Mitchell, Sandra A

9047 Background: Symptomatic adverse events (AE) in cancer trials are reported by clinicians using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE). To integrate the patient perspective into AE reporting, NCI contracted (HHSN261201000043C) to create a patient-reported outcomes companion tool (PRO-CTCAE). We report the validity and reliability of PRO-CTCAE’s 124 items reflecting 78 symptomatic AEs. Methods: English-speaking subjects (n=869; 44% male; median [mdn] age 59; 32% racial/ethnic minority; 34% high school or less; 17% ECOG Performance Status [PS] 2-4) receiving treatment for a range of cancers at 4 NCI-designated cancer centers and 5 sites in NCI's Community Cancer Centers Program completed a web-based survey in clinic including PRO-CTCAE and EORTC QLQ-C30. Pearson correlations were computed between PRO-CTCAE items and QLQ-C30 scales. Differences in PRO-CTCAE item scores between clinician-reported ECOG PS (0-1 vs 2-4) groups were computed. Test-retest reliability of 48 prespecified items was evaluated in a subset (n=79). Results: Correlations in the expected direction were observed for 116/124 PRO-CTCAE items with the QLQ-C30 global health scale (mdn r=-.21; range .08 to -.57). Stronger correlations were seen for PRO-CTCAE items with conceptually related QLQ-C30 domains: fatigue with physical, role and social functioning (-.54 to -.66); anxiety and depression with emotional functioning (-.54 to -.70); and concentration and memory problems with cognitive functioning (-.62 to -.72) [all p <0.001]. Fatigue, nausea, vomiting, pain, dyspnea, insomnia, appetite loss, constipation and diarrhea items strongly correlated with corresponding QLQ-C30 symptom scales (.69 to .79, all p <0.001). Scores for 98/124 PRO-CTCAE items were higher in the ECOG PS 2-4 vs 0-1 group (mdn effect size .3). Test-retest reliability was observed across all tested items (mdn intraclass correlation coeff .77; range .53 to .96). Conclusions: Results demonstrate favorable validity and reliability of PRO-CTCAE in a large, heterogeneous sample of patients undergoing cancer treatment. Further testing in multicenter treatment trials is underway.

Abstract Objective The study sought to describe patient-entered supplemental information on symptomatic adverse events (AEs) in cancer clinical research reported via a National Cancer Institute software system and examine the feasibility of mapping these entries to established terminologies. Materials and Methods Patients in 3 multicenter trials electronically completed surveys during cancer treatment. Each survey included a prespecified subset of items from the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Upon completion of the survey items, patients could add supplemental symptomatic AE information in a free text box. As patients typed into the box, structured dropdown terms could be selected from the PRO-CTCAE item library or Medical Dictionary for Regulatory Activities (MedDRA), or patients could type unstructured free text for submission. Results Data were pooled from 1760 participants (48% women; 78% White) who completed 8892 surveys, of which 2387 (26.8%) included supplemental symptomatic AE information. Overall, 1024 (58%) patients entered supplemental information at least once, with an average of 2.3 per patient per study. This encompassed 1474 of 8892 (16.6%) dropdowns and 913 of 8892 (10.3%) unstructured free text entries. One-third of the unstructured free text entries (32%) could be mapped post hoc to a PRO-CTCAE term and 68% to a MedDRA term. Discussion Participants frequently added supplemental information beyond study-specific survey items. Almost half selected a structured dropdown term, although many opted to submit unstructured free text entries. Most free text entries could be mapped post hoc to PRO-CTCAE or MedDRA terms, suggesting opportunities to enhance the system to perform real-time mapping for AE reporting. Conclusions Patient reporting of symptomatic AEs using a text box functionality with mapping to existing terminologies is both feasible and informative.

Purpose The US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to enable patient reporting of symptomatic adverse events in oncology clinical research. This study was designed to assess the feasibility and resource requirements associated with implementing PRO-CTCAE in a multicenter trial. Methods Patients with locally advanced rectal cancer enrolled in the National Cancer Institute–sponsored North Central Cancer Treatment Group (Alliance) Preoperative Radiation or Selective Preoperative Radiation and Evaluation before Chemotherapy and Total Mesorectal Excision trial were asked to self-report 30 PRO-CTCAE items weekly from home during preoperative therapy, and every 6 months after surgery, via either the Web or an automated telephone system. If participants did not self-report within 3 days, a central coordinator called them to complete the items. Compliance was defined as the proportion of participants who completed PRO-CTCAE assessments at expected time points. Results The prespecified PRO-CTCAE analysis was conducted after the 500th patient completed the 6-month follow-up (median age, 56 years; 33% female; 12% nonwhite; 43% high school education or less; 5% Spanish speaking), across 165 sites. PRO-CTCAE was reported by participants at 4,491 of 4,882 expected preoperative time points (92.0% compliance), of which 3,771 (77.2%) were self-reported by participants and 720 (14.7%) were collected via central coordinator backup. Compliance at 6-month post-treatment follow-up was 333 of 468 (71.2%), with 122 (26.1%) via backup. Site research associates spent a median of 15 minutes on PRO-CTCAE work for each patient visit. Work by a central coordinator required a 50% time commitment. Conclusion Home-based reporting of PRO-CTCAE in a multicenter trial is feasible, with high patient compliance and low site administrative requirements. PRO-CTCAE data capture is improved through centralized backup calls.

Background There is currently a lack of consensus on how health-related quality of life and other patient-reported outcome measures in cancer randomized clinical trials are analyzed and interpreted. This makes it difficult to compare results across randomized controlled trials (RCTs) synthesize scientific research, and use that evidence to inform product labeling, clinical guidelines, and health policy. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data for Cancer Clinical Trials (SISAQOL) Consortium aims to develop guidelines and recommendations to standardize analyses of patient-reported outcome data in cancer RCTs. Methods and Results Members from the SISAQOL Consortium met in January 2017 to discuss relevant issues. Data from systematic reviews of the current state of published research in patient-reported outcomes in cancer RCTs indicated a lack of clear reporting of research hypothesis and analytic strategies, and inconsistency in definitions of terms, including “missing data,”“health-related quality of life,” and “patient-reported outcome.” Based on the meeting proceedings, the Consortium will focus on three key priorities in the coming year: developing a taxonomy of research objectives, identifying appropriate statistical methods to analyze patient-reported outcome data, and determining best practices to evaluate and deal with missing data. Conclusion The quality of the Consortium guidelines and recommendations are informed and enhanced by the broad Consortium membership which includes regulators, patients, clinicians, and academics.

Aims: The US National Cancer Institute recently developed the PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events). PRO-CTCAE is a library of questions for clinical trial participants to self-report symptomatic adverse events (e.g. nausea). The objective of this study is to inform evidence-based selection of a recall period when PRO-CTCAE is included in a trial. We evaluated differences between 1-, 2-, 3-, and 4-week recall periods, using daily reporting as the reference. Methods: English-speaking patients with cancer receiving chemotherapy and/or radiotherapy were enrolled at four US cancer centers and affiliated community clinics. Participants completed 27 PRO-CTCAE items electronically daily for 28 days, and then weekly over 4 weeks, using 1-, 2-, 3-, and 4-week recall periods. For each recall period, mean differences, effect sizes, and intraclass correlation coefficients were calculated to evaluate agreement between the maximum of daily ratings and the corresponding ratings obtained using longer recall periods (e.g. maximum of daily scores over 7 days vs 1-week recall). Analyses were repeated using the average of daily scores within each recall period rather than the maximum of daily scores. Results: A total of 127 subjects completed questionnaires (57% male; median age: 57). The median of the 27 mean differences in scores on the PRO-CTCAE 5-point response scale comparing the maximum daily versus the longer recall period (and corresponding effect size) was −0.20 (−0.20) for 1-week recall, −0.36 (−0.31) for 2-week recall, −0.45 (−0.39) for 3-week recall, and −0.47 (−0.40) for 4-week recall. The median intraclass correlation across 27 items between the maximum of daily ratings and the corresponding longer recall ratings for 1-week recall was 0.70 (range: 0.54–0.82), for 2-week recall was 0.74 (range: 0.58–0.83), for 3-week recall was 0.72 (range: 0.61–0.84), and for 4-week recall was 0.72 (range: 0.64–0.86). Similar results were observed for all analyses using the average of daily scores rather than the maximum of daily scores. Conclusion: A 1-week recall corresponds best to daily reporting. Although intraclass correlations remain stable over time, there are small but progressively larger differences between daily and longer recall periods at 2, 3, and 4 weeks, respectively. The preferred recall period for the PRO-CTCAE is the past 7 days, although investigators may opt for recall periods of 2, 3, or 4 weeks with an understanding that there may be some information loss.

Abstract There is strong evidence that cigarette smoking causes adverse outcomes in people with cancer. However, more research is needed regarding those effects and the effects of alternative tobacco products and of secondhand smoke, the effects of cessation (before diagnosis, during treatment, or during survivorship), the biologic mechanisms, and optimal strategies for tobacco dependence treatment in oncology. Fundamentally, tobacco is an important source of variation in clinical treatment trials. Nevertheless, tobacco use assessment has not been uniform in clinical trials. Progress has been impeded by a lack of consensus regarding tobacco use assessment suitable for cancer patients. The NCI-AACR Cancer Patient Tobacco Use Assessment Task Force identified priority research areas and developed recommendations for assessment items and timing of assessment in cancer research. A cognitive interview study was conducted with 30 cancer patients at the NIH Clinical Center to evaluate and improve the measurement items. The resulting Cancer Patient Tobacco Use Questionnaire (C-TUQ) includes “Core” items for minimal assessment of tobacco use at initial and follow-up time points, and an “Extension” set. Domains include the following: cigarette and other tobacco use status, intensity, and past use; use relative to cancer diagnosis and treatment; cessation approaches and history; and secondhand smoke exposure. The Task Force recommends that assessment occur at study entry and, at a minimum, at the end of protocol therapy in clinical trials. Broad adoption of the recommended measures and timing protocol, and pursuit of the recommended research priorities, will help us to achieve a clearer understanding of the significance of tobacco use and cessation for cancer patients. Clin Cancer Res; 22(8); 1907–13. ©2016 AACR.