Kristen Mason, MS, is a Senior Biostatistician at Rho. She has over 4 years of experience providing statistical support for studies conducted under the Immune Tolerance Network (ITN) and Clinical Trials in Organ Transplantation (CTOT). She has a particular interest in data visualization, especially creating visualizations within SAS using the graph template language (GTL).
The Common Terminology Criteria for Adverse Events (CTCAE) was developed to standardize reporting of adverse events (AEs). Originally developed for oncology trials by the National Cancer Institute (NCI), the CTCAE is now used widely across all types of clinical trials, and as a result has become an essential tool for evaluating trial safety. The CTCAE provides a library of over 800 AEs with guidelines for grading event severity. However, it fails to capture the day to day effects a patient might experience. In order to integrate the patient’s perspective into AE reporting, the NCI developed a patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).
What is PRO-CTCAE?
The PRO-CTCAE consists of 78 AEs with questions regarding the presence/absence, severity, frequency, and/or interference of symptomatic treatment side effects. These AEs were identified as symptoms that can be meaningfully reported by the patient, such as pain, fatigue, and nausea. Responses are provided on a 5-point Likert scale (generic form shown below) and refer to the patient’s experience in the last seven days. The tool is currently available for public use (https://healthcaredelivery.cancer.gov/pro-ctcae) and can be modified to reflect relevant toxicities of interest. The PRO-CTCAE has been translated into 18 languages with more on the way. Finally, the PRO-CTCAE is not intended to replace, but rather enhance, the CTCAE with the patient’s perspective, and therefore these should be used together.
How do the perspectives of the clinician and the patient differ?
Clinicians are often primarily concerned with patient safety, especially in a clinical trial setting. On the other hand, patients have to deal with the reality of managing symptoms that impact their daily life. Clinicians are also frequently exposed to patients with very serious toxicities, which may bias their perception. Furthermore, while an event may not seem serious to the clinician, it could interfere with the patient’s daily activities. Finally, patients may under-report symptoms for a variety of reasons, which could include time constraints of the visit, concerns about discontinuing treatment, or even being removed from the study entirely.
What else can be learned?
Another limitation of the CTCAE is that typically only the maximum severity of the event is reported. In other words, any potential change in AE severity cannot be detected. But, PRO-CTCAE can help answer these questions, such as: did the AE develop slowly or all at once? How long did the patient experience the worst of it?
What are the next steps?
The PRO-CTCAE is a work in progress and continues to be improved. Presently the tool is only intended to assess adults; however, another version is being developed for children and adolescents. Additionally, guidelines will need to be created that provide a standard approach for analyzing this new patient-focused data.