No abstract

Despite the wide use of the New York Heart Association/World Health Organization functional class in clinical care and as a research tool, interrater agreement may be inadequate. Efforts to promote a uniform approach to evaluating functional class might help to standardize PAH care and research.

Pediatric patient-reported outcome (PRO) data can help inform the U.S. Food and Drug Administration’s (FDA) benefit-risk assessment of cancer therapeutics by quantifying symptom and functional outcomes from the patient’s perspective. This study assessed use of PROs in commercial pediatric oncology trials submitted to FDA for regulatory review. FDA databases were searched to identify pediatric oncology product applications approved between 1997 and 2020. Sponsor-submitted documents were reviewed to determine whether PRO data were collected, which instruments were used, and the quality of collected data (sample size, completion rates, and use of fit-for-purpose instruments). The role of PROs in each trial (endpoint hierarchy) was also recorded, along with whether any PRO endpoints were included in product labeling. Seventeen pediatric oncology applications were reviewed, 4 included PRO data: Denosumab, Tisagenlecleucel, Larotrectinib, and Selumetinib. In these 4 instances, PROs served as exploratory endpoints and were not incorporated in product labeling. Trials collecting PRO data were Phase II or Phase I/II single-arm studies with sample sizes of 28 to 88 patients. Symptomatic Adverse Events were characterized using clinician-reported Common Terminology Criteria for Adverse Events (CTCAE) without additional patient self-report. PROs were infrequently utilized in pediatric cancer registration trials. When used, PRO data were limited by lack of a clear research objective and corresponding prospective statistical analysis plan. Contemporary PRO symptom libraries such as the National Cancer Institute’s Pediatric PRO-CTCAE may provide an opportunity to better evaluate the occurrence and impact of symptomatic Adverse Events, from the patient’s perspective, in pediatric oncology trials.

BACKGROUND:The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 Physical Functioning subscale is a widely used patient-reported outcome measure that quantifies cancer patients' physical functioning. Strong floor/ceiling effects can affect a scale's sensitivity to change. The aim of this study was to characterize floor/ceiling effects of the physical functioning domain in patients with advanced/metastatic breast cancer enrolled in commercial clinical trials and a community-based trial. METHODS: The clinical trial cohort comprised patients from 5 registrational trials submitted to the Food and Drug Administration for review (2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017). The community cohort comprised a subgroup of patients from the Alliance Patient Reported Outcomes to Enhance Cancer Treatment (PRO-TECT) trial. The distribution of patient responses to Physical Functioning items and the summed score were assessed at the baseline and 3-month follow-up for both cohorts. Descriptive statistics were used to determine floor/ceiling effects at the item and scale levels. RESULTS: The clinical trial cohort and the community cohort consisted of 2407 and 178 patients, respectively. Twenty-four percent or more of the respondents reported "not at all" for having trouble/needing help with each Physical Functioning item across both cohorts and measurement time points. Fourteen to twenty percent of the patients scored perfectly (100 of 100) on the Physical Functioning subscale summary measure (where higher scores indicated better physical functioning) across both cohorts and time points. CONCLUSIONS: Minor floor effects and notable ceiling effects were found at the item and scale levels of the Physical Functioning subscale, regardless of cohort, and this creates some uncertainty about its ability to detect changes in physical functioning among high-functioning patients. Investigators may consider adding additional high-functioning items from the EORTC's item library to more accurately describe the impact of anticancer treatment on patients' physical functioning.