Adverse symptom event reporting by patients vs clinicians: relationships with clinical outcomes

Abstract

Background: In cancer treatment trials, the standard source of adverse symptom data is clinician reporting by use of items from the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). Patient self-reporting has been proposed as an additional data source, but the implications of such a shift are not understood.

Methods: Patients with lung cancer receiving chemotherapy and their clinicians independently reported six CTCAE symptoms and Karnofsky Performance Status longitudinally at sequential office visits. To compare how patient's vs clinician's reports relate to sentinel clinical events, a time-dependent Cox regression model was used to measure associations between reaching particular CTCAE grade severity thresholds with the risk of death and emergency room visits. To measure concordance of CTCAE reports with indices of daily health status, Kendall tau rank correlation coefficients were calculated for each symptom with EuroQoL EQ-5D questionnaire and global question scores. Statistical tests were two-sided.

Results: A total of 163 patients were enrolled for an average of 12 months (range = 1-28 months), with a mean of 11 visits and 67 (41%) deaths. CTCAE reports were submitted by clinicians at 95% of visits and by patients at 80% of visits. Patients generally reported symptoms earlier and more frequently than clinicians. Statistically significant associations with death and emergency room admissions were seen for clinician reports of fatigue (P < .001), nausea (P = .01), constipation (P = .038), and Karnofsky Performance Status (P < .001) but not for patient reports of these items. Higher concordance with EuroQoL EQ-5D questionnaire and global question scores was observed for patient-reported symptoms than for clinician-reported symptoms.

Conclusions: Longitudinally collected clinician CTCAE assessments better predict unfavorable clinical events, whereas patient reports better reflect daily health status. These perspectives are complementary, each providing clinically meaningful information. Inclusion of both types of data in treatment trial results and drug labels appears to be warranted.

Figures

Figure 1

Cumulative incidence of symptoms and performance status as reported by patients vs clinicians and by month of follow-up, with death considered as a competing risk. A) Moderate (grade 2) or severe (grade 3) symptoms according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0. B) Karnofsky Performance Status. A Karnofsky score of 70 is defined as “Cares for self; unable to carry on normal activity or to do active work,” whereas a score of 60 is defined as “Requires occasional assistance, but is able to care for most of his personal needs” (30).

Figure 2

Relative strengths of concordance of patient-reported and clinician-reported Karnofsky Performance Status and symptoms with two measures of health status (28,29). A) Concordance with EuroQoL EQ-5D questionnaire scores. B) Concordance with 0–100 global question scores. Solid squares = patient reported; open squares = clinician reported. For each relationship, Kendall tau rank correlation coefficients are shown with 95% confidence intervals, with −1 representing perfect negative concordance, 0 representing independence, and +1 representing perfect positive concordance.