Bellinda King-Kallimanis | Trinity College Dublin (original) (raw)
Papers by Bellinda King-Kallimanis
Abstract PD12-12: Floor and ceiling effects in the EORTC QLQ-C30 physical functioning subscale among patients with breast cancer enrolled in commercial clinical trials vs. a community trial
Cancer Research, 2021
Background: The EORTC QLQ-C30 Physical Functioning (PF) subscale is a widely used patient-reporte... more Background: The EORTC QLQ-C30 Physical Functioning (PF) subscale is a widely used patient-reported outcome (PRO) measure that quantifies cancer patients’ physical function. Responsiveness, the degree to which a scale can assess clinical deterioration and improvement, is an important measurement characteristic that can be assessed by looking at floor and ceiling effects. A floor effect is defined as a high proportion of study participants reporting the lowest possible score in the variable of interest, while a ceiling effect is the opposite. We characterized floor and ceiling effects of the PF subscale in patients with breast cancer enrolled in commercial clinical trials vs. a community-based trial.Objectives: (1) Determine floor/ceiling effects of the QLQ-C30 PF items and subscale among patients receiving treatment for breast cancer (2) Compare floor/ceiling effects among patients enrolled in randomized clinical trials vs. those treated in a community care trial.Methods: PF data fro...
Clinical Cancer Research, 2021
On December 16, 2020, the FDA granted regular approval to margetuximab-cmkb (MARGENZA), in combin... more On December 16, 2020, the FDA granted regular approval to margetuximab-cmkb (MARGENZA), in combination with chemotherapy, for the treatment of adult patients with HER2-positive (HER2+) metastatic breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Approval was based on data from SOPHIA, a multicenter, randomized, open-label, active controlled study comparing margetuximab with trastuzumab, in combination with chemotherapy. The primary efficacy endpoint was progression-free survival (PFS) by blinded independent central review. SOPHIA demonstrated a 0.9-month difference in median PFS between the two treatment arms [5.8 vs. 4.9 months, respectively; stratified HR, 0.76 (95% confidence interval: 0.59–0.98; P = 0.0334)]. Overall survival (OS) was immature at the data cut-off date of September 10, 2019. Infusion-related reactions (IRR) are an important safety signal associated with margetuximab plus chemotherapy. In SOPHIA...
Patient-reported pain and pain medication impact in patients with HR+ Her2-neg advanced breast cancer: A U.S. FDA pooled analysis
Journal of Clinical Oncology, 2020
e13027 Background: Despite the ubiquitous prescribing of pain medications (PMs) in cancer clinica... more e13027 Background: Despite the ubiquitous prescribing of pain medications (PMs) in cancer clinical trials, the impact of such prescribing patterns and reporting on the experience of pain is not often investigated. We examined patient-reported pain before initiation of PM reporting and at the next available pain assessment. Our aim was to understand change in patient-reported pain. Methods: We pooled data from 7 phase 3 randomized, controlled, registration trials of CDKI with endocrine therapy in patients with hormone receptor positive, human epidermal growth factor receptor-2 negative MBC. We restricted our analyses to patients who started therapy with no PM reported and looked at patients who had NSAID or opioid medication documented. We calculated change between 2 assessments in patient-reported pain before and after PM using the pain occurrence item (Q9) on the EORTC Quality of Life questionnaire (QLQ-C30). Results: Of the 4200 patients who received at least 1 dose of CDKI/placeb...
Psychiatric Services, 2011
OBJECTIVE-For community-dwelling older adults with depressive symptoms, aims were to: describe be... more OBJECTIVE-For community-dwelling older adults with depressive symptoms, aims were to: describe behavioral health service utilization patterns over a six-month period; and identify factors associated with service use, guided by a multidimensional, comprehensive theoretical model emphasizing the dynamic nature of service use patterns over time and social context. METHODS-144 participants with depressive symptoms completed an in-person baseline interview and six monthly telephone follow-up interviews. Outcomes included use of antidepressants or counseling at each follow-up. Covariates included individual (demographic, need, prior treatment experience, intentions) and social context (stigma, advice) variables. RESULTS-Approximately half of participants received no formal service (antidepressant or counseling; n = 70, 48%). Service use or non-use did not change for most participants. More participants with severe symptoms received antidepressants (25-37%) than those with milder symptoms (10-14%), although more of the milder cases started (62% vs. 49%) and stopped antidepressants (77% vs. 26%) at least once. Fewer individuals received counseling overall, with no clear patterns by symptom severity. In multivariate longitudinal analyses, service use at followup was independently associated with younger age, current major depressive episode, baseline use of antidepressant, intention to begin a new service at baseline, and receipt of advice to use services over follow-up. CONCLUSIONS-Over a six-month period, the majority of older adults with depressive symptoms in this study continued use or non-use of mental health services. Demographic, need, attitudinal and social variables were related to service use over time. Addressing intentions and providing advice may facilitate uptake of services. Older adults commonly experience depressive symptoms (1, 2), with serious health consequences (3-6), although they underutilize mental health services (7, 8). Theoretical frameworks have become increasingly complex in attempts to explain this underutilization, and the network-episode model (NEM; 9, 10, 11) has been recommended to guide this research (12). The NEM emphasizes the dynamic nature of entry and exits in service systems over time and the influence of individuals' social context on service use, in addition Disclosures: None for any author.
Journal of the American Geriatrics Society, 2007
OBJECTIVES: To explore the extent of and factors associated with male nursing home residents who ... more OBJECTIVES: To explore the extent of and factors associated with male nursing home residents who wander. DESIGN: Cross-sectional design with secondary data analyses. SETTING: One hundred thirty-four nursing home facilities operated by the Department of Veterans Affairs. PARTICIPANTS: Fifteen thousand ninety-two nursing home residents with moderate or severe cognitive impairment admitted over a 4-year period. MEASUREMENTS: Selected variables from the Minimum Data Set included ratings recorded at residents' admission to the nursing home (cognitive impairment, mood, behavior problems, activities of daily living, and wandering). RESULTS: In this sample of residents with moderate or severe cognitive impairment, the proportion of wanderers was found to be 21%. Wanderers were more likely to exhibit severe (vs moderate) cognitive impairment, socially inappropriate behavior, resistance to care, use of antipsychotic medication, independence in locomotion or ambulation, and dependence in activities of daily living related to basic hygiene. A sizable proportion of wanderers were found to be wheelchair users (25%) or were wanderers with dual dementia and psychiatric diagnoses (23%), characteristics that are not well documented in the literature. CONCLUSION: These results support previous clinical understanding of wanderers to be those who are more likely to exhibit more-severe cognitive impairment. Based on a statistical model with variables generated from prior research findings, classification as a wanderer was found to be associated with other disruptive activity such as socially inappropriate behavior and resisting care. Two understudied populations of wanderers were documented: wheelchair wanderers and those with comorbid dementia and psychiatric diagnoses. Future longitudinal studies should examine predictors of wandering behavior, and further research should explore the understudied subpopulations of wheelchair and dual-diagnosis wanderers who emerged in this study.
International Journal of Geriatric Psychiatry, 2010
To explore the extent of and factors associated with male residents who change wandering status p... more To explore the extent of and factors associated with male residents who change wandering status post nursing home admission. Design: Longitudinal design with secondary data analyses. Admissions over a 4-year period were examined using repeat assessments with the Minimum Data Set (MDS) to formulate a model understanding the development of wandering behavior. Setting: One hundred thirty-four Veterans Administration (VA) nursing homes throughout the United States. Participants: Included 6673 residents admitted to VA nursing homes between October 2000 and October 2004. Measurements: MDS variables (cognitive impairment, mood, behavior problems, activities of daily living and wandering) included ratings recorded at residents' admission to the nursing home and a minimum of two other time points at quarterly intervals. Results: The majority (86%) of the sample were classified as non-wanderers at admission and most of these (94%) remained non-wanderers until discharge or the end of the study. Fifty-one per cent of the wanderers changed status to non-wanderers with 6% of these residents fluctuating in status more than two times. Admission variables associated with an increased risk of changing status from non-wandering to wandering included older age, greater cognitive impairment, more socially inappropriate behavior, resisting care, easier distractibility, and needing less help with personal hygiene. Requiring assistance with locomotion and having three or more medical comorbidities were associated with a decreased chance of changing from non-wandering to wandering status. Conclusion: A resident's change from non-wandering to wandering status may reflect an undetected medical event that affects cognition, but spares mobility.
American Journal of Public Health, 2010
Objectives. We developed and examined the effectiveness of the Florida Brief Intervention and Tre... more 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 h...
Graphical representations of patient tolerability data: Recommendations from the National Cancer Institute (NCI) Cancer Moonshot Standardization Working Group
Journal of Clinical Oncology
e18612 Background: Effective communication of treatment tolerability data is essential for clinic... more e18612 Background: Effective communication of treatment tolerability data is essential for clinical decision making and improved patient outcomes, yet standardized approaches to the analysis and visualization of tolerability data in cancer clinical trials are currently limited. To address this need, the Standardization Working Group (SWG) was established within the NCI Cancer Moonshot Tolerability Consortium. This abstract describes the SWG’s initiative to develop a publicly accessible online toolkit with a comprehensive set of guidelines, references, and resources for graphical displays of tolerability data. Methods: A multidisciplinary group of PRO researchers including biostatisticians, clinicians, epidemiologists, and representatives from the NCI and FDA convened monthly to discuss toolkit development and content. Considerations for standardization of graphical displays of tolerability data included (1) types of graphical displays, (2) incorporation of missing data, (3) labeling...
Neurourology and Urodynamics, 2017
Uren A1, Cotterill N1, Lasch K2, Deshpande C2, King-Kallimanis B2, van Koeveringe G3, Harding C4,... more Uren A1, Cotterill N1, Lasch K2, Deshpande C2, King-Kallimanis B2, van Koeveringe G3, Harding C4, Oelke M5, Chapple C6, Hillary C6, Belal M7, Bosch R8, Blok B9, Klaver M10, Bongaerts D10, Hakimi Z10, Abrams P1 1. Bristol Urological Institute, Bristol, UK, 2. Pharmerit, Boston, United States, 3. Maastricht University Medical Centre, Maastricht, The Netherlands, 4. Freeman Hospital, Newcastle-upon-Tyne, 5. Hannover Medical School, Hannover, Germany, 6. Royal Hallamshire Hospital, Sheffield, 7. Queen Elizabeth Hospital, Birmingham, UK, 8. University Medical Centre Utrecht, Utrecht, The Netherlands, 9. Erasmus Medical Centre, Rotterdam, The Netherlands, 10. Astellas Pharma B.V., Leiden, The Netherlands
Frailty in relapsed/ refractory multiple myeloma registration trials
e20017 Background: Multiple Myeloma (MM) is predominantly a disease of older adults with a median... more e20017 Background: Multiple Myeloma (MM) is predominantly a disease of older adults with a median age of onset at 70 years. There is growing interest in using criterion other than chronological age, like frailty, to determine fitness for treatment and ultimately improve clinical outcomes in MM. Frailty is the accumulation of aging-associated diseases and disabilities, making patients more vulnerable to adverse outcomes when exposed to stressors like anti-cancer treatment. MM frailty measures have primarily been developed and tested in newly diagnosed patients. MM patients typically relapse, but there is limited knowledge regarding the prevalence of frailty in the relapsed/refractory (RRMM) setting. The aim of this research was to determine the prevalence of frailty in RRMM commercial clinical trials, at the time of trial enrollment, using the International Myeloma Working Group (IMWG) Frailty Index. Methods: We pooled baseline data from 6 RRMM clinical trials submitted for FDA regul...
Depressive Symptoms and Alcohol Abuse/Misuse in Older Adults: Results from the Florida BRITE Project
Previous research has suggested that older adults who misuse alcohol frequently report depressive... more Previous research has suggested that older adults who misuse alcohol frequently report depressive symptoms as an antecedent to drinking. The objective of the present study was to investigate the extent to which higher levels of depressive symptoms were associated with elders' problem drinking by examining screening data from a three-year pilot program known as the Florida BRITE Project. BRITE (BRief Intervention and Treatment for Elders) is a multisite program offering brief interventions for community-based older adults screening positive for alcohol or medication misuse. Depressive symptoms were assessed using the Short Geriatric Depression Scale: alcohol use was assessed with the first three questions from the Alcohol Use Disorders Identification Test and the Short-Michigan Alcoholism Screening Test-Geriatric version. Multivariate logistic regression revealed that older adults with higher levels of depressive symptoms were at greater risk for screening positive for alcohol pr...
Pain medication use in patients with HR+, HER2-neg advanced breast cancer treated with endocrine therapy and a CDK 4/6 inhibitor: A U.S. FDA pooled analysis
Journal of Clinical Oncology
e24145 Background: Pain medications (PMs) are commonly used to treat pain in patients (pts) with ... more e24145 Background: Pain medications (PMs) are commonly used to treat pain in patients (pts) with advanced/metastatic breast cancer (MBC). We examined PM usage patterns in pts receiving CDK 4/6 inhibitor (CDKI) based treatment. Methods: We pooled data from seven phase 3 randomized, controlled trials of CDKI + endocrine therapy in pts with hormone receptor positive, human epidermal growth factor receptor-2 negative MBC. PM were categorized as opioid (includes codeine-containing), NSAID, or other (i.e. bone-directed, antiepileptic, topical PMs). All analyzed pts received at least 1 dose of CDKI/placebo and had concomitant PM with a documented start date. Medications prescribed during hospitalizations were not included. We evaluated percent PM by demographic factors and pts with bone mets, and liver/lung mets. Results: 2416 pts met the inclusion criteria, of which 928 pts started a PM before the study and 1488 pts did not start PM before the study. Of the 1488 pts not on a PM before the...
SPIRIT-PRO Extension explanation and elaboration: guidelines for inclusion of patient-reported outcomes in protocols of clinical trials
BMJ Open
Patient-reported outcomes (PROs) are used in clinical trials to provide valuable evidence on the ... more Patient-reported outcomes (PROs) are used in clinical trials to provide valuable evidence on the impact of disease and treatment on patients’ symptoms, function and quality of life. High-quality PRO data from trials can inform shared decision-making, regulatory and economic analyses and health policy. Recent evidence suggests the PRO content of past trial protocols was often incomplete or unclear, leading to research waste. To address this issue, international, consensus-based, PRO-specific guidelines were developed: the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-PRO Extension. The SPIRIT-PRO Extension is a 16-item checklist which aims to improve the content and quality of aspects of clinical trial protocols relating to PRO data collection to minimise research waste, and ultimately better inform patient-centred care. This SPIRIT-PRO explanation and elaboration (E&E) paper provides information to promote understanding and facilitate uptake of the reco...
Survival outcomes in older men with non-metastatic castration-resistant prostate cancer treated with androgen receptor inhibitors: a US Food and Drug Administration pooled analysis of patient-level data from three randomised trials
The Lancet Oncology
Timing of assessments for PRO measures in advanced RCC clinical trials
Journal of Clinical Oncology
e19101 Background: Efficient and thoughtful collection of PROs in randomized cancer trials is nec... more e19101 Background: Efficient and thoughtful collection of PROs in randomized cancer trials is necessary, especially when comparing drugs with differing administration schedules. Assessment timing for PROs can dramatically influence results. We sought to better understand how different assessment schedules affect interpretation of toxicity using PRO data. Methods: We reviewed 3 randomized trials in advanced/metastatic RCC with a control arm of sunitinib administered 4 weeks on/2 weeks off. All 3 trials used FACT Kidney Symptom Index (FKSI-19 or -DRS) and one also used EORTC QLQ-C30. For each trial, we chose patient-reported diarrhea and bone pain due to their strong association with the therapeutic intervention and the disease, respectively. Results: For the first 12 weeks, all trials had PRO assessments at baseline but had differing schedules thereafter. PRO assessment in Trial 1 was every 3 weeks; Trial 2: week 6 and week 12; Trial 3: every 3 weeks on the investigational arm and at...
Patient-reported diarrhea impact on physical functioning and quality of life in clinical trial data submitted to the U.S. Food and Drug Administration
Journal of Clinical Oncology
e19105 Background: Patient-reported outcomes can provide symptom and function data that complemen... more e19105 Background: Patient-reported outcomes can provide symptom and function data that complement standard oncology endpoints. Frequently, trials will conclude there was no clinically meaningful detriment to health-related quality of life (HRQL) or function, even when notable toxicity is observed. It is possible that mean change from baseline analyses obscures meaningful change in subgroups experiencing symptomatic toxicity. In this study, we explore how patients’ response to a diarrhea item related to physical function (PF) and HRQL in trials submitted to US FDA. Methods: We analyzed 3 randomized, double-blind breast cancer trials (early to late line metastatic) where diarrhea was a more common AE-symptom in the treatment arm, but there was not a large detriment in the mean change from baseline for HRQL and PF. Trials included the EORTC Quality of Life Questionnaire (QLQ-C30), which captures patient-reported HRQL, symptoms, and functioning. Higher scores (range 0-100) indicate bet...
Financial toxicity in patients with multiple myeloma participating in clinical trials: A U.S. Food and Drug Administration pooled analysis
Journal of Clinical Oncology
e19370 Background: Financial toxicity (FT) is a major concern for patients receiving standard can... more e19370 Background: Financial toxicity (FT) is a major concern for patients receiving standard cancer treatment, and FT can lead to worse cancer outcomes. However, little is known about the FT of patients enrolled in clinical trials (CT). While investigational treatment may be provided by sponsors free of charge, patients are subject to increased clinic visits (ie, missed workdays, travel costs) and still bear the cost of usual care. This analysis evaluates patient-reported FT in multiple myeloma (MM) trials submitted to US FDA and explores the relationship between baseline FT and overall response rate (ORR). Methods: We pooled data from 9 MM registration CTs submitted to the FDA that included the EORTC Quality of Life questionnaire (QLQ-C30). The QLQ-C30 includes an item asking patients “Has your physical condition or medical treatment caused you financial difficulties?”. We looked at proportion of patients at baseline reporting any FT and their ORR. We also report prevalence, incid...
FDA analysis of ECOG performance status and safety outcomes
Journal of Clinical Oncology
12024 Background: Patients with poor performance status are often excluded from clinical trials. ... more 12024 Background: Patients with poor performance status are often excluded from clinical trials. The FDA has published several guidances on modernizing oncology clinical trial eligibility criteria to more accurately reflect the patient population. Many patients receiving novel oncology therapeutics are heavily pretreated, and often have comorbidities, organ dysfunction, and frailty syndromes. Little is known about the safety of novel therapeutics in patients with poor performance status. Methods: Data from six randomized trials (n=4465) leading to registration for several solid tumor and malignant hematologic cancers, including multiple therapeutic mechanisms of action, such as EGFR TKI’s, immune checkpoint inhibitors (ICI), and chemotherapy, were pooled. Cumulative incidence of Grade 3-5 adverse events and serious adverse events at Days 30, 90, and 180 were evaluated based on ECOG 0-2. Rates of treatment discontinuation by ECOG was also examined. Results: Cumulative incidence of to...
Exploring open-label bias in patient-reported outcome (PRO) emotional domain scores in cancer trials
Journal of Clinical Oncology
Patient-reported outcomes in PD-1/PD-L1 inhibitor registration trials: FDA analysis of data submitted and future directions
Journal of Clinical Oncology
134 Background: Patient-reported outcome measures (PROs) can capture the patient’s experience wit... more 134 Background: Patient-reported outcome measures (PROs) can capture the patient’s experience with disease and treatment. Anti-PD-1/PD-L1 therapies have unique symptomatic side effects; PRO data can help to better understand the patient experience on therapy. Health-related quality of life (HRQL) components most impacted by therapy include disease symptoms, symptomatic toxicity and physical function. Methods: We reviewed FDA registration trials for 5 immunotherapy agents (anti-PD-1/PD-L1) to evaluate trial design and PRO assessment. We assessed whether the PRO strategy assessed physical function and symptomatic immune-related adverse events (irAEs) by reviewing whether trials used a well-defined physical function domain and 8 symptoms related to irAEs reported in product labels (fatigue, diarrhea, cough, shortness of breath, musculoskeletal pain, rash, pruritis and fever). Results: Data from 25 trials across 7 disease types and 1 tumor agnostic indication were evaluated. Of these, 1...
Abstract PD12-12: Floor and ceiling effects in the EORTC QLQ-C30 physical functioning subscale among patients with breast cancer enrolled in commercial clinical trials vs. a community trial
Cancer Research, 2021
Background: The EORTC QLQ-C30 Physical Functioning (PF) subscale is a widely used patient-reporte... more Background: The EORTC QLQ-C30 Physical Functioning (PF) subscale is a widely used patient-reported outcome (PRO) measure that quantifies cancer patients’ physical function. Responsiveness, the degree to which a scale can assess clinical deterioration and improvement, is an important measurement characteristic that can be assessed by looking at floor and ceiling effects. A floor effect is defined as a high proportion of study participants reporting the lowest possible score in the variable of interest, while a ceiling effect is the opposite. We characterized floor and ceiling effects of the PF subscale in patients with breast cancer enrolled in commercial clinical trials vs. a community-based trial.Objectives: (1) Determine floor/ceiling effects of the QLQ-C30 PF items and subscale among patients receiving treatment for breast cancer (2) Compare floor/ceiling effects among patients enrolled in randomized clinical trials vs. those treated in a community care trial.Methods: PF data fro...
Clinical Cancer Research, 2021
On December 16, 2020, the FDA granted regular approval to margetuximab-cmkb (MARGENZA), in combin... more On December 16, 2020, the FDA granted regular approval to margetuximab-cmkb (MARGENZA), in combination with chemotherapy, for the treatment of adult patients with HER2-positive (HER2+) metastatic breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Approval was based on data from SOPHIA, a multicenter, randomized, open-label, active controlled study comparing margetuximab with trastuzumab, in combination with chemotherapy. The primary efficacy endpoint was progression-free survival (PFS) by blinded independent central review. SOPHIA demonstrated a 0.9-month difference in median PFS between the two treatment arms [5.8 vs. 4.9 months, respectively; stratified HR, 0.76 (95% confidence interval: 0.59–0.98; P = 0.0334)]. Overall survival (OS) was immature at the data cut-off date of September 10, 2019. Infusion-related reactions (IRR) are an important safety signal associated with margetuximab plus chemotherapy. In SOPHIA...
Patient-reported pain and pain medication impact in patients with HR+ Her2-neg advanced breast cancer: A U.S. FDA pooled analysis
Journal of Clinical Oncology, 2020
e13027 Background: Despite the ubiquitous prescribing of pain medications (PMs) in cancer clinica... more e13027 Background: Despite the ubiquitous prescribing of pain medications (PMs) in cancer clinical trials, the impact of such prescribing patterns and reporting on the experience of pain is not often investigated. We examined patient-reported pain before initiation of PM reporting and at the next available pain assessment. Our aim was to understand change in patient-reported pain. Methods: We pooled data from 7 phase 3 randomized, controlled, registration trials of CDKI with endocrine therapy in patients with hormone receptor positive, human epidermal growth factor receptor-2 negative MBC. We restricted our analyses to patients who started therapy with no PM reported and looked at patients who had NSAID or opioid medication documented. We calculated change between 2 assessments in patient-reported pain before and after PM using the pain occurrence item (Q9) on the EORTC Quality of Life questionnaire (QLQ-C30). Results: Of the 4200 patients who received at least 1 dose of CDKI/placeb...
Psychiatric Services, 2011
OBJECTIVE-For community-dwelling older adults with depressive symptoms, aims were to: describe be... more OBJECTIVE-For community-dwelling older adults with depressive symptoms, aims were to: describe behavioral health service utilization patterns over a six-month period; and identify factors associated with service use, guided by a multidimensional, comprehensive theoretical model emphasizing the dynamic nature of service use patterns over time and social context. METHODS-144 participants with depressive symptoms completed an in-person baseline interview and six monthly telephone follow-up interviews. Outcomes included use of antidepressants or counseling at each follow-up. Covariates included individual (demographic, need, prior treatment experience, intentions) and social context (stigma, advice) variables. RESULTS-Approximately half of participants received no formal service (antidepressant or counseling; n = 70, 48%). Service use or non-use did not change for most participants. More participants with severe symptoms received antidepressants (25-37%) than those with milder symptoms (10-14%), although more of the milder cases started (62% vs. 49%) and stopped antidepressants (77% vs. 26%) at least once. Fewer individuals received counseling overall, with no clear patterns by symptom severity. In multivariate longitudinal analyses, service use at followup was independently associated with younger age, current major depressive episode, baseline use of antidepressant, intention to begin a new service at baseline, and receipt of advice to use services over follow-up. CONCLUSIONS-Over a six-month period, the majority of older adults with depressive symptoms in this study continued use or non-use of mental health services. Demographic, need, attitudinal and social variables were related to service use over time. Addressing intentions and providing advice may facilitate uptake of services. Older adults commonly experience depressive symptoms (1, 2), with serious health consequences (3-6), although they underutilize mental health services (7, 8). Theoretical frameworks have become increasingly complex in attempts to explain this underutilization, and the network-episode model (NEM; 9, 10, 11) has been recommended to guide this research (12). The NEM emphasizes the dynamic nature of entry and exits in service systems over time and the influence of individuals' social context on service use, in addition Disclosures: None for any author.
Journal of the American Geriatrics Society, 2007
OBJECTIVES: To explore the extent of and factors associated with male nursing home residents who ... more OBJECTIVES: To explore the extent of and factors associated with male nursing home residents who wander. DESIGN: Cross-sectional design with secondary data analyses. SETTING: One hundred thirty-four nursing home facilities operated by the Department of Veterans Affairs. PARTICIPANTS: Fifteen thousand ninety-two nursing home residents with moderate or severe cognitive impairment admitted over a 4-year period. MEASUREMENTS: Selected variables from the Minimum Data Set included ratings recorded at residents' admission to the nursing home (cognitive impairment, mood, behavior problems, activities of daily living, and wandering). RESULTS: In this sample of residents with moderate or severe cognitive impairment, the proportion of wanderers was found to be 21%. Wanderers were more likely to exhibit severe (vs moderate) cognitive impairment, socially inappropriate behavior, resistance to care, use of antipsychotic medication, independence in locomotion or ambulation, and dependence in activities of daily living related to basic hygiene. A sizable proportion of wanderers were found to be wheelchair users (25%) or were wanderers with dual dementia and psychiatric diagnoses (23%), characteristics that are not well documented in the literature. CONCLUSION: These results support previous clinical understanding of wanderers to be those who are more likely to exhibit more-severe cognitive impairment. Based on a statistical model with variables generated from prior research findings, classification as a wanderer was found to be associated with other disruptive activity such as socially inappropriate behavior and resisting care. Two understudied populations of wanderers were documented: wheelchair wanderers and those with comorbid dementia and psychiatric diagnoses. Future longitudinal studies should examine predictors of wandering behavior, and further research should explore the understudied subpopulations of wheelchair and dual-diagnosis wanderers who emerged in this study.
International Journal of Geriatric Psychiatry, 2010
To explore the extent of and factors associated with male residents who change wandering status p... more To explore the extent of and factors associated with male residents who change wandering status post nursing home admission. Design: Longitudinal design with secondary data analyses. Admissions over a 4-year period were examined using repeat assessments with the Minimum Data Set (MDS) to formulate a model understanding the development of wandering behavior. Setting: One hundred thirty-four Veterans Administration (VA) nursing homes throughout the United States. Participants: Included 6673 residents admitted to VA nursing homes between October 2000 and October 2004. Measurements: MDS variables (cognitive impairment, mood, behavior problems, activities of daily living and wandering) included ratings recorded at residents' admission to the nursing home and a minimum of two other time points at quarterly intervals. Results: The majority (86%) of the sample were classified as non-wanderers at admission and most of these (94%) remained non-wanderers until discharge or the end of the study. Fifty-one per cent of the wanderers changed status to non-wanderers with 6% of these residents fluctuating in status more than two times. Admission variables associated with an increased risk of changing status from non-wandering to wandering included older age, greater cognitive impairment, more socially inappropriate behavior, resisting care, easier distractibility, and needing less help with personal hygiene. Requiring assistance with locomotion and having three or more medical comorbidities were associated with a decreased chance of changing from non-wandering to wandering status. Conclusion: A resident's change from non-wandering to wandering status may reflect an undetected medical event that affects cognition, but spares mobility.
American Journal of Public Health, 2010
Objectives. We developed and examined the effectiveness of the Florida Brief Intervention and Tre... more 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 h...
Graphical representations of patient tolerability data: Recommendations from the National Cancer Institute (NCI) Cancer Moonshot Standardization Working Group
Journal of Clinical Oncology
e18612 Background: Effective communication of treatment tolerability data is essential for clinic... more e18612 Background: Effective communication of treatment tolerability data is essential for clinical decision making and improved patient outcomes, yet standardized approaches to the analysis and visualization of tolerability data in cancer clinical trials are currently limited. To address this need, the Standardization Working Group (SWG) was established within the NCI Cancer Moonshot Tolerability Consortium. This abstract describes the SWG’s initiative to develop a publicly accessible online toolkit with a comprehensive set of guidelines, references, and resources for graphical displays of tolerability data. Methods: A multidisciplinary group of PRO researchers including biostatisticians, clinicians, epidemiologists, and representatives from the NCI and FDA convened monthly to discuss toolkit development and content. Considerations for standardization of graphical displays of tolerability data included (1) types of graphical displays, (2) incorporation of missing data, (3) labeling...
Neurourology and Urodynamics, 2017
Uren A1, Cotterill N1, Lasch K2, Deshpande C2, King-Kallimanis B2, van Koeveringe G3, Harding C4,... more Uren A1, Cotterill N1, Lasch K2, Deshpande C2, King-Kallimanis B2, van Koeveringe G3, Harding C4, Oelke M5, Chapple C6, Hillary C6, Belal M7, Bosch R8, Blok B9, Klaver M10, Bongaerts D10, Hakimi Z10, Abrams P1 1. Bristol Urological Institute, Bristol, UK, 2. Pharmerit, Boston, United States, 3. Maastricht University Medical Centre, Maastricht, The Netherlands, 4. Freeman Hospital, Newcastle-upon-Tyne, 5. Hannover Medical School, Hannover, Germany, 6. Royal Hallamshire Hospital, Sheffield, 7. Queen Elizabeth Hospital, Birmingham, UK, 8. University Medical Centre Utrecht, Utrecht, The Netherlands, 9. Erasmus Medical Centre, Rotterdam, The Netherlands, 10. Astellas Pharma B.V., Leiden, The Netherlands
Frailty in relapsed/ refractory multiple myeloma registration trials
e20017 Background: Multiple Myeloma (MM) is predominantly a disease of older adults with a median... more e20017 Background: Multiple Myeloma (MM) is predominantly a disease of older adults with a median age of onset at 70 years. There is growing interest in using criterion other than chronological age, like frailty, to determine fitness for treatment and ultimately improve clinical outcomes in MM. Frailty is the accumulation of aging-associated diseases and disabilities, making patients more vulnerable to adverse outcomes when exposed to stressors like anti-cancer treatment. MM frailty measures have primarily been developed and tested in newly diagnosed patients. MM patients typically relapse, but there is limited knowledge regarding the prevalence of frailty in the relapsed/refractory (RRMM) setting. The aim of this research was to determine the prevalence of frailty in RRMM commercial clinical trials, at the time of trial enrollment, using the International Myeloma Working Group (IMWG) Frailty Index. Methods: We pooled baseline data from 6 RRMM clinical trials submitted for FDA regul...
Depressive Symptoms and Alcohol Abuse/Misuse in Older Adults: Results from the Florida BRITE Project
Previous research has suggested that older adults who misuse alcohol frequently report depressive... more Previous research has suggested that older adults who misuse alcohol frequently report depressive symptoms as an antecedent to drinking. The objective of the present study was to investigate the extent to which higher levels of depressive symptoms were associated with elders' problem drinking by examining screening data from a three-year pilot program known as the Florida BRITE Project. BRITE (BRief Intervention and Treatment for Elders) is a multisite program offering brief interventions for community-based older adults screening positive for alcohol or medication misuse. Depressive symptoms were assessed using the Short Geriatric Depression Scale: alcohol use was assessed with the first three questions from the Alcohol Use Disorders Identification Test and the Short-Michigan Alcoholism Screening Test-Geriatric version. Multivariate logistic regression revealed that older adults with higher levels of depressive symptoms were at greater risk for screening positive for alcohol pr...
Pain medication use in patients with HR+, HER2-neg advanced breast cancer treated with endocrine therapy and a CDK 4/6 inhibitor: A U.S. FDA pooled analysis
Journal of Clinical Oncology
e24145 Background: Pain medications (PMs) are commonly used to treat pain in patients (pts) with ... more e24145 Background: Pain medications (PMs) are commonly used to treat pain in patients (pts) with advanced/metastatic breast cancer (MBC). We examined PM usage patterns in pts receiving CDK 4/6 inhibitor (CDKI) based treatment. Methods: We pooled data from seven phase 3 randomized, controlled trials of CDKI + endocrine therapy in pts with hormone receptor positive, human epidermal growth factor receptor-2 negative MBC. PM were categorized as opioid (includes codeine-containing), NSAID, or other (i.e. bone-directed, antiepileptic, topical PMs). All analyzed pts received at least 1 dose of CDKI/placebo and had concomitant PM with a documented start date. Medications prescribed during hospitalizations were not included. We evaluated percent PM by demographic factors and pts with bone mets, and liver/lung mets. Results: 2416 pts met the inclusion criteria, of which 928 pts started a PM before the study and 1488 pts did not start PM before the study. Of the 1488 pts not on a PM before the...
SPIRIT-PRO Extension explanation and elaboration: guidelines for inclusion of patient-reported outcomes in protocols of clinical trials
BMJ Open
Patient-reported outcomes (PROs) are used in clinical trials to provide valuable evidence on the ... more Patient-reported outcomes (PROs) are used in clinical trials to provide valuable evidence on the impact of disease and treatment on patients’ symptoms, function and quality of life. High-quality PRO data from trials can inform shared decision-making, regulatory and economic analyses and health policy. Recent evidence suggests the PRO content of past trial protocols was often incomplete or unclear, leading to research waste. To address this issue, international, consensus-based, PRO-specific guidelines were developed: the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-PRO Extension. The SPIRIT-PRO Extension is a 16-item checklist which aims to improve the content and quality of aspects of clinical trial protocols relating to PRO data collection to minimise research waste, and ultimately better inform patient-centred care. This SPIRIT-PRO explanation and elaboration (E&E) paper provides information to promote understanding and facilitate uptake of the reco...
Survival outcomes in older men with non-metastatic castration-resistant prostate cancer treated with androgen receptor inhibitors: a US Food and Drug Administration pooled analysis of patient-level data from three randomised trials
The Lancet Oncology
Timing of assessments for PRO measures in advanced RCC clinical trials
Journal of Clinical Oncology
e19101 Background: Efficient and thoughtful collection of PROs in randomized cancer trials is nec... more e19101 Background: Efficient and thoughtful collection of PROs in randomized cancer trials is necessary, especially when comparing drugs with differing administration schedules. Assessment timing for PROs can dramatically influence results. We sought to better understand how different assessment schedules affect interpretation of toxicity using PRO data. Methods: We reviewed 3 randomized trials in advanced/metastatic RCC with a control arm of sunitinib administered 4 weeks on/2 weeks off. All 3 trials used FACT Kidney Symptom Index (FKSI-19 or -DRS) and one also used EORTC QLQ-C30. For each trial, we chose patient-reported diarrhea and bone pain due to their strong association with the therapeutic intervention and the disease, respectively. Results: For the first 12 weeks, all trials had PRO assessments at baseline but had differing schedules thereafter. PRO assessment in Trial 1 was every 3 weeks; Trial 2: week 6 and week 12; Trial 3: every 3 weeks on the investigational arm and at...
Patient-reported diarrhea impact on physical functioning and quality of life in clinical trial data submitted to the U.S. Food and Drug Administration
Journal of Clinical Oncology
e19105 Background: Patient-reported outcomes can provide symptom and function data that complemen... more e19105 Background: Patient-reported outcomes can provide symptom and function data that complement standard oncology endpoints. Frequently, trials will conclude there was no clinically meaningful detriment to health-related quality of life (HRQL) or function, even when notable toxicity is observed. It is possible that mean change from baseline analyses obscures meaningful change in subgroups experiencing symptomatic toxicity. In this study, we explore how patients’ response to a diarrhea item related to physical function (PF) and HRQL in trials submitted to US FDA. Methods: We analyzed 3 randomized, double-blind breast cancer trials (early to late line metastatic) where diarrhea was a more common AE-symptom in the treatment arm, but there was not a large detriment in the mean change from baseline for HRQL and PF. Trials included the EORTC Quality of Life Questionnaire (QLQ-C30), which captures patient-reported HRQL, symptoms, and functioning. Higher scores (range 0-100) indicate bet...
Financial toxicity in patients with multiple myeloma participating in clinical trials: A U.S. Food and Drug Administration pooled analysis
Journal of Clinical Oncology
e19370 Background: Financial toxicity (FT) is a major concern for patients receiving standard can... more e19370 Background: Financial toxicity (FT) is a major concern for patients receiving standard cancer treatment, and FT can lead to worse cancer outcomes. However, little is known about the FT of patients enrolled in clinical trials (CT). While investigational treatment may be provided by sponsors free of charge, patients are subject to increased clinic visits (ie, missed workdays, travel costs) and still bear the cost of usual care. This analysis evaluates patient-reported FT in multiple myeloma (MM) trials submitted to US FDA and explores the relationship between baseline FT and overall response rate (ORR). Methods: We pooled data from 9 MM registration CTs submitted to the FDA that included the EORTC Quality of Life questionnaire (QLQ-C30). The QLQ-C30 includes an item asking patients “Has your physical condition or medical treatment caused you financial difficulties?”. We looked at proportion of patients at baseline reporting any FT and their ORR. We also report prevalence, incid...
FDA analysis of ECOG performance status and safety outcomes
Journal of Clinical Oncology
12024 Background: Patients with poor performance status are often excluded from clinical trials. ... more 12024 Background: Patients with poor performance status are often excluded from clinical trials. The FDA has published several guidances on modernizing oncology clinical trial eligibility criteria to more accurately reflect the patient population. Many patients receiving novel oncology therapeutics are heavily pretreated, and often have comorbidities, organ dysfunction, and frailty syndromes. Little is known about the safety of novel therapeutics in patients with poor performance status. Methods: Data from six randomized trials (n=4465) leading to registration for several solid tumor and malignant hematologic cancers, including multiple therapeutic mechanisms of action, such as EGFR TKI’s, immune checkpoint inhibitors (ICI), and chemotherapy, were pooled. Cumulative incidence of Grade 3-5 adverse events and serious adverse events at Days 30, 90, and 180 were evaluated based on ECOG 0-2. Rates of treatment discontinuation by ECOG was also examined. Results: Cumulative incidence of to...
Exploring open-label bias in patient-reported outcome (PRO) emotional domain scores in cancer trials
Journal of Clinical Oncology
Patient-reported outcomes in PD-1/PD-L1 inhibitor registration trials: FDA analysis of data submitted and future directions
Journal of Clinical Oncology
134 Background: Patient-reported outcome measures (PROs) can capture the patient’s experience wit... more 134 Background: Patient-reported outcome measures (PROs) can capture the patient’s experience with disease and treatment. Anti-PD-1/PD-L1 therapies have unique symptomatic side effects; PRO data can help to better understand the patient experience on therapy. Health-related quality of life (HRQL) components most impacted by therapy include disease symptoms, symptomatic toxicity and physical function. Methods: We reviewed FDA registration trials for 5 immunotherapy agents (anti-PD-1/PD-L1) to evaluate trial design and PRO assessment. We assessed whether the PRO strategy assessed physical function and symptomatic immune-related adverse events (irAEs) by reviewing whether trials used a well-defined physical function domain and 8 symptoms related to irAEs reported in product labels (fatigue, diarrhea, cough, shortness of breath, musculoskeletal pain, rash, pruritis and fever). Results: Data from 25 trials across 7 disease types and 1 tumor agnostic indication were evaluated. Of these, 1...