During a session presented at the 2016 ASCO Annual Meeting that discussed the benefits and challenges of assessing patient-reported outcomes (PROs) in the era of precision medicine and the integration of PROs into clinical trial data and regulatory reviews, ONS member Sandra A. Mitchell, PhD, CRNP, from the National Cancer Institute (NCI), presented the NCI’s PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. 

The PRO-CTCAE was developed to capture patient reports of the frequency, severity, and/or interference of symptoms, which is designed to be used as a companion to the CTCAE to capture the patient experience of symptomatic toxicities in clinical trials. The system includes 78 symptomatic AEs drawn from CTCAE with items evaluated based on frequency, severity, interference, amount, and presence of these symptoms. 

The software includes the following.

  • Creation and management of customized surveys
  • Patient interface
  • Conditional branching
  • Write-ins with automatic mapping to standardized terminology
  • Automated alerts

The portal features

  • A psychometrically robust library of items
  • Electronic system that fits data collection smoothly into trials workflow and offers favorable user-experience
  • Accommodations for patients with limited English proficiency and/or digital literacy
  • Meaningful data to improve understanding of symptomatic AEs.

A study of the PRO-CTCAE demonstrated favorable validity, reliability, and responsiveness in a large, heterogeneous sample of patients undergoing cancer treatment (N = 940). Most PRO-CTCAE items (n = 119/124) reached a statistically significant and meaningful effect size on at least one validity criteria (p < 0.05). A majority of the item tests (n = 27) also exhibited acceptable test-retest reliability and were sensitive to differences between groups.

Mitchell then compared PRO-CTCAE and clinician CTCAE grade.

    • Responses are scored from 0–4
    • Up to three questions per AE item: frequency, severity, interference
    • Best way to combine these attributes is still under study
  • CTCAE 
    • Bundles the constructs of frequency, severity, and interference
    • Grading dependent upon clinician judgement of medical significance (life-threatening, need for intervention)

Additional work is needed to allow for clinical and protocol-specific decision-making (e.g., dose adjustments) based on individual PRO-CTCAE scores, Mitchell said. 

PRO-CTCAE is under observation with more than 100 adopters in 12 countries, with collaborations among national and international organizations (e.g., U.S. Food and Drug Administration, Danish Cancer Society, Italian NCI). 

“PRO reporting of symptomatic AEs yields data that is actionable clinically in real time (trial eligibility, dose reductions), essential to determinations of benefit and harm at the study level, and crucial to regulators, sponsors, and the public,” Mitchell said. 

Work is ongoing to enhance the interpretability and scale for wide-spread implementation of PRO-CTCAE. “[The] interpretation and clinical utility of PRO-CTCAE is still evolving,” Mitchell concluded.