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Underreporting of Symptomatic Adverse Events in Phase I Clinical Trials

2021; Oxford University Press; Volume: 113; Issue: 8 Linguagem: Inglês

10.1093/jnci/djab015

1460-2105

Zachary Veitch, Daniel Shepshelovich, Christina Gallagher, Lisa Wang, Albiruni R. Abdul Razak, Anna Spreafico, Philippe L. Bédard, Lillian L. Siu, Lori M. Minasian, Aaron R. Hansen,

Cancer survivorship and care

Abstract Background Clinician reporting of symptomatic adverse events (AEs) in phase I trials uses the Common Terminology Criteria for Adverse Events (CTCAE). The utility of the patient-reported outcomes (PROs) version of the CTCAE (PRO-CTCAE) in this setting is unknown. This prospective, observational study compared patient- and clinician-reported symptomatic AEs in phase I patients. Methods Phase I study–eligible patients at Princess Margaret were surveyed with the PRO-CTCAE full-item library (78 symptomatic AEs) at baseline (BL), mid-cycle 1, and mid-cycle 2 (C2). Patient and trial characteristics, best response, and survival data were collected. Presence or absence of patient- (PRO-CTCAE) or clinician-reported symptomatic AEs were compared (kappa) at defined timepoints and overall (BL+ mid-cycle 1 + C2). Results Of 292 patients approached from May 2017 to January 2019, a total of 265 (90.8%) were consented, with 243 (91.7%) evaluable and 552 PRO-CTCAE surveys (completion rate = 98.7%) included in analyses. Evaluation of overall patient-reported symptomatic AEs identified 50 PRO-CTCAE and 11 CTCAE items with 10% or greater reporting frequency. Nineteen CTCAE items were reported as 1% or less despite matched PRO-CTCAE items reporting as 10% or greater. Underreported categories included sexual health, bodily emissions, and cognition. Clinician- relative to patient-reporting frequency (ratio) demonstrated 9 symptomatic AEs with a 50-fold or more lower clinician reporting rate. Overall patient–clinician agreement for individual symptomatic AEs ranged from poor (κ = 0.00-0.19) to moderate (κ = 0.40-0.59), with discordance driven by lack of clinician reporting. Dyspnea (κ = 0.54) and peripheral neuropathy (κ = 0.63) at BL and limb edema (κ = 0.55) at C2 demonstrated the highest patient–clinician agreement. Conclusions Poor to moderate patient–clinician agreement for symptomatic AEs suggests clinician underreporting in phase I trials. Analyses of severity and interference PRO categories are ongoing.