Comparison of alpha-2 agonist versus alpha-1 antagonist for post-traumatic stress disorder-associated nightmares in pediatric patients.

Introduction: Posttraumatic stress disorder (PTSD) in children and adolescents has a high prevalence of accompanying sleep disturbances. Currently, pediatric treatment of PTSD-related nightmares is extrapolated from adult studies. This study aims to determine the effectiveness and safety of clonidine and guanfacine compared with prazosin for the treatment of PTSD-related nightmares. Methods: This was a retrospective, single-center, medical record review of patients 5 to 17 years old admitted to an inpatient psychiatric unit from January 2015 to September 2021. Patients with a new initiation of an alpha-2 agonist (clonidine or guanfacine) or an alpha-1 antagonist (prazosin) with a diagnosis of PTSD, other trauma- or stressor-related disorder or unspecified anxiety disorder were included. The primary endpoint was the percentage of patients with a decrease in the frequency of nightmares. Results: A total of 59 patients were included in the study: 37 in the alpha-2 agonist group and 22 in the alpha-1 antagonist group. There was no statistically significant difference in reduction of nightmares with both groups having a high percentage of patients showing response (alpha-2 agonist: 91.9%, alpha-1 antagonist: 86.4%). Time to decrease in nightmares was comparable between groups with a relatively quick onset. Within the alpha-2 agonist group, clonidine (1.59 ± 1.06 days) compared with guanfacine (3.18 ± 1.74 days) had a statistically significant faster time to reduction in nightmares (p = .005). Discussion: Both pharmacologic classes of medications were effective treatment options for pediatric PTSD-associated nightmares with a low incidence of adverse effects. There was a quick time to onset seen with all agents.

Validation of Patient-Reported Outcomes in Patients With Nonmetastatic Breast Cancer Receiving Comprehensive Nodal Irradiation in the RadComp Trial.

PURPOSE: Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT). METHODS AND MATERIALS: The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups validity). PRO change scores were mapped to change in other variables (sensitivity to change). RESULTS: Most correlations between PROs and validity indicators were large (≥0.5). Mean score for Satisfaction with Breast Cosmetic Outcomes was higher (better) for those with a lumpectomy compared with those with a mastectomy (P < .001). Mean scores for the FACT-B Trial Outcome Index and for PROMIS Fatigue and Ability to Participate in Social Roles and Activities were better for those with good baseline performance status compared with those with poorer baseline performance status (P < .05). At completion of RT and post-RT, mean scores for Satisfaction with Breast Cosmetic Outcomes and BREAST-Q Radiation were significantly different (P < .001) across categories for all Functional Assessment of Chronic Illness Therapy -Treatment Satisfaction - General items. There were medium-sized correlations between change scores for FACT-B Trial Outcome Index, Fatigue, Anxiety, and Ability to Participate in Social Roles and change scores in the Visual Analog Scale. CONCLUSIONS: For patients with nonmetastatic breast cancer receiving radiation in the RadComp PRCT, our findings demonstrate high reliability and validity for important PRO measures, supporting their psychometric strength and usefulness to reflect the effect of RT on health-related quality of life.

Analysis of laboratory data transmission between two healthcare institutions using a widely used point-to-point health information exchange platform: a case report.

Objective: The objective was to identify information loss that could affect clinical care in laboratory data transmission between 2 health care institutions via a Health Information Exchange platform. Materials and Methods: Data transmission results of 9 laboratory tests, including LOINC codes, were compared in the following: between sending and receiving electronic health record (EHR) systems, the individual Health Level Seven International (HL7) Version 2 messages across the instrument, laboratory information system, and sending EHR. Results: Loss of information for similar tests indicated the following potential patient safety issues: (1) consistently missing specimen source; (2) lack of reporting of analytical technique or instrument platform; (3) inconsistent units and reference ranges; (4) discordant LOINC code use; and (5) increased complexity with multiple HL7 versions. Discussion and Conclusions: Using an HIE with standard messaging, SHIELD (Systemic Harmonization and Interoperability Enhancement for Laboratory Data) recommendations, and enhanced EHR functionality to support necessary data elements would yield consistent test identification and result value transmission.

Effects of a change in recall period on reporting severe symptoms: an analysis of a pragmatic multisite trial.

BACKGROUND: Optimal methods for deploying electronic patient-reported outcomes to manage symptoms in routine oncologic practice remain uncertain. The electronic symptom management (eSyM) program asks chemotherapy and surgery patients to self-report 12 common symptoms regularly. Feedback from nurses and patients led to changing the recall period from the past 7 days to the past 24 hours. METHODS: Using questionnaires submitted during the 16 weeks surrounding the recall period change, we assessed the likelihood of reporting severe or moderate and severe symptoms across 12 common symptoms and separately for the 5 most prevalent symptoms. Interrupted time-series analyses modeled the effects of the change using generalized linear mixed-effects models. Surgery and chemotherapy cohorts were analyzed separately. Study-wide effects were estimated using a meta-analysis method. RESULTS: In total, 1692 patients from 6 institutions submitted 7823 eSyM assessments during the 16 weeks surrounding the recall period change. Shortening the recall period was associated with lower odds of severe symptom reporting in the surgery cohort (odds ratio = 0.65, 95% confidence interval = 0.46 to 0.93; P = .02) and lower odds of moderate and severe symptom reporting in the chemotherapy cohort (odds ratio = 0.83, 95% confidence interval = 0.71 to 0.97; P = .02). Among the most prevalent symptoms, 24-hour recall was associated with a lower rate of reporting postoperative constipation but no differences in reporting rates for other symptoms. CONCLUSION: A shorter recall period was associated with a reduction in the proportion of patients reporting moderate-severe symptoms. The optimal recall period may vary depending on whether electronic patient-reported outcomes are collected for active symptom management, as a clinical trial endpoint, or another purpose. ClinicalTrials.gov ID NCT03850912.

Perceived Barriers Toward Patient-Reported Outcome Implementation in Cancer Care: An International Scoping Survey.

PURPOSE: Implementation of patient-reported outcomes (PROs) collection is an important priority in cancer care. We examined perceived barriers toward implementing PRO collection between centers with and without PRO infrastructure and administrators and nonadministrators. PATIENTS AND METHODS: We performed a multinational survey of oncology practitioners on their perceived barriers to PRO implementations. Multivariable regression models evaluated for differences in perceived barriers to PRO implementation between groups, adjusted for demographic and institutional variables. RESULTS: Among 358 oncology practitioners representing six geographic regions, 31% worked at centers that did not have PRO infrastructure and 26% self-reported as administrators. Administrators were more likely to perceive concerns with liability issues (aOR, 2.00 [95% CI, 1.12 to 3.57]; P = .02) while having nonsignificant trend toward less likely perceiving concerns with disruption of workflow (aOR, 0.58 [95% CI, 0.32 to 1.03]; P = .06) and nonadherence of PRO reporting (aOR, 0.53 [95% CI, 0.26 to 1.08]; P = .08) as barriers. Respondents from centers without PRO infrastructure were more likely to perceive that not having access to a local PRO expert (aOR, 6.59 [95% CI, 3.81 to 11.42]; P < .001), being unsure how to apply PROs in clinical decisions (aOR, 4.20 [95% CI, 2.32 to 7.63]; P < .001), and being unsure about selecting PRO measures (aOR, 3.36 [95% CI, 2.00 to 5.66]; P < .001) as barriers. Heat map analyses identified the largest differences between participants from centers with and without PRO infrastructure in agreed-upon barriers were (1) not having a local PRO expert, (2) being unsure about selecting PRO measures, and (3) not recognizing the role of PROs at the institutional level. CONCLUSION: Perceived barriers toward PRO implementation differ between administrators and nonadministrators and practitioners at centers with and without PRO infrastructure. PRO implementation teams should consider as part of a comprehensive strategy including frontline clinicians and administrators and members with PRO experience within teams.

Disparities in electronic health record portal access and use among patients with cancer.

BACKGROUND: Electronic health record-linked portals may improve health-care quality for patients with cancer. Barriers to portal access and use undermine interventions that rely on portals to reduce cancer care disparities. This study examined portal access and persistence of portal use and associations with patient and structural factors before the implementation of 3 portal-based interventions within the Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium. METHODS: Portal use data were extracted from electronic health records for the 12 months preceding intervention implementation. Sociodemographic factors, mode of accessing portals (web vs mobile), and number of clinical encounters before intervention implementation were also extracted. Rurality was derived using rural-urban commuting area codes. Broadband access was estimated using the 2015-2019 American Community Survey. Multiple logistic regression models tested the associations of these factors with portal access (ever accessed or never accessed) and persistence of portal use (accessed the portal ≤20 weeks vs ≥21 weeks in the 35-week study period). RESULTS: Of 28 942 eligible patients, 10 061 (35%) never accessed the portal. Male sex, membership in a racial and ethnic minority group, rural dwelling, not working, and limited broadband access were associated with lower odds of portal access. Younger age and more clinical encounters were associated with higher odds of portal access. Of those with portal access, 25% were persistent users. Using multiple modalities for portal access, being middle-aged, and having more clinical encounters were associated with persistent portal use. CONCLUSION: Patient and structural factors affect portal access and use and may exacerbate disparities in electronic health record-based cancer symptom surveillance and management.

The Longitudinal Implementation Strategy Tracking System (LISTS): feasibility, usability, and pilot testing of a novel method.

BACKGROUND: Systematic approaches are needed to accurately characterize the dynamic use of implementation strategies and how they change over time. We describe the development and preliminary evaluation of the Longitudinal Implementation Strategy Tracking System (LISTS), a novel methodology to document and characterize implementation strategies use over time. METHODS: The development and initial evaluation of the LISTS method was conducted within the Improving the Management of SymPtoms during And following Cancer Treatment (IMPACT) Research Consortium (supported by funding provided through the NCI Cancer MoonshotSM). The IMPACT Consortium includes a coordinating center and three hybrid effectiveness-implementation studies testing routine symptom surveillance and integration of symptom management interventions in ambulatory oncology care settings. LISTS was created to increase the precision and reliability of dynamic changes in implementation strategy use over time. It includes three components: (1) a strategy assessment, (2) a data capture platform, and (3) a User's Guide. An iterative process between implementation researchers and practitioners was used to develop, pilot test, and refine the LISTS method prior to evaluating its use in three stepped-wedge trials within the IMPACT Consortium. The LISTS method was used with research and practice teams for approximately 12 months and subsequently we evaluated its feasibility, acceptability, and usability using established instruments and novel questions developed specifically for this study. RESULTS: Initial evaluation of LISTS indicates that it is a feasible and acceptable method, with content validity, for characterizing and tracking the use of implementation strategies over time. Users of LISTS highlighted several opportunities for improving the method for use in future and more diverse implementation studies. CONCLUSIONS: The LISTS method was developed collaboratively between researchers and practitioners to fill a research gap in systematically tracking implementation strategy use and modifications in research studies and other implementation efforts. Preliminary feedback from LISTS users indicate it is feasible and usable. Potential future developments include additional features, fewer data elements, and interoperability with alternative data entry platforms. LISTS offers a systematic method that encourages the use of common data elements to support data analysis across sites and synthesis across studies. Future research is needed to further adapt, refine, and evaluate the LISTS method in studies with employ diverse study designs and address varying delivery settings, health conditions, and intervention types.

Systematic symptom management in the IMPACT Consortium: rationale and design for 3 effectiveness-implementation trials.

Cancer and its treatment produce deleterious symptoms across the phases of care. Poorly controlled symptoms negatively affect quality of life and result in increased health-care needs and hospitalization. The Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium was created to develop 3 large-scale, systematic symptom management systems, deployed through electronic health record platforms, and to test them in pragmatic, randomized, hybrid effectiveness and implementation trials. Here, we describe the IMPACT Consortium's conceptual framework, its organizational components, and plans for evaluation. The study designs and lessons learned are highlighted in the context of disruptions related to the COVID-19 pandemic.

Implementing cancer symptom management interventions utilizing patient-reported outcomes: a pre-implementation evaluation of barriers and facilitators.

PURPOSE: Symptoms can negatively impact quality of life for patients with a history of cancer. Digital, electronic health record (EHR)-integrated approaches to routine symptom monitoring accompanied by evidence-based interventions for symptom management have been explored as a scalable way to improve symptom management, particularly between clinic visits. However, little research has evaluated barriers and facilitators to implementing these approaches in real-world settings, particularly during the pre-implementation phase. Pre-implementation assessment is critical for informing the selection and sequencing of implementation strategies and intervention adaptation. Thus, this study sought to understand pre-implementation perceptions of a remote cancer symptom monitoring and management intervention that uses electronic patient-reported outcome measures for symptom assessment. METHODS: We interviewed 20 clinical and administrative stakeholders from 4 geographic regions within an academic medical center and its affiliated health system during the months prior to initiation of a stepped-wedge, cluster randomized pragmatic trial. Transcripts were coded using the Consolidated Framework for Implementation Research [CFIR] 2.0. Two study team members reviewed coded transcripts to understand how determinants were relevant in the pre-implementation phase of the trial and prepared analytic memos to identify themes. RESULTS: Findings are summarized in four themes: (1) ability of the intervention to meet patient needs [recipient characteristics], (2) designing with care team needs in mind [innovation design and adaptability], (3) fit of the intervention with existing practice workflows [compatibility], and (4) engaging care teams early [engaging deliverers]. CONCLUSION: Attention to these aspects when planning intervention protocols can promote intervention compatibility with patients, providers, and practices thereby increasing implementation success.

Development and usability testing of an electronic patient-reported outcome (ePRO) solution for patients with inflammatory diseases in an Advanced Therapy Medicinal Product (ATMP) basket trial.

BACKGROUND: Electronic patient-reported outcome (ePRO) systems are increasingly used in clinical trials to provide evidence of efficacy and tolerability of treatment from the patient perspective. The aim of this study is twofold: (1) to describe how we developed an electronic platform for patients to report their symptoms, and (2) to develop and undertake usability testing of an ePRO solution for use in a study of cell therapy seeking to provide early evidence of efficacy and tolerability of treatment and test the feasibility of the system for use in later phase studies. METHODS: An ePRO system was designed to be used in a single arm, multi-centre, phase II basket trial investigating the safety and activity of the use of ORBCEL-C™ in the treatment of patients with inflammatory conditions. ORBCEL-C™ is an enriched Mesenchymal Stromal Cells product isolated from human umbilical cord tissue using CD362+ cell selection. Usability testing sessions were conducted using cognitive interviews and the 'Think Aloud' method with patient advisory group members and Research Nurses to assess the usability of the system. RESULTS: Nine patient partners and seven research nurses took part in one usability testing session. Measures of fatigue and health-related quality of life, the PRO-CTCAE™ and FACT-GP5 global tolerability question were included in the ePRO system. Alert notifications to the clinical team were triggered by PRO-CTCAE™ and FACT-GP5 scores. Patient participants liked the simplicity and responsiveness of the patient-facing app. Two patients were unable to complete the testing session, due to technical issues. Research Nurses suggested minor modifications to improve functionality and the layout of the clinician dashboard and the training materials. CONCLUSION: By testing the effectiveness, efficiency, and satisfaction of our novel ePRO system (PROmicsR), we learnt that most people with an inflammatory condition found it easy to report their symptoms using an app on their own device. Their experiences using the PROmicsR ePRO system within a trial environment will be further explored in our upcoming feasibility testing. Research nurses were also positive and found the clinical dashboard easy-to-use. Using ePROs in early phase trials is important in order to provide evidence of therapeutic responses and tolerability, increase the evidence based, and inform methodology development. TRIAL REGISTRATION: ISRCTN, ISRCTN80103507. Registered 01 April 2022, https://www.isrctn.com/ISRCTN80103507.

More and more patients tell clinicians how they feel by completing questionnaires electronically. Therefore, it is important to assess how easy it is for patients to do this. In this study, we describe how we developed an electronic platform for patients to report their symptoms and how we tested the usability of this platform with patient partners and research nurses. Once the electronic platform was developed, quality of life and symptoms questionnaires were programmed onto it. Alerts were sent to the clinical team if specific scores were obtained on the symptoms questionnaires. Although two patient partners were not able to finish the testing session because of technical issues, the ones who completed the session liked its simplicity and responsiveness. The research nurses also liked the system and only suggested minor modifications. Following this testing, we refined the electronic platform to test it further in a larger study which investigates the safety and use of a drug. We hope that thanks to this electronic platform, we will obtain useful information on the safety and efficacy of treatment.

Using IT to Improve Outcomes for Children Living With Cancer (SyMon-SAYS): Protocol for a Single-Institution Waitlist Randomized Controlled Trial.

BACKGROUND: Children and adolescents with cancer may experience multiple disease- and treatment-related symptoms that negatively affect health-related quality of life. Routine symptom surveillance thus constitutes an important component of supportive care in pediatric oncology. The Symptom Monitoring and Systematic Assessment and Reporting System in Young Survivors (SyMon-SAYS) system will administer, score, interpret, and display the results of symptom assessments captured weekly using patient-reported outcomes presented via the electronic health record (EHR) portal between clinic visits in oncology ambulatory settings, when patients are likely to be more symptomatic. This study is testing a digital system for routine symptom surveillance that includes EHR-based reports to clinicians and alerts for severe symptoms. OBJECTIVE: In this randomized trial, we are examining the effects of the SyMon-SAYS system on perceived barriers to symptom management, self-efficacy, and symptom severity. Better self-management and timely clinical intervention to address symptoms promote adherence to treatment plans, strengthen child and parent self-efficacy, improve interactions between children, parents, and their clinical providers, and optimize clinical outcomes. METHODS: The SyMon-SAYS system is integrated into the EHR to streamline the presentation of symptom scores and delivery of alerts for severe symptoms to clinicians using EHR (Epic) messaging functionalities. Children (aged 8 to 17 years) complete the weekly symptom assessment and review the symptom report by logging into the patient portal (Epic MyChart). This single-institution waitlist randomized controlled trial is recruiting 200 children (aged 8-17 years) with cancer and their parents, guardians, or caregivers. Participating dyads are randomly assigned to receive the intervention over 16 weeks (Group A: 16-week SyMon-SAYS intervention; Group B: 8-week usual care and then an 8-week SyMon-SAYS intervention). Analyses will (1) evaluate the efficacy of SyMon-SAYS at week 8 and the maintenance of those effects at week 16; (2) evaluate factors associated with those efficacy outcomes, including contextual factors, adherence to the SyMon-SAYS intervention, demographic characteristics, and clinical factors; and (3) evaluate predictors of adherence to the SyMon-SAYS intervention and preference of SyMon-SAYS versus usual care. RESULTS: Data collection is currently in progress. We hypothesize that at 8 weeks, those receiving the SyMon-SAYS intervention will report decreased parent-perceived barriers to managing their children's symptoms, increased parent and child self-efficacy, decreased child symptom burden, and ultimately better child health-related quality of life, compared to waitlist controls. Feasibility, acceptability, and engagement from the perspectives of the children with cancer, their parents, and their clinicians will be examined using mixed methods. CONCLUSIONS: We anticipate that this system will facilitate prompt identification of problematic symptoms. Additionally, we hypothesize that with the availability of graphical symptom reports over time, and timely provider responses, children or parents will become better informed and take an active role in managing their symptoms, which will further improve clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04789720; https://clinicaltrials.gov/study/NCT04789720. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50993.

Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048).

PURPOSE: The standard of care for locally advanced rectal cancer in North America is neoadjuvant pelvic chemoradiation with fluorouracil (5FUCRT). Neoadjuvant chemotherapy with fluorouracil and oxaliplatin (FOLFOX) is an alternative that may spare patients the morbidity of radiation. Understanding the relative patient experiences with these options is necessary to inform treatment decisions. METHODS: PROSPECT was a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX versus 5FUCRT, which enrolled adults with rectal cancer clinically staged as T2N+, cT3N-, or cT3N+ who were candidates for sphincter-sparing surgery. Neoadjuvant FOLFOX was given in six cycles over 12 weeks, followed by surgery. Neoadjuvant 5FUCRT was delivered in 28 fractions over 5.5 weeks, followed by surgery. Adjuvant chemotherapy was suggested but not mandated in both groups. Enrolled patients were asked to provide patient-reported outcomes (PROs) at baseline, during neoadjuvant treatment, and at 12 months after surgery. PROs included 14 symptoms from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Additional PRO instruments measured bowel, bladder, sexual function, and health-related quality of life (HRQL). RESULTS: From June 2012 to December 2018, 1,194 patients were randomly assigned, 1,128 initiated treatment, and 940 contributed PRO-CTCAE data (493 FOLFOX; 447 5FUCRT). During neoadjuvant treatment, patients reported significantly lower rates of diarrhea and better overall bowel function with FOLFOX while anxiety, appetite loss, constipation, depression, dysphagia, dyspnea, edema, fatigue, mucositis, nausea, neuropathy, and vomiting were lower with 5FUCRT (all multiplicity adjusted P < .05). At 12 months after surgery, patients randomly assigned to FOLFOX reported significantly lower rates of fatigue and neuropathy and better sexual function versus 5FUCRT (all multiplicity adjusted P < .05). Neither bladder function nor HRQL differed between groups at any time point. CONCLUSION: For patients with locally advanced rectal cancer choosing between neoadjuvant FOLFOX and 5FUCRT, the distinctive PRO profiles inform treatment selection and shared decision making.

Development of consensus-based considerations for use of adult proxy reporting: an ISOQOL task force initiative.

AIMS: Many large-scale population-based surveys, research studies, and clinical care allow for inclusion of proxy reporting as a strategy to collect outcomes when patients are unavailable or unable to provide reliable self-report. Prior work identified an absence of methodological guidelines regarding proxy reporting in adult populations, including who can serve as a proxy, and considerations for data collection, analysis, and reporting. The primary objective of this work by the ISOQOL Proxy Task Force was to review documents and clinical outcome assessment measures with respect to proxy reporting and to develop, through consensus, considerations for proxy reporting. METHODS: We assembled an international group with clinically relevant and/or methodological expertise on proxy use in adult populations. We conducted a targeted review of documentation based on regulatory, non-regulatory, professional society, and individual measure sources. Using a standardized collection form, proxy-related information was extracted from each source including definitions of a proxy, characteristics of a proxy, domains addressable or addressed by a proxy, and observer-reporting. RESULTS: The definition of proxy was inconsistent across 39 sources, except regulatory documents which defined a proxy as a person other than the patient who reports on an outcome as if she/he were the patient. While proxy report was discouraged in regulatory documentation, it was acknowledged there were instances where self-report was impossible. Many documentation sources indicated proxies would be well-justified in certain contexts, but did not indicate who could act as a proxy, when proxies could be used, what domains of patient health they could report on, or how data should be reported. Observer-reported outcomes were typically defined as those based on observed behaviors, however there was not a consistent differentiation between proxy and observer reporting. Based on information extracted from these resources, we developed a checklist of considerations when including proxy-reported measures or using proxies in study design, data collection, analysis, interpretation and reporting of proxy reported data. CONCLUSION: Our targeted review highlights a lack of clarity in capturing, interpreting and reporting data from proxies in adult populations. We provide a checklist of considerations to assist researchers and clinicians with including proxies in research studies and clinical care. Lastly, our review identified areas where further guidance and future research are necessary.

Cultural adaptation of the Italian version of the Patient-Reported Outcomes Common Terminology Criteria for Adverse Event (PRO-CTCAE®).

INTRODUCTION: US National Cancer Institute's (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) is a library of 78 symptom terms and 124 items enabling patient reporting of symptomatic adverse events in cancer trials. This multicenter study used mixed methods to develop an Italian language version of this widely accepted measure, and describe the content validity and reliability in a diverse sample of Italian-speaking patients. METHODS: All PRO-CTCAE items were translated in accordance with international guidelines. Subsequently, the content validity of the PRO-CTCAE-Italian was explored and iteratively refined through cognitive debriefing interviews. Participants (n=96; 52% male; median age 64 years; 26% older adults; 18% lower educational attainment) completed a PRO-CTCAE survey and participated in a semi-structured interview to determine if the translation captured the concepts of the original English language PRO-CTCAE, and to evaluate comprehension, clarity and ease of judgement. Test-retest reliability of the finalized measure was explored in a second sample (n=135). RESULTS: Four rounds of cognitive debriefing interviews were conducted. The majority of PRO-CTCAE symptom terms, attributes and associated response choices were well-understood, and respondents found the items easy to judge. To improve comprehension and clarity, the symptom terms for nausea and pain were rephrased and retested in subsequent interview rounds. Test-retest reliability was excellent for 41/49 items (84%); the median intraclass correlation coefficient was 0.83 (range 0.64-0.94). DISCUSSION: Results support the semantic, conceptual and pragmatic equivalence of PRO-CTCAE-Italian to the original English version, and provide preliminary descriptive evidence of content validity and reliability.

Development and psychometric testing of a pediatric chronic graft-versus-host disease symptom scale: protocol for a two-phase, mixed methods study.

Background: Chronic graft-versus-host disease (cGVHD) is a debilitating late complication of hematopoietic stem cell transplantation. It is often accompanied by extensive symptom burden. No validated cGVHD patient-reported outcome (PRO) measure exists to evaluate cGVHD symptom bother in children and adolescents younger than 18 years. This paper presents the study protocol for a multi-center, two-phase protocol to develop a psychometrically valid pediatric cGVHD Symptom Scale (PCSS) and a companion caregiver-proxy measure to capture the symptom burden experienced by children with cGVHD. In the first phase of the study, our aim is to evaluate the comprehension, clarity and ease of response of the PCSS through cognitive interviewing and to iteratively refine the measure to optimize content validity. In the second phase of the study, we will quantitatively examine the measurement properties of the PCSS in children and their caregiver-proxies. Methods and analysis: Eligible participants are children/adolescents ages 5-17 with cGVHD who are receiving systemic immunosuppressive treatment or have recently tapered to discontinuation. In the first phase, we are enrolling 60 child and caregiver-proxy dyads in three child age strata (5-7, 8-12, and 13-17 years old). Semi-scripted cognitive debriefing interviews are conducted to assess comprehension, clarity, and ease of response of each PCSS item with the child alone, and then jointly with the caregiver-proxy to explore discordant ratings. In phase two, an age-stratified cohort of 120 child-caregiver dyads will be enrolled to evaluate test-retest reliability, construct validity, and responsiveness. Anchors for known-groups validity include the PedsQL module and clinical variables, including cGVHD clinician-rated severity scores. In participants ages 13-17, we will also compare responses on the PCSS with those from the Lee cGVHD Symptom Scale, to gauge the youngest age at which adolescent respondents can comprehend this adult measure. Discussion: This study will yield a well-validated, counterpart measure to the Lee cGVHD Symptom Scale for use in children with cGVHD and their caregiver-proxies. This new patient-reported outcome measure can be integrated into clinical trials and care delivery for pediatric transplant survivors to improve the precision and accuracy with which their cGVHD symptom experience is captured. Clinical trial registration: www.ClinicalTrials.gov, NCT04044365.

Clinician and Patient Reporting of Symptomatic Adverse Events in Cancer Clinical Trials: Using CTCAE and PRO-CTCAE® to Provide Two Distinct and Complementary Perspectives.

Inclusion of the patient perspective in the reporting of symptomatic adverse events provides different and complementary information to clinician reporting using the Common Terminology Criteria for Adverse Events (CTCAE). The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) is designed for patients to self-report their symptomatic adverse events in a manner that complements CTCAE reporting. Using CTCAE and PRO-CTCAE together offers the potential to refine our understanding of the prevalence and trajectory of lower grade AEs that can lead to elective discontinuation of therapy and diminished quality of life. This review addresses the development of PRO-CTCAE with an emphasis on the differences between PRO-CTCAE scores and CTCAE severity grades. This distinction is important when evaluating, grading and reporting toxicity and tolerability in cancer clinical trials.

Glycemic Index Versus Wheat Fiber on Arterial Wall Damage in Diabetes: A Randomized Controlled Trial.

OBJECTIVE: High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet. RESEARCH DESIGN AND METHODS: The study randomized 169 men and women with well-controlled type 2 diabetes to counseling on a low GI-diet or whole-grain wheat-fiber diet for 3 years. Change in carotid vessel wall volume (VWV) (prespecified primary end point) was assessed by MRI as an indication of arterial damage. RESULTS: Of 169 randomized participants, 134 completed the study. No treatment differences were seen in VWV. However, on the whole-grain wheat-fiber diet, VWV increased significantly from baseline, 23 mm3 (95% CI 4, 41; P = 0.016), but not on the low-GI diet, 8 mm3 (95% CI -10, 26; P = 0.381). The low-GI diet resulted in preservation of renal function, as estimated glomerular filtration rate, compared with the reduction following the wheat-fiber diet. HbA1c was modestly reduced over the first 9 months in the intention-to-treat analysis and extended with greater compliance to 15 months in the per-protocol analysis. CONCLUSIONS: Since the low-GI diet was similar to the whole-grain wheat-fiber diet recommended for cardiovascular risk reduction, the low-GI diet may also be effective for CVD risk reduction.