Patient-reported Outcome Items Research Articles

Novel Approaches Identifying Relevant Patient-Reported Outcomes in Patients With Inflammatory Bowel Diseases-LISTEN 1.

Several patient-reported outcomes (PROs) have been established and are widely used in the assessment of patients with inflammatory bowel disease (IBD). However, it has never been investigated which PRO items are experienced by and are considered most relevant for IBD patients. A review of IBD-related disease scores by a steering committee led to the identification of relevant PRO questions and assignment to 16 different PRO categories (9 symptoms and 7 impacts) that characterize patient's disease burden. In a cross-sectional study, a digital patient survey was carried out to determine the self-reported experience by multiple response, the relevance of these PRO categories by pairwise comparison and the suitability of the respective questions and answer possibilities by yes-or-no-question. Sixty patients with Crohn's disease (CD) (56.7% women; mean age 40.6 years; mean disease duration 12.4 years) and 60 patients with ulcerative colitis (UC) (51.7% women; mean age 37.3 years; mean disease duration 9.0 years) participated in the patient survey. All predefined symptoms and impacts, with the exception of nausea, were experienced by at least 50% of patients. Stool urgency and pain were rated the 2 most important symptoms in CD patients with similar ratings for relevance. Stool urgency was also the most important symptom in patients with UC, followed by stool frequency. Differences in self-reported experience between CD and UC patients were seen for the symptoms of rectal bleeding, pain, and nausea. Most important impact of symptoms in both patient groups were general wellbeing followed by social activities, while sexual activity was the least relevant impact category. Stool urgency was the most relevant and most self-reported symptom for both CD and UC. Relevance and self-reported experience of pain and rectal bleeding differed between the 2 diseases. Therefore, the future collection of PROs should take these disease specificities into consideration.

Development of patient-reported outcomes item set to evaluate acute treatment toxicity to pelvic online magnetic resonance-guided radiotherapy

BackgroundA new technology in cancer treatment, the MR-linac, provides online magnetic resonance-guided radiotherapy (MRgRT) that combines real-time visualization of the tumor and surrounding tissue with radiation therapy to deliver treatment more accurately. Online MRgRT makes it possible to minimize treatment volume, potentially reducing acute treatment toxicity. Patient-reported outcomes (PRO) add the patient perspective to evaluating treatment toxicity related to new technology. The objective of this mixed-methods study was to develop and explore the content validity of a set of PRO items to evaluate acute pelvic toxicity to radiotherapy including online MRgRT.MethodsA literature review and chart audit were conducted to identify symptomatic adverse events (AEs) to be selected from the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) library and European Organisation for Research and Treatment of Cancer (EORTC) item library. To validate the content, the item set was applied in a prospective pilot cohort of patients referred for primary pelvic RT with curative intent. Patients reported symptoms weekly during RT (4–8 weeks) and the subsequent 4 weeks. Follow-up reports were collected at 8, 12, and 24 weeks after RT. To ensure symptom coverage clinician-reported toxicity and individual patient interviews were conducted. The symptomatic AEs were included in the final item set if ≥20% of patients reported them.ResultsEighteen acute symptomatic AEs were selected for the initial item set. Forty patients (32 prostate cancer, 8 cervical cancer) were included in the pilot study. Patients with prostate cancer and those with cervical cancer both reported all 18 acute AEs. However, vomiting was not reported by > 20% of patients thus excluded from the item set. Adding a few diagnosis-specific AEs to the final item set was required for both prostate and cervical cancer patients.ConclusionsA PRO item set for patients with pelvic cancer treated with radiotherapy with a curative intent was developed and content validity explored. In the pilot study, the item set captured the most common acute symptomatic AEs for patients with prostate and cervical cancer related to pelvic RT including online MRgRT. Further validation of the content in broader disease sites would be needed in future studies.

More flexible response functions for the PROMIS physical functioning item bank by application of a monotonic polynomial approach.

In developing item banks for patient reported outcomes (PROs), nonparametric techniques are often used for investigating empirical item response curves, whereas final banks usually use parsimonious parametric models. A flexible approach based on monotonic polynomials (MP) provides a compromise by modeling items with both complex and simpler response curves. This paper investigates the suitability of MPs to PRO data. Using PROMIS Wave 1 data (N = 15,725) for Physical Function, we fitted an MP model and the graded response model (GRM). We compared both models in terms of overall model fit, latent trait estimates, and item/test information. We quantified possible GRM item misfit using approaches that compute discrepancies with the MP. Through simulations, we investigated the ability of the MP to perform well versus the GRM under identical data collection conditions. A likelihood ratio test (p < 0.001) and AIC (but not BIC) indicated better fit for the MP. Latent trait estimates and expected test scores were comparable between models, but we observed higher information for the MP in the lower range of physical functioning. Many items were flagged as possibly misfitting and simulations supported the performance of the MP. Yet discrepancies between the MP and GRM were small. The MP approach allows inclusion of items with complex response curves into PRO item banks. Information for the physical functioning item bank may be greater than originally thought for low levels of physical functioning. This may translate into small improvements if an MP approach is used.

Coverage of symptomatic toxicities from the common terminology criteria for adverse events (CTCAE) framework within the european organization for research and treatment of cancer (EORTC) item library.

e24117 Background: The EORTC Item Library is an online, interactive platform comprised of 950 distinct questions (items) from 67 different EORTC patient-reported outcome (PRO) questionnaires, covering a range of symptomatic toxicities, types of functioning, and impact on quality of life. These PROs provide a patient-centred perspective, complementing clinician adverse event (AE) reporting using classifications like the CTCAE. In order to summarize the coverage of symptomatic toxicities and facilitate the identification of items through use of a standardized framework, a mapping study was carried out, aimed at creating a coding system to classify EORTC items according to the CTCAE and link them to corresponding AEs. Methods: All items were searched for within the CTCAE (v5.0) using a deductive approach. Items were coded as linked if they were described within an AE’s title, description, or grading. Items not suitable for CTCAE coding were inductively assigned a descriptive classification. Descriptive classifications were also applied along with CTCAE codes when they provided additional information. Symptoms described in EORTC items but not located in the CTCAE were coded as missing and additional codes were assigned to highlight EORTC items capturing multiple underlying issues and diagnosis only CTCAE codes. Two raters independently coded 249 items and agreement was calculated. The remaining 701 items were coded by one rater and verified by the second, with a third introduced to discuss any discrepancies until a consensus was reached. Results: Agreement for raters following independent coding was 77.9% for at least one AE per item. In total, 625 (65.8%) items were linked to 208 different AEs. Fatigue was the most commonly linked AE, representing 4.9% of linked AEs. The majority of linked items were associated with one (65.6%) or two (23.5%) AEs, with some linked to three or more (10.9%). Multiple linkage resulted from different symptoms relating to the same issue/diagnosis or one symptom relating to multiple diagnoses. Two symptoms captured by six EORTC items but not found in the CTCAE were identified: bowel urgency and tenesmus. Seven descriptive non-CTCAE classifications emerged, with most of these covering the emotional impact of symptom, diagnosis, or treatment (33.6%) and information/satisfaction with care (31.7%). Nineteen items (2%) were linked to multiple underlying issues, and 43 (4.5%) to diagnosis only CTCAE codes. Conclusions: The EORTC Item Library provides extensive coverage of CTCAE symptomatic toxicities, along with other issues that are important to cancer patients, including emotional well-being and satisfaction with care services. Classifying symptomatic PRO items following the CTCAE clinical framework may facilitate future PRO selection and use in clinical trials and routine care.

Multicenter Prospective Cohort Study of the Patient-Reported Outcome Measures PRO-CTCAE and CAT EORTC QLQ-C30 in Major Abdominal Cancer Surgery (PATRONUS): A Student-Initiated German Medical Audit (SIGMA) Study

BackgroundThe patient-reported outcomes (PRO) version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and the computerized adaptive testing (CAT) version of the EORTC quality-of-life questionnaire QLQ-C30 have been proposed as new PRO measures in oncology; however, their implementation in patients undergoing cancer surgery has not yet been evaluated.MethodsPatients undergoing elective abdominal cancer surgery were enrolled in a prospective multicenter study, and postoperative complications were recorded according to the Dindo–Clavien classification. Patients reported PRO data using the CAT EORTC QLQ-C30 and the PRO-CTCAE to measure 12 core cancer symptoms. Patients were followed-up for 6 months postoperatively. The study was carried out by medical students of the CHIR-Net SIGMA study network.ResultsData of 303 patients were obtained and analyzed across 15 sites. PRO-CTCAE symptoms ‘poor appetite’, ‘fatigue’, ‘exhaustion’ and ‘sleeping problems’ increased after surgery and climaxed 10–30 days postoperatively. At 3–6 months postoperatively, no PRO-CTCAE symptom differed significantly to baseline. Patients reported higher ‘social functioning’ (p = 0.021) and overall quality-of-life scores (p < 0.05) 6 months after cancer surgery compared with the baseline level. There was a lack of correlation between postoperative complications or death and any of the PRO items evaluated. Feasibility endpoints for student-led research were met.ConclusionThe two novel PRO questionnaires were successfully applied in surgical oncology. Postoperative complications do not affect health-reported quality-of-life or common cancer symptoms following major cancer surgery. The feasibility of student-led multicenter clinical research was demonstrated, but might be enhanced by improved student training.

Phenotyping patients based on longitudinal heterogeneity of engagement patterns with the ASTHMAXcel PRO mobile health application

The ASTHMAXcel PRO mobile application delivers asthma education and assesses and tracks patient-reported outcomes (PROs), which are collected via in-app quizzes and push notifications. We seek to identify distinct patient phenotypes based on heterogeneity of engagement patterns. Adult patients with persistent asthma completed virtual study sessions at baseline (app download), 2 weeks, and 4 weeks. The number of PRO items submitted by each user was tracked through the app’s administration panel and leaderboard, and used to evaluate app usage patterns. We evaluated user interface satisfaction and acceptance through the QUIS and UTAUT questionnaires, respectively. A total of 25 patients answered a mean 8.4 (± 8.2) PROs from app download to 2 weeks and a mean 2.1 (± 4.4) PROs from 2- to 4 weeks. Four phenotypes were identified: never engaged (4, 16%); low engagers with subsequent decrease (10, 40%); late engagers (low engagers with subsequent increase) (4, 16%); and high engagers with subsequent disengagement (7, 28%). Of those who never engaged, 3 (75%) had a high school diploma or lesser education and reported improved satisfaction between baseline and 4 week (p < 0.03). For the late engagers, 3 (75%) were tech school or college graduates. For the high engagers with subsequent disengagement, satisfaction improved between baseline and 4 week (p < 0.03). Phenotyping e- health users regarding engagement over time, rather than simply a single metric such as total app usage time, allows for opportunities in delivering personalized push notification content and assessing differences in clinical outcomes among different subtypes.

PIN167 Patient-Reported Outcomes to Capture the Signs, Symptoms and Impacts of COVID-19 and the IMPACT of the Pandemic on People with and without Infection

In this unprecedented era of conducting clinical research during a global pandemic a Patient-Reported Outcomes (PRO) tool is required to (1) provide a comprehensive epidemiological understanding of SARS-COV-2 (COVID-19) symptoms, clustering and resolution; (2) provide data on the impact of both infection and the pandemic on people’s lives; and (3) offer a full understanding of treatment benefit in studies designed to treat or vaccinate against COVID-19. A review of the literature (March 2020) used COVID-19 and signs, symptoms and impacts search terms. A preliminary conceptual model was developed and novel PRO items were drafted. A review of social media (June 2020) informed an updated conceptual model and PRO items. Joint concept elicitation-cognitive interviews were completed with people who had experienced COVID-19 (June-July 2020). The literature (25 articles), social media (>200 million mentions) and interviews (n=10) highlighted a heterogenous list of signs, symptoms and impacts of COVID-19 infections, and a broad list of impacts of the pandemic in general. Novel PROs are intended to be comprehensive, so the incidence and severity of 42 signs and symptoms are measured. Fifteen additional items ask about the impact of infection (physical, emotional and social) and 18 about the impact of the pandemic. The PRO is adaptive (modular) to allow administration to people with and without COVID-19 infection. Weekly- and daily-recall versions were tested in cognitive interviews resulting in adjustments to ensure understandability. Novel content-valid PROs have been developed to measure the signs, symptoms and impacts of COVID-19 pandemic and infection. These are currently being employed in a large longitudinal study to evaluate their psychometric measurement properties.

Development of the symptoms and impacts questionnaire for Crohn's disease and ulcerative colitis.

SummaryBackgroundPatient‐reported outcome (PRO) measures historically used in inflammatory bowel disease have been considered inadequate to support future drug labelling claims by regulatory agencies.AimsTo develop PRO tools for use in Crohn's disease (CD) and ulcerative colitis (UC) following guidance issued by the US FDA and the ISPOR (International Society for Pharmacoeconomics and Outcomes Research).MethodsConcept elicitation and cognitive interviews were conducted in adult patients (≥18 years) across the United States and Canada. Semi‐structured interview guides were used to collect data, and interview transcripts were coded and analysed. Concept elicitation results were considered alongside existing literature and clinical expert opinion to identify candidate PRO items. Cognitive interviews evaluated concept relevance, interpretability and structure, and facilitated instrument refinement. Concept elicitation participants, except those with an ostomy, underwent centrally read endoscopy to assess inflammatory status.ResultsIn all, 54 participants (mean age: 46.2 years; 66.7% female) were included in the CD concept elicitation interviews. In total, 80 symptom concepts and 61 impact concepts were identified. After three waves of cognitive interviews, the 31‐item Symptoms and Impacts Questionnaire for CD (SIQ‐CD) was developed. In the UC concept elicitation phase, 53 participants were interviewed (mean age: 41.4 years; 49.1% female). In total, 79 symptoms concepts and 49 impact concepts were identified. Following two waves of cognitive interviews, the 29‐item Symptoms and Impacts Questionnaire for UC (SIQ‐UC) was developed. Both instruments include four symptom and six impact domains.ConclusionsWe developed PROs to support CD and UC drug labelling claims. Psychometric validation studies to evaluate instrument reliability and responsiveness are ongoing.

Development and Content Validity Testing of Patient-Reported Outcome Items for Children to Self-Assess Symptoms of the Common Cold.

Background and objectiveNo pediatric patient-reported outcome instruments specific to the common cold are found in the literature. This study involved development and content validity testing of patient-reported outcome items (questions and response options) assessing cold symptoms in children aged 6–11 years.MethodsDraft patient-reported outcome instructions, items, response scales, and recall periods were developed based on the literature and existing measures. Qualitative interviews were conducted with children (n = 39) who were currently (n = 31) or had recently (n = 8) experienced a cold and ten parents of a subset of children aged 6–8 years. The interviews were conducted over two rounds and included open-ended concept elicitation questioning, a free-drawing task, a card sorting task, and a task involving circling parts of the body, followed by cognitive debriefing of draft items. Thematic analysis of verbatim transcripts was performed to analyze the qualitative data. The findings were used to support revisions to the draft patient-reported outcome.ResultsTen symptom concepts were reported by the children during concept elicitation. The creative tasks helped the children to describe their symptoms, generally using consistent language to do so, irrespective of age. Nineteen patient-reported outcome items were developed and subject to cognitive debriefing. Debriefing with both children and parents informed several small revisions and provided evidence that the majority of children found most patient-reported outcome items easy to understand, and that the items were mainly interpreted consistently and as intended.ConclusionsThis in-depth qualitative study has supported identification of relevant symptom concepts and the development and refinement of patient-reported outcome items to assess those concepts. The findings support the content validity of the items and suggest that they can be used with confidence in children aged 9 years and older. For children aged 6–8 years, it is recommended the items are administered with initial adult supervision to explain the more difficult concepts or through parent/interviewer administration.

Impact of Abiraterone Acetate plus Prednisone or Enzalutamide on Patient-reported Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer: Final 12-mo Analysis from the Observational AQUARiUS Study

BackgroundFew studies have examined patient-reported outcomes (PROs) with abiraterone acetate plus prednisone (abiraterone) versus enzalutamide in metastatic castration-resistant prostate cancer (mCRPC). ObjectiveTo determine the impact of abiraterone and enzalutamide on PROs. Design, setting, and participantsAQUARiUS (NCT02813408) was a prospective, 12-mo, observational study in patients with mCRPC from Denmark, France, and the UK. InterventionAbiraterone or enzalutamide treatment according to routine practise. Outcome measurements and statistical analysisPROs were collected over 12 mo using Functional Assessment of Cancer Therapy—Cognitive Function (FACT-Cog), Brief Fatigue Inventory—Short Form (BFI-SF), Brief Pain Inventory—Short Form, and European Organisation for Research and Treatment of Cancer—Quality of Life Questionnaire (QLQ-C30) at baseline and routine visits. Outcomes included mean change in PROs, patients with clinically meaningful worsening (CMW) in PROs, and safety. Data were analysed using repeated measures linear and logistic models adjusted for baseline characteristics. Results and limitationsAbiraterone-treated (N = 105) and enzalutamide-treated (N = 106) patients were included. Key PRO items (cognitive impairments and fatigue) were significantly (p < 0.05) in favour of abiraterone versus enzalutamide during the study. “Perceived cognitive impairment” and “comments from others” (FACT-Cog); “fatigue right now”, “usual level of fatigue”, and “worst level of fatigue” (BFI-SF); and “cognitive functioning” and “fatigue” (QLQ-C30) were significantly in favour of abiraterone over enzalutamide for three or more consecutive periods up to month 12. From study initiation, significantly fewer patients receiving abiraterone experienced one or more CMW episode in cognition and fatigue. Fatigue and asthenia (adverse events) were lower with abiraterone than with enzalutamide (5% vs 15% and 10% vs 11%, respectively). There were no treatment-related deaths. Limitations included lack of randomisation. ConclusionsIn a real-world setting, this 12-mo analysis suggests an advantage of abiraterone acetate plus prednisone over enzalutamide on fatigue and cognitive function; this finding occurred early after treatment initiation. This difference should be considered when choosing treatment. Patient summaryThis study looked at the effect of two treatments (abiraterone acetate plus prednisone and enzalutamide) for metastatic castration-resistant prostate cancer on patient quality of life over 12 mo. Using established questionnaires, patients reported that they experienced less fatigue and cognitive impairments (including memory loss and reduced thinking abilities) with abiraterone acetate plus prednisone than with enzalutamide.

535P - Pre-specified pilot analysis of a randomised pilot/phase II/III trial comparing standard dose vs dose-escalated concurrent chemoradiotherapy (CRT) in anal cancer (PLATO-ACT5)

BackgroundThe PLATO platform consists of 3 anal cancer trials (ACT) across the loco-regional disease spectrum (ACT3, 4 and 5). ACT5 tests the benefit of RT dose escalation using intensity modulated RT (IMRT) in locally advanced disease. We planned to analyse treatment compliance, acute toxicity and patient reported outcomes (PROs) on the first 60 patients (pts) prior to the phase II/III trial (final target n=640) to evaluate the need for protocol modifications. MethodsPts with T2 N1-3, T3-4 N any M0 squamous cancer of the anus entered a prospective, multi-centre, open-labelled randomised 3-arm trial, and received 28 fractions (F) of IMRT at total standard dose of 53.2Gy or escalated to 58.8Gy or 61.6Gy to the gross tumour (40Gy in 28F elective nodal irradiation in all arms). All pts received concurrent mitomycin 12mg/m2day 1 and capecitabine (CAP) 825mg/m2 twice daily (week days) or 5-fluorouracil 1000mg/m2 days 1-4 and 29-32. Compliance to RT (no delay >3 days due to toxicity) and chemotherapy, worst acute toxicity during treatment (CTCAEv4) and PROs up to 6 months (EORTC-QLQ C30 and ANL27) were analysed. Results60 pts were enrolled from 12 UK sites (53.2Gy n=19; 58.8Gy n=21; 61.6Gy n=20). 78% female, median age 61 years (36 -77), 67% T2/3 and 28% ECOG PS1. All pts received planned RT dose with no delays >3days. Chemotherapy (5FU n=18; CAP n=42) modifications were: 8.3% (n=5) overall dose reductions and 35% (n=15) temporary CAP omissions (range 1-5 days). Pts had acceptable acute toxicity/PROs for both experimental arms not requiring protocol modification. Worst reported CTCAE toxicity grade (G) per pt: G2 51.7% (n=31), G3 47.6% (n=28, 19 radiation dermatitis, 7 diarrhoea), G4 1.7% (n=1; thrombocytopenia). PRO compliance was 86.7% at 6 months. Pre-specified PRO items on quality of life, pain, and bowel toxicity were worst in final treatment week, improving by 6 weeks and returned to baseline or better by 6 months. ConclusionsRT dose intensification appears safe with acceptable compliance, acute toxicity and PROs at 6 months. Data Monitoring Committee approved phase II with no treatment schedule changes but included a 6 month clinician toxicity assessment. Phase II will open in June 2019. Clinical trial identificationISRCTN88455282. Legal entity responsible for the studyUniversity of Leeds. FundingCancer Research UK. DisclosureAll authors have declared no conflicts of interest.

Training Subjects On Key Concepts From Patient-Reported Outcomes (PROs) Improves Understanding And Data Accuracy.

ObjectivesThe majority of subjects do not understand how to accurately report PRO data due to conceptual misunderstandings. This study demonstrates how even a short 2-sentence instruction can improve subject understanding.MethodsFor this study, 613 subjects completed an online survey, in which they were asked to provide responses to commonly seen PRO questions from various therapeutic areas. Demographic data were also collected.ResultsSubjects were provided with scenarios relating to pain severity, the definition of a rescue laxative, reporting stool counts, reporting a bleeding event, and itch severity. After subjects provided an initial response to the question, they were provided with minimal training information consisting of 1–2 sentences and asked to provide a response again to the same question. A 16% increase in mean response accuracy was found amongst all 5 questions evaluated by subjects.ConclusionPatient understanding of PRO items often seen as key endpoints in clinical trials was shown to increase with minimal training thus increasing the accuracy of data collected.

Patient-reported outcomes item selection for bladder cancer patients in chemo- or immunotherapy

BackgroundSelection of specific patient-reported outcomes (PROs) for cancer patients requires careful consideration to the purpose and population at aim. Here we report the process of choosing which items to include in a bladder cancer population in chemo- or immunotherapy based on the Patient-Reported Outcomes Version of the Common Terminology Criteria of Adverse Events (PRO-CTCAE).MethodsInitial PRO-CTCAE symptoms were chosen through 1) medical record audit 2) patient interviews 3) summary of product characteristics from European Medicines Agency and Food and Drug Administration for the applied chemotherapies, and 4) toxicity reporting from Phase 2 and 3 trials for immunotherapies applied in patients with urothelial cancer. The selected questions were applied in a prospective cohort of 78 bladder cancer patients receiving chemo- or immunotherapy at Rigshospitalet and Herlev Hospital, Denmark. Symptoms tested in this population were selected for the final module if they appeared in ≥3 of the following groupings a) the most prevalent PRO-CTCAE symptoms grade ≥ 2 overall during treatment b) the PRO-CTCAE symptoms reported in conjunction with hospital admissions or mentioned in focus group interviews discussing which symptoms were prevalent in this patient group with specialized c) nurses or d) physicians. The authors also included symptoms in the final module if they were present in two of the above groups and defined as actionable by clinicians.ResultsFrom the initial selection of PRO-CTCAE symptoms, a total of 45 PRO-CTCAE symptoms explored by 84 PRO-CTCAE questions were retrieved. Through the second selection process based on the described criteria, the study group agreed on 15 PRO-CTCAE symptoms explored by 30 PRO-CTCAE items to be appropriate and relevant for the bladder population during medical oncological treatment.ConclusionsThe selection of disease specific PROs in a bladder cancer population was feasible. The process revealed several steps of selection needed in order to reach a final module for clinical application.

Errors in answering migraine patient-reported outcome measure questions: patients consider training necessary in clinical trials

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; In migraine clinical trials, patients’ understanding of the terminology used in patient-reported outcome (PRO) measures is important as variability in completing PRO measures can reduce the power to detect treatment efficacy. This study examines patients’ understanding of how to complete PRO measures in the absence of training, if minimal training can improve the accuracy of answering PRO items, and patients’ opinion on the necessity of training and their preference for the method of training.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Participants reporting a diagnosis of migraine completed online surveys. Participants were given scenarios of how to report headache days and pain severity. Respondents were asked about their opinions on the necessity of training, and their preference for the method of training. In a second study, participants were given a hypothetical scenario on how to report pain severity before and after a short training.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The majority of participants had different criteria to interpret PRO questions and provided incorrect answers to our scenarios. In the second study, with minimal training, errors were reduced by 7.5%. Over 90% of participants viewed educational materials and training as necessary and preferred electronic modes of training with the ability to review training materials as needed for the duration of the trial.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Patient training may improve data quality and inter-rater reliability in clinical trials. Electronic interactive training could be used as an approach to reduce inconsistencies in PRO measures and improve data quality.&lt;/p&gt;

Big data analysis of associations between patient reported outcomes, observer reported toxicities, and overall quality of life in head and neck cancer patients treated with radiation therapy

PurposeTo assess associations between a variety of patient-reported outcomes (PROs), observer reported toxicities (ORTs), and patient-reported overall quality of life (QOL) for head and neck cancer patients treated with radiotherapy, in order to identify important items for inclusion in prospective patient reporting in the clinic. Methods612 patients completed 27 PRO items from three questionnaires at 1273 follow-up visits, and clinicians provided ORTs according to CTCAE criteria. Using a big data approach, we measured associations among all PROs, between all PROs and ORTs, and between PROs/ORTs and QOL with Pearson (ρ) and Kendall (τ) correlation coefficients, and a novel analysis method based on receiver operating characteristic (ROC) curves used to detect thresholds in response levels demonstrating strong interactions. ResultsPROs most strongly associated with QOL were recreation/entertainment, activity, and fatigue, with ρ = 0.51–0.60. Several PROs assessing a common functional outcome (eg. xerostomia) were highly associated with each other (PRO-PRO), with maximum ρ = 0.84. Maximum ORT-PRO correlations were ρ = 0.61 (dysgeusia versus taste), and ρ = 0.5 for ORT-QOL (dry mouth – day). The ROC method identified response thresholds with high area under the curve (AUC) scores for many ORT-PRO associations with maximum AUCavg = 0.78. ConclusionsPRO associations identified activity, lifestyle and fatigue as items for strong consideration for inclusion in questionnaires in the clinic, and suggest that outcome information can be captured in fewer items than the 27 in this study. The ability of clinicians to assess patient toxicities is highest with more severe toxicities, underscoring the need for PRO collection in patient visits to understand and address patient symptoms.

Clostridium difficile Infection\u2013Daily Symptoms (CDI-DaySyms\u2122) questionnaire: psychometric characteristics and responder thresholds

BackgroundThe purpose of the current study was to determine the final content validation, psychometric characteristics, clinically meaningful improvement, and responder thresholds of the Clostridium difficile infection (CDI)–Daily Symptoms (CDI-DaySyms™) patient-reported outcome (PRO) questionnaire.MethodsThis validation study was part of two phase III studies (NCT01987895 and NCT01983683) conducted in patients with mild-to-moderate or severe CDI who completed the CDI-DaySyms™ daily throughout the treatment period. The questionnaire was evaluated in three stages: final PRO item content validation (Stage I); psychometric evaluation of reliability and construct validity (Stage II); and determination of clinically meaningful improvement and responder thresholds using distribution-based methods (Stage III).ResultsThe analysis included 168 patients. Most patients were female and Caucasian with mild-to-moderate CDI. The mean age was 57.1 years. Initial item analysis supported by confirmatory factor analysis demonstrated the relevance of 10 items grouped into three distinct domains (Diarrhea Symptoms, Abdominal Symptoms, and Systemic/Other Symptoms). Domain scores demonstrated acceptable internal consistency and test-retest reliability, were sensitive to change, and correlated in expected directions with other relevant symptom and disease-severity measures. Responder thresholds were defined as score changes of − 1.00, − 0.80, and − 0.70 in the Diarrhea Symptoms, Abdominal Symptoms, and Systemic/Other Symptoms domains, respectively.ConclusionsThe CDI-DaySyms™ is a valid measure of patient-reported CDI symptoms, with good measurement properties, which supports its utility as an endpoint in clinical studies. Further studies confirming responder thresholds based on anchor-based methods are required.Trial registrationNCT01987895, registered November 20, 2013; NCT01983683, registered November 14, 2013.

Abstract P5-14-06: Prioritization of patient reported outcomes by women with metastatic breast cancer

Abstract Introduction: An emphasis on patient-centered care has led to a growing interest in collecting patient-reported outcomes (PROs) in the setting of cancer care. Routine collection of actionable PROs has been shown to improve patient satisfaction with care and even prolong survival. However, completion rates of PROs outside of the research setting are low, which may be due to an incomplete understanding of the outcomes patients value most. Prior work has focused primarily on symptom burden, but patients are also affected by disease and treatment across multiple domains (e.g. physical, psychological, social, and financial). To address this knowledge gap, we conducted a qualitative study among women with metastatic breast cancer (MBC) to identify the optimal patient-centered approach to collecting PRO data. Methods: We conducted 1-on-1 interviews with patients who had started a treatment regimen for MBC within the past 6 weeks at the Breast Center at Smilow Cancer Hospital of Yale New Haven Hospital to determine which PROs were most personally relevant. We assessed heterogeneity across patients in their prioritization. Patients were asked which of a list of six PRO domains they would like their provider to have information about and then ranked the domains by order of importance (from most to least important). The following domains were created from the NCCN Distress Thermometer: physical well-being, emotional well-being, treatment burden, functional status, financial concerns, and social well-being. For each ranked domain, patients were asked to rank items within the domain using a card sorting exercise where the number of items ranged from 5 to 15. Patients were then asked where and how often they preferred to report PROs. Results: Ten women with MBC completed the card sorting exercise: mean age was 58 years (+/- 12), 7 were white, 2 African American and 1 Asian; 1 identified as Hispanic. After 10 interviews, it was apparent that no single set of domain rankings was common across patients. Patient prioritization of PRO domains was unique and varied. Selection and prioritization of PRO domains and items within each domain were unique and varied. Five women reported “physical well-being” as the most important domain; treatment burden and emotional well-being were also selected as most important or ranked as highly important. Participants preferred reporting MBC PROs while in the waiting room for all domains except emotional well-being (from home was the preference). However, participants were willing to complete PRO assessment in the waiting room for about ten minutes and at home for twenty minutes. Conclusion: Substantial variation exists in how women with MBC rate the importance of specific PRO domains and items within each domain. Importantly, “physical symptoms” was not the top concern for half of the interviewed patients. This is an important finding, given that previous published studies of patient-reported outcomes have focused on one domain, such as symptoms and side effects or the financial burden of treatment. Our findings support the development of multi-dimensional tools for the collection of PROs. Although toxicity and physical symptoms are of utmost concern, clinicians should not neglect other dimensions of quality of life in women with MBC. Citation Format: Mougalian SS, Aminawung JA, Presley C, Canavan ME, Holland ML, Hu X, Gross CP. Prioritization of patient reported outcomes by women with metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-14-06.

The use of PRO in adverse event identification during cancer therapy – choosing the right questions to ask

Background: Adequate and timely monitoring of adverse events to cancer treatment is from our view dependent on a suitable Patient Reported Outcome (PRO) tool developed for the specific patient population based on cytostatic drugs included in the treatment. Therefore, a systematic method for construction of PRO questionnaires including selection of the appropriate questions is needed.Purpose: The purpose of the present study was to develop and test a method of item selection for a PRO questionnaire to monitor adverse events in oncologic routine treatment of metastatic prostate cancer patients.Patient and methods: Documentation on common symptomatic adverse events for the three drugs was collected from five different sources: 1) FDA product summary information; 2) EMA product summary information; 3) phase 3 Randomized Controlled Trials (RCT) leading to drug approval; 4) audit of the electronic patient files focusing on the oncologist’s documentation of adverse events and 5) individual patient interview (n = 16) focusing on adverse events. The Patient Reported Outcome of Common Terminology Criteria for Adverse Events (PRO-CTCAE) was used as PRO item library. Selected symptoms were transformed into corresponding PRO-CTCAE questions. The questionnaire was tested by patients in a pilot test (n = 12). Patients for interviews and pilot testing were included by purposive sampling.Results: A method for constructing a PRO questionnaire was developed, and a questionnaire of 25 PRO-CTCAE symptoms with 46 questions including an open write-in space for additional adverse events was constructed and tested.Conclusion: This study demonstrates a systematic method to select questions on adverse events for a PRO questionnaire in a specific cancer population receiving oncologic treatment. The present study reveals that audit of patient files and patient interviews in our setting only add little to the information on adverse events obtained from FDA, EMA and RCT. The obtained questionnaire was found useful and acceptable by patients.

Development of Health Pathways to Standardize Cancer Care Pathways Informed by Patient-Reported Outcomes and Clinical Practice Guidelines.

High-quality symptom management and supportive care are essential components of comprehensive cancer care. We aimed to describe the development of an evidence-based automated decisional algorithm for patients with cancer that had specific, actionable, clinical, evidence-based recommendations to improve patient care, communication, and management. We reviewed existing literature and clinical practice guidelines to identify priority domains of patient care and potential clinical recommendations. Two multidisciplinary clinical advisory groups used a two-stage consensus decision-making approach to determine domains of care and patient-reported outcome (PRO) measures and subsequently developed automated algorithms with clear clinical recommendations amendable to intervention in clinical settings. Algorithms were developed to inform management of patient symptoms, distress, and unmet needs. Three PRO measures were chosen: Distress Thermometer and problem checklist, Edmonton Symptom Assessment Scale, and the Supportive Care Needs Survey-Screening Tool 9. PRO items were mapped to five domains of patient well-being: physical, emotional, practical, social and family, and maintenance of well-being. A total of 15 actionable clinical recommendations tailored to specific issues of concern were established. Using automated algorithms and clinical recommendations provides a platform for streamlining and systematizing the use of PROs to inform risk-stratified guideline-informed care. The series of algorithms, which set out systematized care pathways for the clinical care of patients with cancer, can be used to potentially inform patient-centered care.

Measuring Patient Reported Outcomes in Multiple Myeloma: Are Legacy Instruments Fit for Purpose

Introduction:Measuring patient-reported outcomes (PROs) in oncology clinical trials is important to capture the patient perspective on quality of survival and the outcomes of health-related quality of life (HRQoL), symptoms, and functional status. In multiple myeloma (MM) randomized clinical trials (RCTs) the common PRO instruments include the EORTC QLQ-C30 and the EQ-5D as generic measures of a patient's health status. While these legacy PRO instruments have been widely used in the MM population, it is important to continue to assess the instruments psychometric properties for the specific context of use and target population.The purpose of this research was to investigate the strengths and limitations of the PRO instruments when analyzed free from developer construct and scoring recommendations to assess fit for purpose in various MM clinical trial populations.Methods:Data for the analysis included 3 MM RCTs (n=1,773) (Dimopoulos 2016, Palumbo 2016, Mateos 2018). The PRO analysis set consisted of 33 items from the EORTC QLQ-C30 and EQ-5D-5L collected at baseline and during the treatment phase of the RCTs. Item analysis and modern psychometric methods were applied to the PRO item pool as a 4-step process: (1) descriptive analysis of the items, (2) assessment of factor structure, (3) performance of factors across RCT populations (treatment naive, relapsed/refractory MM), and (4) assessment of meaningful change.Items were characterized using polychoric correlations to examine the inter-item association and relationships before determining appropriate factor structures. An exploratory factor analysis (EFA) followed by multidimensional item response theory (MIRT) and bifactor IRT models were conducted to determine how items fit into factors and to test a total symptom and total impact scoring option. Differential item functioning (DIF) was conducted to evaluation item and domain performance across study populations (treatment naïve vs. relapsed/refractory) and longitudinally (baseline vs. week 24). Meaningful change in these new domain constructs was evaluated using anchor-based techniques based on the EORTC-QLQ-C30 and EQ-5D-5L global items. A novel provisional latent class model approach creating responder groups was also developed and applied to assess meaningful change.Results:The 33 items from the EORTC QLQ-C30 and EQ-5D-5L demonstrated strong inter-item correlations supportive of pre-specified domain structures and consistent across RCT study populations. The EFA supported 3-domain structures for both symptoms and impacts separately. These domains were broadly consistent with the PRO instrument developer specifications but unique in several regards. These domains were statistically identical across RCTs. Model fit showed that a proposed bi-factor IRT (Symptom domain and Impact domain) fit better than the MIRT suggesting that subdomains are less useful than total domain scores. An extensive DIF analysis within this IRT framework found no evidence of substantial DIF effects. All evidence indicated that the items performed similarly across sample populations and time points.Anchor-based meaningful change calculations for the newly created total symptom score and the total impact score demonstrated separation between global health anchor groups but the meaningful change estimates were small. The latent class models demonstrated that treatment arms differed significant in responder rates within 1 RCT.Conclusions:The analyses confirmed psychometrically robust EORTC QLQ-C30 and EQ-5D-5L items in the MM population under newly specified factor structures. In addition, performance of the items allows for calculation of a total symptom score and total impacts score. The newly developed total domains performed identically across MM populations (treatment naïve versus relapsed/refractory). The results only focus on the on-treatment phase of the RCT so future research is needed to determine how psychometric methods can be adjusted to better accommodate survival status and censoring for progression in oncology RCTs. The psychometric properties and consistency of the findings across the newly created symptom and impact total domain structures support the results that daratumumab maintains HRQoL in patients with MM. DisclosuresGries:Janssen Research & Development, LLC: Employment. Fastenau:Janssen Research & Development, LLC: Employment. Iaconangelo:Janssen Research &Development, LLC: Consultancy. Serrano:Janssen Research & Development, LLC: Consultancy.