Summary
PRO-CTCAE is a patient-reported outcome (PRO) measurement system developed to evaluate symptomatic toxicity in patients on cancer clinical trials.It was designed to be used as a companion to the Common Terminology Criteria for Adverse Events (CTCAE), the standard lexicon for adverse event reporting in cancer clinical trials.The PRO-CTCAE Item Library (PDF, 164 KB) includes 124 items representing 78 symptomatic toxicities drawn from the CTCAE.PRO-CTCAE has been developed and tested with a conditional branching logic that helps to reduce respondent burden. Conditional branching is employed for electronic administration of PRO-CTCAE symptom terms that have two or more attributes (e.g., fatigue severity and interference or pain frequency, severity and interference). The logic branches from frequency, then to severity, and then to interference. For example, if frequency is greater than "Never", you next pose the severity question, and if severity is greater than "None", you pose the interference question.For more information on development and testing of the PRO-CTCAE Measurement System, refer to https://healthcaredelivery.cancer.gov/pro-ctcae/testing.htmlScoringThere are 80 core symptom based questions. Some questions are only asking for it's presence/absence (choices are yes or no) and some questions will include up to 3 parts representing symptom attributes. Questions with multiple parts will be labeled as 1a., 1b., and 1c. The letters a, b ,c represent symptom attributes, to include:FrequencySeverityInterferenceAmountAttribute based questions will have choices with a value of 0 to 4.Note: If the first attribute question is none or 0, the second and third attribute questions will not appear.See the following document for how each symptom is represented https://healthcaredelivery.cancer.gov/pro-ctcae/item-library.pdfQuestions asking about one of the above attributes will be scored with a Composite Grade or 1-3.-Grade 0 (Absent): 0 points-Grade 1 (Mild): 1 point-Grade 2 (Moderate): 2 points-Grade 3 (Severe): 3 or 4 pointsScoring for questions with only one attribute (A):-Grade 0: 0 points-Grade 1: 1 point-Grade 2: 2 points-Grade 3: 3 or 4 pointsScoring for questions with only two attributes (A):A1 (points)A2 (points)Grade0-0101 (max=1)111 (max=1)201 (A1 only elevated)2121222223+ (any)3+ (any)3One important practical note: one research group applying Basch et al.'s conversion tables specifically excluded configurations where a patient rated severity as zero but interference above zero, treating these as illogical combinations suggesting data entry error rather than valid responses. This is clinically relevant for Mouth/Throat Sores specifically — it would be unusual (though not impossible) for a patient to report no severity but meaningful interference. That group excluded rather than graded those combinations. The branch logic for this item: If the patient answers "None" on the severity question (S=0), the interference question will be hidden by branch logic and auto-coded as 0. The S=0/I>0 combination will never actually occur.Scoring for questions with three attributes (A):-Grade 0:Note: If first attribute 0 then other two attributes will not be asked -Grade 1The full set of Grade 1 combinations:F (points)S (points)I (Points)Reason10-max=1110max=1111max=1120*200F only elevated** *When F=1, Grade 2 only triggers when both S and I are elevated (at least one = 2, the other > 0). A lone S=2 or lone I=2 with F=1 stays Grade 1 per boundary rule.**When F=2, Grade 2 triggers as soon as either S or I is > 0 — because frequency being elevated means S and I are no longer isolated. The only F=2 exceptions that stay Grade 1 are S=0/I=0.-Grade 2:The full set of Grade 2 combinationsF (Points)S (points)I (points)121112122210211220221212222 The key thing to notice is the asymmetry between F=1 and F=2 rows:-When F=1, Grade 2 only triggers when both S and I are elevated (at least one = 2, the other > 0). A lone S=2 or lone I=2 with F=1 stays Grade 1 per boundary rule.-When F=2, Grade 2 triggers as soon as either S or I is > 0 — because frequency being elevated means S and I are no longer isolated. The only F=2 exceptions that stay Grade 1 are S=0/I=0. -Grade 3: With F>0 enforced by branch logic, and any attribute ≥3 triggering Grade 3, here are all combinations systematically. F, S, and I each run 0–4 but at least one must be ≥3:Where F=3 or F=4 (S and I can be anything 0–4):F (points)S (points)I (points)30-31032033034030-31132133134130-31232233234230-31332333334330-31432433434440-41042043044040-41142143144140-41242243244240-41342343344340-414424434444 Where F=1 or F=2, S≥3 or I≥3 (F alone doesn't trigger, but S or I does):F (points)S (points)I (points)130140131141113114132142123124133143134144230240231241213214232242223224233243234244Overview PublicationsKluetz PG, Chingos DT, Basch EM, Mitchell SA. Patient-Reported Outcomes in Cancer Clinical Trials: Measuring Symptomatic Adverse Events With the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Am Soc Clin Oncol Educ Book. 2016;35:67-73. Review. [View Abstract]Minasian LM, O'Mara A, Mitchell SA. Clinician and Patient Reporting of Symptomatic Adverse Events in Cancer Clinical Trials: Using CTCAE and PRO-CTCAE® to Provide Two Distinct and Complementary Perspectives Patient Relat Outcome Meas. 2022 Dec 8;13:249-258. doi:10.2147/PROM.S256567. [View Abstract]Smith AW, Mitchell SA, K De Aguiar C, Moy C, Riley WT, Wagster MV, M Werner E. News from the NIH: Person-centered outcomes measurement: NIH-supported measurement systems to evaluate self-assessed health, functional performance, and symptomatic toxicity. Transl Behav Med. 2016 Sep;6(3):470-4. [Look up in PubMed]More publications can be found at https://healthcaredelivery.cancer.gov/pro-ctcae/pubs.html