IPA Agreement 8/2016

The purpose of this IPA is to inform the development of a research strategy to accomplish this goal, and to assist in the design, conduct, interpretation, and dissemination of a series of research studies (using both primary and secondary data analyses) to accomplish this overall objective of proposing an empirically-supported schema for mapping PRO-CTCAE responses into single grades. In our planned approach, we will borrow Standard Setting methods originally created to identify high and low achievers in the context of educational testing (see for example Cutscores: A manual for setting standards of performance on educational and occupational tests; Zieky, Perie, and Livingston), and adapted by Dr. Karon Cook and Dr. David Cella (Cook et al., QOLR, 2014; Cella et al., QOLR, 2014). These methods will be used to systematically elicit input from key stakeholders (clinicians and patients) in order to combine PRO-CTCAE responses for frequency, severity and/or interference to define meaningful thresholds for PRO-CTCAE core symptomatic toxicities that correspond to/are calibrated to CTCAE grades and may be expressed as a single parameter/grade/score. While the thresholds derived using these consensus judgments of patients and clinicians may be specific to each symptomatic toxicity, for the purposes of parsimony, we will look for commonalities in the thresholds. We will also evaluate the reproducibility and generalizability of these thresholds across diverse panels of clinician and patient respondents. The result of this research effort will be empirically-derived, patient-centered cut scores and CTCAE-linked or single patient grades for frequency/severity/interference PRO-CTCAE response levels, that enhance the interpretation of PRO-CTCAE in cancer clinical trials.