Validity of patient-reported outcomes to describe the symptom experience of patients enrolled on phase I clinical trials.

Abstract

12107 Background: Symptoms are common among patients enrolled in phase I trials. To integrate the patient perspective, the National Cancer Institute developed a patient-reported outcomes version of the CTCAE (PRO-CTCAE) to capture symptomatic adverse events (AEs) directly from patients; however, the tool has not been used often in early phase trials or in palliative care studies. Our overall objective was to assess the validity of PRO-CTCAE items to previously validated assessments of quality of life (FACT-G) and psychological distress (Distress Thermometer). We utilized data from a randomized trial testing a palliative care intervention for patients with cancer enrolled on phase I trials. Methods: Patients (n = 481) were accrued to the parent study prior to initiating a Phase I clinical trial with data collected at baseline, 4, and 12 weeks. We determined the correlation of PRO-CTCAE with Distress Level, FACT-G total and subscale domain scores. Aggregate scores using PRO-CTCAE were calculated to explore the effect of overall symptom frequency, severity, and interference by calculating the total of all scored items classified within each of those domains. We used these metrics to identify associations between this and other validated tools. Results: Patients were predominantly female (56.8%), over age 60, and 30.7% were minority populations. Correlations between PRO-CTCAE items and corresponding FACT-G (total and subscales) and Distress levels reached statistical significance for all items (p < 0.001). Importantly, many of symptoms captured would have been missed using HRQOL assessment tools. Some of these symptoms affected nearly 50% of patients and were frequently rated as severe or very severe. The correlation coefficient for Distress Level for all PRO-CTCAE items was small to moderate (Pearson r = 0.33 to 0.46). Pearson’s correlation coefficient for FACT-G total was moderate ( r = -0.45 to -0.69). Mood items of the PRO-CTCAE had stronger associations (Pearson r > 0.5). PRO-CTCAE symptom interference scores had the strongest correlation with Distress (Pearson r = 0.46) and FACT-G Total (Pearson r = -0.69). Conclusions: Patients entering Phase I trials are willing to report on symptoms they experience as a result of advancing disease and adverse effects from experimental treatment. Evidence demonstrates favorable validity of PRO-CTCAE in a heterogeneous US sample of patients undergoing cancer treatment on phase I trials. The granular assessment of symptomatic AEs may be on increasing importance as we enter a new therapeutic era in oncology. Clinical trial information: NCT01828775 .