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Concerns regarding use of patient-reported outcomes in biomarker studies of chemotherapy-induced peripheral neuropathy

The Pharmacogenomics Journal volume 19, pages 411–416 (2019)Cite this article

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Since the early 2000s, there has been a major push toward supplementing CTCAE with validated patient-reported outcome (PRO) information, which has several potential advantages. Incidence and severity of toxicity tend to be higher when using PRO than CTCAE, and matched comparisons generally report poor to modest agreement, which is lowest for subjective toxicities. PRO can also provide more detailed symptom information and use a larger dynamic range, potentially enabling earlier detection and identification of subtle changes in severity [2]. In parallel with the integration of PRO into clinical research, real-time collection and sharing of PRO with clinicians during treatment has been reported to improve patient survival [3]. One of the main benefits of using PRO in clinical practice is that they reflect the effect the AE is having on the patient’s quality of life, enabling clinicians and patients to make shared treatment decisions based on the individual patient’s personal preferences and treatment goals.

PN data collected via CTCAE has substantial inter-observer variability and a known floor effect [4]. Several PRO tools have been developed to collect chemotherapy-induced PN including the Patient Neurotoxicity Questionnaire, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy (EORTC CIPN-20) [5]. More than a dozen studies have directly compared one of these PRO instruments, scored according to published guidelines, with CTCAE (Table 1). Across these studies, the incidence and severity of PN is consistently higher when collected via PRO, and the correlations between CTCAE and PRO PN are poor to moderate (correlation coefficients: 0.2–0.7). The limited correlation is often used as evidence to support the conclusion that PRO PN data are more sensitive and reliable than CTCAE data, however, this conclusion is difficult to empirically test without an objective benchmark to anchor comparisons.

Table 1 Comparisons of patient- and clinician-reported peripheral neuropathy
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Acknowledgements

I would like to acknowledge Lynn Henry, Karen Farris, Steve Erickson, Ellen Lavoie Smith and Jane Perlmutter for their critical review and feedback.

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  1. Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, 48109-1065, USA

    Daniel L. Hertz

  2. University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA

    Daniel L. Hertz

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Hertz, D.L. Concerns regarding use of patient-reported outcomes in biomarker studies of chemotherapy-induced peripheral neuropathy. Pharmacogenomics J 19, 411–416 (2019). https://doi.org/10.1038/s41397-019-0093-1

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