Incorporation Of Patient-reported Outcomes Research Articles

Application of Patient-Reported Outcome Measurements in Adult Tumor Clinical Trials in China: Cross-Sectional Study.

International health policies and researchers have emphasized the value of evaluating patient-reported outcomes (PROs) in clinical studies. However, the characteristics of PROs in adult tumor clinical trials in China remain insufficiently elucidated. This study aims to assess the application and characteristics of PRO instruments as primary or secondary outcomes in adult randomized clinical trials related to tumors in China. This cross-sectional study identified tumor-focused randomized clinical trials conducted in China between January 1, 2010, and June 30, 2022. The ClinicalTrials.gov database and the Chinese Clinical Trial Registry were selected as the databases. Trials were classified into four groups based on the use of PRO instruments: (1) trials listing PRO instruments as primary outcomes, (2) trials listing PRO instruments as secondary outcomes, (3) trials listing PRO instruments as coprimary outcomes, and (4) trials without any mention of PRO instruments. Pertinent data, including study phase, settings, geographic regions, centers, participant demographics (age and sex), funding sources, intervention types, target diseases, and the names of PRO instruments, were extracted from these trials. The target diseases involved in the trials were grouped according to the American Joint Committee on Cancer Staging Manual, 8th Edition. Among the 6445 trials examined, 2390 (37.08%) incorporated PRO instruments as part of their outcomes. Within this subset, 26.82% (641/2390) listed PRO instruments as primary outcomes, 52.72% (1260/2390) as secondary outcomes, and 20.46% (489/2390) as coprimary outcomes. Among the 2,155,306 participants included in these trials, PRO instruments were used to collect data from 613,648 (28.47%) patients as primary or secondary outcomes and from 74,287 (3.45%) patients as coprimary outcomes. The most common conditions explicitly using specified PRO instruments included thorax tumors (217/1280, 16.95%), breast tumors (176/1280, 13.75%), and lower gastrointestinal tract tumors (173/1280, 13.52%). Frequently used PRO instruments included the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire-30, the visual analog scale, the numeric rating scale, the Traditional Chinese Medicine Symptom Scale, and the Pittsburgh Sleep Quality Index. Over recent years, the incorporation of PROs has demonstrated an upward trajectory in adult randomized clinical trials on tumors in China. Nonetheless, the infrequent measurement of the patient's voice remains noteworthy. Disease-specific PRO instruments should be more effectively incorporated into various tumor disease categories in clinical trials, and there is room for improvement in the inclusion of PRO instruments as clinical trial end points.

Abstract 1302: Development and implementation of a systematic approach to measure patient-reported outcomes in early-phase cancer trials

Abstract Background: There has been a shift in the clinical trial landscape toward early-phase studies where data from well-designed and pivotal phase I/II trials is leading to accelerated drug approval. Our goal was to develop a standardized approach to the measurement and reporting of patient-reported outcomes (PROs) in early-phase trials to improve assessment of tolerability, address noted barriers to inclusion, and enhance patient-provider communication to inform treatment decisions and ultimately improve outcomes. Methods: The Office of Patient Centered Outcomes Research (OPCORe) was established in 2022 within the Center for Cancer Research at the National Cancer Institute (NCI) with the mission to advance understanding of the clinical benefit and tolerability of cancer therapies by integrating patient-centered approaches into CCR clinical trials by fostering education and collaboration with stakeholders. Implementation of regulatory/consortia guidelines related to use of core constructs, assessment frequency, and hypothesis-driven objectives and analysis plans through protocol template, development of data capture, email-based alerts and data visualization for clinical providers was developed and standardized templates for protocol language, research staff education, tools for workflow, and tracking implemented. Results: The OPCORe protocol template includes measurement of 3 constructs, including tolerability, clinical benefit and disease-specific impact, as well as anchors of meaningful change. Core symptomatic toxicities are measured to inform understanding across trials with agent/class-specific symptomatic toxicities added to assure relevance. Baseline and standardized weekly electronic capture of tolerability during early cycles with alerts to clinical research staff if moderate-severe toxicities reported helps facilitate patient check-ins. Repeat PROs assessments in later cycles are expanded to include disease-specific assessments and align with disease evaluation to further inform clinical impact. To date, we have collaborated with 7 research groups and developed approaches for first-in-human, phase I, and phase II studies with trial start-up and data collection in process. Conclusion: The value of including PROs in cancer trials is increasingly recognized by regulators, clinicians, patients, and advocates to advance understanding of the clinical benefit & tolerability of emerging therapies. Standardization and incorporation of PROs in earlier phase trials may enable PROs to be optimized, improve later phase trial design, and help inform health policy, support drug approval, and promote shared decision making between providers and patients to inform treatment decisions. Citation Format: Amanda L. King, Jason E. Levine, Elizabeth Vera, Yuti Gandhi, Elaine Novakovich, Theresa Yu, Sefanit Berhanu, Ciara Locke, Kaelyn Julmeus, Tito Mendoza, Terri S. Armstrong. Development and implementation of a systematic approach to measure patient-reported outcomes in early-phase cancer trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1302.

People first: a participatory community approach on patient-reported outcomes in tuberculosis.

Patient-reported outcomes (PROs) play a crucial role in understanding the impact of tuberculosis (TB) on both individuals and communities. Despite advances in TB treatment, conventional outcome definitions often overlook essential components of people with TB's experiences, leading to disparities in treatment understanding. The incorporation of PROs in TB scientific research can help bridge the gap between the health system and people's needs and expectations. PROs can offer valuable insights into non-observable constructs like health literacy, self-efficacy and overall wellbeing, contributing to the comprehensive assessment of diagnosis, treatment and research end-points. Participatory community approaches, such as Community-Based Participatory, emphasise the engagement and involvement of relevant stakeholders in designing interventions tailored to their needs. Key stakeholders, including healthcare professionals, researchers, clinical trial investigators, public health officials, and community health workers, TB survivors and people with TB, can play a vital role in promoting patient-centred care and engaging directly with the TB-affected community. An increased and cross-collaborative effort for the inclusion of PROs in TB research can entail their potential role in developing effective treatment regimens and promoting adherence, while maximising community engagement and improving outcomes for those affected by TB.

Assessment of Advanced Diagnostic Bronchoscopy Outcomes for Peripheral Lung Lesions: A Delphi Consensus Definition of Diagnostic Yield and Recommendations for Patient-centered Study Designs. An Official American Thoracic Society/American College of Chest Physicians Research Statement.

Background: Advanced diagnostic bronchoscopy targeting the lung periphery has developed at an accelerated pace over the last two decades, whereas evidence to support introduction of innovative technologies has been variable and deficient. A major gap relates to variable reporting of diagnostic yield, in addition to limited comparative studies. Objectives: To develop a research framework to standardize the evaluation of advanced diagnostic bronchoscopy techniques for peripheral lung lesions. Specifically, we aimed for consensus on a robust definition of diagnostic yield, and we propose potential study designs at various stages of technology development. Methods: Panel members were selected for their diverse expertise. Workgroup meetings were conducted in virtual or hybrid format. The cochairs subsequently developed summary statements, with voting proceeding according to a modified Delphi process. The statement was cosponsored by the American Thoracic Society and the American College of Chest Physicians. Results: Consensus was reached on 15 statements on the definition of diagnostic outcomes and study designs. A strict definition of diagnostic yield should be used, and studies should be reported according to the STARD (Standards for Reporting Diagnostic Accuracy Studies) guidelines. Clinical or radiographic follow-up may be incorporated into the reference standard definition but should not be used to calculate diagnostic yield from the procedural encounter. Methodologically robust comparative studies, with incorporation of patient-reported outcomes, are needed to adequately assess and validate minimally invasive diagnostic technologies targeting the lung periphery. Conclusions: This American Thoracic Society/American College of Chest Physicians statement aims to provide a research framework that allows greater standardization of device validation efforts through clearly defined diagnostic outcomes and robust study designs. High-quality studies, both industry and publicly funded, can support subsequent health economic analyses and guide implementation decisions in various healthcare settings.

Frequency of standardized patient-reported outcome measures in routine clinical care of patients with cancer.

342 Background: Patient-reported outcomes (PROs) assess a patient’s self-reported health status, including disease symptoms, treatment experience, functional outcomes, and quality of life. Incorporation of PROs has been linked to improved patient symptom control and increased shared decision making. Standardized PRO measures (PROMs) are becoming more frequent as an endpoint for clinical trials, however their use is less frequent in routine care for patients with cancer. The goal of this study was to assess the utilization of PROMs and identify barriers to their use. Methods: US-licensed oncologists/hematologists convened at one of three live meetings in 2023 to review recent clinical updates. Respondent demographics were collected ahead via an online survey. During the meetings, participants responded to queries on their use and perceptions of PROs and PROMs. Responses were captured via audience response system technology; not all participants answered every question. Pooled data were summarized using descriptive statistics. Results: Of the 146 respondents, 77.4% self-identified as community-setting providers, spent 84.3% of their time seeing patients, saw an average of 19.8 patients/day, and averaged 17.7 years of experience. Respondents found PROs to be most useful in early detection/management of treatment toxicities and symptoms (63.8%) and tailoring of clinical/supportive care (56%). The majority of PROs are typically recorded through informal verbal inquiries, while 18.1% and 10.9% of respondents use validated and non-validated PROMs, respectively. Few respondents (11.3%) administer PROMs to every patient at every visit, while over one-third (38.3%) never administer PROMs. Within the practice, medical assistants and nurses are most likely to be the provider administering PROMs. PROMs are most commonly administered when the patient is in the office and are infrequently administered through other means. Lack of time to administer or review PRO surveys (45.1%), and lack of reimbursement (38.9%) and EMR integration (38.9%) were the most common reported barriers to using PROMs in the respondents’ practices. Conclusions: Despite the majority of respondents finding PROs useful in practice, a minority use formal measures to record PROs. Further, usage is infrequent across patient visits. Lack of time, lack of reimbursement, and logistic barriers are the most common reasons for not using PROMs in routine care. These barriers may be overcome by efforts or guideline changes from regulatory agencies, payors, or clinical guideline organizations. Future work will assess how physicians are using PROMs in treatment selection for their patients with cancer.

A Predictive Model of Severe Cytokine Release Syndrome After Coadministration of CD19- and CD22-Chimeric Antigen Receptor T-Cell Therapy in Children With B-Cell Hematological Malignancies Based on Patient-Reported Outcomes.

Chimeric antigen receptor T-cell therapy-related severe cytokine release syndrome (sCRS) has seriously affected the life safety of patients. To explore the influencing factors of sCRS in children with B-cell hematological malignancies and build a risk prediction model. The study recruited 115 children with B-cell hematological malignancies who received CD19- and CD22-targeted chimeric antigen receptor T-cell therapy. A nomogram model was established based on symptomatic adverse events and highly accessible clinical variables. The model discrimination was evaluated by the area under the receiver operating characteristic curve. The calibration of our model was evaluated by the calibration curve and Hosmer-Lemeshow test. The bootstrap self-sampling method was used to internally validate. Thirty-seven percent of the children experienced sCRS. Indicators included in the nomogram were tumor burden before treatment, thrombocytopenia before pretreatment, and the mean value of generalized muscle weakness and headache scores. The results showed that the area under the receiver operating characteristic curve was 0.841, and the calibration curve showed that the probability of sCRS predicted by the nomogram was in good agreement with the actual probability of sCRS. The Hosmer-Lemeshow test indicated that the model fit the data well (χ2 = 5.759, P = .674). The concordance index (C-index) obtained by internal validation was 0.841 (0.770, 0.912). The nomogram model constructed has a good degree of discrimination and calibration, which provides a more convenient and visual evaluation tool for identifying the sCRS. Incorporation of patient-reported outcomes into risk prediction models enables early identification of sCRS.

Predicting which patients with cirrhosis will develop overt hepatic encephalopathy: Beyond psychometric testing.

It remains challenging to identify covert hepatic encephalopathy and predict progression to overt hepatic encephalopathy. Psychometric testing is a widely used diagnostic modality, but it is often inaccurate and difficult to implement in diverse populations, making it a less than ideal assessment. Alternatively, by using easily accessible data from the electronic health record, simple clinical assessment tools, and patient-reported outcomes, we may be better able to predict hepatic encephalopathy across multiple populations. Furthermore, incorporation of patient-reported outcomes into our diagnostic toolset not only aids detection of covert hepatic encephalopathy and prediction of overt hepatic encephalopathy, but also allows us to target therapies and track their impact. Herein, we outline a potential algorithm based on these easily integrated tools to promote patient risk-stratification and early therapeutic intervention.

Incomplete reporting of patient-reported outcomes in multiple sclerosis: A meta-epidemiological study of randomized controlled trials

BackgroundMultiple Sclerosis significantly affects quality of life, which is often measured by patient-reported outcomes. The incorporation of patient-reported outcomes within clinical trials supplements the efficacy of outcomes in order to provide a patient's perspective for clinicians. Our objective was to evaluate current literature for completeness of reporting of PROs in randomized controlled trials (RCTs) for the management of MS. MethodsWe used MEDLINE, Embase, and Cochrane Central Register of Controlled Trials to search for RCT publications investigating the management of MS. After duplicate screening via Rayyan, RCTs fitting our inclusion criteria were abstracted employing the Consolidated Standards of Reporting Trials - Patient-Reported Outcome (CONSORT-PRO) adaptation and the Cochrane Collaboration Risk of Bias (RoB) 2.0 tool. Mean percent completion of an adaptation of CONSORT-PRO was calculated to address completeness of reporting. In addition, bivariate regression models were used to evaluate relationships between trial characteristics and completeness of reporting. ResultsOur search returned 3,966 results and 92 RCTs were included for data abstraction and analysis. We found an overall completion of 48.68% (SD=19.03). Sixty-five (of 92; 70.65%) of the RCTs were evaluated as having ‘high’ RoB. There were significant associations between completeness of reporting and the following: mention of CONSORT within published RCTs (t=2.55, p=.013), length of PRO follow-up (t=2.9, p=.005; t=2.14, p=.035), and sample size (t=3.12, p=.002). No other significant associations were found. ConclusionOur study found incomplete adherence to the CONSORT-PRO adaptation among RCTs pertaining to MS. Of the most underreported items, the failure to report a hypothesis and define an approach to missing data threaten the validity of the evidence acquired from RCTs. Furthermore, PROs provide an opportunity to supplement trial outcomes with the patient's perspective. Thus, trialists of future RCTs may improve PRO reporting with increased adherence to the CONSORT-PRO adaptation.

Utility Estimation of Rituximab Versus Bendamustine-Rituximab Induction in Indolent Non-Hodgkin Lymphomas Using Patient-Reported Quality of Life Survey Data

BackgroundRituximab induction (RI) and bendamustine-rituximab (BR) induction are both options for the frontline management of indolent non-Hodgkin lymphomas (NHLs). Although BR induces longer progression-free survival than RI, BR confers more toxicity and a longer duration of initial induction than RI. The effects of RI versus BR on health-related quality of life (HRQoL) after induction treatment, and the implications on patient utility and quality-adjusted life-years (QALYs), have not been previously studied. We conducted a cost-utility analysis of RI versus BR utilizing patient-reported HRQoL survey data.MethodsPatient-reported utility data were collected from the Hoogland Lymphoma Biobank, which enrolls patients with lymphoma at the University of Chicago and prospectively administers serial patient-level HRQoL surveys utilizing the Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-Lymphoma (FACT-LYM) instruments. Patients with indolent NHLs (follicular lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma) who were treated with frontline RI (4 doses of weekly rituximab) or BR (6 months of monthly BR) and who had completed HRQoL surveys at both of the following timepoints were included: within 6 months of treatment completion (timepoint 1) and 6-12 months after treatment completion (timepoint 2). Individual FACT-G scores were converted into EQ-5D utility index scores using a United States-based validated mapping algorithm (Teckle et al., Health Qual Life Outcomes, 2013). Cost-utility analysis was performed by trial-based methodology in which patient-level QALYs are estimated using area-under-the-curve (AUC) between timepoints 1 and 2. Incremental cost utility ratio (ICUR) was calculated utilizing cost and life years gained inputs of RI and BR from previous cost-effectiveness literature. All HRQoL scores for RI versus BR at both timepoints were compared with unpaired two-tailed t-tests.ResultsThere were 19 patients treated with RI and 13 patients treated with BR (Table 1). At timepoint 1, the BR cohort had significantly worse physical and emotional wellbeing on the FACT-G compared to the RI cohort, with emotional wellbeing significantly worse in the BR cohort at timepoint 2 (Table 2). EQ-5D utility index was stable at both timepoints for the RI cohort, and was initially lower in the BR cohort at timepoint 1 compared to RI but improved by timepoint 2 (Table 2). During the initial 12-month observation period after treatment completion, quality of life was higher for RI compared to BR (+0.02); however, when accounting for life years gained, the BR cohort had more QALYs (+1.53) (Table 3). Compared with RI, BR had an ICUR of $37,442.ConclusionsAlthough HRQoL was inferior in the BR cohort in the first year after treatment completion, particularly in the emotional wellbeing domain on FACT-G, BR induction conferred higher QALYs owing to more life years gained as compared to RI induction. Given a cost-effectiveness threshold of $100,000 in the United States (Vanness et al., Ann Intern Med, 2021), BR induction is likely to be cost effective when considering patient-reported HRQoL over the first year after treatment completion. The present analysis is limited by the small number of patients from which utility values at each timepoint were derived; however, calculation of QALYs using a database of prospectively-collected HRQoL data is feasible. Further incorporation of patient-reported outcomes into cost-utility analysis is warranted, particularly with larger datasets. [Display omitted] DisclosuresSmith: Alexion, AstraZeneca Rare Disease: Other: Study investigator; Celgene, Genetech, AbbVie: Consultancy.

PMH40 Effects of AXS-05 on Patient Reported Depressive Symptoms in Major Depressive Disorder: Results from the GEMINI Trial

Patient reported outcomes (PROs) are directly reported by the patient, without interpretation of patient response by a clinician. Incorporation of PROs into clinical trials allows for a more complete assessment of investigational therapies. This analysis evaluates the antidepressant effects of AXS-05 compared to placebo using PROs. GEMINI (N=327) was a randomized, double-blind, placebo-controlled, multi-center trial, in which adults with moderate-severe MDD were randomized 1:1 to AXS-05 (dextromethorphan HBr 45 mg-bupropion HCl 105 mg) or placebo, twice daily for 6 weeks. The primary efficacy outcome, change from baseline in MADRS total score, demonstrated a rapid and statistically significant improvement starting at Week 1, which was maintained through Week 6 (primary timepoint). PROs for depression used in this trial were: the Quick Inventory of Depressive Symptomatology (Self-Report) (QIDS-SR-16) and the Patient Global Impression of Improvement (PGI-I) for depression. Clinician-reported measures in GEMINI included the MADRS and CGI-I. Improvements from baseline on the QIDS-SR-16, were statistically significant for AXS-05 vs. placebo beginning at Week 1 (3.7 vs. 2.5, p=0.010) and at every timepoint thereafter: Week 2 (5.6 vs. 3.6, respectively, p<0.001), Week 3 (6.5 vs 4.1, respectively, p<0.001), Week 4 (7.5 vs 4.9, p<0.001), and Week 6 (7.7 vs 5.7, respectively, p=0.001). Percentages of patients reporting very much/much improved on the PGI-I were statistically significant for AXS-05 vs. placebo beginning at Week 1 (13.5% vs. 4.9%, p=0.008) and at every timepoint thereafter: Week 2 (30.0% vs. 18.2%, p=0.015), Week 3 (43.2% vs. 18.2%, p<0.001), Week 4 (46.9% vs. 28.0%, p=0.001), and Week 6 (47.2% vs. 31.3%, p=0.007). Patients self-reported that treatment with AXS-05 resulted in rapid, substantial, and statistically significant improvements in depressive symptoms consistent with clinician-reported measures (MADRS, CGI-I), starting at Week 1 and sustained through Week 6.

PMS25 Patient-Reported Outcome Labeling for Rheumatoid Arthritis Drugs Approved in the United States: 2010-2019

Patient-reported outcomes (PROs), defined as any report on the status of a patient’s health condition that comes directly from the patient, have played an increasingly important role in drug development. In 2009 the Food and Drug Administration (FDA) issued final guidance on using PRO measures to support labeling claims, as a means of incorporating the patient perspective into the drug approval process. For rheumatoid arthritis (RA), a chronic inflammatory disease associated with physical symptoms like pain and stiffness, but also changes to functional capacity and quality of life (QOL), PROs are critical to demonstrate the treatment benefit of new drugs. This analysis evaluates the incorporation of PROs into labeling for recent primary approvals of RA drugs. The FDA’s novel drug approvals (2010-2019) were reviewed to identify RA drugs. Drug approval packages and product labeling were accessed via the [email protected] database and analyzed for PRO endpoints, measures, and labeling claims. Clinical trial designs and published study results were retrieved via the ClinicalTrials.gov website and PubMed. Five novel drugs received primary approval for RA indications between 2010 and 2019. Trials supporting approval of all 5 products assessed patients’ perception of their disease activity, functional capacity, QOL, pain and fatigue. Three of the 5 products (60%) evaluated patients’ work limitations/productivity during pivotal trials, while 1 of the 5 (20%) evaluated quality of sleep. All 5 products incorporated PROs in their labeling, with more recent approvals having a greater number of PRO claims. All RA drugs approved in the past decade used PRO assessments during development, and all acquired labeling claims. Our findings underscore the significant impact RA symptoms have on patients’ day-to-day functioning and QOL, the importance of PROs in RA drug development, and the need to standardize functional domains and validated instruments used in registrational trials.

Patient-reported fatigue refines prognosis in higher-risk myelodysplastic syndromes (MDS): a MDS-CAN study.

The incorporation of patient-reported outcomes with traditional disease risk classification was found to strengthen survival prediction in patients with myelodysplastic syndromes (MDS). In the present Canadian MDS registry analysis, we validate a recently reported prognostic model, the Fatigue-International Prognostic Scoring System among higher-risk patients [FA-IPSS(h)], which incorporates patients' reported fatigue, assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30), with a threshold of ≥45points, in higher IPSS score, stratifying them into distinct subgroups with different survival outcomes. We further validated this concept, using the Revised IPSS >3·5 as cut-off for the definition of higher-risk MDS, and patients' reported fatigue according to Edmonton Symptom Self-Assessment Scale (ESAS) Global Fatigue Scale (GFS), a single-item fatigue rating scale, which is easier to deploy. This emphasises the power of self-reported fatigue at refining overall survival predictions in higher-risk MDS and further bolsters the importance of considering patient-related outcomes in global assessments.

Analysis of Patient-Reported Outcome Utilization Within National Clinical Trials Network Cooperative Group Radiation Oncology Trials Over the Past 2 Decades

When treating cancer, both quantity and quality of life are valuable, though oncology trials have long placed greater emphasis on the former. The goal of this work was to evaluate how patient-reported outcomes (PROs) have been incorporated into radiation therapy trials within the National Clinical Trials Network over the last 2 decades to measure quality of life and to assess how PRO data have been disseminated in publications upon trial conclusion. This cross-sectional study analyzed the frequency of use of PROs in National Clinical Trials Network cooperative group radiation therapy phase 2 and 3 clinical trials over the past 2 decades. A literature review was performed to determine the publication outcomes of PRO data, including only trials that used PROs in their design and were mature enough to have published results. Fifty-seven (56.4%) of the 101 trials included in this study included PROs in their design. Brain and head and neck trials demonstrated the largest proportional incorporation of PROs (81.8% and 76.9%, respectively), and thoracic and breast trials used the fewest (18.8% and 37.5%, respectively). The EQ-5D family of questionnaires was the most commonly used PROs, used in 22.8% of trials included. The literature review demonstrated a pattern of increased publication of PRO data alongside survival endpoints in manuscripts derived from these trials over time. Though there is room for improvement, the field of radiation oncology has embraced the incorporation of PROs into multicenter, high-impact clinical trials over the past 2 decades and has increased its publication of this data alongside survival data from these trials.

Fatigue, However Measured, Continues to Refine Prognosis in Higher Risk MDS: An MDS-CAN Study

Fatigue, However Measured, Continues to Refine Prognosis in Higher Risk MDS: An MDS-CAN Study

Genital Gender-Affirming Surgery Without Urethral Lengthening in Transgender Men—A Clinical Follow-Up Study on the Surgical and Urological Outcomes and Patient Satisfaction

BackgroundGenital gender-affirming surgery (gGAS) with urethral lengthening (UL) in transgender men is associated with high urological complication and reoperation rates. Since 2009, we offer gGAS without UL to avoid these complications. AimThe aim of this study was to assess what portion of the transgender men opted for gGAS without UL and to assess functional, surgical outcomes, and patient satisfaction after gGAS without UL. Material and methodsRetrospective data were collected from patients’ charts. The International Prostate Symptom Score, uroflowmetry, and 24-hour frequency voiding chart were used to assess voiding, and a self-constructed semistructured questionnaire was used to assess patient-reported outcomes. Transgender men who underwent gGAS without UL between January 2009 and January 2018 were included, and 56 transgender men were approached to complete the patient-reported outcome measurement. The simple statistical analysis combined with the Mann-Whitney U test and the Wilcoxon signed-rank test was used. Outcomes68 transgender men were included. Median follow-up time was 24 (6–129) months. Uroflowmetry and the International Prostate Symptom Score were completed by 44 transgender men, whereas 13 completed the frequency voiding chart preoperatively and postoperatively, respectively. The patient-reported outcome measurement was completed by 40 of 56 (71%) transgender men. ResultPostoperative surgical and urological complications occurred in 9 of 68 (13%) and 8 of 68 (12%) patients, respectively. Storage and voiding function remained unchanged. The median quality of life because of urinary symptoms was scored as “pleased.” Sexual functioning and voiding were scored satisfactory and very satisfactory in 18 of 40 (45%) and 21 of 40 (53%) patients, respectively. The number of patients satisfied with the penis and neoscrotum was 25 of 40 (63%) and 26 of 40 (65%), respectively. Increased self-esteem was reported by 32 of 40 (80%), 32 of 40 (80%) would undergo the surgery again, and 28 of 40 (70%) would recommend it to others. Clinical ImplicationsgGAS without UL should be part of the surgical armamentarium in centers performing gender-affirming surgery. Strengths and limitationsStrengths of this study comprise the number of patients, the completeness of data, incorporation of patient-reported outcomes, and description of a relatively new surgical approach that may be well-suitable for a subgroup of transgender men. Limitations are the retrospective study design and the lack of validated questionnaires. ConclusiongGAS without UL shows good surgical and urological outcomes. After extensive counseling, the majority of this selective group of patients shows favorable patient-reported outcomes.Pigot GLS, Al-Tamimi M, Nieuwenhuijzen JA, et al. Genital Gender-Affirming Surgery Without Urethral Lengthening in Transgender Men—A Clinical Follow-Up Study on the Surgical and Urological Outcomes and Patient Satisfaction. J Sex Med 2020;17:2478–2487.

Response and Intervention to Elevated ESAS Scores: A Chart Audit of Gynecologic Oncology Clinics

While the incorporation of patient-reported outcomes (PROs) in oncology has several benefits, data pertaining to symptom management practices are limited. The objective of this study was to evaluate health care professional (HCP) documentation of elevated PRO symptom scores and subsequent intervention. This was a retrospective chart review of gynecologic oncology patients within a single institution. The Edmonton Symptom Assessment System (revised version) (ESAS-r) is a validated, PRO tool that evaluates 9 common symptoms and is completed prior to each clinic visit. Symptom management intervention guidelines exist for each symptom based on severity: mild (1-3), moderate (4-6) and severe (≥7). Biopsy-proven gynecologic oncology patients with any ESAS symptom score ≥4 were eligible. A stratified sampling method was used: 100 patients were randomly selected with 20 per year from 2012 to 2016. Patient, tumor and treatment characteristics were collected. HCP documentation of symptoms with score ≥4 and subsequent interventions were assessed by 2 independent oncologists. Interventions were categorized as: counselling, investigation, treatment or referral. Descriptive statistics were used to report symptom prevalence, HCP documented response and intervention. Fisher’s exact test evaluated documentation and intervention rates according to individual symptom severity and total ESAS score. Between January 2012 and December 2016, a total of 5849 patients completed the ESAS. Symptoms scores were ≥ 4 in 3216 patients (55%) and ≥ 7 in 1446 (25%). In our sample of 100, ovarian malignancies were most common (42%), followed by endometrial (34%). Median age was 55 years (range 47-63). The median total ESAS score was 24 (range: 17-39). The most prevalent symptoms were tiredness (70%), anxiety (61%) and poor appetite (40%). Overall, documentation of a least one symptom ≥ 4 occurred in 50 patients (50%), most commonly for pain (71%) and tiredness (36%) and least commonly for depression (11%) and nausea (4%). An intervention was offered to only 32 patients (32%), most commonly for pain (56%) and least commonly for nausea (4%). The primary intervention was a treatment recommendation (12/32; 38%). Higher median total ESAS score was associated with higher rate of documentation (p=0.002) and higher rate of intervention (p<0.001). Similarly, higher symptom severity was significantly associated with higher rate of documentation, except for anxiety and nausea, and higher rate of intervention, except for anxiety, nausea and tiredness. A significant proportion of gynecologic oncology patients report elevated symptom scores that should prompt an intervention. However, HCPs document symptoms in only half of patients and offer interventions in only one third, warranting further evaluation. A study exploring the barriers and facilitators of optimal ESAS use is underway.

We\u2019re not all cut from the same cloth: TAILORing treatments for children with chronic conditions

BackgroundFinding the optimal treatment for a chronic condition can be a complex and lengthy endeavor for both the patient and the clinician. To address this challenge, we developed an “N-of-1” quality improvement infrastructure to aid providers and patients in personalized treatment decision-making using systematic assessment of patient-reported outcomes during routine care.MethodsUsing the REDCap data management infrastructure, we implemented three pediatric pilots of the Treatment Assessments in the Individual Leading to Optimal Regimens (TAILOR) tool, including children receiving early intervention, children with attention deficit hyperactivity disorder, and children with challenging behaviors in the classroom setting. This retrospective review of data summarizes utilization and satisfaction data during our pilot experience with the tool.ResultsThe three pilots included a combined total of 109 children and 39 healthcare providers, with 67 parents and 77 teachers invited to share data using brief surveys administered using TAILOR. Overall survey response rates ranged from 38% to 84% across the three pilots, with response rates notably higher among teachers as compared with parents. Satisfaction data indicated positive impressions of the tool’s utility.DiscussionThese experiences show the utility of the TAILOR framework for supporting collection and incorporation of patient-reported outcomes into the care of individuals with chronic conditions.

Management of gastroesophageal reflux disease: Patient and physician communication challenges and shared decision making.

Gastroesophageal reflux disease (GERD) is a common upper esophageal condition and typical symptoms can include heartburn and sensation of regurgitation while atypical symptoms include chronic cough, asthma, hoarseness, dyspepsia and nausea. Typically, diagnosis is presumptive given the presence of typical and atypical symptoms and is an indication for empiric therapy. Treatment management can include lifestyle modifications and/or medication therapy with proton pump inhibitor (PPI) class being the preferred and most effective. Complete symptom resolution is not always achieved and long-term PPI therapy can put patients at risk for serious side effects and needless expense. The brain-gut connection and hypervigilance plays an important role in symptom resolution and treatment success, especially in the case of non-PPI responders. Hypervigilance is a combination of increased esophageal sensory sensitivity in combination with exaggerated threat perception surrounding esophageal symptoms. Hypervigilance requires a different approach to GERD managements, where continued PPI therapy and surgery are usually not recommended. Rather, helping physicians and patients understand the brain-gut connection can guide and improve care. Education and reassurance should be the main pillars or treatment. However, it is important not to suggest the symptoms are due to anxiety alone, this often leads to patient dissatisfaction. Patient dissatisfaction with treatment reveals the need for a more patient-centered approach to GERD management and better communication between patients and providers. Shared decision making (SDM) with the incorporation of patient-reported outcomes (PRO) promotes patient adherence and satisfaction. SDM is a joint discussion between clinician and patient in which a mutually shared solution is explored for GERD symptoms. For SDM to work the physician needs to capture patients’ perceptions which may not be obtained in the standard interview. This can be done through the use of PROs which promote a dialogue with patients about their symptoms and treatment priorities in the context of the SDM patient encounter. SDM could potentially help in the management of patient expectations for GERD treatment, ultimately positively impacting their health-related quality of life.

Patient-Reported Outcome Labeling for Malignant Hematology Drugs Approved in the United States: 2011-2017

Introduction: Patient-reported outcomes (PROs), defined as any report on the status of a patient's health condition that comes directly from the patient without interpretation by anyone else, play an increasingly important role in drug development. In 2009 the FDA issued final guidance on using PRO measures to support labeling claims, to incorporate the patient perspective into the drug approval process. The 21st Century Cures Act emphasizes PROs as a differentiating element in the FDA approval process of new drugs, beyond traditional clinical outcome measures. Further, recent data has shown that intervention based on PROs can improve survival in metastatic cancers (Basch et al; 2017). The incorporation of PROs into the labeling of new drugs for malignant hematology disorders has not been studied and is the subject of this investigation.Methods: We reviewed the FDA's Novel New Drug Summaries (2011-2017) to identify drugs approved for malignant hematology indications. Drug approval packages and product labeling were accessed via the Drugs@FDA database and analyzed for PRO endpoints, measures, and labeling claims. Clinical trial designs and published study results were retrieved via the ClinicalTrials.gov website and PubMed.Results: Of 250 novel drugs approved by the FDA between 2011 and 2017, 22 (8.8%) were approved for malignant hematology indications. Interestingly, only 1 had PRO-based claims in their labeling, even though 13 of the 22 drugs (59%) collected PRO data in pivotal trials that led to their approval. Notably, the proportion of malignant hematology trials assessing PROs has increased over time, with 4 of the 5 drugs approved in 2017 for malignant hematology indications evaluating PROs in their development programs, compared with 9 of the 17 drugs approved in the preceding 6 years (80% vs. 53%). PROs evaluated included generic instruments such as the EQ-5D, and disease-specific instruments such as the EORTC QLQ-C30 (see table). Reasons cited for rejection of PRO data inclusion in drug labeling were single arm trial design, excessive missing data, statistical issues, and use of an inappropriate PRO instrument.Conclusions: While the FDA encourages PRO data submission as part of the new drug approval process, and although more than half of all malignant hematology drugs approved in the past 7 years assessed PROs during development, only 1 was able to successfully acquire labeling claims. Whether this is due to lack of PRO expertise on clinical development teams or absence of strong regulatory guidance on how best to implement PROs remains unknown and requires further research. Designing strategies to develop, validate and report PROs effectively is needed to meet regulatory requirements and enhance patients' voices in their own care. [Display omitted] DisclosuresNabhan:Cardinal Health: Employment, Equity Ownership.

Patient-Reported Outcomes with Chimeric Antigen Receptor T Cell Therapy: Challenges and Opportunities.

Patient-reported outcomes (PROs) are an important tool to assess the impact of a new therapy on symptom burden and health-related quality of life (HRQoL). Chimeric antigen receptor T (CAR-T) cell therapies have been approved for use in relapsed or refractory leukemia and lymphoma based on promising efficacy in clinical trials. However, data are lacking on patient-reported toxicity and impact on HRQoL. This review provides an overview of the incorporation of PROs in CAR-T cell therapy and the specific challenges in this context. The first step is to demonstrate feasibility of PRO monitoring in the acute phase after CAR-T cell infusion. Apart from core PRO domains like physical functioning, disease-related symptoms, and symptomatic adverse effects, important measures to consider are cognitive functioning and financial toxicity. Because there are no validated PRO instruments in the setting of CAR-T cell therapy, universally validated measures like Patient-Reported Outcomes Measurement Information System (PROMIS) could be considered, which is also recommended in the setting of hematopoietic stem cell transplantation. Given the timeline of toxicities with CAR-T cell therapy, PRO instruments should be administered at baseline and at least weekly in the first 30 days. Subsequently, frequent monitoring of PROs in the first year might be helpful in identifying short- and intermediate-term toxicities, functional limitations, and neuropsychiatric effects. The major potential challenge in acute phase would be missing data when patients develop severe cytokine release syndrome or neurotoxicity. Designing a strategy for handling missing data is crucial. The long-term safety of CAR-T cell therapy is not well characterized because of short follow-up in most studies reported thus far. PROs should be measured at least yearly after the first year to identify potential late effects like cognitive deficit or autoimmune manifestations. Collaboration between institutions performing cellular therapy and engagement with patients, clinicians, and statisticians with expertise in PROs are crucial for setting a comprehensive agenda on integration of PROs with CAR-T cell therapy.