Development, Testing, and Implementation

Initial Development and Testing of PRO-CTCAE

From 2009 to 2015, the development and testing of PRO-CTCAE was funded through two contracts awarded to Memorial-Sloan Kettering Cancer Center (HHSN261200800043C and HHSN261201000063C), and partial support from the contract to develop the NCI NCCCP program (HHSN261200800001E). The National Cancer Institute’s overall goal with these contracts was to develop a measurement system that:

  • includes a psychometrically robust library of items;
  • integrates smoothly into clinical trials workflow;
  • is well accepted by clinicians, regulators and patients;
  • offers features that accommodate the needs of patients with limited English proficiency or lower digital literacy; and
  • supplies meaningful data to improve our understanding of symptomatic adverse effects of cancer treatment.

Continued Activities in the Testing and Implementation of PRO-CTCAE

Since the inception of the two contracts to develop the PRO-CTCAE measurement system, this work has been strategically directed by a multi-disciplinary team of leaders in patient-reported outcomes measurement in cancer clinical trials, drawn from across four NCI divisions. This team continues to guide the scientific development of the PRO-CTCAE measurement system, and directs efforts to scale the system for use across a wide variety of cancer clinical trials contexts, including early phase trials and precision medicine trials.

The current evidence base supports the use of PRO-CTCAE to provide descriptive reporting of symptomatic toxicities, alongside CTCAE grading by clinicians. Additional work is needed to understand the utility of PRO-CTCAE in various trial designs, to transform PRO-CTCAE scores into a CTCAE grade, and to interpret PRO-CTCAE scores in making decisions at the level of the patient, or drawing conclusions at the level of the trial, with respect to dose-limiting toxicity, dosing or schedule adjustments, and overall tolerability, including comparative tolerability.

There are more than 100 early adopters of PRO-CTCAE, including investigators in academic settings and in industry-sponsored trials. PRO-CTCAE is being used in a variety of study designs, including treatment trials and observational studies.

Partnerships established with these investigators:

    • ensure continuing integrity of the PRO-CTCAE tool while it is still in active development;
    • stimulate efficient and coordinated testing of PRO-CTCAE;
    • allow for sharing of data and collaborative analysis; and
    • generate evidence about best approaches for data interpretation and reporting in particular study contexts and specific patient populations.

Collaborations with leading national and international organizations to promote implementation and testing in cancer clinical trials and observational studies include:

    • NCI’s National Clinical Trials Network (NCTN) and Early Therapeutics Clinical Trials Network (ETCTN);
    • US Food and Drug Administration;
    • Italian NCI, Danish Cancer Society, European Medicines Agency, Swedish Medical Products Agency.

Activities in the next phase of PRO-CTCAE development are designed to ensure that the PRO-CTCAE system fulfills the requirements of a mature patient-reported outcome (PRO) measure (see Figure 1 below), and that data derived from PRO-CTCAE are interpretable and meaningful to trialists/clinicians, patients, and regulatory agencies. A pediatric version of PRO-CTCAE is currently in development.

Figure 1: PRO Maturity Model

Graphic titled: Figure 1: PRO Maturity Model[D]

Source: Smith AW, Mitchell SA, Deaguiar C, Moy C, Riley WT, Wagster M, Werner E. Person-Centered Outcomes Measurement: NIH-Supported Measurement Systems to Evaluate Self-Assessed Health, Function, and Symptomatic Toxicity. Translational Behavioral Medicine, 1-5. doi:10.1007/s13142-015-0345-9.