Validity and usefulness of a single-item measure of patient-reported bother from side effects of cancer therapy

Abstract

Background: The improving efficacy of cancer treatment has resulted in an increasing array of treatment-related symptoms and associated burdens imposed on individuals undergoing aggressive treatment of their disease. Often, clinical trials compare therapies that have different types, and severities, of adverse effects. Whether rated by clinicians or patients themselves, it can be difficult to know which side effect profile is more disruptive or bothersome to patients. A simple summary index of bother can help to adjudicate the variability in adverse effects across treatments being compared with each other.

Methods: Across 4 studies, a total of 5765 patients enrolled in cooperative group studies and industry-sponsored clinical trials were the subjects of the current study. Patients were diagnosed with a range of primary cancer sites, including bladder, brain, breast, colon/rectum, head/neck, hepatobiliary, kidney, lung, ovary, pancreas, and prostate as well as leukemia and lymphoma. All patients were administered the Functional Assessment of Cancer Therapy-General version (FACT-G). The single item "I am bothered by side effects of treatment" (GP5), rated on a 5-point Likert scale, is part of the FACT-G. To determine its validity as a useful summary measure from the patient perspective, it was correlated with individual and aggregated clinician-rated adverse events and patient reports of their general ability to enjoy life.

Results: Analyses of pharmaceutical trials demonstrated that mean GP5 scores ("I am bothered by side effects of treatment") significantly differed by maximum adverse event grade (P<.001) in all trials, with a clear trend toward increasing GP5 scores with level of increasing adverse event grade. Effect sizes ranged from 0.13 to 0.46. Analyses of cooperative group trials demonstrated a significant correlation between GP5 and item GF3 ("I am able to enjoy life") in the predicted direction.

Conclusions: The single FACT-G item "I am bothered by side effects of treatment" is significantly associated with clinician-reported adverse events and with patients' ability to enjoy their lives. It has promise as an overall summary measure of the burden of a given set of treatment toxicities compared with another. Future research can identify the contribution of individual side effects compared with one another in terms of how each may contribute to overall bother. Cancer 2018;124:991-7. © 2017 American Cancer Society.

Keywords: cancer treatment; clinical trials; measurement science; oncology practice; outcomes; patient-reported outcomes (PROs); quality of life.

Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES

Jennifer L. Beaumont has acted as a paid consultant for Novartis and received honorarium from GlaxoSmithKline for work performed outside of the current study. Daniel Mroczek was supported by National Institutes of Health/National Institute on Aging grant R01-AG018436 for work performed as part of the current study. David Cella was supported by a grant from Novartis for work performed as part of the current study and has had a patent issued for FACIT.org.

© 2017 American Cancer Society.

Figures

Figure 1

Mean Functional Assessment of Cancer Therapy-General version (FACT-G) single-item GP5 (“I am bothered by side effects of treatment”) scores by maximum adverse event (AE) grade. COMPARZ indicates Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma; ENESTnd, Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients; SE, standard error.

Figure 2

Mean number of adverse events (AEs) of any grade by Functional Assessment of Cancer Therapy-General version (FACT-G) single-item GP5 (“I am bothered by side effects of treatment”) response on day 28 of cycle 2 of the COMPARZ (Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma) study. SE, standard error.

Figure 3

Mean EuroQOL 5 Dimensions (EQ-5D) index scores by Functional Assessment of Cancer Therapy-General version (FACT-G) single-item GP5 (“I am bothered by side effects of treatment”) response in the National Comprehensive Cancer Network study (533 patients). SE indicates standard error.