Validity and Reliability of the US National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).
OBJECTIVE
To integrate the patient perspective into adverse event reporting, the National Cancer Institute developed a patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).


OBJECTIVE
To assess the construct validity, test-retest reliability, and responsiveness of PRO-CTCAE items.


METHODS
A total of 975 adults with cancer undergoing outpatient chemotherapy and/or radiation therapy enrolled in this questionnaire-based study between January 2011 and February 2012. Eligible participants could read English and had no clinically significant cognitive impairment. They completed PRO-CTCAE items on tablet computers in clinic waiting rooms at 9 US cancer centers and community oncology practices at 2 visits 1 to 6 weeks apart. A subset completed PRO-CTCAE items during an additional visit 1 business day after the first visit.


METHODS
Primary comparators were clinician-reported Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30).


RESULTS
A total of 940 of 975 (96.4%) and 852 of 940 (90.6%) participants completed PRO-CTCAE items at visits 1 and 2, respectively. At least 1 symptom was reported by 938 of 940 (99.8%) participants. Participants' median age was 59 years; 57.3% were female, 32.4% had a high school education or less, and 17.1% had an ECOG PS of 2 to 4. All PRO-CTCAE items had at least 1 correlation in the expected direction with a QLQ-C30 scale (111 of 124, P<.05 for all). Stronger correlations were seen between PRO-CTCAE items and conceptually related QLQ-C30 domains. Scores for 94 of 124 PRO-CTCAE items were higher in the ECOG PS 2 to 4 vs 0 to 1 group (58 of 124, P<.05 for all). Overall, 119 of 124 items met at least 1 construct validity criterion. Test-retest reliability was 0.7 or greater for 36 of 49 prespecified items (median [range] intraclass correlation coefficient, 0.76 [0.53-.96]). Correlations between PRO-CTCAE item changes and corresponding QLQ-C30 scale changes were statistically significant for 27 prespecified items (median [range] r=0.43 [0.10-.56]; all P≤.006).


CONCLUSIONS
Evidence demonstrates favorable validity, reliability, and responsiveness of PRO-CTCAE in a large, heterogeneous US sample of patients undergoing cancer treatment. Studies evaluating other measurement properties of PRO-CTCAE are under way to inform further development of PRO-CTCAE and its inclusion in cancer trials.
Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona.
Amylou C
AC
Dueck
Department of Symptom Research, University of Texas MD Anderson Cancer Center, Houston.
Tito R
TR
Mendoza
Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, Maryland.
Sandra A
SA
Mitchell
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill.
Bryce B
BB
Reeve
Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, Maryland.
Kathleen M
KM
Castro
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Lauren J
LJ
Rogak
Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, New York.
Thomas M
TM
Atkinson
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill.
Antonia V
AV
Bennett
Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, Maryland.
Andrea M
AM
Denicoff
Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland.
Ann M
AM
O'Mara
Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, New York.
Yuelin
Y
Li
Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, Maryland.
Steven B
SB
Clauser
Department of Clinical Research, Cancer Program of Our Lady of the Lake and Mary Bird Perkins, Baton Rouge, Louisiana.
Donna M
DM
Bryant
Gibbs Cancer Center and Research Institute, Spartanburg, South Carolina.
James D
JD
Bearden
Helen F. Graham Cancer Center and Research Institute, Christiana Care Health System, Newark, Delaware.
Theresa A
TA
Gillis
Center for Cancer Prevention and Treatment, St. Joseph Hospital of Orange, Orange, California.
Jay K
JK
Harness
Helen and Harry Gray Cancer Center, Hartford Hospital, Hartford, Connecticut.
Robert D
RD
Siegel
patient advocate and cancer survivor, Brooklyn, New York.
Diane B
DB
Paul
Department of Symptom Research, University of Texas MD Anderson Cancer Center, Houston.
Charles S
CS
Cleeland
Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts.
Deborah
D
Schrag
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Jeff A
JA
Sloan
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Amy P
AP
Abernethy
Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia.
Deborah W
DW
Bruner
Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, Maryland.
Lori M
LM
Minasian
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill5Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Ethan
E
Basch
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000145:classification*; D000368:Aged; D000369:Aged, 80 and over; D000553:Ambulatory Care; D000970:Antineoplastic Agents / Q000009:adverse effects*; D059248:Chemoradiotherapy / Q000009:adverse effects*; D034201:Computers, Handheld; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054547:National Cancer Institute (U.S.); D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000532:radiotherapy*; D011788:Quality of Life; D011832:Radiation Injuries / Q000145:classification* / Q000209:etiology; D011878:Radiotherapy / Q000009:adverse effects; D015203:Reproducibility of Results; D057566:Self Report; D011795:Surveys and Questionnaires; D009626:Terminology as Topic; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
D000970:Antineoplastic Agents