Understanding reliability of the observer-reported communication ability measure within Angelman syndrome through the lens of generalizability theory.

AIMS: Caregivers rate improved communication ability as one of the most desired outcomes for successful interventions for individuals with Angelman syndrome (AS). When measuring communication ability in clinical trials, the reliability of such measures is critical for detecting significant changes over time. This study examined the reliability of the Observed-Reported Communication Ability (ORCA) measure completed by caregivers of individuals with AS. METHODS: The ORCA measure was completed by 249 caregivers with 170 caregivers completing the ORCA measure again after 5-12 days. Generalizability theory was used to examine the following sources of measurement error in ORCA scores: concepts, subdomains, assessment points, and the interactions among those facets and the object of measurement: communication ability. Three generalizability studies were conducted to understand the reliability of the ORCA measure for different measurement designs. Decision studies were carried out to demonstrate the optimization of measurement procedures of the ORCA measure. RESULTS: G and Phi coefficients of the original measurement design exceeded the 0.80 threshold considered sufficiently reliable to make relative and absolute decisions about the communication ability of individuals with AS based on their caregivers' observed scores. The optimization procedures indicated that increasing the number of communication concepts and/or assessment points leads to more reliable estimates of communication. CONCLUSION: The ORCA measure was able to reliably distinguish different levels of communication ability among individuals with AS. Multiple assessment points and or more concepts would provide more precise estimates of an individual's communication ability but at the cost of survey fatigue.

Quality of Life in Adults with Chronic Cough: A Mixed Methods Study Informing the Development of a Quantitative Patient Preference Study.

OBJECTIVES: This study aimed to describe quality of life for patients with chronic cough (CC) and identify meaningful attributes that affect patient treatment preferences to inform the design of a quantitative preference study. METHODS: Eligible patients (≥ 18 years) with a CC (> 8 weeks) participated in qualitative interviews with two defined steps. Step one: concept elicitation and bidding games were used to collect descriptions of patient experiences with CC and identify important CC-related attributes. Step two: attributes were confirmed using concept elicitation and bidding games and prioritized using structured card sort activities. Purposive sampling ensured diversity of patient experiences. Qualitative content analysis was used to analyze participant narratives, and descriptive statistics were used to summarize card sort results. This study follows a fully mixed concurrent dominant status design, with qualitative (dominant) and quantitative components. RESULTS: A total of 20 participants were interviewed with a mean age of 61.4 years (range 24-79 years). Coughing episodes, described as intense consecutive coughs that made catching breath difficult, were important to most participants (n = 17). Participants emphasized the emotional impact of episodes including feelings of uncertainty, loss of control, self-consciousness, and fear. Severity of CC was most often judged by frequency (n = 11) and intensity (n = 12) of cough. Daily, physical, or social activities were impacted for most participants. Impact on sleep (n = 14) included waking during the night, difficulty falling asleep, and daytime fatigue. Medication-related taste disturbances were an important consideration for what participants were willing to accept in exchange for cough relief. CONCLUSIONS: This study emphasizes the importance of coughing episodes for adults with CC and provides initial evidence that taste alterations are an important component of patient treatment decisions for CC.

Validation of the Observer-Reported Communication Ability (ORCA) measure for individuals with Rett syndrome.

PURPOSE: The study goal was to validate the Observer-Reported Communication Ability (ORCA) measure for use with females with Rett Syndrome (RTT). METHODS: Qualitative interviews, including concept elicitation and cognitive interviewing methods, were conducted with 19 caregivers of individuals with RTT ages 2 and older. A quantitative study was then conducted in 279 caregivers to evaluate construct validity and reliability. RESULTS: After minor modifications were made, the modified ORCA measure was well understood and captured key communication concepts. Quantitative data showed evidence for reliable scores (α = 0.90, test-retest intraclass correlation = 0.88), minimal floor and no ceiling effects, and strong correlation with the Communication and Symbolic Behaviors Scale (r = 0.73). CONCLUSIONS: This study provided initial support that the modified ORCA measure is an acceptable caregiver-reported measure of communication ability for females with RTT. Future work should include evaluation of longitudinal validity of the measure and its associations with clinician- and performance-based measures in diverse samples.

Patient experience of spontaneous intracranial hypotension (SIH): qualitative interviews for concept elicitation.

BACKGROUND & OBJECTIVES: Spontaneous intracranial hypotension (SIH) is an underdiagnosed and debilitating condition caused by a spinal cerebrospinal fluid (CSF) leak. Although SIH can lead to substantial morbidity and disability, little data exists about patients' perspectives. Without hearing directly from patients, our understanding of the full experience of having SIH is limited, as is our ability to identify and use appropriate patient-reported outcome measures (PROMs) within clinical care and research. The purpose of this study was to conduct qualitative interviews with confirmed SIH patients to fully describe their experiences and identify relevant concepts to measure. METHODS: Patients were recruited from an SIH specialty clinic at a large, U.S.-based healthcare center. Patients undergoing an initial consultation who were ≥ 18 years old, English-speaking, met the International Classification of Headache Disorders-3 criteria for SIH, and had a brain MRI with contrast that was positive for SIH were eligible to participate. During semi-structured qualitative interviews with a trained facilitator, participants were asked to describe their current SIH symptoms, how their experiences with SIH had changed over time, and the aspects of SIH that they found most bothersome. Analysts reviewed the data, created text summaries, and wrote analytic reports. RESULTS: Fifteen participants completed interviews. Common symptoms reported by patients included headache, tinnitus, ear fullness/pressure/pain, and neck or interscapular pain. Patients reported that their symptoms worsened over the course of their day and with activity. The most bothersome aspect of SIH was disruption to daily activities and limits to physical activities/exercise, which were severe. With regard to symptoms, the most bothersome and impactful included physical pain and discomfort (including headache), as well as fatigue. CONCLUSIONS: Patients reported a diverse set of symptoms that were attributed to SIH, with devastating impacts on functioning and high levels of disability. Researchers considering use of PROMs for SIH should consider inclusion of both symptom scales and aspects of functioning, and future work should focus on evaluating the validity of existing measures for this patient population using rigorous qualitative and quantitative methods in diverse samples. Additionally, these data can be used to assist clinicians in understanding the impacts of SIH on patients.

Swahili translation and cultural adaptation of the pediatric patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE).

BACKGROUND: The pediatric patient-reported outcomes version of the common terminology criteria for adverse event measure was developed and validated for use in pediatric cancer clinical trials to better capture the symptom experiences through direct self-report. The study aim was to develop and validate a Swahili language version of the patient-reported outcomes version of the common terminology criteria for adverse event measure. METHODS: The pediatric version of 15 core symptom adverse events, and the corresponding questions, were selected from the patient-reported outcomes version of the common terminology criteria for adverse event library, then forward and back translated into Swahili by bilingual translators. The translated items were further refined using concurrent cognitive interviewing. Each round of interviews included five children, ages 8-17 years-old, receiving cancer therapy at Bugando Medical Centre, the cancer referral hospital for Northwest Tanzania, and continued until at least 80% of participants understood the question. RESULTS: Three rounds of cognitive interviews were completed involving 13 patients and 5 caregivers. Among patients, 50% of questions (19/38) were fully comprehended after the first interview round. Two Adverse Events (anxiety and peripheral neuropathy) were the most difficult for participants to understand, associated with education level and experience. Goal comprehension was achieved after three rounds of interviews with no further revisions required. All parents in the first cognitive interview group comprehended the survey, with no additional revisions. CONCLUSION: A Swahili patient-reported outcomes version of the common terminology criteria for adverse event was effective in eliciting patient-reported Adverse Events related to cancer treatment, with good comprehension for children aged 8-17 years. This survey is important to incorporate patient self-reporting of symptomatic toxicities and is an effective tool to increase capacity for pediatric cancer clinical trials throughout East Africa, further reducing global disparities in cancer care.

Validation of the Observer-Reported Communication Ability (ORCA) Measure for Individuals With Angelman Syndrome.

There is a critical need for high-quality clinical outcome assessments to capture the important aspects of communication ability of individuals with Angelman syndrome (AS). To center the perspective of caregivers, our team developed the novel Observer-Reported Communication Ability (ORCA) measure using best practice guidelines, with the goal of developing a measure that could be administered to caregivers directly without the need for a certified administrator for use in clinical trials. To refine the draft measure, we conducted two rounds of cognitive interviews with 24 caregivers and a quantitative study including 249 caregivers. The results from both studies support the overall content validity, construct validity, and the reliability of the ORCA measure for individuals with AS > 2 years old for use in research contexts. Future work should explore the responsiveness of ORCA measures to changes over time in a diverse sample.

Exploring Communication Ability in Individuals With Angelman Syndrome: Findings From Qualitative Interviews With Caregivers.

Communication deficits have a substantial impact on quality of life for individuals with Angelman syndrome (AS) and their families, but limited qualitative work exists to support the necessary content of measures aiming to assess communication for these individuals. Following best practices for concept elicitation studies, we conducted individual qualitative interviews with caregivers and clinicians to elicit meaningful aspects of communication for individuals with AS. Caregivers were able to discuss their child's specific communication behaviors within a large number of expressive, receptive, and pragmatic functions via numerous symbolic and non-symbolic modalities. These results aligned well with published literature on communication in AS and will be used to inform the design of a novel caregiver-reported measure. Future studies on communication in individuals with AS should focus on gathering quantitative data from large samples of diverse caregivers, which would allow for estimations of the frequency of specific behaviors across the population.

Investigating gender-based differential item functioning on the Kansas City Cardiomyopathy Questionnaire (KCCQ) using qualitative content analysis.

PURPOSE: The purpose of this study is to evaluate potential gender-based differences in interpreting the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) and to explore if there are aspects of health-related quality of life (HRQOL) not captured by the KCCQ-23 that are important to assess in men and/or women with heart failure (HF). METHODS: Patients ≥ 22 years of age with clinician-diagnosed HF and left ventricular ejection fraction ≤ 40% were recruited from two academic medical centers to participate in semi-structured concept elicitation and cognitive debriefing interviews. Enrollment was stratified by patient-identified gender (half women/half men). All interviews were conducted over the phone/web and audio recorded. Interviews were transcribed and descriptive qualitative content analysis was used to summarize findings overall and by gender. RESULTS: Twenty-five adults (56% women) diagnosed with HF participated. The average age was 67 years (range: 25-88). Women attributed a wider variety of symptoms to HF than men. Some participants had difficulty differentiating whether their experiences were due to HF, side effects of their medications, or age. We found very little evidence that participants interpreted KCCQ-23 items differently based on gender. CONCLUSIONS: Overall, our findings indicate that interpretation of the KCCQ-23 items were similar in men and women. However, some modifications to items may improve clarity of interpretation for a wide range of patients.

Longitudinal use of patient reported outcomes in pediatric leukemia and lymphoma reveals clinically relevant symptomatic adverse events.

BACKGROUND: Leukemia and lymphoma (LL) are the most common cancer diagnoses of childhood with high survival rates, but not without impact on the child's functioning and quality of life. This study aimed to use patient-reported data to describe the symptomatic adverse event (AE) experiences among children with LL diagnoses. METHODS: Two hundred and fifty seven children and adolescents aged 7-18 years with a first LL diagnosis completed the Pediatric Patient-Reported version of the Common Terminology Criteria for Adverse Events (Ped-PRO-CTCAE) and Patient-Reported Outcome Measurement Information System (PROMIS) Pediatric measures before starting a treatment course (T1) and after the treatment (T2). RESULTS: Fatigue was the most severe AE (68.1% at T1; 67% at T2) and caused the most interference over time. Gastrointestinal AEs were also quite common (e.g., nausea 46.3% at T1 and 48.9% at T2; abdominal pain 42.4% at T1; 46.5% at T2). In general, symptoms were present both at T1 and T2 and did not change significantly in severity or interference. The prevalence of AEs varied by LL disease group (e.g., nausea was most common in acute lymphoblastic leukemia (ALL), fatigue was most severe in ALL and Hodgkin Lymphoma (HL), acute myeloid leukemia had the fewest AEs). CONCLUSION: Despite current supportive care regimens, many children with LL continue to report fatigue, pain, insomnia, and gastrointestinal symptoms as the most frequent or severe symptoms during therapy.

AUGS-PERFORM: A New Patient-Reported Outcome Measure to Assess Quality of Prolapse Care.

Patient-reported outcomes (PRO) are important for measuring quality of care, particularly for interventions aimed at improving symptom bother such as procedures for pelvic organ prolapse. We aimed to create a concise yet comprehensive PRO measurement tool to assess pelvic organ prolapse care in high-volume clinical environments. Methods: The relevant concepts to measure prolapse treatment quality were first established through literature review, qualitative interviews, and a patient and provider-driven consensus-building process. Extant items mapping to these concepts, or domains, were identified from an existing pool of patient-reported symptoms and condition-specific and generic health-related quality of life measures. Item classification was performed to group items assessing similar concepts while eliminating items that were redundant, inconsistent with domains, or overly complex. A consensus meeting was held in March 2020 where patient and provider working groups ranked the remaining candidate items in order of relevance to measure prolapse treatment quality. After subsequent expert review, the revised candidate items underwent cognitive interview testing and were further refined. Results: Fifteen relevant PRO instruments were initially identified, and 358 items were considered for inclusion. After 2 iterative consensus reviews and 4 rounds of cognitive interviewing with 19 patients, 11 final candidate items were identified. These items map 5 consensus-based domains that include awareness and bother from prolapse, physical function, physical discomfort during sexual activity, pain, and urinary/defecatory symptoms. Conclusions: We present a concise set of candidate items that were developed using rigorous patient-centered methodology and a national consensus process, including urogynecologic patients and providers.

Initial Content Validation and Roadmap for a New Patient-Reported Outcome Measure of Pain Intensity.

Measures of pain intensity (eg, numeric rating scales [NRS]) are widely used in clinical research and practice. While these measures have evidence for validity and reliability, poor standardization of instructions, and response options limits precision of pain assessment, allows for inconsistency in interpretation, and presents a challenge for comparison and aggregation of study results. Despite these pitfalls, the 0 to 10 NRS remains the most commonly used primary outcome measure in clinical trials of pain treatments and is the core measure recommended by regulatory agencies. The purpose of this study was to describe the first phase in the development of a pain intensity measure that is easily interpretable, psychometrically sound, and that adheres to FDA qualification processes. The Analgesic, Anesthetic, and Addiction Clinical Trial, Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership conducted concept elicitation interviews (N = 44; 22 with acute pain; 22 with chronic pain) to understand the patient perspective on rating pain intensity and to identify actionable suggestions for improved clarity and meaningfulness of instructions, recall periods, and response options. This article summarizes interview findings, describes how patient input and FDA feedback informed preliminary candidate measures, and provides an overview of the FDA qualification process. PERSPECTIVE: Concept elicitation interviews informed the development of content-valid candidate measures of acute and chronic pain intensity for planned use in clinical trials of pain treatments, and comprise the initial stage in FDA clinical outcome assessment qualification. Measures will subsequently be evaluated through cognitive interviews and a series of psychometric studies.

Lack of Concordance in Symptomatic Adverse Event Reporting by Children, Clinicians, and Caregivers: Implications for Cancer Clinical Trials.

PURPOSE: To examine concordance in symptomatic adverse event (AE) grading using the Common Terminology Criteria for Adverse Events (CTCAE 4.0) for clinicians and its patient-reported outcome (PRO) versions for children (Ped-PRO-CTCAE) and caregivers (Ped-PRO-CTCAE [Caregiver]). METHODS: Children age 7-18 years with a first cancer diagnosis, their clinicians, and caregivers completed CTCAE-based measures before starting a treatment course (T1) and after the treatment (T2). Grades (0-3) were assigned by each reporter for 15 core AEs spanning physical and mental health. Mean grades were compared between reporters using two-sample t-tests; agreement was estimated using weighted kappa (κ) statistics. Multivariable mixed regression models were used to evaluate associations of clinical factors with AE reporting concordance. Significance was set at α = .05 (two-sided). RESULTS: There were 438 child-clinician-caregiver triads with complete data at either T1 or T2. For children, the mean age was 13 years (standard deviation = 3.4), 53.7% were male, 32.6% non-White, and 56.4% had leukemia/lymphoma. At T1, clinician mean AE grades were significantly lower (ie, better) than children for all AEs and remained significantly lower at T2 except for constipation, nausea, anorexia, neuropathy, and anxiety. Caregiver mean AE grades were similar to children at T1 and significantly higher (ie, worse) at T2 for nausea, vomiting, anorexia, pain, fatigue, anxiety, and depression. Agreement for child-clinician grading was poor-to-fair at T1 (κ range, 0.08-0.34) and T2 (0.11-0.35), and for child-caregiver, was fair-to-good at T1 (0.34-0.65) and T2 (0.24-0.60). No factors were consistently associated with reporter concordance across AEs. CONCLUSION: Compared with children, symptomatic AEs were consistently under-reported by clinicians with low agreement and over-reported by caregivers with low-moderate agreement. Direct reporting by children using Ped-PRO-CTCAE or similar measures should be routinely incorporated for toxicity assessment in clinical trials.

Patients' Experiences With Staphylococcus aureus and Gram-Negative Bacterial Bloodstream Infections: Results From Cognitive Interviews to Inform Assessment of Health-Related Quality of Life.

BACKGROUND: We previously conducted a concept elicitation study on the impact of Staphylococcus aureus and gram-negative bacterial bloodstream infections (SAB/GNB) on health-related quality of life (HRQoL) from the patient's perspective and found significant impacts on HRQoL, particularly in the physical and functional domains. Using this information and following guidance on the development of patient-reported outcome (PRO) measures, we determined which combination of measures and items (ie, specific questions) would be most appropriate in a survey assessing HRQoL in bloodstream infections. METHODS: We selected a variety of measures/items from the Patient-Reported Outcomes Measurement Information System (PROMIS) representing different domains. We purposefully sampled patients ~6-12 weeks post-SAB/GNB and conducted 2 rounds of cognitive interviews to refine the survey by exploring patients' understanding of items and answer selection as well as relevance for capturing HRQoL. RESULTS: We interviewed 17 SAB/GNB patients. Based on the first round of cognitive interviews (n = 10), we revised the survey. After round 2 of cognitive interviewing (n = 7), we finalized the survey to include 10 different PROMIS short forms/measures of the most salient HRQoL domains and 2 adapted questions (41 items total) that were found to adequately capture HRQoL. CONCLUSIONS: We developed a survey from well-established PRO measures that captures what matters most to SAB/GNB patients as they recover. This survey, uniquely tailored to bloodstream infections, can be used to assess these meaningful, important HRQoL outcomes in clinical trials and in patient care. Engaging patients is crucial to developing treatments for bloodstream infections.

Can Steps per Day Reflect Symptoms in Children and Adolescents Undergoing Cancer Treatment?

BACKGROUND: Multiple symptoms occur in children receiving cancer therapy. Decreased steps per day may be associated with burdensome symptoms. OBJECTIVE: To evaluate associations between self-reported symptoms (pain interference, anxiety, depressive symptoms, psychological stress, and fatigue) and function (physical function-mobility and physical activity) and cumulative symptom count with steps per day. METHODS: Five sites enrolled English-speaking children, 8 to 17 years, receiving treatment for a first cancer diagnosis. Patient-reported outcome (PRO) surveys were administered before (T1) and after (T2) a course of chemotherapy. Garmin VivoFit 3 (Garmin International, Olathe, KS) accelerometers were worn 7 days prior to each data point. Univariate changes in scores over time were evaluated with dependent-sample t tests. Pearson correlations examined associations between PRO domains and step count. Multivariable mixed-effect models examined associations between steps and PROs. RESULTS: Participants' (n = 65) steps per day decreased during treatment (4099 [T1] and 3135 [T2]; P < .01), with larger reductions observed during hospitalization and in younger children compared with adolescents. Steps significantly correlated with PROMIS (Patient-Reported Outcome Measurement Information System) Pediatric physical activity and physical function-mobility. Decreased steps per day were associated with increased fatigue and cumulative symptom count. CONCLUSIONS: In children and adolescents with cancer, steps per day can serve as an indicator of fatigue, cumulative symptom count, physical activity, and physical functioning-mobility. IMPLICATIONS FOR PRACTICE: Child self-reports of physical activity and physical function are valid during cancer therapy and should be captured. In the absence of self-report, decreasing step count may prompt additional assessments related to fatigue or cumulative symptom count and trigger early interventions to support physical activity and physical function-mobility.

The predictive trifecta? Fatigue, pain, and anxiety severity forecast the suffering profile of children with cancer.

BACKGROUND: Fatigue, pain, and anxiety, symptoms commonly experienced by children with cancer, may predict pediatric symptom suffering profile membership that is amenable to treatment. METHODS: Three latent profiles (Low, Medium, and High symptom suffering) from 436 pediatric patients undergoing cancer care were assessed for association with three single-item symptoms and socio-demographic variables. RESULTS: Pediatric-PRO-CTCAE fatigue, pain, and anxiety severity scores at baseline were highly and significantly associated with the Medium and High Suffering profiles comprised of PROMIS pediatric symptom and function measures. The likelihood of membership in the Medium Suffering group was 11.37 times higher for patients who experienced fatigue severity than those with did not, while experience of pain severity increased the likelihood of the child's membership in the Medium Suffering profile by 2.59 times and anxiety by 3.67 times. The severity of fatigue increased the likelihood of presence in the High Suffering group by 2.99 times while pain severity increased the likelihood of the child's membership in the High Suffering profile by 6.36 times and anxiety by 16.75 times. Controlling for experience of symptom severity, older patients were more likely to be in the Higher or Medium Suffering profile than in the Low Suffering profile; no other socio-demographic or clinical variables had a significant effect on the latent profile classification. CONCLUSION: Clinician knowledge of the strong association between fatigue, pain, and anxiety severity and suffering profiles may help focus supportive care to improve the cancer experience for children most at risk from time of diagnosis through treatment.

Recommended scoring approach for the pediatric patient-reported outcomes version of the Common Terminology Criteria for Adverse Events.

BACKGROUND: Collecting symptom, function, and adverse event (AE) data directly from children and adolescents undergoing cancer care is more comprehensive and accurate than relying solely on their caregivers or clinicians for their interpretations. We developed the pediatric patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (Ped-PRO-CTCAE) measurement system with input from children, parents, and clinicians. Here, we report how we determined the recommended Ped-PRO-CTCAE item scoring approach. METHODS: Data from 271 patients were analyzed using three scoring approaches: (a) at the AE attribute (frequency, severity, interference) using ordinal and dichotomous measures; (b) a weighted composite AE item score by AE attribute (0.5 - frequency; 1.0 - severity; 1.5 - interference); and (c) overall number of AEs endorsed. Associations of each AE attribute, AE item score, and overall AE score with the Patient-Reported Outcome Measurement Information System (PROMIS) Pediatric measures were examined. The ability of the overall Ped-PRO-CTCAE AE score to identify patients with PROMIS symptom T-scores worse than reference population scores was assessed. Clinician preference for score information display was elicited through interviews with five pediatric oncology clinical trialists. RESULTS: The diverse scoring approaches yielded similar outcomes, including positive correlations of the Ped-PRO-CTCAE attributes, AE item score, and the overall AEs score with the PROMIS Pediatric measures. Clinicians preferred the most granular display of scoring information (actual score reported by the child and corresponding descriptive term). CONCLUSIONS: Although three scoring approaches yielded similar results, we recommend the AE attribute level of one score per Ped-PRO-CTCAE AE attribute for its simplicity of use in care and research.

Ovarian Cancer Epidemiology, Healthcare Access and Disparities (ORCHiD): methodology for a population-based study of black, Hispanic and white patients with ovarian cancer.

INTRODUCTION: Less than 40% of patients with ovarian cancer (OC) in the USA receive stage-appropriate guideline-adherent surgery and chemotherapy. Black patients with cancer report greater depression, pain and fatigue than white patients. Lack of access to healthcare likely contributes to low treatment rates and racial differences in outcomes. The Ovarian Cancer Epidemiology, Healthcare Access and Disparities study aims to characterise healthcare access (HCA) across five specific dimensions-Availability, Affordability, Accessibility, Accommodation and Acceptability-among black, Hispanic and white patients with OC, evaluate the impact of HCA on quality of treatment, supportive care and survival, and explore biological mechanisms that may contribute to OC disparities. METHODS AND ANALYSIS: We will use the Surveillance Epidemiology and Ends Results dataset linked with Medicare claims data from 9744 patients with OC ages 65 years and older. We will recruit 1641 patients with OC (413 black, 299 Hispanic and 929 white) from cancer registries in nine US states. We will examine HCA dimensions in relation to three main outcomes: (1) receipt of quality, guideline adherent initial treatment and supportive care, (2) quality of life based on patient-reported outcomes and (3) survival. We will obtain saliva and vaginal microbiome samples to examine prognostic biomarkers. We will use hierarchical regression models to estimate the impact of HCA dimensions across patient, neighbourhood, provider and hospital levels, with random effects to account for clustering. Multilevel structural equation models will estimate the total, direct and indirect effects of race on treatment mediated through HCA dimensions. ETHICS AND DISSEMINATION: Result dissemination will occur through presentations at national meetings and in collaboration with collaborators, community partners and colleagues across othercancer centres. We will disclose findings to key stakeholders, including scientists, providers and community members. This study has been approved by the Duke Institutional Review Board (Pro00101872). Safety considerations include protection of patient privacy. All disseminated data will be deidentified and summarised.

Patients, caregivers, and clinicians differ in performance status ratings: Implications for pediatric cancer clinical trials.

BACKGROUND: The Lansky Play-Performance Scale (LPPS) is often used to determine a child's performance status for cancer clinical trial eligibility. Differences between clinician and caregiver LPPS ratings and their associations with child-reported functioning have not been evaluated. METHODS: Children aged 7 to 18 years who were receiving cancer treatment and their caregivers were recruited from 9 pediatric cancer centers. Caregivers and clinicians reported LPPS scores, and children completed Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric functioning and symptom measures before treatment (time 1 [T1]) and after treatment (time 2 [T2]). t tests and mixed-linear models were used to assess differences in caregiver and clinician LPPS scores; polyserial correlations quantified associations between PROMIS and LPPS scores. RESULTS: Of 482 children, 281 had matched caregiver- and clinician-reported LPPS T1/T2 scores. Caregivers rated children significantly worse on the LPPS than clinicians at both T1 (mean, 73.3 vs 87.4; P < .01) and T2 (mean, 67.9 vs 83.1; P < .01). These differences were not related to a child's age (P = .89), diagnosis (P = .17), or sex (P = .64) or to the time point (P = .45). Small to moderate associations existed between caregiver- and clinician-reported LPPS ratings and child-reported PROMIS scores for mobility (caregiver T1/T2 r = 0.51/0.45; P < .01; clinician T1/T2 r = 0.40/0.35; P < .01), fatigue (caregiver T1/T2 r = -0.46/-0.37; P < .01; clinician T1/T2 r = -0.26/-0.27; P < .01), and pain interference (caregiver T1/T2 r = -0.32/-0.30; P < .01; clinician T1/T2 r = -0.17/-0.31; P < .01). Caregivers and clinicians assigned significantly lower LPPS scores at T2 (caregiver Δ = -5.37; P < .01; clinician Δ = -4.20; P < .01), whereas child-reported PROMIS scores were clinically stable. CONCLUSIONS: Significant differences between clinician and caregiver LPPS ratings of child performance were sustained over time; their associations with child reports were predominantly small to moderate. These data suggest that clinician-reported LPPS ratings by themselves are inadequate for determining clinical trial eligibility and should be supplemented by appropriate measures of a child's functional status reflecting the child and caregiver perspectives.

Subjective Toxicity Profiles of Children in Treatment for Cancer: A New Guide to Supportive Care?

CONTEXT: Children and adolescents with cancer experience treatment-related, subjective adverse events (AEs). Identifying distinct groups of patients who predictably experience higher prevalence of AEs could guide patient care. OBJECTIVES: Study aims were to 1) identify groups of children and adolescents reporting AEs using the Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Ped-PRO-CTCAE); 2) determine whether demographic and clinical characteristics predict AE group membership; and 3) examine whether AE group membership was related to the distal outcome of psychological stress. METHODS: Four hundred seventy-seven patients self-reported AEs via the Ped-PRO-CTCAE at T1 (beginning of treatment) and the PROMIS Pediatric Psychological Stress measure at T2 (7-28 days later). Latent class analysis was conducted to identify groups of patients and the relationships of the groups with demographic and clinical characteristics, and with stress. RESULTS: Three distinct a priori unknown AE groups were identified (high AE prevalence, moderate AE prevalence, and low AE prevalence). Females, blacks, patients with high psychological stress, and patients more recently diagnosed were more likely to be in the high AE prevalence group. Gender, age, race, and time since diagnosis were associated with psychological stress. CONCLUSION: Children with cancer are heterogeneous in experiencing subjective AEs. Gender, race, and time since diagnosis were significantly associated with higher subjective AE prevalence that may lead to psychological stress.