arm completion rate differences existed, differences favoring the experimental arm were more common in open-label trials compared with double-blind trials. Procedures must be put in place to improve reporting of PRO completion and reduce missingness, particularly in open-label trials. [ABSTRACT FROM AUTHOR]

People with cancer experience a variety of symptoms, as shown by the authors, that can fluctuate in severity because of changes in cancer status and health status or because of treatment interventions. The inclusion of patient-reported outcome (PRO) measures in both clinical care and clinical trials are now recognized as a powerful tool in understanding symptoms and treatment side effects and how these affect a person's quality of life. First, beyond variation in assessment time, the symptom severity data are presented at an aggregate level and not by disease or treatment stage, which precludes any inference about symptom burden in this patient population. [Extracted from the article]

Reply to "Another look at floor and ceiling effects in the EORTC QLQ-C30 Physical Functioning subscale and possible solutions" We thank Vachon and colleagues for their comments on our publication regarding floor and ceiling effects in the European Organisation of Research and Treatment for Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Physical Functioning (PF) domain.1 In this article, we assessed the QLQ-C30 PF domain for floor and ceiling effects at both the item and scale levels in patients with advanced/ metastatic breast cancer. We agree with Vachon et al that the presence of floor and ceiling effects is not unique to the QLQ-C30 PF domain and is a potential concern for most static questionnaires in which lower and higher bounds exist. [Extracted from the article]

Objectives: To calculate the prevalence of all falls, non-accidental falls and syncope in an older population and characterize cardiovascular risk profiles. Design: Prospective, longitudinal cohort study. Setting: The first two waves of data from the Irish Longitudinal Study on Ageing (TILDA). Participants: 8172 community-dwelling adults aged 50 years and older resident in the Republic of Ireland Measurements: Self-reported history of all falls, non-accidental falls and syncope in the year preceding the first two waves of data collection. Demographic factors and self-reported cardiovascular conditions were used to characterize cardiovascular risk profiles. Results: The prevalence of all falls in the past year was 19.2% or 192 per thousand persons and increased with age (50–64 years 17.5%; 65–74 years 19.4%; 75+ years 24.4%). Non-accidental falls had an estimated prevalence of 5.1% or 51 falls per thousand persons and accounted for 26.5% of all falls reported and also increased with age (50–64 years 4.0%; 65–74 years 5.5%; 75+ years 8.0%). The prevalence for syncope was estimated to be 4.4% or 44per thousand persons but did not show a similar age gradient. Participants with at least 5 cardiovascular conditions were more likely to report all falls (OR = 2.07, 95% CI 1.18–3.64, p<0.05) and NAF (OR = 2.89, 95%CI 1.28–6.52, p<0.05). Conclusions: The prevalence of all falls and non-accidental falls increases with age but the same pattern was not consistently observed for syncope. There is an increased odds of reporting all three outcomes with increasing number of self-reported cardiovascular conditions. Further work is needed to uncover the interplay between cardiovascular disease and subsequent falls. [ABSTRACT FROM AUTHOR]

Perceptions of aging have been shown to impact the psychological and physical health of older adults. Experimental studies have found that priming older adults with negative attitudes toward aging results in immediate declines in psychological, physical and cognitive functions. Longitudinal studies have supported this work illustrating the longer term impact of negative and positive perceptions of aging on psychological and physical health. However, it is surprising that there are a limited number of studies that have investigated the longitudinal association between perceptions of aging and cognitive function. The aim of this article is therefore to explore the association between perceptions of aging and cognitive function across a number of domains in a population representative sample of adults aged 50 and older. The sample was assessed twice over 2 years. Negative perceptions of aging at baseline were independently associated with longitudinal decline in verbal fluency and self-rated memory over a 2-year period after adjustment for physical and mental health. These findings suggest that negative perceptions of aging may play a role in cognitive decline in the older population. Furthermore, aging perceptions may be a modifiable factor to target for future interventions. [ABSTRACT FROM AUTHOR]

Cultural and healthcare delivery differences across global sites can affect how patients interact with their healthcare team and their willingness to report bothersome symptoms. Although cross-trial comparisons are problematic, the US Food and Drug Administration (FDA) product labeling and published literature are often used to guide shared decision making when discussing treatment options with patients. Whether this resulted from geographical and cultural differences in the clinician-patient interaction that are attenuated when patients report their symptoms on a survey, more systematic PRO assessment (same question every time), or other reasons, assessment of symptomatic AEs using clinician and patient-reported assessment remains a fertile area for further study (4). [Extracted from the article]

Objectives: We explored the measurement properties of frailty with the goal of optimizing frailty assessment according to phenotype definition of Fried and comparing measurement properties across countries. Study Design and Setting: Data are from the Survey of Health, Ageing and Retirement in Europe (n = 27,938), a population-based study of community-dwelling adults aged ≥50 years. Frailty was specified as a unidimensional construct, and measurement invariance across the 12 countries was tested. To assess our measurement model, we used confirmatory factor analysis (CFA) and multigroup CFA to assess measurement invariance. Results: The unidimensional model fit the data well (adjusted c2(48) = 82.74, P = 0.001), and the same structure was satisfactory for all countries. Inclusion of equality constraints led to significant model deterioration (adjusted Χ2diff(88) = 995.05, P < 0.001), suggesting differences in parameters across countries. Spain was removed from further analyses, and equality constraints for Greece, Sweden, Israel, Italy, and France were not tenable. Accounting for these led to satisfactory model fit (adjusted Χ2(113) = 414.33, P < 0.001). Significant mean frailty differences were identified. Conclusion: The relationships between the construct of frailty and indicators, although broadly constant, do vary across some countries. Furthermore, there was evidence of differing levels of frailty for the middle-aged and older populations across European countries. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the validity of current measurement models for the control, autonomy, self-realisation, and pleasure (CASP) measure of quality of life (QoL)—a second-order four-factor CASP-19 model and a second-order three-factor CASP-12 version—in a recent population survey. A previous large sample study did not report good fit for these measurement models. The study also aims to re-develop the model and propose a well-fitting alternative. Methods: To evaluate the current measurement models, confirmatory factor analysis (CFA) was used. A cross-sectional sample ( n = 6,823) representative of the Irish community-dwelling population aged 50 and over was obtained from the Irish Longitudinal Study of Ageing (TILDA). Model revision was based on descriptive statistics, exploratory factor analysis and examination of fit diagnostic statistics. Revised models were tested using CFA. Results: The results of the CFA did not support the validity of the established measurement models. A reformulated 12-item, two-factor model comprising control/autonomy and self-realisation/pleasure, with residual covariances for negatively worded items, had excellent fit to the data (χ 2 161.90, df = 44, p < 0.001; RMSEA = 0.03, 90 % CI 0.02–0.03), and a clearer conceptual rationale. The same model with one overall QoL factor had similar excellent fit. Conclusions: We recommend the use of the single-factor model (CASP-R12) when assessing overall quality of life. The dimensions of control/autonomy and self-realisation/pleasure can be examined separately by researchers interested in those constructs. Researchers using structural equation modelling can use the well-fitting measurement model outlined here including adjustment for residual covariances. [ABSTRACT FROM AUTHOR]

Purpose: The objectives of this study were to investigate the psychometric properties of the SF-36 in a sample of older adults with chronic conditions and to test whether measurement bias exists based on the levels of comorbidity. Methods: Participants included were 979 cognitively intact older adults with comorbidities who were interviewed at their homes. We examined the psychometric properties of the SF-36 and conducted confirmatory factor analysis (CFA) to investigate the assumption of measurement invariance by the levels of comorbidity. Results: Overall data quality was high and scaling assumptions were generally met with few exceptions. Floor and ceiling effects were present for the role-physical and role-emotional subscales. Using CFA, we found that a three-factor measurement model fits the data well. We identified two violations of measurement invariance. Results showed that participants with high comorbidity level place more emphasis on social functioning (SF) and bodily pain (BP) in relation to physical health-related quality of life (HRQoL) than those with low comorbidity level. Conclusions: Measurement bias was present for the SF and BP components of the SF-36 physical HRQoL measure. Researchers should be cautious when considering the use of SF-36 in clinical studies among older adults with comorbidities. [ABSTRACT FROM AUTHOR]

Older offenders are the fastest growing group in the U.S. prison system, although little is known about older offenders who commit homicides, their victims, or the details of the crime. The current study investigated covariates associated with four categories of homicide: intimate, family, acquaintance, and unrelated victims. Using the Chicago Homicide Dataset, a subsample was created of offenders 50 years and older (n = 972). In a multinomial multivariate regression, where unrelated homicides were defined as the base outcome, it was revealed in intimate and family comparisons that women were at a significantly higher risk of victimization. Crimes that occurred in residences were significantly associated with all three homicides groups compared with unrelated homicides. The use of alcohol was significant in crimes where an acquaintance was the victim. The results suggest that earlier identification of at-risk older adults and more social support in the community could be integral in the prevention of violent crimes. [ABSTRACT FROM PUBLISHER]

Objective: To evaluate the preferences of an ethnically diverse national sample of older Americans regarding length of life versus health quality. Method: A time trade-off task administered as part of the 2002 wave of the Health and Retirement Study. Results: Respondents equated 6.86 (SD = 3.46) years of perfect health with 10 years of life in imperfect health. Women and those who ranked their health less favorably were more likely to give up years of life for perfect health. Relative to Whites, Blacks were more willing to live longer in imperfect health. Those of lower levels of education were more likely to prefer 10 years of life in imperfect health. Discussion: There is wide variability in responses to the time trade-off task that is partially associated with self-rated health, gender, ethnicity, and education. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the preferences of an ethnically diverse national sample of older Americans regarding length of life versus health quality. Method: A time trade-off task administered as part of the 2002 wave of the Health and Retirement Study. Results: Respondents equated 6.86 (SD = 3.46) years of perfect health with 10 years of life in imperfect health. Women and those who ranked their health less favorably were more likely to give up years of life for perfect health. Relative to Whites, Blacks were more willing to live longer in imperfect health. Those of lower levels of education were more likely to prefer 10 years of life in imperfect health. Discussion: There is wide variability in responses to the time trade-off task that is partially associated with self-rated health, gender, ethnicity, and education. [ABSTRACT FROM PUBLISHER]

Objectives. We developed and examined the effectiveness of the Florida Brief Intervention and Treatment for Elders (BRITE) project, a 3-year, state-funded pilot program of screening and brief intervention for older adult substance misusers. Methods. Agencies in 4 counties conducted screenings among 3497 older adults for alcohol, medications, and illicit substance misuse problems and for depression and suicide risk. Screening occurred in elders' homes, senior centers, or other selected sites. Individuals who screened positive for substance misuse were offered brief intervention with evidence-based practices and rescreened at discharge from the intervention program and at follow-up interviews. Results. Prescription medication misuse was the most prevalent substance use problem, followed by alcohol, over-the-counter medications, and illicit substances. Depression was prevalent among those with alcohol and prescription medication problems. Those who received the brief intervention had improvement in alcohol, medication misuse, and depression measures. Conclusions. The BRITE program effectively shaped state policy by responding to legislative mandates to address the needs of an increasing, but under-served, elder population. The pilot paved the way for obtaining a federally funded grant to expand BRITE to 27 sites in 17 counties in Florida. (Am J Public Health. 2010;100:108-114. doi:10.2105/AJPH.2008.149534) [ABSTRACT FROM AUTHOR]

The electronic patient-reported outcome (ePRO) Dataset Structure and Standardization Project is a multistakeholder initiative formed by Critical Path Institute's PRO Consortium and Electronic Clinical Outcome Assessment (eCOA) Consortium to address issues related to ePRO dataset structure and standardization and to provide best practice recommendations for clinical trial sponsors and eCOA providers. Given the many benefits of utilizing electronic modes to capture PRO data, clinical trials are increasingly using these methods, yet there are challenges to using data generated by eCOA systems. Clinical Data Interchange Standards Consortium (CDISC) standards are used in clinical trials to ensure consistency in data collection, tabulation, and analysis and to facilitate regulatory submission. Currently, ePRO data are not required to follow a standard model, and the data models used often vary by eCOA provider and sponsor. This lack of consistency creates risks for programming and analysis and difficulties for analytics functions generating the required analysis and submission datasets. There is a disconnect between data standards used for study data submission and those used for data collection via case report forms and ePRO forms, which would be mitigated through the application of CDISC standards for ePRO data capture and transfer. The project was formed to collate and examine the issues arising from the lack of adoption of standardized approaches and this paper details recommendations to address those issues. Recommendations to address issues with ePRO dataset structure and standardization include adopting CDISC standards in the ePRO data platform, timely involvement of key stakeholders, ensuring ePRO controls are implemented, addressing issues of missing data early in development, ensuring quality control and validation of ePRO datasets, and use of read-only datasets. • Expanding adoption of Clinical Data Interchange Standards Consortium (CDISC) standards by clinical trial sponsors has significantly improved the regulatory reviewability of clinical trial data submissions. CDISC is not yet universally embedded as the default format of datasets generated from electronic patient-reported outcome (ePRO) systems. Because Food and Drug Administration and Pharmaceuticals and Medical Devices Agency require submissions to be CDISC-compliant, extensive mapping of ePRO data is required to ensure compliance and reviewability, posing risks to data traceability, quality, and security. • Involvement of key data management and analytics stakeholders to design ePRO systems from capture to delivery would ensure adoption of strategies that deliver the highest quality data without the need for manual processing. Surveys administered to ePRO providers and sponsors validated the perception that the content of data specifications and the default structure of ePRO provider databases are opportunities for CDISC standards to become more wholly embedded. • The authors have developed best practice recommendations covering the application of CDISC standards for ePRO datasets, involvement of key stakeholders, and strategies to manage ePRO dataset content, quality control, and validation. Universal adoption of these recommendations will maintain the quality of ePRO data, reduce risk to data provenance, and reduce the burden on all stakeholders to ensure compliance with regulatory submission requirements. [ABSTRACT FROM AUTHOR]

The use of item libraries for patient-reported outcome (PRO) measurement in oncology allows for the customisation of PRO assessment to measure key health-related quality of life concepts of relevance to the target population and intervention. However, no high-level recommendations exist to guide users on the design and implementation of these customised PRO measures (item lists) across different PRO measurement systems. To address this issue, a working group was set up, including international stakeholders (academic, independent, industry, health technology assessment, regulatory, and patient advocacy), with the goal of creating recommendations for the use of item libraries in oncology trials. A scoping review was carried out to identify relevant publications and highlight any gaps. Stakeholders commented on the available guidance for each research question, proposed recommendations on how to address gaps in the literature, and came to an agreement using discussion-based methods. Nine primary research questions were identified that formed the scope and structure of the recommendations on how to select items and implement item lists created from item libraries. These recommendations address methods to drive item selection, plan the structure and analysis of item lists, and facilitate their use in conjunction with other measures. The findings resulted in high-level, instrument-agnostic recommendations on the use of item-library-derived item lists in oncology trials. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine six-month trajectories of depressive symptoms and their predictors for community-dwelling older adults. Innovations included monthly assessments, examination of non-linear trajectories, and inclusion of coping styles as predictors.Method: Data were derived from a six-month longitudinal study of 144 community-dwelling older adults with depressive symptoms (Short-Geriatric Depression Scale [S-GDS]≥5) with seven waves of data. Descriptive analyses and individual growth curve modeling were conducted.Results: The majority of participants changed symptom levels over time; most participants with severe symptoms at baseline remained at least mildly depressed at six months. Younger participants were more depressed at baseline and improved slightly more than older participants. Those who used more active and emotional support coping had faster improvement and maintained gains, whereas those who used less of these coping styles demonstrated worse symptoms over the six-month follow-up period.Limitations: The most significant limitations are the convenience sampling methods and relatively small sample size, although the large number of assessments (7 waves) increases precision of the statistical methods used.Conclusions: Findings suggest that it may be beneficial to target interventions to older adults with more severe depressive symptoms and who display low levels of active and emotional support coping. Behavioral interventions that improve these coping styles may help depressed older adults recover and maintain treatment gains over time. [ABSTRACT FROM AUTHOR]

Time-to-event endpoints for patient-reported outcomes, such as time to deterioration of symptoms or function, are frequently used in cancer clinical trials. Although time-to-deterioration endpoints might seem familiar to cancer researchers for being similar to survival or disease-progression endpoints, there are unique considerations associated with their use. The complexity of time-to-deterioration endpoints should be weighed against the information that they add to the tumour, survival, and safety data used to inform the risks and benefits of an investigational drug. Here we use the estimand framework to show how analytical decisions answer different clinical questions of interest, some of which might be uninformative. Challenges including the consideration of intercurrent events, the difficulty in maintaining adequate completion rates, and considerable patient and trial burden from long-term, serial, patient-reported outcome measurements render time to deterioration a problematic approach for widespread use. For trials in which a comparative benefit in symptoms or function is an objective, an analysis at pre-specified relevant timepoints could be a better approach. [ABSTRACT FROM AUTHOR]

Introduction: Walking speed is a meaningful marker of physical function in the aging population. While it is a primarily physical measure, experimental studies have shown that merely priming older adults with negative stereotypes about aging results in immediate declines in objective walking speed. What is not clear is whether this is a temporary experimental effect or whether negative aging stereotypes have detrimental effects on long term objective health. We sought to explore the association between baseline negative perceptions of aging in the general population and objective walking speed 2 years later. Method: 4,803 participations were assessed over 2 waves of The Irish Longitudinal Study on Ageing (TILDA), a prospective, population representative study of adults aged 50+ in the Republic of Ireland. Wave 1 measures – which included the Aging Perceptions Questionnaire, walking speed and all covariates - were taken between 2009 and 2011. Wave 2 measures – which included a second measurement of walking speed and covariates - were collected 2 years later between March and December 2012. Walking speed was measured as the number of seconds to complete the Timed Up-And-Go (TUG) task. Participations with a history of stroke, Parkinson’s disease or an MMSE < 18 were excluded. Results: After full adjustment for all covariates (age, gender, level of education, disability, chronic conditions, medications, global cognition and baseline TUG) negative perceptions of aging at baseline were associated with slower TUG speed 2 years later (B=.03, 95% CI = .01 to 05, p< .05). Conclusions: Walking speed has previously been considered to be a consequence of physical decline but these results highlight the direct role of psychological state in predicting an objective aging outcome. Negative perceptions about aging are a potentially modifiable risk factor of some elements of physical decline in aging. [ABSTRACT FROM AUTHOR]

• Lung cancer patients on systemic therapy are willing and able to complete weekly electronic patient-reported outcome (PRO) surveys from home for long-term monitoring between office visits. • Concerning (i.e., severe and worsening) symptoms captured by electronic PRO monitoring are extremely common in patients with metastatic lung cancer. • Treating clinicians were able to provide recommendations based on electronic PRO responses of lung cancer patients. • The great majority of lung cancer patients participating in electronic PRO monitoring reported satisfaction with the system and would recommend it to others. Patients with lung cancer have high symptom burden and diminished quality of life. Electronic patient-reported outcome (PRO) platforms deliver repeated longitudinal surveys via web or telephone to patients and alert clinicians about concerning symptoms. This study aims to determine feasibility of electronic PRO monitoring in lung cancer patients receiving treatment in community settings. Adults receiving treatment for advanced or metastatic lung cancer at 26 community sites were invited to participate in a prospective trial of weekly electronic PRO symptom monitoring for 12 months (NCT03249090). Surveys assessing patients' satisfaction with the electronic PRO system were administered at 3 months. Descriptive statistics were generated for demographics, survey completion rates, symptom occurrence, and provider PRO alert management approaches. Pairwise relationships between symptom items were evaluated using intra-individual repeated-measures correlation coefficients. Lung cancer patients (n = 118) participating in electronic PROs were older (mean 64.4 vs 61.9 years, p = 0.03), had worse performance status (p = 0.002), more comorbidities (p = 0.02), and less technology experience than patients with other cancers. Of delivered weekly PRO surveys over 12 months, 91% were completed. Nearly all (97%) patients reported concerning (i.e., severe or worsening) symptoms during participation, with 33% of surveys including concerning symptoms. Pain was the most frequent and longest lasting symptom and was associated with reduced activity level. More than half of alerts to clinicians for concerning symptoms led to intervention. The majority (87%) would recommend using electronic PRO monitoring to other lung cancer patients. Remote longitudinal weekly monitoring of patients with lung cancer using validated electronic PRO surveys was feasible in a multicenter, community-based pragmatic study. A high symptom burden specific to lung cancer was detected and clinician outreach in response to alerts was frequent, suggesting electronic PROs may be a beneficial strategy for identifying actionable symptoms and allow opportunities to optimize well-being in this population. [ABSTRACT FROM AUTHOR]

Objective: The Medical Assessment and Planning Unit (MAPU) model provides a multidisciplinary and 'front end loading' approach to acute medical care. The objective of this study was to evaluate the impact of a 10-bed MAPU in Royal Melbourne Hospital (RMH) on hospital length of stay. METHODS: A pre-post study design was used. Cases were defined as all general medical patients admitted to the RMH between 1 August 2003 and 31 January 2004. MAPU patients were defined as general medical patients who had been discharged from RMH MAPU unit as part of their RMH inpatient admission. Historical controls were defined as all general medical patients admitted to the RMH between 1 August 2002 and 31 January 2003. RESULTS: There was a reduction in median length of stay that did not reach statistical significance. During the study period, median emergency department length of stay for MAPU patients was 10.3 h compared with 13.2 h for non-MAPU patients who were admitted directly to general wards. CONCLUSIONS: The reductions in length of stay are likely to be of clinical significance at the emergency department (ED) level. The MAPU model also contributes to providing care appropriate care for older admitted patients. [ABSTRACT FROM AUTHOR]

Objectives: Unblinded trials are common in oncology, but patient knowledge of treatment assignment may bias response to questionnaires. We sought to ascertain the extent of possible bias arising from patient knowledge of treatment assignment.Methods: This is a retrospective analysis of data from 2 randomized trials in multiple myeloma, 1 double-blind and 1 open label. We compared changes in patient reports of symptoms, function, and health status from prerandomization (screening) to baseline (pretreatment but postrandomization) across control and investigational arms in the 2 trials. Changes from prerandomization scores at ~2 and 6 months on treatment were evaluated only across control arms to avoid comparisons between 2 different experimental drugs. All scores were on 0- to 100-point scales. Inverse probability weighting, entropy balancing, and multiple imputation using propensity score splines were used to compare score changes across similar groups of patients.Results: Minimal changes from screening were seen at baseline in all arms. In the control arm, mean changes of <7 points were seen for all domains at 2 and 6 months. The effect of unblinding at 6 months in social function was a decline of less than 6 points (weighting: -3.09; 95% confidence interval -8.41 to 2.23; balancing: -4.55; 95% confidence interval -9.86 to 0.76; imputation: -5.34; 95% confidence interval -10.64 to -0.04).Conclusion: In this analysis, we did not find evidence to suggest that there was a meaningful differential effect on how patients reported their symptoms, function or health status after knowing their treatment assignment. [ABSTRACT FROM AUTHOR]

Patient-reported outcome (PRO) measures describe how a patient feels or functions and are increasingly being used in benefit-risk assessments in the development of cancer drugs. However, PRO research objectives are often ill-defined in clinical cancer trials, which can lead to misleading conclusions about patient experiences. The estimand framework is a structured approach to aligning a clinical trial objective with the study design, including endpoints and analysis. The estimand framework uses a multidisciplinary approach and can improve design, analysis, and interpretation of PRO results. On the basis of the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use E9(R1) addendum, we provide an overview of the estimand framework intended for a multistakeholder audience. We apply the estimand framework to a hypothetical trial for breast cancer, using physical function to develop specific PRO research objectives. This Policy Review is not an endorsement of a specific study design or outcome; rather, it is meant to show the application of principles of the estimand framework to research study design and add to ongoing discussion. Use of the estimand framework to review medical products and label PROs in oncology can improve communication between stakeholders and ultimately provide a clearer interpretation of patient experience in the development of oncological drugs. [ABSTRACT FROM AUTHOR]

With the advent of patient-focused drug development, the US Food and Drug Administration (FDA) has redoubled its efforts to review patient-reported outcome (PRO) data in cancer trials submitted as part of a drug's marketing application. This Review aims to characterise the statistical analysis of PRO data from pivotal lung cancer trials submitted to support FDA drug approval between January, 2008, and December, 2017. For each trial and PRO instrument identified, we evaluated prespecified PRO concepts, statistical analysis, missing data and sensitivity analysis, instrument completion, and clinical relevance. Of the 37 pivotal lung cancer trials used to support FDA drug approval, 25 (68%) trials included PRO measures. The most common prespecified PRO concepts were cough, dyspnoea, and chest pain. At the trial level, the most common statistical analyses were descriptive (24 trials [96%]), followed by time-to-event analyses (19 trials [76%]), longitudinal analyses (12 trials [48%]), and basic inferential tests or general linear models (10 trials [40%]). Our findings indicate a wide variation in the analytic techniques and data presentation methods used, with very few trials reporting clear PRO research objectives and sensitivity analyses for PRO results. Our work further supports the need for focused research objectives to justify and to guide the analytic strategy of PROs to facilitate the interpretation of patient experience. [ABSTRACT FROM AUTHOR]

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

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

Background: The Montreal Cognitive Assessment (MoCA) is a very widely used test for mild cognitive impairment. Differing recommendations have been made regarding its utility in providing a profile of performance across several cognitive domains.Objectives: To examine the factor structure of the MoCA in a nationally representative population study of older Irish adults and evaluate its utility in providing domain-specific information.Methods: A cross-sectional analysis of wave 1 data from the Irish Longitudinal Study on Ageing was undertaken. Data from a subset of 2342 participants assessed using the MoCA were analyzed using both confirmatory factor analytic (CFA) and exploratory factor analytic (EFA) methods.Results: Mean age was 72.64 (range 65 to 98), 53% female. The CFA provided evidence of adequate overall model fit for a previously proposed 6-factor model. In contrast, EFA yielded a 3-factor solution and test items cross-loaded onto a number of factors with no clear pattern of underlying cognitive domains. Using EFA to explore the 6-factor model yielded good fit, but again test items cross-loaded onto a number of factors with no clear pattern evident.Conclusion: Lack of concordance between the CFA and EFA findings demonstrates that the correspondence between individual tests and their assumed cognitive domains is not robust, reflecting at least in part a current lack of consensus on how core cognitive constructs are defined and on what subcomponents can be subsumed under different cognitive domains. The MoCA should not be viewed as a substitute for more in-depth neuropsychological assessment when domain-specific information is required. [ABSTRACT FROM AUTHOR]

Purpose: To illustrate how structural equation modeling (SEM) can be used for response shift detection with random measurement occasions and health state operationalized as fixed group membership (Study 1) or with fixed measurement occasions and health state operationalized as time-varying covariates (Study 2).Methods: In Study 1, we explored seven items of the Performance Scales measuring physical and mental aspects of perceived disability of 771 stable, 629 progressive, and 1,552 relapsing MS patients. Time lags between the three measurements varied and were accounted for by introducing time since diagnosis as an exogenous variable. In Study 2, we considered the SF-12 scales measuring physical and mental components of HRQoL of 1,767 patients. Health state was accounted for by exogenous variables relapse (yes/no) and symptoms (worse/same/better).Results: In Study 1, progressive and relapsing patients reported greater disability than stable patients but little longitudinal change. Some response shift was found with stable and relapsing patients. In Study 2, relapse and symptoms were associated with HRQoL, but no change and only little response shift was found.Conclusions: While small response shifts were found, they had little impact on the evaluation of true change in performance and HRQoL. [ABSTRACT FROM AUTHOR]

The present study examined mental health care preferences and barriers to mental health care among younger (aged 18 to 64, N = 119) and older (aged 65 to 101, N = 136) groups of Latinos from various sites in one county. Multivariate analyses revealed that older age group membership was associated with greater preference for seeking advice from a family doctor but less preference for mental health professionals (e.g., consultations with psychiatrist or psychologist and individual/group counseling), classes on stress management, and advice from a friend. In terms of barriers, older age group membership was linked to greater endorsement for the beliefs that all one's problems are physical and that one's problems are one's own business. Interestingly, younger group membership was shown to increase the odds of reporting feelings of shame of needing counseling and family disapproval. The findings provide important implications for interventions targeted at improving access to mental health care among Hispanics. Based on the similarities and differences found between young and old, both general and age-specific strategies need to be developed in order to increase effectiveness of these programs. [ABSTRACT FROM AUTHOR]