Advancing patient-centric care: integrating patient reported outcomes for tolerability assessment in early phase clinical trials - insights from an expert virtual roundtable.

Early phase clinical trials provide an initial evaluation of therapies' risks and benefits to patients, including safety and tolerability, which typically relies on reporting outcomes by investigator and laboratory assessments. Use of patient-reported outcomes (PROs) to inform risks (tolerability) and benefits (improvement in disease symptoms) is more common in later than early phase trials. We convened a two-day expert roundtable covering: (1) the necessity and feasibility of a universal PRO core conceptual model for early phase trials; (2) the practical integration of PROs in early phase trials to inform tolerability assessment, guide dose decisions, or as real-time safety alerts to enhance investigator-reported adverse events. Participants (n = 22) included: patient advocates, regulators, clinicians, statisticians, pharmaceutical representatives, and PRO methodologists working across diverse clinical areas. In this manuscript, we report major recommendations resulting from the roundtable discussions corresponding to each theme. Additionally, we highlight priority areas necessitating further investigation.

Significant individual change should be used as a lower bound for anchor based estimates of meaningful change on patient-reported outcome scores.

Interpretation of patient-reported outcome (PRO) scores has been supported by identifying score thresholds or ranges that indicate clinical importance. There has been a recent focus on the estimation of meaningful within patient change (MWPC). While much attention has been focused on anchor-based methods, some researchers prefer that a lower bound to these estimates should exceed a change score that could be observed due to measurement error alone as a safeguard against misclassifying individual patients as changed when they have not. The standard error of measurement (SEM) is often used as the lower bound of anchor estimates. Here, we argue that the SEM is not an the best lower bound for MWPCs. Instead, statistically significant individual change as calculated by the reliable change index (RCI) should be used as the lower bound. Our argument is based on two points. First, conceptually, the SEM does not provide specific enough information to serve as a lower bound for MWPCs, which should be based on the level of observed score change that is unlikely to be due to chance alone. Second, the SEM is not appropriate for direct application to observed scores, and requires a multiplier when examining observed change instead of true change. We conclude with recommendations for using the RCI with a thoughtful range of p-values in combination with anchor estimates.

Risk of significant functional impairment across cancer diagnosis and care continuum.

BACKGROUND: The authors examined baseline physical functional (PF) impairment among cancer outpatients in the National Cancer Institute Cancer Moonshot study Northwestern University Improving the Management of Symptoms During and Following Cancer Treatment (NU IMPACT). They hypothesized that PF impairment, measured with the Patient Reported Outcome Measurement Information System-Physical Function (PROMIS-PF) survey, would (1) be common and more prevalent for patients receiving treatment compared with no treatment and (2) differ across tumor types, independent of cancer continuum phase. METHODS: Adults who were diagnosed with cancer in NU IMPACT (n = 2273) were sampled, and their PROMIS-PF scores were compared across tumor types and cancer continuum (curative, noncurative, or no treatment), with scores ≤40 indicating moderate-severe impairment. Multivariable logistic regression models were used to evaluate the relation among patient and cancer factors and PF scores using a 95% confidence interval. RESULTS: Forty percent of the surveyed patients reported moderate-severe PF impairment. Patients with melanoma reported the least impairment, and those with lung cancer were 6.5 times more likely to have moderate-severe impairment (95% confidence interval, 2.393-17.769). The noncurative group was 1.5 times more likely to have moderate-severe impairment (95% confidence interval, 1.045-2.145; mean score, 43; p < .001) than the curative (mean score, 6) and no treatment (mean score, 48) groups. One-third of those who reported PF impairment also had significant pain and/or fatigue. CONCLUSIONS: A sizeable minority experienced PF impairment across tumor types for which pain and/or fatigue co-occurred, particularly in the noncurative group. The PROMIS-PF survey effectively identified variations in physical function. Future studies will explore how screening for PF impairment can be used to refer patients for appropriate cancer rehabilitation services.

Exploring the Relationship Among Financial Hardship, Anxiety, and Depression in Patients With Cancer: A Longitudinal Study.

PURPOSE: Financial hardship (FH) is a complex issue in cancer care, affecting material conditions, well-being, and coping behaviors. This study aimed to longitudinally examine FH, anxiety, depressive symptoms, and their associations while incorporating social determinants of health and health care cost covariates in a sample of patients diagnosed with cancer. METHODS: This prospective, longitudinal cohort study analyzed data from 2,305 participants from the Northwestern University Improving the Management of Symptoms during and following Cancer Treatment trial. Outcomes assessed at baseline and at 3, 6, 9, and 12 months postbaseline included depressive symptoms, anxiety, and FH. Analysis involved random intercept cross-lagged panel models to explore between- and within-person effects, incorporating factors such as age, sex, insurance status, neighborhood area deprivation, health care charges, out-of-pocket costs, and health literacy. RESULTS: The cohort had a mean age of 60.7 (standard deviation [SD] = 12.7) years and was mostly female (64.9%) and White (86.2%). Correlations were found between FH and depressive symptoms (r = 0.310) and anxiety (r = 0.289). A predictive relationship was observed between FH and depressive symptoms, with baseline and 6-month depressive symptom levels predicting later FH (baseline ß = .079, P = .070; 6-month ß = .072, P = .081) and 9-month FH significantly predicting 12-month depressive symptoms (ß = .083, P = .025), even after accounting for health care charges and out-of-pocket costs. Baseline and 9-month anxiety showed a predictive relationship with subsequent FH (baseline ß = .097, P = .023; 9-month ß = .071, P = .068). CONCLUSION: FH emerged as a prominent issue, with nearly half of participants experiencing some level of FH. Depressive symptoms and anxiety were related to FH. These findings underscore the need for a comprehensive approach in cancer care that concurrently addresses anxiety, depressive symptoms, and FH, recognizing their interconnected impact.

Determining Predictors of Actual Living Kidney Donation Based on Potential Donor Characteristics.

BACKGROUND: Living donor kidney transplantation is the optimal treatment for end-stage kidney disease; however, few living donor candidates (LDCs) who begin evaluation actually donate. While some LDCs are deemed medically ineligible, others discontinue for potentially modifiable reasons. METHODS: At five transplant centers, we conducted a prospective cohort study measuring LDCs' clinical and psychosocial characteristics, educational preparation, readiness to donate, and social determinants of health. We followed LDCs for 12 months after evaluation to determine whether they donated a kidney, opted to discontinue, had modifiable reasons for discontinuing, were medically ineligible, or had other recipient-related reasons for discontinuing. RESULTS: Among 2184 LDCs, 18.6% donated, 38.2% opted to or had modifiable reasons for discontinuing, and 43.2% were deemed ineligible due to medical or recipient-related reasons. Multivariable analyses comparing successful LDCs with those who did not complete donation for modifiable reasons (N = 1241) found that LDCs who discussed donation with the recipient before evaluation (OR, 2.31; 95% CI, 1.54-3.46), had completed high school (OR, 2.01; 95% CI, 1.21-3.35), or were a "close relation" to their recipient (OR, 1.89; 95% CI, 1.33-2.69) were more likely to donate. Conversely, LDCs who reported religion as important (OR, 0.55; 95% CI, 0.38-0.80), were Non-White (OR, 0.70; 95% CI, 0.49-1.00), or had overall higher anxiety scores (OR, 0.92; 95% CI, 0.86-0.99) were less likely to donate. CONCLUSION: With fewer than a fifth of LDCs donating, developing programs to provide greater emotional support and facilitate open discussions between LDCs and recipients earlier may increase living donation rates.

Validity of a single-item indicator of treatment side effect bother in patients with head and neck cancer.

PURPOSE: Patients with head/neck squamous cell carcinomas (HNSCC) experience significant tumor- and treatment-related side effects. No efficient summary measure capturing the totality of side effect burden currently exists. We examined associations between a single patient-reported outcome (PRO) item evaluating side effect bother (FACT GP5, "I am bothered by side effects of treatment") with overall side effects in HNSCC. METHODS: We performed a retrospective secondary analysis of development of the Functional Assessment of Cancer Therapy (FACT) Head/Neck Symptom Index (FHNSI-10), which included completing FACT-HN (including Head/Neck Cancer Subscale (HNCS) and Trial Outcome Index (TOI)) and the pain intensity numeric rating scale (NRS). We calculated Spearman's correlations between GP5 and these measures of patient-reported global health, head/neck side effects, and pain intensity NRS. A correlation of > 0.4 was considered sufficient evidence of association. RESULTS: Ninety-seven patients completed baseline and 85 completed 3-month follow-up surveys. GP5 was highly correlated with FACT-HN total score (baseline r = 0.66, 3 months r = 0.67) and FHNSI-10 (baseline r = 0.63, 3 months r = 0.65). GP5 correlated with multiple FACT-HN subscales including FACT-G, physical well-being, functional well-being, HNCS, and TOI (range baseline r = 0.53-0.77, range 3 months r = 0.49-0.77). Worsening GP5 score was associated with worsening overall HNCS (p = 0.002), worsening FHNSI-10 score (p < 0.001), and worsening mean pain intensity (p < 0.001). CONCLUSION: GP5 exhibited validity within HNSCC, exhibiting substantial correlations with a number of HNSCC-related PRO measures including FACT-HN and FHNSI-10. Worsening GP5 was associated with worsening HNCS, FHNSI summary score, and pain intensity. GP5 has promise as a summary indicator of symptom and side effect bother in HNSCC.

Shared decision-making and disease management in advanced cancer and chronic kidney disease using patient-reported outcome dashboards.

OBJECTIVES: To assess the use of a co-designed patient-reported outcome (PRO) clinical dashboard and estimate its impact on shared decision-making (SDM) and symptomatology in adults with advanced cancer or chronic kidney disease (CKD). MATERIALS AND METHODS: We developed a clinical PRO dashboard within the Northwestern Medicine Patient-Reported Outcomes system, enhanced through co-design involving 20 diverse constituents. Using a single-group, pretest-posttest design, we evaluated the dashboard's use among patients with advanced cancer or CKD between June 2020 and January 2022. Eligible patients had a visit with a participating clinician, completed at least two dashboard-eligible visits, and consented to follow-up surveys. PROs were collected 72 h prior to visits, including measures for chronic condition management self-efficacy, health-related quality of life (PROMIS measures), and SDM (collaboRATE). Responses were integrated into the EHR dashboard and accessible to clinicians and patients. RESULTS: We recruited 157 participants: 66 with advanced cancer and 91 with CKD. There were significant improvements in SDM from baseline, as assessed by collaboRATE scores. The proportion of participants reporting the highest level of SDM on every collaboRATE item increased by 15 percentage points from baseline to 3 months, and 17 points between baseline and 6-month follow-up. Additionally, there was a clinically meaningful decrease in anxiety levels over study period (T-score baseline: 53; 3-month: 52; 6-month: 50; P < .001), with a standardized response mean (SRM) of -0.38 at 6 months. DISCUSSION: PRO clinical dashboards, developed and shared with patients, may enhance SDM and reduce anxiety among patients with advanced cancer and CKD.

Implementation of a Co-Design Strategy to Develop a Dashboard to Support Shared Decision Making in Advanced Cancer and Chronic Kidney Disease.

Background: Shared decision making (SDM) is the process by which patients and clinicians exchange information and preferences to come to joint healthcare decisions. Clinical dashboards can support SDM by collecting, distilling, and presenting critical information, such as patient-reported outcomes (PROs), to be shared at points of care and in between appointments. We describe the implementation strategies and outcomes of a multistakeholder collaborative process known as "co-design" to develop a PRO-informed clinical dashboard to support SDM for patients with advanced cancer or chronic kidney disease (CKD). Methods: Across 14 sessions, two multidisciplinary teams comprising patients, care partners, clinicians, and other stakeholders iteratively co-designed an SDM dashboard for either advanced cancer (N = 25) or CKD (N = 24). Eligible patients, care partners, and frontline clinicians were identified by six physician champions. The co-design process included four key steps: (1) define "the problem", (2) establish context of use, (3) build a consensus on design, and (4) define and test specifications. We also evaluated our success in implementing the co-design strategy using measures of fidelity, acceptability, adoption, feasibility, and effectiveness which were collected throughout the process. Results: Mean (M) scores across implementation measures of the co-design process were high, including observer-rated fidelity and adoption of co-design practices (M = 19.1 on a 7-21 scale, N = 36 ratings across 9 sessions), as well as acceptability based on the perceived degree of SDM that occurred during the co-design process (M = 10.4 on a 0 to 12 adapted collaboRATE scale). Capturing the feasibility and adoption of convening multistakeholder co-design teams, min-max normalized scores (ranging from 0 to 1) of stakeholder representation demonstrated that, on average, 95% of stakeholder types were represented for cancer sessions (M = 0.95) and 85% for CKD sessions (M = 0.85). The co-design process was rated as either "fully" or "partially" effective by 100% of respondents, in creating a dashboard that met its intended objective. Conclusions: A co-design process was successfully implemented to develop SDM clinical dashboards for advanced cancer and CKD care. We discuss key strategies and learnings from this process that may aid others in the development and uptake of patient-centered healthcare innovations.

Patient-Reported Outcome Screens for Cognitive Dysfunction and Predicts Admissions in Cirrhosis.

INTRODUCTION: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis, leading to preventable hospitalizations and increased mortality. Despite the availability of validated neuro-psychometric tests to diagnose HE, only 10% of clinicians regularly screen for HE due to lack of time, equipment, and trained personnel. MATERIALS AND METHODS: We studied the association between patient-reported cognitive function and the National Institutes of Health Toolbox Cognition Battery (a validated measure of HE) in patients with cirrhosis. A single-center prospective study of adult patients undergoing liver transplantation evaluation was performed from 10/2020 to 12/2021. Cognition was assessed using the National Institutes of Health Toolbox Cognition Battery and a brief Patient-Reported Outcomes Measurement Information System (PROMIS) survey. RESULTS: Twenty-three liver transplantation candidates were enrolled; the mean age was 56.4 (±9.7) years, 39% were female and the most common etiologies of cirrhosis were primary biliary cirrhosis/primary sclerosing cholangitis/overlap syndrome (30%), hepatitis C (22%) and alcohol-associated liver disease (22%). The mean MELD-Na was 14.9 (±6.4). The mean PROMIS Cognitive Function T-score (PROMISCF) was 49.2 (±9.6). The mean T-scores for the List Sort Working Memory test, Flanker Inhibitory Control and Attention test, and Pattern Comparison Processing Speed test were 46.4 (±9.9), 37.8 (±6.2), and 50.22 (±16.4), respectively. PROMISCF correlated with the List Sort Working Memory test (r = 0.45, P = .03). The mean hospitalization rate was 1.6 days admitted per month. On adjusted multivariate analysis, PROMISCF predicted total hospitalization days (P < .001), hospital admissions (P = .01), and hospitalization rate (P < .001). CONCLUSIONS: A brief survey can screen for HE and predict hospitalizations in patients with cirrhosis.

Overall side effect assessment of oxaliplatin toxicity in rectal cancer patients in NRG oncology/NSABP R04.

PURPOSE: Regulatory guidance suggests capturing patient-reported overall side effect impact in cancer trials. We examined whether the Functional Assessment of Cancer Therapy (FACT) GP5 item ("I am bothered by side effects of treatment") post-neoadjuvant chemotherapy/radiotherapy differed between oxaliplatin vs. non- oxaliplatin arms in the National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 trial of stage II-III rectal cancer patients. METHODS: The R-04 neoadjuvant trial compared local-regional tumor control between patients randomized to receive 5-fluorouracil or capecitabine with radiation, with or without oxaliplatin (4 treatment arms). Participants completed surveys at baseline and immediately after chemoradiotherapy. GP5 has a 5-point response scale: "Not at all" (0), "A little bit" (1), "Somewhat" (2), "Quite a bit" (3), and "Very much" (4). Logistic regression compared the odds of reporting moderate-high side effect impact (GP5 2-4) between patients receiving oxaliplatin or not after chemoradiotherapy, controlling for relevant patient characteristics. We examined associations between GP5 and other patient-reported outcomes reflecting side effects. RESULTS: Analyses were performed among 1132 study participants. Participants receiving oxaliplatin were 1.58 times (95% CI: 1.22-2.05) more likely to report moderate-high side effect bother at post-chemotherapy/radiation. In both arms, worse overall side effect impact was associated with patient-reported diarrhea, nausea, vomiting, and peripheral sensory neuropathy (p < 0.01 for all). CONCLUSION: This secondary analysis of R-04 found that GP5 distinguished between patients receiving oxaliplatin or not as part of their post-neoadjuvant chemoradiotherapy, adding patient-centric evidence on the reduced tolerability of oxaliplatin and demonstrating that GP5 is sensitive to known toxicity differences between treatments. CLINICALTRIALS: GOV: NCT00058474.

Obstacles to Biosimilar Acceptance and Uptake in Oncology: A Review.

Importance: Biosimilar drugs provide cost-effective yet clinically indistinguishable replications of target drugs. During initial development, this class of biologic medicines was expected to revolutionize pharmaceutical markets; however, following US Food and Drug Administration approval of the first biosimilar drug in 2015, the commercialization of biosimilars has been limited. The lack of biosimilar use may be especially salient in oncology, given that biosimilar distribution in this particularly high-cost area of medicine would bring savings on the order of many billions of dollars. Observations: While researchers have focused on salient economic barriers to biosimilar uptake in the US, the present review provides insight regarding noneconomic barriers. This review discusses psychological, attitudinal, and educational factors among both health care professionals and payers in the US that may play a role in slowing biosimilar uptake. More specifically, these factors include a lack of health care professional education, concerns of safety and efficacy, and overly complex product naming systems. Conclusions and Relevance: The pathway to biosimilar use has been obstructed by economic elements as well as attitudinal and psychological factors. For biosimilar drugs to achieve their potential in decreasing treatment costs and thus increasing patient access, it will be essential for both economic and noneconomic factors to be identified and systematically addressed.

The challenge of using patient reported outcome measures in clinical practice: how do we get there?

BACKGROUND: As patient-reported outcome measures (PROMs) become available to clinicians for routine clinical decision-making, many wonder how to define a meaningful change in a patient's PROM score. Some PROMs have a specific threshold that indicates meaningful change, but since those numbers are based on population averages, they do not necessarily apply to the varying experiences of each individual patient. Rather than viewing this as a weakness of PROMs, it is worth considering how clinicians use other existing measures in clinical decision-making-and whether PROMs can be used similarly. BODY: An informal survey of 43 clinicians reported using measures such as weight, blood pressure, and blood chemistry to inform clinical decision-making. Although clinicians were very consistent with what constituted a meaningful change for some measures (e.g., ECOG performance status), other measures had considerable variability (e.g., weight), often informed by their specialization (for example, differing thresholds for meaningful weight change for adult primary care, pediatrics, and oncology). For interpreting change in measures, they relied on clinical experience (44%), published literature (38%), and established guidelines (35%). In open-response comments, many clarified that the results of any measure had to be taken in the context of each individual patient before making treatment decisions. In short, clinicians already apply individualized clinical judgment when interpreting score changes in existing clinical measures. As clinicians gain familiarity with PROMs, PROMs will likely be utilized in the same way. CONCLUSION: Like other clinical measures from weight to blood chemistry, change in a PROM score is but one piece of a patient's clinical story. Rather than relying on a hard-and-fast number for defining clinically meaningful change in a PROM score, providers should-and many already do-consider the full scope of a patient's experience as they make treatment decisions.

Patient-Reported Adverse Events and Early Treatment Discontinuation Among Patients With Multiple Myeloma.

Importance: There is substantial interest in capturing cancer treatment tolerability from the patient's perspective using patient-reported outcomes (PROs). Objective: To examine whether a PRO question, item 5 from the Functional Assessment of Cancer Therapy-General General Physical Wellbeing Scale (GP5), was associated with early treatment discontinuation (ETD) due to adverse events. Design, Setting, and Participants: This prospective survey study was conducted from February to April 2023. Among participants in the ECOG-ACRIN E1A11 trial (a phase 3, parallel design trial conducted between 2013 and 2019), patients with newly diagnosed multiple myeloma were randomized to receive bortezomib (VRd) or carfilzomib (KRd) plus lenalidomide and dexamethasone as induction therapy. The GP5 item was administered at baseline (pretreatment) and at 1 month, 2.8 months, and 5.5 months postbaseline. Eligible participants included patients with newly diagnosed multiple myeloma treated at community oncology practices or academic medical centers in the US. Exposures: GP5 response options were "very much," "quite a bit," "somewhat," "a little bit," and "not at all." Responses at each assessment while undergoing treatment (1 month, 2.8 months, and 5.5 months) were categorized as high adverse event bother (ie, "very much," and "quite a bit") and low adverse event bother (ie, "somewhat," "a little bit," or "not at all"). In addition, change from baseline to each assessment while undergoing treatment was calculated and categorized as worsening by 1 response category and 2 or more response categories. Main Outcome and Measure: ETD due to adverse events (yes vs no) was analyzed using logistic regression adjusting for treatment group, performance status, gender, race, and disease stage. Results: Of the 1087 participants in the original trial, 1058 (mean [SD] age 64 [9] years; 531 receiving VrD [50.2%]; 527 receiving KRd [49.8%]) responded to item GP5 and were included in the secondary analysis. A small proportion (142 patients [13.4%]) discontinued treatment early due to AEs. For those with high adverse-effect bother, GP5 while undergoing treatment was associated with ETD at 1 month (adjusted odds ratio [aOR], 2.20; 95% CI, 1.25-3.89), 2.8 months (aOR, 3.41; 95% CI, 2.01-5.80), and 5.5 months (aOR, 4.66; 95% CI, 1.69-12.83). Worsening by 2 or more response categories on the GP5 was associated with ETD at 2.8 months (aOR, 3.02; 95% CI, 1.64-5.54) and 5.5 months (aOR, 5.49; 95% CI, 1.45-20.76). Conclusions and Relevance: In this survey study of the E1A11 trial, worse GP5 response was associated with ETD. These findings suggest that simple assessment of adverse-effect bother while receiving treatment is an efficient way to indicate treatment tolerability and ETD risk.

[Special issue PRO] Considering endpoints for comparative tolerability of cancer treatments using patient report given the estimand framework.

Regulatory agencies are advancing the use of systematic approaches to collect patient experience data, including patient-reported outcomes (PROs), in cancer clinical trials to inform regulatory decision-making. Due in part to clinician under-reporting of symptomatic adverse events, there is a growing recognition that evaluation of cancer treatment tolerability should include the patient experience, both in terms of the overall side effect impact and symptomatic adverse events. Methodologies around implementation, analysis, and interpretation of "patient" reported tolerability are under development, and current approaches are largely descriptive. There is robust guidance for use of PROs as efficacy endpoints to compare cancer treatments, but it is unclear to what extent this can be relied-upon to develop tolerability endpoints. An important consideration when developing endpoints to compare tolerability between treatments is the linkage of trial design, objectives, and statistical analysis. Despite interest in and frequent collection of PRO data in oncology trials, heterogeneity in analyses and unclear PRO objectives mean that design, objectives, and analysis may not be aligned, posing substantial challenges for the interpretation of results. The recent ICH E9 (R1) estimand framework represents an opportunity to help address these challenges. Efforts to apply the estimand framework in the context of PROs have primarily focused on efficacy outcomes. In this paper, we discuss considerations for comparing the patient-reported tolerability of different treatments in an oncology trial context.

Recommendations to address respondent burden associated with patient-reported outcome assessment.

Patient-reported outcomes (PROs) are increasingly used in healthcare research to provide evidence of the benefits and risks of interventions from the patient perspective and to inform regulatory decisions and health policy. The use of PROs in clinical practice can facilitate symptom monitoring, tailor care to individual needs, aid clinical decision-making and inform value-based healthcare initiatives. Despite their benefits, there are concerns that the potential burden on respondents may reduce their willingness to complete PROs, with potential impact on the completeness and quality of the data for decision-making. We therefore conducted an initial literature review to generate a list of candidate recommendations aimed at reducing respondent burden. This was followed by a two-stage Delphi survey by an international multi-stakeholder group. A consensus meeting was held to finalize the recommendations. The final consensus statement includes 19 recommendations to address PRO respondent burden in healthcare research and clinical practice. If implemented, these recommendations may reduce PRO respondent burden.

Patient-Reported Outcome Measures for Patients With CKD: The Case for Patient-Reported Outcomes Measurement Information System (PROMIS) Tools.

Chronic kidney disease (CKD), kidney failure, and kidney replacement therapies are associated with high symptom burden and impaired health-related quality of life (HRQOL). Symptoms change with disease progression or transition between treatment modalities and frequently go unreported and unmanaged. Tools that reliably monitor symptoms may improve the management of patients with CKD. Patient-reported outcome measures (PROMs) assess symptom severity; physical, psychological, social, and cognitive functioning; treatment-related side effects; and HRQOL. Systematic use of PROMs can improve patient-provider communication, patient satisfaction, clinical outcomes, and HRQOL. Potential barriers to their use include a lack of engagement, response burden, and limited guidance about PROM collection, score interpretation, and workflow integration. Well-defined, acceptable, and effective clinical response pathways are essential for implementing PROMs. PROMs developed by the Patient-Reported Outcomes Measurement Information System (PROMIS) address some challenges and may be suitable for clinical use among patients with CKD. PROMIS tools assess multiple patient-valued, clinically actionable symptoms and functions. They can be administered as fixed-length, customized short forms or computer adaptive tests, offering precise measurement across a range of symptom severities or function levels, tailored questions to individuals, and reduced question burden. Here we provide an overview of the potential use of PROMs in CKD care, with a focus on PROMIS.

Reliability, validity, and change thresholds of the NCCN/FACT Bladder Symptom Index (NFBlSI-18) in patients with advanced urothelial cancer.

BACKGROUND: The NCCN/FACT Bladder Symptom Index-18 (NFBlSI-18) is a bladder cancer-specific instrument. We aimed to psychometrically evaluate the reliability and validity of NFBlSI-18 and estimate change thresholds for total, disease-related symptoms-physical (DRS-P), DRS-emotional (DRS-E), and function/well-being (F/WB) scales in patients with locally advanced/metastatic urothelial cancer (la/mUC). METHODS: JAVELIN Bladder 100 trial data were analyzed. Anchors to evaluate validity included: 5-level EuroQoL-5D utility index (EQ-5D-5L UI), visual analog scale (VAS), Eastern Cooperative Oncology Group (ECOG) performance status, and number of symptoms. Responsiveness to change was tested by anchoring to time to tumor progression (TTP), best overall response (BOR), and differences in means between ECOG categories to estimate meaningful between-group differences. Meaningful within-group change thresholds were estimated using receiver operating characteristic curve analysis, anchoring to change in EQ-5D-5L UI. Significant within-individual patient change thresholds were estimated with reliable and likely change indexes. RESULTS: Correlations with EQ-5D-5L UI and VAS ranged from 0.53 to 0.73. Standardized effect sizes were >0.20. Compared with patients with TTP of ≥6 months, patients with TTP of >0-2 and 3-5 months had larger declines; results for BOR were similar. Thresholds (points) for meaningful between-group differences were: total, 6-11; DRS-P, 3-6; and DRS-E and F/WB, 1. Thresholds (points) for meaningful within-group worsening were: total, 4; and DRS-P, 3, and for significant individual change they were: total, 3-9; DRS-P, 2-6; DRS-E, 1-3; and F/WB, 2-4. CONCLUSIONS: NFBlSI-18 exhibited evidence of reliability, validity, and responsiveness to assess quality of life in studies of la/mUC, and change thresholds are established for future studies. PLAIN LANGUAGE SUMMARY: The NCCN/FACT Bladder Symptom Index-18 (NFBlSI-18) is a questionnaire used to assess quality of life for people with advanced bladder cancer. People with advanced bladder cancer who took part in the JAVELIN Bladder 100 study completed the NFBlSI-18 when they joined the study and after each treatment with avelumab maintenance or best supportive care. This study showed that NFBlSI-18 is suitable for capturing bladder cancer symptoms and is able to detect important changes in a person's quality of life over time. This study also provides thresholds for changes in NFBlSI-18 scores, which will be useful for future studies.

Brief PROMIS Assessment Screens for Frailty and Predicts Hospitalizations in Liver Transplant Candidates.

BACKGROUND: Frailty is prevalent in patients with end-stage liver disease and predicts waitlist mortality, posttransplant mortality, and frequency of hospitalizations. The Liver Frailty Index (LFI) is a validated measure of frailty in liver transplant (LT) candidates but requires an in-person assessment. METHODS: We studied the association between patient-reported physical function and LFI in a single-center prospective study of adult patients with cirrhosis undergoing LT evaluation from October 2020 to December 2021. Frailty was assessed with the LFI and 4-m gait speed. Patient-reported physical function was evaluated using a brief Patient-Reported Outcomes Measurement Information System (PROMIS) survey. RESULTS: Eighty-one LT candidates were enrolled, with a mean model of end-stage liver disease-sodium of 17.6 (±6.3). The mean LFI was 3.7 (±0.77; 15% frail and 59% prefrail) and the mean PROMIS Physical Function score was 45 (±8.6). PROMIS Physical Function correlated with LFI ( r = -0.54, P < 0.001) and 4-m gait speed ( r = 0.48, P < 0.001). The mean hospitalization rate was 1.1 d admitted per month. After adjusting for age, sex, and model of end-stage liver disease-sodium, patient-reported physical function-predicted hospitalization rate ( P = 0.001). CONCLUSIONS: This study suggests that a brief patient-reported outcome measure can be used to screen for frailty and predict hospitalizations in patients with cirrhosis.

Importance of Low- and Moderate-Grade Adverse Events in Patients' Treatment Experience and Treatment Discontinuation: An Analysis of the E1912 Trial.

PURPOSE: Despite defined grades of 1 to 5 for adverse events (AEs) on the basis of Common Terminology Criteria for Adverse Events criteria, mild (G1) and moderate (G2) AEs are often not reported in phase III trials. This under-reporting may inhibit our ability to understand patient toxicity burden. We analyze the relationship between the grades of AEs experienced with patient side-effect bother and treatment discontinuation. METHODS: We analyzed a phase III Eastern Cooperative Oncology Group-American College of Radiology Imaging Network trial with comprehensive AE data. The Likert response Functional Assessment of Cancer Therapy-GP5 item, "I am bothered by side effects of treatment" was used to define side-effect bother. Bayesian mixed models were used to assess the impact of G1 and G2 AE counts on patient side-effect bother and treatment discontinuation. AEs were further analyzed on the basis of symptomatology (symptomatic or asymptomatic). The results are given as odds ratios (ORs) and 95% credible interval (CrI). RESULTS: Each additional G1 and G2 AEs experienced during a treatment cycle increased the odds of increased self-reported patient side-effect bother by 13% (95% CrI, 1.06 to 1.21) and 35% (95% CrI, 1.19 to 1.54), respectively. Furthermore, only AEs defined as symptomatic were associated with increased side-effect bother, with asymptomatic AEs showing no association regardless of grade. Count of G2 AEs increased the odds of treatment discontinuation by 59% (95% CrI, 1.32 to 1.95), with symptomatic G2 AEs showing a stronger association (OR, 1.75; 95% CrI, 1.28 to 2.39) relative to asymptomatic G2 AEs (OR, 1.45; 95% CrI, 1.12 to 1.89). CONCLUSION: Low- and moderate-grade AEs are related to increased odds of increased patient side-effect bother and treatment discontinuation, with symptomatic AEs demonstrating greater magnitude of association than asymptomatic. Our findings suggest that limiting AE capture to grade 3+ misses important contributors to treatment side-effect bother and discontinuation.